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ERRNVPHGLFRVRUJ

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LIPPINCO TT WILLIAMS & WILKINS, a WOLTERS KLUWER business
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©2010 Mayo Foundation for Medical Education and Research. All rights reserved. This book
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Library of Congress Cataloging-in-Publication Data

Unni, K. Krishnan, 1941–
Dahlin ’s bone tumors : gen eral aspects an d data on 10,165 cases / K. Krish nan Unn i,
Carrie Y. Inwards.—6th ed.
p. ; cm.
Includes bibliograph ical referen ces an d in dex.
ISBN 978-0-7817-6242-7 ( alk. paper)
1. Bon es—Tumors. I. In wards, Carrie Y. II. Mayo Foundation for Medical Education
and Research. III. Title. IV. Title: Bone tumors.
[ DNLM: 1. Bone Neoplasms. 2. Neoplasm Staging. WE 258 U58d 2010]
RC280.B6D33 2010
616.99'471—dc22
2009030870

Care has been taken to confi rm the accuracy of the information presented and to describe
generally accepted practices. H owever, the authors, editors, and publisher are not responsible
for errors or omissions or for any consequences from application of the information in
this book and make no warranty, express or implied, with respect to the contents of the
publication.

Th e auth ors, editors, an d publish er h ave exerted efforts to en sure th at drug selection an d
dosage set forth in this text are in accordance with current recommendations and practice at
the time of publication.

However, in view of ongoing research, changes in government regulations, and the constant
fl ow of in formation relatin g to drug th erapy an d drug reaction s, th e reader is urged to ch eck
the package insert for each drug for any change in indications and dosage and for added
warnings and precautions. This is particularly important when the recommended agent is a
n ew or in frequen tly employed drug.

Some drugs and medical devices presented in this publication have Food and Drug
Admin istration ( FDA) clearan ce for limited use in restricted research settin gs. It is th e
responsibility of h ealth care providers to ascertain th e FDA status of each drug or device
planned for use in their clinical practice.

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 To Dave and H elen Dahlin
and our families,
Sheila, Akhil, Aditiya, and Adosh
David, Sarah, and Ryan

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Preface
The Fifth Edition of Bone Tumors included statistics on
bone tumors from the Mayo Clinic fi les until the end
of 1993. This updated Sixth Edition contains informa-
tion about cases recorded until the end of 2003. We
have tried to remain true to the format fi rst used by
Dr. David C. Dahlin in the First Edition of this book.
However, we have made some modifi cations. In the fi rst
chapter, more emphasis has been placed on the han-
dling of bone specimens, both biopsy and larger speci-
mens, and grading and staging of neoplasms. There is
much confusion in the literature about grading of sar-
comas. General concepts about grading schemes used
at Mayo Clinic are provided. These schemes have been
elaborated on in the appropriate sections concerning
specifi c neoplasms. Staging of neoplasms is one of the
more important advances in our understanding of bone
tumors. The grade of the tumor is the cornerston e on
which staging is based.
Most of th e illustration s h ave been replaced. More
atten tion h as been paid to computed tomographic
and magnetic reson an ce images. The emphasis is still
on diagn oses based on h istologic section s stained with
h ematoxylin an d eosin. H owever, results of immu-
n operoxidase studies have been incorporated wh en
con sidered importan t.
iv
Several clinicopathologic studies incorporating large
numbers of cases have been done since the Fifth Edition
of this book. Such large numbers were possible because
of the consultation cases. Although follow-up informa-
tion may not be ideal in these cases, these large studies
have provided important information about radio-
graphic and histologic variations in different tumor
types. Chondroblastoma, osteoblastoma, and parosteal
osteosarcoma are examples in which this new informa-
tion has been incorporated. The section on neoplasm
simulators has been expanded to include some con-
ditions, such as neuropathic joint, that may present as
a neoplasm. The diagnosis should be made on radio-
graphic grounds, and the pathologist should not have
to look at the biopsy specimen. However, we see a num-
ber of cases every year in which this condition has been
mistaken for a neoplasm.
We hope that pathologists, orthopedic surgeons,
radiologists, and oncologists will fi nd the information
provided in this book to be useful to their practice.
K. K. Unni, M.B.B.S.
C. Y. Inwards, M.D.
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Surgeons in the Department of Orthopedics at Mayo
Clinic have had a long-standing interest in the man-
agement of patients with bone tumors. Drs. Ralph K.
Ghormley, Henry W. Meyerding, and Mark B. Coventry,
amon g others, contributed immensely in this area.
However, it was Dr. Jack Ivins who established ortho-
pedic oncology as a separate discipline at Mayo Clinic.
In addition to being an expert surgeon, Dr. Ivins was a
wonder ful human being, and we learned a great deal
from him. The work that these men started is contin-
ued by Drs. Franklin Sim, Douglas Pritchard, Thomas
Shives, and Michael Rock. To these men, we are very
grateful for the collaborative studies over the years, and
without them, of course, there would be no Mayo Clinic
series.
Orthopedic oncology is probably the fi nest example
of a multidisciplinary approach to caring for patients.
Radiology plays a vital role in this man agement.
Dr. David Pugh was a giant in the fi eld of orthope-
dic radiology. Drs. John Beabout, Richard McLeod,
an d, more recently, Doris Wenger, Ronald Swee, Kay
Cooper, Mark Adkins, and Mark Collins, contin ued this
great tradition. Without the help of these radiologists,
the practice of orthopedic pathology would be much
more diffi cult and much less fun. Dr. Doris Wenger has
been particularly helpful in improving the illustrations
pertaining to imaging in this edition.
Acknowledgments
It was the work of Dr. David C. Dahlin, however, that
put Mayo Clinic on the map in the fi eld of bone tumors.
Without question, Dr. Dahlin was one of the great
surgical pathologists of our time and certainly the great-
est bone tumor pathologist. As he himself said, he taught
us everything we know but not everything he knew. He
was generous to a fault toward us. This book is his brain-
child and it will always remain associated with him.
Debbie M. Balzum typed and retyped the manu-
script, working long hours. We are grateful for her
patience. Several members of the Section of Media Sup-
port Services helped in obtaining negatives and devel-
oping prints. The Section of Scientifi c Publications was
extremely helpful, especially O. Eugene Millhouse, PhD,
who per formed the laborious task of editing the
manuscript, and Roberta Schwartz, Kristin M. Nett, and
Kenna Atherton.
We have been very lucky in being associated with
some of the foremost surgical pathologists in the world.
More than anything, they have taught us a philosophy
of surgical pathology that we think is invaluable.
Drs. Malcolm Dockerty, Lewis Woolner, Edward Soule,
J. Aidan Carney, George Farrow, Ed Harrison, and Louis
Weiland have all been responsible for our training. We
are grateful that Dr. Lester Wold was an integral part of
our orthopedic pathology team. We continue to benefi t
by the work done by our younger colleagues.
v
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Contents

Preface iv
Acknowledgments v

1 Introduction and Scope of Study 1

2 Osteochondroma (Osteocartilaginous Exostosis) 9
3 Chondroma 22
4 Benign Chondroblastoma 41
5 Chondromyxoid Fibroma 50
6 Chondrosarcoma (Primary, Secondary, D edifferentiated, and Clear Cell) 60
7 Mesenchymal Chondrosarcoma 92
8 Osteoma 98
9 Osteoid Osteoma 10 2
10 Osteoblastoma (Giant Osteoid Osteoma) 11 2
11 Osteosarcoma 12 2
12 Parosteal Osteosarcoma (Juxtacortical Osteosarcoma) 15 8
13 Fibrosarcoma and D esmoplastic Fibroma 16 9
14 Benign Fibrous H istiocytoma 17 9
15 Malignant Fibrous H istiocytoma 18 4
16 Myeloma 19 1
17 Malignant Lymphoma of Bone 20 1
18 Ewing Tumor 21 1
19 Giant Cell Tumor (Osteoclastoma) 22 5
20 Malignancy in Giant Cell Tumor of Bone 24 3
21 Chordoma 24 8
22 Benign Vascular Tumors 26 2
23 Angiosarcoma and H emangiopericytoma 27 2
24 Adamantinoma of Long Bones 28 6

vi
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 ■ Contents vii

2 5 Miscellaneous U nusual Tumors of Bone 29 5

2 6 Conditions That Commonly Simulate Primary N eoplasms of Bone 30 5
2 7 Odontogenic and Related Tumors 38 1

Index 393

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Introduction and
Scope of Study
Tumors of bone are among the most uncommon of all
types of neoplasms. For instance, it is estimated that
2,900 new sarcomas of bone are recorded in the United
States per year. In comparison, 169,500 new cases of
carcinoma of the lung and 193,700 new cases of breast
carcinoma are diagnosed. On a numeric basis, obvi-
ously, bone tumors are relatively unimportant. How-
ever, many of the bone tumors affect young children
and are managed by radical surgery, with or without
radiotherapy and chemotherapy, which may have signif-
icant side effects. Most centers do not acquire extensive
experience in handling bone tumors. Hence, surgical
pathologists in most institutions are not familiar with
neoplasms of bone; consequently, a reasonably straight-
forward diagnosis may be a diffi cult one.
A team approach is necessary in the management
of a patient with a bone tumor. Good communication
among radiologists, orthopedic surgeons, and patholo-
gists is important for accurate diagnosis of most of these
neoplasms. A pathologist who tries to make a diagno-
sis on a diffi cult bone lesion without the advantage of
information about the clinical and radiographic fea-
tures is at a distinct disadvantage. Close cooperation of
the different specialties with one another ensures that
mistakes are kept to a minimum.
The importan ce of radiographs in th e in terpre-
tation of bone tumors can n ot be overemphasized.
Radiograph s, after all, are th e gross represen tation
of th e n eoplasm. Alth ough it is important for surgical
path ologists dealin g with n eoplasms of bon e to have
a rudimen tary un derstan din g of th e in terpretation of
radiograph s, it is even more importan t to h ave a radi-
ologist available wh o is in terested and h as en ough
experien ce to be helpful. Pathologists with a special
in terest in bone tumors may refuse to make a diagn o-
sis on a bon e biopsy specimen if th e radiograph s are
n ot available for review. Th is approach is too extreme.
If th e biopsy shows an osteosarcoma, th e diagn osis is
C H APT ER
1
an osteosarcoma regardless of wh at th e radiograph s
show. Kn owin g th at th e radiograph ic features support
the diagnosis of osteosarcoma will be comfortin g, but
it is n ot strictly necessary to review the radiograph s
person ally. O n th e oth er h an d, in some in stan ces, it
is foolh ardy to ren der a diagn osis with out havin g th e
radiograph s available for review. Most cartilaginous
tumors belong in th is category.
For most bone tumors, the patient’s local symptoms
and the results of physical examination are relatively
nonspecifi c. The usual symptoms—pain or swelling or
both—serve mainly as a guide to the correct site for the
radiographic studies and for biopsies. Accordingly, clin-
ical features of bone tumors have been relegated to a
relatively minor place in the discussion to follow. Clini-
cal judgment is always important; an osteoid osteoma,
in which referred pain may be at a site distant from the
lesion, may deceive an unwary clinician.
Laboratory studies are of little aid in th e diagn osis
of th e average bon e tumor. Myeloma, with its some-
times practically path ogn omon ic alteration of protein s
in th e serum or urin e, is a n otable exception . Alkalin e
ph osph atase levels may be in creased with an osteoid-
producin g n eoplasm, eith er primary or metastatic.
In creased levels of acid ph osph atase suggest metastatic
prostatic carcin oma. Th e omin ous n ature of a rapidly
growin g sarcoma, such as Ewin g tumor, may be in di-
cated by systemic eviden ce, in cludin g fever, an emia,
an d a rapid eryth rocyte sedimen tation rate.
Neoplasms of bone are being studied with several
new modalities, including immunohistochemical stains,
fl ow cytometry, and cytogenetics. These methods may
prove very important in the future. When such studies
are of practical importance, they have been so indi-
cated in the text. As of now, however, a diagnosis on
which therapy must be predicated and prognosis esti-
mated depends on the correct interpretation of mate-
rial removed by biopsy and stained by techn iques that
1
2 Chapter 1 ■
have been known for decades, augmented signifi cantly
by gross pathologic alterations, including those seen on
the radiograph. Electron microscopy is of very limited
value in the diagnostic interpretation of bone tumors.
Immunoperoxidase stains also have contributed very
little to improving our diagnostic skills in bone tumors,
with the notable exception of small cell malignancies.
In the chapters that follow, the information pro-
vided is based mainly on the personal experience of the
authors and not an exhaustive review of the literature.
Hence, the bibliography is short, and as in earlier edi-
tions, specifi c references are not cited in the text.
IMAGIN G MOD ALITIES
The following section provides some basic information
about the different imagin g modalities commonly used
in the work-up of a patient with a bone tumor.
BON E SCAN
Radioisotope bone scans are used to localize a bone
lesion and are especially useful to detect multicentric
disease. A positive bone scan merely suggests bone for-
mation, which may be reactive, and hence provides no
information about the type of pathologic process.
PLAIN RAD IOGRAPH
Plain radiographs provide the most useful information
about th e type of lesion being studied.
LOCATION
The type of bone involved is very important information;
one should hardly consider the diagnosis of adamanti-
noma if the radiograph does not show involvement of
the tibia. The site of involvement within the bone also is
of critical importance. We see even experienced ortho-
pedic surgeons list “tumor of the hip.” Does this mean
the joint, the proximal femur, or the acetabulum? Most
tumors and tumor-like conditions arise in the metaphy-
sis of long bones, but a few are typically epiphyseal. Cor-
tical involvement is characteristic of adamantinoma.
The type of defect produced in the bone provides
diagnostic clues. An area of lytic destruction is described
as being geographic. If the lesion is well demarcated, a
benign process is suggested. If, in addition, the lesion
is circumscribed with sclerosis, a benign lesion is highly
likely. If the lesion is poorly demarcated or “margin-
ated,” an aggressive lesion is likely. However, it is not
necessarily malignant.
A rapidly evolving lesion produces small defects in
bone with interspersed normal tissue. This pattern is
referred to as moth-eaten. Osteomyelitis and malignant
tumors ( especially small cell tumors) frequently pro-
duce this pattern.
If the lesion is extremely fast growing, it produces
minute defects that may be diffi cult to detect on plain
radiographs. This feature is suggestive of small cell
malignancies such as Ewing tumor.
The pattern of involvement of the cortex also pro-
vides clues to the nature of the lesion. A thickened cor-
tex means that the bone has responded to the lesion
present, and hence it is likely to be indolent. If the cor-
tex is breached and the periosteum lifted, periosteal
new bone is usually formed. The Codman triangle is
composed of reactive new bone formation at the site
where the periosteum is lifted off and has no diagnostic
signifi cance. Slow-growing lesions are generally asso-
ciated with thick continuous layers of periosteal new
bone, whereas aggressive lesions are associated with
thin discontinuous layers of new bone.
PRACTICAL APPROACH TO RAPID
H ISTOLOGIC D IAGN OSIS
Successful th erapy for malign an t disease requires th at
treatmen t be accomplish ed before systemic dissemi-
n ation h as occurred. It is axiomatic, th erefore, th at
wh en th e treatmen t of ch oice is ablative surger y, th e
procedure sh ould be don e at th e earliest practical
momen t in an attempt to remove th e tumor before
n eoplastic embolization leads to death of th e patien t.
At least 90% of bone tumors have soft portions that
can be sectioned and examined for immediate diag-
nosis. In most cases, these soft portions afford the best
material for diagnosis. For example, a sclerosing osteo-
sarcoma almost invariably has noncalcifi ed zones at its
periphery. Study of the radiograph guides the surgeon
to these zones, from which biopsy specimens can be
obtained for early diagnosis. Protracted decalcifi cation
of densely sclerotic portions of the tumor or adjacent
cortical bone only delays therapy.
Fresh frozen sections allow an immediate, accurate,
defi nitive diagnosis of more than 90% of bone tumors.
The rare lesion that is too diffi cult or too ossifi ed for
rapid interpretation can also be easily recognized. As
with fi xed sections of various types, good histologic
preparations and sound basic understanding of the
pathologic features are requisites for successful interpre-
tation of frozen sections. Defi ciency in either requisite
tends to make one deprecate this diagnostic medium.
At Mayo Clinic, the frozen-section laboratory is
adjacent to the surgical suites. The surgeon frequently
comes to the frozen-section laboratory carrying the
biopsy specimen and the corresponding radiograph.
It is important to examine the biopsy specimen grossly
to separate fragments of bone from the soft, fl eshy

material that almost all bone tumors have. This step
is important even if frozen sections are not obtained.
Some neoplasms, such as lymphoma, may be associated
with a sclerotic reaction. It may be necessary to tease
out small fragments of fl eshy tumor with the tip of a
scalpel blade. Th is material can be processed separately
an d does not require decalcifi cation.
At our institution, a freezing microtome, rather than
a cryostat, is used for making frozen sections. The biopsy
material is placed on the stage, which is then cooled.
The tissue freezes from the bottom toward the top.
When about half of the material is frozen, the unfrozen
material from the top is cut off with a microtome; this
material usually does not have many frozen-section arti-
facts and can be used for permanent sections. A section
is obtained from the frozen tissue, and the section is
rolled off the blade with a glass rod. The tissue is stained
with methylene blue, and excess stain is washed off. The
stained section is mounted with water. The whole pro-
cess should take no more than 30 to 45 seconds.
This method has several advantages. First and most
important perhaps is the identifi cation of viable and
diagnostic material. Even if a specifi c diagnosis is not
made on the frozen section, the surgeon can be reas-
sured that diagnostic material has been obtained and it
is not necessary to obtain better material. Second, if the
lesion under consideration is deemed to be in fectious,
cultures can be done. Third, a defi nite diagnosis can be
made with assurance in most tumors. Many malignant
neoplasms are no longer treated surgically immediately
after diagnosis is made. However, many of the benign
an d low-grade malignant tumors can be treated imme-
diately. This has the advantages of not subjecting the
patient to a second anesthetic procedure and reduc-
in g hospital stay. Fresh frozen sections can also be used
for checking the adequacy of margins. Obviously, it is
impossible to check all margins on a large sarcoma of
bone or soft tissue. However, at least margins deemed
“close” by the surgeon can be checked microscopically.
A margin that is free only microscopically may be too
close.
If a diagn osis can n ot be made immediately, it
sh ould still be possible to make on e with in 24 h ours.
As men tion ed above, almost all bon e tumors h ave soft
portion s. It is very importan t to separate th e mate-
rial from th e bon y fragmen ts with wh ich it may be
admixed. Th is material sh ould be processed with out
decalcifi cation . H owever, decalcifi cation may be n eces-
sary in some rare in stan ces, even for diagn ostic mate-
rial. Decalcifi cation is certain ly n ecessary for larger
specimen s, such as resection s for osteosarcoma after
ch emoth erapy. Several differen t decalcifi cation meth -
ods are available. At Mayo Clin ic, 20% formic acid an d
10% formalin are routin ely used. Th e solution is made
by mixin g 400 mL of formic acid in 1,600 mL of 10%
■ Introduction and Scope of Study 3
formalin . It is importan t to make th in slices of tissue so
th at decalcifi cation is rapid. Examin in g th e specimen
periodically to make sure th at overdecalcifi cation does
n ot occur is importan t.
Core needle biopsy and fi ne-needle aspiration are
also popular methods for diagnosing bone lesions; the
latter has more or less replaced the former. At our insti-
tution, we use a method that combines the two. The
biopsy is per formed by a radiologist under computed
tomographic guidance with a 14- to 16-gauge needle.
Smears are made and stained with a Papanicolaou tech-
nique. If they yield diagnostic material, the radiolo-
gist is so informed, and the small core of tissue that is
always obtained is used to make permanen t sections.
We occasionally make a frozen section from the core if
the smears are negative. The biopsy may be repeated if
both are negative.
We reviewed our experience with fi ne-needle aspira-
tions for the period from April 1993 to April 2003. The
number of procedures performed each year has changed
little (about 84 per year) . It was disappointing that the
number of nondiagnostic biopsies has not diminished
with increasing experience. Part of the explanation may
be that aspirations are done in lesions, such as cysts,
with little hope of obtaining diagnostic material. As with
any “new” technique, there is a temptation to overuti-
lize it. Next to “nondiagnostic” (39%), metastatic carci-
noma was the most common diagnosis made. Myeloma,
lymphoma, and osteosarcoma were the most common
“primary” neoplasms diagnosed.
Per forming fi ne-needle aspirations clearly has advan-
tages. The most obvious is the avoidance of using an
operating room. The chance for contamination of the
biopsy site is also reduced. Fine-needle aspiration is
often said to be cost-effective; however, a negative biopsy
adds to the cost. Increasingly, oncologists are demand-
ing special studies, such as cytogenetics and molecular
studies, before a patient is admitted to a protocol. Radi-
ologists are responding by taking multiple cores for this
purpose. It must be remembered that we do not exam-
ine the tissue that is used for special studies; hence, we
cannot be sure that the material being studied is repre-
sentative.
A special laboratory for handling specimens of
bone is not necessary. The gross dissection is simi-
lar whether the specimen is a major resection or an
amputation. Comparing the gross specimen with the
radiograph is important to determine the exact loca-
tion of the neoplasm. The soft tissue surrounding the
bone and the attached neoplasm are dissected away, so
that only the bone and the attached neoplasm are left
behind. The specimen is cut in half with a band saw
or a butcher’s meat saw. The specimen is washed gen-
tly with running water and bone dust is removed with
a brush. Cleaning the specimen avoids artifacts in the
4 Chapter 1 ■
microscopic sections caused by bone dust. An alternate
method is to freeze the entire specimen and bisect it.
Although this method has the advantage of preserving
the gross anatomy, it has the disadvantages of delay and
freezing and thawing artifacts.
GRAD IN G AN D STAGIN G
OF BON E TU MORS
The grading system used at Mayo Clinic essentially
follows the grading system that Dr. A. C. Broders pro-
posed for epithelial malignant tumors. The grade of the
neoplasm depends on the cellularity of the lesion and
the cytologic features of the neoplastic cells. Low-grade
neoplasms simulate the appearance of the putative cell
of origin of the neoplasm. High-grade malignant lesions
have such undifferen tiated malignant cells that their cell
of origin is, at best, conjectural. Although more com-
mon in h igher grade neoplasms, necrosis is not used as a
criterion for grading. Similarly, mitotic fi gures are more
common in higher grade malignant lesions, but mitotic
count is not used for grading tumors. Most bone tumors
are graded 1 to 4, with the exception of cartilage tumors
and vascular neoplasms, which have only three grades.
Grading of a neoplasm demands a morphologic varia-
tion within a given entity. For example, because Ewing
sarcoma has little variation from tumor to tumor, there
is no practical way to grade Ewing sarcoma. This is true
also of some low-grade neoplasms, such as adamanti-
noma. In some neoplasms, such as chordomas, experi-
ence has shown that variation in cytologic features is not
correlated with clin ical prognosis. Hence, there is no
point in grading chordomas.
This grading system is admittedly subjective, but no
more so than other gradin g systems. Orthopedic oncol-
ogists demand that tumors be graded because the grade
of the neoplasm is an important part of staging. Fortu-
nately, it is only necessary to say whether the neoplasm
is low grade or high grade.
The stagin g system used by th e Musculoskeletal
Tumor Society is a distin ct advan ce in th e managemen t
of patien ts with bon e tumors. Tumors are staged pri-
marily on th e grade of th e neoplasm an d th e exten t
of in volvemen t. Wh en n o distan t metastases are pres-
ent, all low-grade tumors are stage I an d all h igh -grade
tumors are stage II. If the n eoplasm is con fi ned to th e
bon e, it is con sidered stage A, and if th e tumor has
also in volved th e soft tissues, it is con sidered stage B.
H en ce low-grade tumors can be divided in to stages
IA and IB, depen ding on th e an atomic exten t of th e
n eoplasm. Similarly, high -grade tumors, th at is, stage
II, can also be divided in to A and B on th e basis of
the an atomic extent of th e tumor. All tumors with dis-
tan t metastasis are considered stage III regardless of
oth er consideration s. This stagin g system promotes
the use of un iform criteria for comparison of results of
treatmen t from differen t institutions aroun d the world.
It also affords progn ostic in formation .
It is useful to know the terminology orthopedic oncol-
ogists use in referring to surgical margins. When the
entire compartment in which the neoplasm is situated
is removed completely, radical margin is the term used.
In a tumor involving the distal femur, a radical margin
requires that the entire femur be removed. When the
tumor is removed completely with surrounding normal
tissue, wide margin is the term used. This surrounding
tissue should also include the so-called reactive zone
around the neoplasm. The reactive zone is an area com-
posed of capillary proliferation apparently surrounding
a tumor as it grows. When the tumor is removed com-
pletely but the resection margin does not remove the
entire reactive zone, the term marginal margin is used.
The resection is considered to be intralesional when the
tumor is removed but no attempt is made to obtain nor-
mal tissues around it.
CLASSIFICATION
The classifi cation in this book ( Table 1.1) is similar to
that advocated by Lichtenstein. One signifi can t differ-
ence is that little attempt is made to draw a relationship
between benign and malignant tumors, because so few of
the latter take origin from the former. The classifi cation
is based on the cytologic features or the recognizable
products of the proliferating cells. In most instances,
the tumors are considered to arise from the type of tis-
sue they produce, but such an assumption cannot be
proven. For example, most chondrosarcomas begin in
portions of bone that normally contain no obviously
benign cartilaginous zones. In any event, basing clas-
sifi cation on what is actually seen histologically allows
reduplication of results on subsequent analysis. Some of
the lesions in the general classifi cation are probably not
neoplasms in the strict sense.
The tabulated statistics in this book are of an unse-
lected series of bone tumors, except for the following
factors. A case is included when a complete surgical
specimen or adequate biopsy material was obtained and
excluded when histologic verifi cation of the diagnosis
according to modern pathologic concepts was impos-
sible. The pathologic features have been reviewed in
most of these cases as part of clinicopathologic studies.
All patients were seen at Mayo Clinic for care, a circum-
stance that could have introduced a possible selection
factor of questionable signifi cance. The material col-
lected in the consultation fi les is not used in the tabu-
lations. However, material from this source is used for
better understanding of the radiographic and histologic
features of many of these neoplasms.
 ■ Introduction and Scope of Study 5

TABL E 1.1. D istribution of Bone Tumors by H istologic Type and by Age of Patients

Age Distribution by Decades Total no

of
Histologic Type 1 2 3 4 5 6 7 8 9 10 Patients
Benign
Hematopoietic 0
Chondrogenic
Osteochondroma 115 502 184 111 55 33 14 10 1,024
Ch on droma 40 88 76 86 88 54 28 14 4 478
Ch on droblastoma 4 89 24 13 5 11 1 147
Ch on dromyxoid fi broma 5 11 18 6 4 5 1 50
Osteogenic
Osteoid osteoma 53 200 89 37 8 3 4 2 396
Osteoblastoma 6 49 33 10 3 5 1 1 108
Unknown origin
Gian t cell tumor 4 98 236 166 94 49 18 5 1 671
Histiocytic
( Fibrous) Histiocytoma 1 3 1 3 1 1 10
Notochordal 0
Vascular
Hemangioma 5 16 18 23 36 26 18 6 1 149
Lipogenic
Lipoma 1 1 3 2 3 1 11
Neurogenic
Neurilemmoma 5 6 3 3 1 3 2 23
Total benign 232 1,059 688 457 302 190 91 42 6 3,067

Malignant
Hematopoietic
Myeloma 1 10 66 165 288 311 184 40 4 1,069
Malign an t lymph oma 23 70 89 86 123 171 184 119 36 4 905
Chondrogenic
Primary ch on drosarcoma 7 56 128 209 222 217 154 68 11 1 1,073
Secondary chondrosarcoma 10 42 39 34 20 8 2 155
Dedifferen tiated 2 3 10 26 46 27 23 7 1 145
ch on drosarcoma
Clear cell 3 3 7 8 3 2 26
Mesen ch ymal 8 14 17 5 1 1 46
Osteogenic
Osteosarcoma 94 874 329 170 164 129 134 47 11 1,952
Parosteal osteosarcoma 13 29 21 8 4 75
Unknown origin
Ewing tumor 101 356 98 37 14 5 611
Malign an t gian t cell tumor 8 11 11 6 3 39
Adaman tin oma 2 12 17 3 2 2 2 40
Malign an t fi brous 1 13 8 16 21 11 20 6 2 98
h istiocytoma
Fibrogenic
Desmoplastic fi broma 2 5 3 1 1 3 1 16
Fibrosarcoma 6 32 35 55 39 51 38 23 6 285
Notochordal
Ch ordoma 8 18 28 53 80 108 92 41 8 1 437
Vascular
An giosarcoma 3 17 17 17 15 17 14 8 1 109
Hemangiopericytoma 2 3 4 3 2 1 15
Lipogenic
Liposarcoma 1 1 2
Neurogenic 0
Total malignant 247 1,492 861 822 942 1,086 989 525 123 11 7,098
6 Chapter 1 ■
H EMATOPOIETIC TU MORS
Hematopoietic tumors, 1,974 in number, were the third
most prevalent tumors of bone in the fi les at Mayo
Clinic. Included were 1,069 myelomas and 905 lympho-
mas. In the previous editions of this book, hematopoi-
etic tumors were the most prevalent tumors. However,
in this edition, we have included only those cases of
myeloma diagnosed with a closed or open biopsy of a
bone tumor and not those diagnosed with a bone mar-
row biopsy.
CH ON D ROGEN IC TU MORS
Th e largest group con sisted of 3,118 ch on drogen ic
tumors. Th ese tumors were placed in th is group
because th eir h istologic appearan ce proved or sug-
gested a relation sh ip to h yalin e cartilage. Th is group
formed more th an 30% of th e total series, an d th e
osteoch on dromas ( osteocartilagin ous exostosis) con -
stituted 32.8% of th e ch on drogen ic group. Th e osteo-
ch on droma results from th e growth of its cartilage cap,
wh ich makes th e lesion basically ch on drogen ic. Ch on -
droma, wh eth er cen trally or subperiosteally located, is
a tumor of h yalin e cartilage th at may con tain variable
amoun ts of calcifi cation an d ossifi cation with in its sub-
stan ce. Ben ign ch on droblastoma h as been differen ti-
ated from th e “wastebasket” of gian t cell tumor of bon e
because its proliferatin g cells produce foci of a matrix
substan ce similar to th at of h yalin e cartilage. Alth ough
ch on dromyxoid fi broma h as a variegated h istologic
appearan ce, large or small zon es ordin arily bear a
strikin g resemblan ce to h yalin e cartilage. Both primary
an d secon dary ch ondrosarcomas occur. Approximately
10% of eith er type dedifferen tiate in to h igh ly malig-
n an t n eoplasms. Mesen ch ymal ch on drosarcoma is rec-
ogn ized as a distin ctive lesion .
OSTEOGEN IC TU MORS
Of th e 2,531 osteogenic tumors, 1,952 were osteosarco-
mas. For a tumor to qualify for this group, the malig-
nant neoplastic cells of the tumor must, in at least some
portions, produce recognizable osteoid substance. With
this basic qualifi cation, the osteosarcomas logically fall
into three classes, namely, osteoblastic, chondroblastic,
and fi broblastic, depending on the dominant histologic
structure. The basic biologic behavior of these tumor
subtypes, however, is similar, as shown in the chapter on
osteosarcoma.
Periosteal osteosarcoma is now recognizable as a sep-
arate entity, and its features will be illustrated. The 67
telangiectatic osteosarcomas are described in Chapter 11.
The clinically indolent and pathologically slowly pro-
gressing low-grade tumors that have become generally
known as parosteal, or juxtacortical, osteosarcomas
have been placed in a separate subdivision. In addi-
tion, there are 21 examples of low-grade intraosseous
osteosarcomas.
The Mayo Clinic fi les contained 396 osteoid osteo-
mas. They have arbitrarily been classifi ed as bone
tumors, notwithstanding the controversy about whether
this lesion is a true neoplasm or some peculiar reaction
in bone. The 108 tumors that may be called giant osteoid
osteoma, or osteoblastoma, still generate controversy.
TU MORS OF U N KN OWN ORIGIN
Th e most frequen t tumor of un kn own origin recorded
in th e Mayo Clin ic fi les was ben ign gian t cell tumor
( 671 examples) . Almost as prevalen t was Ewin g tumor
( 611 cases) . Th e gian t cells of th e ben ign gian t cell
tumor appear to arise from stromal cells, th e exact ori-
gin of wh ich is un kn own . It h as been suggested th at
th e mon on uclear cells arise from un differen tiated
mesen ch ymal cells of bon e. Th e diagn osis of malig-
n an t gian t cell tumor can n ot be substan tiated un less
typical zon es of ben ign gian t cell tumor can be dem-
on strated in th e curren t or previous tissue from th e
same case. O n ly 39 examples of malign an t gian t cell
tumor are recorded in th e Mayo Clin ic fi les. Adaman -
tin oma of lon g bon es, still con sidered of un kn own ori-
gin , accoun ted for on ly 44 tumors ( in 40 patien ts) in
th e series.
FIBROGEN IC TU MORS
In the fourth edition of th is book, fi broma of bon e, or
metaph yseal fi brous defect, was in cluded as a ben ign
coun terpart of a fi brogenic tumor. Th is lesion is n ow
categorized as a neoplasm simulator because it is
n ot con sidered to be a true n eoplasm. O n ly one exam-
ple of th e rare an d con troversial fi brocartilagin ous
mesen ch ymoma was foun d in th e series. Th ere were
16 examples of desmoplastic fi broma; alth ough classed
amon g th e malignan t tumors, they probably occupy a
gray zon e between ben ign an d malignan t n eoplasms.
H en ce, fi brosarcoma becomes th e domin an t tumor in
this group.
H ISTIOCYTIC TU MORS
Neoplasms of apparent histiocytic origin are still uncom-
mon in bone. Benign and atypical fi brous histiocytoma
is a nebulous diagnosis at best. The term malignant
fi brous histiocytoma is used when the tumor is pleomor-
phic and shows no matrix production. Only 98 tumors
were classifi ed as malignant fi brous histiocytoma in the
Mayo Clinic fi les.
 TABL E 1.2. Skeletal D istribution of Bone Tumors

Maxilla
and Nasal
Femur Tibia Fibula Tarsals Foot Patella Humerus Radius Ulna Carpals Hand Scapula Clavicle Ribs Sternum Vertebrae Sacrum Innominate Skull Mandible Cavity Total

Benign
Osteoch on droma 320 153 40 8 3 0 147 21 10 0 15 43 4 24 0 22 4 70 0 0 0 884
Ch on droma 81 22 13 1 17 1 72 6 5 2 180 11 0 0 2 5 1 7 0 0 0 426
Ch on droblastoma 42 26 1 12 0 4 29 1 1 0 0 6 0 3 0 1 0 13 7 1 0 147
Ch on dromyxoid 6 16 1 0 7 0 1 2 2 1 1 1 1 0 0 1 0 8 2 0 0 50
fi broma
Osteoid osteoma 147 72 6 19 4 0 34 7 12 6 27 6 0 0 0 36 8 9 2 2 0 397
Osteoblastoma 11 9 2 5 0 1 5 0 1 1 1 1 1 2 0 34 10 9 2 11 2 108
Giant cell tumor 203 166 16 7 2 1 35 75 15 5 11 1 0 5 2 42 56 34 6 0 0 682
Fibrous 2 1 0 0 1 0 1 0 0 0 0 0 0 0 0 5 0 0 0 0 0 10
histiocytoma
Heman gioma 9 4 2 2 0 1 3 1 1 0 1 4 1 5 0 37 3 5 55 6 9 149
Lipoma 3 1 1 1 0 0 1 0 1 0 0 0 0 1 0 0 0 0 2 0 0 11
Neurilemmoma 2 1 0 0 0 0 0 0 0 0 0 1 0 1 0 0 9 0 3 6 0 23
Total ben ign 826 471 82 55 34 8 328 113 48 15 236 74 7 41 4 183 91 155 79 26 11 2,887
Malignant
Myeloma 157 11 1 0 0 0 86 5 4 0 0 27 37 157 32 296 52 138 41 6 7 1,057
Malign an t 200 60 4 5 1 3 83 6 13 1 2 35 18 61 22 125 47 130 39 36 14 905
lymphoma
Primary 224 65 31 12 9 0 133 9 3 1 14 55 6 120 28 61 24 237 9 2 29 1,072
chondrosarcoma
Secon dary 27 12 7 2 1 0 11 0 0 1 0 8 2 7 0 9 5 62 0 0 1 155
chondrosarcoma
Dedifferentiated 57 6 1 0 0 0 20 0 0 0 0 5 0 5 0 3 0 48 0 0 0 145
chondrosarcoma
Clear cell 11 0 0 0 0 0 5 0 1 0 0 0 0 2 1 3 0 2 0 0 1 26
chondrosarcoma *
Mesenchymal 6 1 1 0 1 0 1 1 0 0 0 1 0 4 0 4 2 4 1 5 4 36
ch on drosarcoma
Osteosarcoma 771 357 62 16 3 1 185 25 10 0 5 36 14 40 11 47 40 178 46 63 74 1,984
Parosteal 53 9 3 0 0 0 8 0 2 0 0 0 0 0 0 0 0 0 0 0 0 75
osteosarcoma
Ewin g tumor 131 50 41 13 16 0 56 13 13 1 4 27 11 48 2 25 36 115 6 6 0 614
Malignant giant 16 6 0 0 0 0 5 0 0 0 0 0 0 0 0 2 5 5 0 0 0 39
cell tumor
Adaman tin oma 2 34 4 0 0 0 0 1 2 0 0 0 0 0 0 0 0 0 0 0 0 43
( Fibrous) 35 14 1 0 0 0 8 1 3 0 0 2 0 0 1 2 6 12 6 1 6 98
h istiocytoma
Desmoplastic 2 2 0 1 0 0 1 2 1 0 0 2 0 0 0 0 0 2 0 3 0 16
fi broma
Fibrosarcoma 75 42 5 4 0 0 23 1 1 0 3 7 1 9 1 14 18 44 7 19 12 286
Chordoma 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 70 197 0 170 0 0 437
An giosarcoma 13 11 2 2 6 2 11 1 2 0 7 1 2 5 0 15 2 20 5 0 2 109
Heman giopericytoma 2 1 0 0 0 0 1 0 0 0 0 0 0 1 1 2 1 4 1 1 0 15

Total malign an t 1,771 682 162 55 37 6 632 65 54 4 35 206 91 457 98 675 434 999 332 142 149 7,086
Total series 2,597 1,153 244 110 71 14 960 178 102 19 271 280 98 498 102 858 525 1,154 411 168 160 9,973

7
*Th ese tumors are in cluded in th e primary ch on drosarcoma group.
8 Chapter 1 ■
N OTOCH ORD AL TU MORS
The series included 437 chordomas. Metastasis of noto-
chordal tumors is somewhat unusual, and because death
usually results from local recurrence and extension, the
lesion has been placed in the category of malignant
tumors.
TU MORS OF VASCU LAR ORIGIN
Although angiomas are commonly seen on radiographs,
only 149 hemangiomas were recorded in the Mayo
Clinic fi les. The terms hemangioendothelioma, hemangio-
endothelial sarcoma, and angiosarcoma have all been used
for malignant tumors of endothelial origin, and 109
such examples were located in the Mayo Clinic fi les.
Primary hemangiopericytoma in bone, extremely rare,
accounted for only 15 tumors noted in the Mayo Clinic
fi les.
LIPOGEN IC TU MORS
The present series included 11 lipomas of bone and
only 2 primary liposarcomas. Most tumors with multi-
nucleated giant cells possessing foamy cytoplasm that
suggests origin from adipose connective tissue were
classifi ed with the osteosarcomas or with the malignant
fi brous h istiocytomas. This decision was based on the
observation that oth er tumors containing zones of obvi-
ous osteosarcoma or qualifying as fi brous histiocytomas
had similar histologic appearances.
N EU ROGEN IC TU MORS
Primary neurilemmoma of bone is uncommon. There
were 23 examples in the Mayo Clinic fi les. Six involved
the mandible and nine the sacrum. When the tumor
involves the presacral region, it is frequently diffi cult to
know whether it should be considered a primary bone
neoplasm or a soft-tissue lesion invading bone second-
arily. There were no malignant neurogenic tumors orig-
inatin g in bone.
U N CLASSIFIED TU MORS
A few tumors had to be excluded from the total series
because there was insuffi cient tissue for accurate classi-
fi cation. Another group, constituting approximately 1%
of the total, did not fi t into a niche in the classifi cation.
These neoplasms form a h eterogeneous group that, for
the time being, must be called unclassifi ed.
SKELETAL AN D AGE D ISTRIBU TION
The skeletal distribution of the various types of bone
tumors in Table 1.2 affords the reader a convenient
guide for comparative incidence, whether interest is in
a specifi c neoplasm or in an affected bone. The knowl-
edge that some tumors almost never occur in a certain
bone and that other tumors have a predilection for
certain bones often is of assistance in arriving at the cor-
rect diagnosis. It is noteworthy, for instance, that only 5
of the 1,984 osteosarcomas affected bones of the hands
and wrist and that all but 4 of the 103 lesions of the ster-
num were malignant.
Some tumors have a decided predilection for patients
of certain age groups. This knowledge is often useful
in arriving at a preoperative diagnosis. In the succeed-
ing chapters, the age distribution for each neoplasm is
shown by a bar graph. Tables 1.1 and 1.2 show the spe-
cifi c data for each neoplasm.
BIBLIOGRAPH Y
1951 Lich ten stein , L.: Classifi cation of Primary Tumors of Bon e.
Cancer, 4:335–341.
1951 Pugh, D. G.: Roentgenologic Diagnosis of Diseases of Bones.
New York, Th omas Nelson & Son s, 316 pp.
1953 Dockerty, M. B.: Rapid Frozen Sections—Technique of Their
Preparation and Staining. Surg Gynecol Obstet, 97:113–120.
1955 Schajowicz, F.: Aspiration Biopsy in Bone Lesions: Cytological
and Histological Techniques. J Bone Joint Surg, 37A:465–471.
1958 Jaffe, H. L.: Tumors and Tumorous Conditions of the Bones
an d Join ts. Ph iladelph ia, Lea & Febiger, 629 pp.
1971 Murray, R. O. and Jacobson, H. G.: The Radiology of Skel-
etal Disorders: Exercises in Diagnosis. Baltimore, Williams &
Wilkins Compan y, 1,320 pp.
1972 Lich ten stein , L.: Bon e Tumors, ed. 4. St. Louis, C.V. Mosby
Compan y, 441 pp.
1973 Edeiken, J. and Hodes, P. J.: Roentgen Diagnosis of Diseases
of Bon e, ed. 2, vols. 1 an d 2. Baltimore, Williams & Wilkin s
Compan y, 1,156 pp.
1973 The Netherlands Committee on Bone Tumours: Radio-
logic Atlas of Bon e Tumours, vols. 1 an d 2. Baltimore, Williams
& Wilkin s Compan y, 600 pp.
1981 Madewell, J. E., Ragsdale, B. D., and Sweet, D. E.: Radio-
logic an d Path ologic An alysis of Solitary Bon e Lesion s. Part I:
Intern al Margin s. Radiol Clin North Am, 19:715–748.
1981 Ragsdale, B. D., Madewell, J. E., and Sweet, D. E.: Radio-
logic and Path ologic An alysis of Solitary Bone Lesion s. Part II:
Periosteal Reactions. Radiol Clin North Am, 19:749–783.
1981 Sweet, D. E., Madewell, J. E., and Ragsdale, B. D.: Radio-
logic an d Path ologic An alysis of Solitary Bon e Lesion s. Part
III: Matrix Pattern s. Radiol Clin North Am, 19:785–814.
1989 Mirra, J. M.: Bone Tumors: Clinical, Radiologic, and Patho-
logic Correlation s. Ph iladelph ia, Lea & Febiger, 1,831 pp.
1990 Campanacci, M.: Bone and Soft Tissue Tumors. New York,
Springer-Verlag, 1,131 pp.
1991 Huvos, A. G.: Bone Tumors: Diagnosis, Treatment, and Prog-
nosis, ed. 2. Philadelphia, W.B. Saunders Company, 784 pp.
1994 Schajowicz, F.: Tumors and Tumorlike Lesions of Bone:
Pathology, Radiology, and Treatment, ed. 2. New York, Springer-
Verlag, 649 pp.
1998 Dor fman, H. D. and Czerniak, B.: Bone Tumors. St. Louis,
Mosby, 1,261 pp.

Osteochondroma
(Osteocartilaginous Exostosis)
Osteochondromas arise on the sur face of bone and
are composed of a cartilage-capped osseous stalk that
is continuous with the underlying bone. The majority
of osteochondromas occur as solitary lesions. However,
approximately 15% of osteochondromas occur in the
settin g of multiple osteochondromas or hereditary multiple
exostoses, an autosomal dominant disorder characterized
by multiple osteochondromas. In almost 90% of patients
with hereditary multiple exostoses, germline mutations
in the tumor-suppressor genes EXT1 or EXT2 are found.
In addition, EXT1 has been found to act as a tumor sup-
pressor gene in the cartilage cap of solitary nonheredi-
tary osteochondromas. Growth of osteochondromas
usually parallels that of the patient, and the lesion often
becomes quiescent wh en the epiphyses have closed.
Spontaneous regression has been described.
Bony spurs that result from trauma or degenerative
joint disease may simulate the appearance of osteochon-
dromas but do n ot belong in the same group.
Some patien ts with multiple h ereditary exostoses
also h ave oth er developmen tal abn ormalities of bon e
such as sh orten in g of th e uln a an d displacemen t of th e
radius outward. Th e fi bula also may be sh orten ed. In
addition , th ere is lack of tubulation of th e lon g bon es,
wh ich may be especially promin en t in th e femoral n eck
region . Each tumor in patien ts with multiple h eredi-
tary exostoses h as a ch aracteristic th at will be described
for th e solitary form. Th e exact risk of ch on drosar-
comatous ch an ge in patien ts with multiple exostoses
is un kn own because of selection factors related to
th e in dication for surgery in in dividual patien ts with
ben ign or suspected malign an t tumors an d th e lack
of follow-up from birth to death in a large group of
selected patien ts with multiple osteoch on dromas ( th e
same drawbacks apply to th e calculation of th e risk for
patien ts with oth er ben ign con dition s, such as multiple
ch on dromas) . Peterson , after follow-up studies in a
n umber of patien ts with multiple h ereditary exostoses,
C H APT ER
2
th ough t th at malign an t ch an ge occurs in fewer th an
1% of patien ts.
In a study of 75 patients with chondrosarcoma second-
ary to osteochondroma, Garrison and coauthors found
that 27.3% of patients with multiple osteochondromas
who underwent surgery had secondary chondrosar-
comas, whereas only 3.2% of patients with the solitary
form had malignant change. A later study by Ahmed
and coauthors found the incidence to be 36.3% and
7.6%, respectively. However, these fi gures are probably
an exaggeration because of selection factors. Patients
with secondary malignant lesions are much more likely
to seek medical attention. Most patients with multiple
exostoses have many, sometimes innumerable, lesions
that may be grossly deforming, although an occasional
patient has only two or three lesions. One patient in the
Mayo Clinic series had polyposis of the colon.
Subungual exostoses are peculiar projections from
the distal portion of the terminal phalanx, usually the
fi rst toe. They are almost certainly a form of heterotopic
ossifi cation. These exostoses are not included in the
data on osteochondromas, although they possess some
of the radiographic and pathologic features of osteo-
chondroma.
IN CID EN CE
Osteochondromas accounted for 33.4% of the benign
bone tumors and 10.1% of all tumors in the Mayo Clinic
series. Of all tumors in the chondrogenic series, 32.8%
were osteochondromas. Most osteochondromas are
asymptomatic and are never found, and many of those
that are discovered are never excised, so that the actual
incidence is much greater than these fi gures for surgi-
cal cases indicate. Approximately 86% of the patients
( 884) had solitary lesions. One patient with a lesion of
the proximal fi bula had received radiation treatment
for a desmoid tumor previously ( Fig. 2.1) .
9
10 Chapter 2 ■
SEX
Approximately 62% of the patients in both the solitary
and the multiple exostoses groups were males. The lit-
erature indicates little sex predilection.
AGE
At the time of the fi rst excision of the osteochondroma,
approximately 60% of the patients were younger than
20 years, and 49% were in the second decade of life.
The ages of patients with multiple exostoses closely par-
alleled th e ages of patients with single exostosis.
LOCALIZATION
O steoch on dromas may occur on an y bon e in wh ich
en ch on dral ossifi cation develops. Th ey usually occur in
th e metaph yseal region of th e lon g bon es of th e limbs.
Rarely, th ey are n ear or in th e middle of such bon es.
Th e lower en d of th e femur, th e upper end of th e
h umerus, an d th e upper en d of th e tibia, in th at order,
were most frequen tly in volved. Th e ilium con tributed
53 of th e 70 osteochon dromas arisin g from th e in n omi-
n ate bon e. O n ly 26 patien ts with solitary lesion s h ad
in volvemen t of th e small bon es of th e h an ds an d feet.
In volvemen t of th e small bon es is n ot un common in
patien ts with multiple h ereditary exostoses. An osteo-
ch on droma-like lesion of a small bon e is much more
F igu r e 2.1. Distribution of osteo-
chondromas by age and sex of the
patient and site of the lesion. Skel-
etal site not counted in patients with
multiple exostoses (1,024 patients
and 884 sites).
likely to be a reactive process. Th e bon es of th e skull
an d jaw were n ot in volved with osteoch on droma.
SYMPTOMS
Th e patien t’s symptoms are gen erally related to th e
size of th e tumor. Th e most common complain t is th at
of a h ard swellin g, usually of lon g duration . Pain may
result from impin gemen t of th e tumor on n eigh bor-
in g structures an d from weigh t-bearin g or oth er activ-
ity. Pain or mass effect may be caused by an overlyin g
bursa. An overlyin g bursa was sign ifi can t en ough to
be described in 13 of th e cases. Th e bursa may sug-
gest a soft tissue mass an d h en ce th e possibility of a
secon dar y ch on drosarcoma. Ultrasoun d examin ation
h as been suggested to be of use in recogn izin g th e
bursa. Th e bursa may con tain osteocartilagin ous loose
bodies or even n odules of syn ovial ch on dromatosis.
O n e in stan ce of n odules of ch on drosarcoma situated
in a bursa overlyin g a secon dary ch on drosarcoma an d
simulatin g ch on dromatosis h as been described. Pain
may also result from a fracture th rough th e stalk of th e
osteoch on droma.
PH YSICAL FIN D IN GS
A palpable mass is ordinarily the only fi nding. Secondary
effects may occur, especially when the tumor impinges
on the spinal canal.

RAD IOGRAPH IC FEATU RES
The characteristic radiographic appearance is a projec-
tion composed of a cortex continuous with that of the
underlying bone and spongiosa, similarly continuous.
The adjacent cortex often fl ares to become the base of
the tumor. The projection may have a broad base or
be distinctly pedunculated. Irregular zones of calcifi ca-
tion may be present, especially in the cartilaginous cap,
but extensive calcifi cation with radiolucent irregulari-
ties of the cap should arouse the suspicion of malignant
ch ange. Osteochondroma commonly arises at the site of
tendon insertions, and the direction of growth is often
along the line of the tendon’s pull. Pedunculated osteo-
ch ondromas characteristically point away from the near-
est joint. The affected bone is often abnormally wide at
the level of an osteochondroma because of failure of
normal tubulation. Such widening is especially likely
in patients with multiple exostoses. In some instances,
computed tomograph ic images and magnetic reso-
nance images may be useful in demonstrating the conti-
nuity between th e osteochondroma and the underlying
bone, especially in lesions of fl at bones. These modern
techn iques are also helpful in accurately delineating
the thickness of the cartilage cap ( Figs. 2.2–2.6) .
F igu r e 2.2. An teroposterior radiograph of an osteoch on -
droma in volving th e righ t femur.
■ Osteochondroma (Osteocartilaginous Exostosis) 11
GROSS PATH OLOGIC FEATU RES
The gross pathologic features confi rm the radiographic
pattern. Sessile exostoses may be fl at, whereas pedun-
culated ones are somewhat long and slender, and varia-
tions between these exist. Many are caulifl ower-shaped,
with or without a stalk ( Fig. 2.7) .
The cortex and periosteal covering of the tumor are
continuous with those of the underlying bone. A bursa
may develop over the exostosis. The marrow of the
tumor may be fatty or hematopoietic, often mirroring
the status of the spongiosa of the underlying bone with
which it merges ( Figs. 2.6 & 2.8) .
The gross specimen should be cut perpendicular
to the bony stalk so that the true thickness of the car-
tilage cap can be measured. This cap may cover the
entire external sur face of a sessile tumor, but it covers
only the rounded end of a stalked exostosis. The cap is
ordinarily 2 to 3 mm thick and has a smooth sur face.
The cartilage may be 1 cm or more in thickness in the
actively growing benign exostosis of adolescents (Fig. 2.7) .
Irregularity and thickening of the cap, especially in an
adult, demands careful histologic study because of the
likelihood of secondary chondrosarcoma. Although a
rare thinner cap may be associated with malignancy,
F igu r e 2.3. Coron al T1-weigh ted MRI of an osteoch ondroma
involvin g the left femur. The lesion h as a thin cartilage cap.
12 Chapter 2 ■

F igu r e 2.4. Large osteochondroma of the proximal

humerus. A: The cortex of the humerus sweeps out in to the
cortex of th e osteoch on droma, an d th e medullary cavity is
similarly con tinuous. Alth ough th e lesion is large, th e carti-
lage cap is th in an d regular. B: Gross appearan ce. Th e carti-
lage cap is th in an d smooth . Much of th e lesion is composed
of bon e. Th ere is fatty an d h ematopoietic marrow with in th e
stalk.

F igu r e 2.5. Multiple h ereditary exostoses.

The individual osteochondromas have the
same appearance as those in patients with soli-
tary exostoses. There is lack of tubulation of
the distal femur.
 ■ Osteochondroma (Osteocartilaginous Exostosis) 13

F igu r e 2.6. A bursa associated with an osteoch on droma

produced a large mass, suggesting the diagnosis of secondary
ch on drosarcoma. F igu r e 2.7. Typical gross appearance of an osteochondroma.
Th e cartilage cap is somewh at th ick but smooth . Th e ch alky-
white areas are calcifi cation.

F igu r e 2.8. A bursa associated with an osteoch on droma in th e left femur. A: Th e computed
tomogram sh ows th at th e patien t h as multiple h ereditary exostoses, because a lesion in volves th e
right femur also. Th is occurren ce clin ically suggested a secondary chondrosarcoma. B: The bursa
after removal from the sur face of the osteochondroma. A secondary chondrosarcoma involving the
ilium developed approximately 10 years later.
14 Chapter 2 ■
secondary chondrosarcomas are usually at least 2 cm
in thickness. Cystic change within a cartilage cap also
is a cause for concern. If the cartilaginous rim is thin
and regular and the underlying spongiosa appears to
be normal, the tumor is always benign. If the exostosis
is arrested, as may occur in adults, there may be practi-
cally no cartilaginous cap. This appearance is especially
likely with the rare osteochondroma associated with an
overlying bursa. The osteochondroma giving rise to the
bursa may be tiny and overlooked.
H ISTOPATH OLOGIC FEATU RES
Under low power, a regular cartilage cap merges into
underlying bone. A thin, pink, fi brous lining over the
cartilage cap represents the periosteum of the under-
lying bone lifted off by the growth of the osteochon-
droma. The superfi cial portions of the cartilage cap
contain chondrocytes in clusters and in lacunae. Toward
the base of the lesion, where enchondral ossifi cation
occurs, the lacunae tend to line up in columns, simu-
lating the appearance of n ormal epiphyseal plate. The
typical benign chondrocyte has a small nucleus that may
F igu r e 2.9. Low-power appearan ce of an osteoch on droma.
Th e ch on drocytes h ave an orderly arran gemen t in th e carti-
lage cap, and there is maturation into trabecular-appearing
bon e. Th e in tertrabecular spaces con tain fatty an d h ematopoi-
etic marrow.
be diffi cult to see under low power. When bone growth is
active, binucleated cartilage cells may be seen fairly fre-
quently in benign exostoses. Malignant transformation
of an exostosis is nearly always to a chondrosarcoma;
the histologic features are described in a later chapter.
Other sarcomas arising in osteochondromas are rare,
hence, medical curiosities. Islands of cartilage are some-
times embedded in the underlying cancellous bone, and
these islands may undergo degeneration with irregular
calcifi cation, which is sometimes visible on radiographs.
As indicated by the gross appearance, the cartilaginous
cap involutes after the osteochondroma ceases to grow
and may even disappear entirely. Trauma may produce
fi broblastic proliferation and even new bone formation
in the stalk of an osteochondroma. Ordinarily, fatty or
hematopoietic marrow is found between bony trabecu-
lae. Spindle cell proliferation should suggest the pos-
sibility of a parosteal osteosarcoma, which may closely
simulate the appearance of an osteochondroma. Radio-
graphic features are extremely useful in differentiat-
ing these two entities. In osteochondroma, the lesion
and the underlying marrow are always continuous, but
in parosteal osteosarcoma, there is no such continuity
( Figs. 2.9–2.14) .
F igu r e 2.10. Junction between the cartilage cap and the
bon y stalk. It is not un usual to see residual islan ds of cartilage
in the middle of bony trabeculae in the stalk. This appearance
is not invasion and does not suggest malignancy.
 ■ Osteochondroma (Osteocartilaginous Exostosis) 15

F igu r e 2.11. Th e ch on drocytes in th e cartilage cap h ave a

very characteristic columnar arrangement toward the base,
where enchondral ossifi cation occurs. The appearance is simi- F igu r e 2.12. Focal myxoid change may be seen in the carti-
lar to that in an epiphyseal plate. lage cap. However, large areas of myxoid change and cystifi ca-
tion are worrisome for secondary chondrosarcoma.

F igu r e 2.13. Calcifi cation ( A) and degenerative change ( B) within the cartilage cap.
16 Chapter 2 ■
F igu r e 2.14. H igh -power appearan ce of th e cartilage cap
in an osteochondroma. The lesion is hypocellular, although
ch on drocytes are somewh at en larged an d h yperch romatic.
TREATMEN T
An osteocartilaginous exostosis in itself is insuffi cient
reason for surgical extirpation because malignant trans-
formation occurs in only about 1% of clinically recog-
nized osteochondromas. Removal is indicated if the
tumor is unsightly, is producing pain or disability, has
radiographic features of malignancy, or shows an abnor-
mal increase in size.
Removal of the tumor fl ush with the bone of origin is
appropriate when surgical intervention is indicated. The
entire cartilaginous cap should be removed. In some
locations, such as a rib, block excision of the affected
bone is best, especially if the diagnosis is uncertain.
Although chondrosarcoma is much more common in
patients with multiple exostoses, the precursor tumors
are too numerous to allow prophylactic removal. The
same general principles for removal are used whether
the tumor is multiple or solitary.
PROGN OSIS
Osteochondroma is nearly always cured by complete
excision. In our series, just over 2% of the tumors either
were recurrent when the patient came to Mayo Clinic or
recurred after excision at Mayo Clinic. These recurrent
lesions required a second operation at intervals that
varied from 1 year to 26 years, although all recurrent
lesions were benign. Second operations in these cases
were curative. Failure to remove the entire cartilaginous
cap or even its underlying periosteum probably is the
basis for most recurrences. Sometimes a nearby similar
cartilaginous focus is inadvertently left behind and pro-
duces a second tumor.
Recurrence suggests that the original tumor was a
chondrosarcoma. Such was the case in some of the ear-
lier tumors erroneously classifi ed as osteochondroma in
this series.
SARCOMA IN SOLITARY
OSTEOCH ON D ROMA
Eighty-two exostoses not included in the foregoing
data on osteochondromas gave rise to chondrosarcomas.
The features of th ese tumors are furth er elaborated in
the chapter on ch ondrosarcoma. Radiographic, gross,
and microscopic evidence related these malignant
tumors to the benign precursor. These 82 tumors
accounted for 8.5% of all solitary exostoses in which
treatment was surgical, but this fi gure does not accurately
represent the incidence of malignant change, because
so many benign tumors are not treated surgically. Fur-
thermore, patients with sarcomatous change probably
are seen in tertiary medical centers.
In the Mayo Clinic series, two osteosarcomas arose
in a parosteal or juxtacortical location but within the
lesions that bore stigmata of preexisting osteoch on-
droma. One lesion was on the medial aspect and one
on the posterior medial aspect of the distal portion of
the shaft of the femur, but n either was characteristic
of ordinary parosteal osteosarcoma. In addition, four
dedifferentiated chon drosarcomas arose in solitary
exostoses.
SARCOMA IN MU LTIPLE EXOSTOSES
None of the 140 patients with multiple exostoses whose
data are included in Fig. 2.1 had sarcoma, but an addi-
tional 44 patients with multiple exostoses have been
treated for secondary chondrosarcoma at Mayo Clinic.
Although this is approximately a 24% incidence of
malignant change, the selection factors in our series
make fi rm conclusions unwise. A single osteosarcoma
complicated multiple exostoses; it occurred in an osteo-
chondroma of the temporal bone. A single dedifferen-
tiated chondrosarcoma arose in a patient with multiple
exostoses.
 ■ Osteochondroma (Osteocartilaginous Exostosis) 17

SU BU N GU AL EXOSTOSES

The 88 exostoses removed from the distal portions of

the distal phalan xes were not included in the data on
tumors. Patients with these lesions frequently give such
a convincing history of trauma or of repeated or chronic
infection at the site of the lump that these factors seem
likely to have a part in the genesis of the exostoses.
The proliferating fi brocartilaginous tissue in a grow-
ing subungual exostosis resembles callus in its morpho-
logic tendency to mature into bony trabeculae, further
supporting the likelihood that the tumor is a response
to injury. A recent study has demonstrated consistent
ch romosomal rearrangements in subungual exostoses,
suggesting that they are true neoplasms. Sometimes the
advancing margin of these lesions grows so actively that
it mimics sarcoma, much in the way a stress fracture
may. Attention to the lack of true anaplasia and to the
orderly progression to mature bone provides the clue to
benignity ( Figs. 2.15–2.17) .
These frequently painful projections from the distal
phalanges are under the nail and are rarely more than
1 cm in greatest dimension. Pain and swelling are the
symptoms. Ulceration and infection may be present and
make subungual melanoma a clinical consideration. Of
the 88 subungual exostoses in the Mayo Clin ic series,
59 in volved the nail bed of the big toe. Sixteen others
involved the nails of other toes, and 13 involved the fi n-
gers and thumb. Of the patients in these series, 28 were
male and 60 were female; 63% of the patients were in F igu r e 2.16. Subungual exostosis involving the distal pha-
lanx of the great toe. Although the lesion is attached to the
the second and third decades of life. cortex of th e ph alan x, th ere is n o con tin uity between th e
Although the name “subungual exostosis” suggests a medullary cavity an d th e lesion .
relationship to osteochondroma, there are radiographic
and microscopic differences. In subungual exostoses,
radiographs show an outgrowth of trabeculated bone

F igu r e 2.17. Gross specimen of subungual exostosis. The

cartilage cap is th ick, an d th e n ail is lifted off.

projecting from the distal portion of the phalanx. How-

F igu r e 2.15. A subungual exostosis presenting as an ulcer-
ated and polypoid lesion arising from the nail bed of the fi rst
toe of a 6-year-old girl ( Courtesy of Dr. Bern ard Poletti, Los
An geles, Californ ia.) .
ever, the cortex of the underlying bone does not fl are
out into the cortex of the subungual exostoses, and the
continuity of the spongiosa expected in a true osteo-
chondroma is absent ( Fig. 2.16) . Microscopically, there
18 Chapter 2 ■
F igu r e 2.18. Low-power appearan ce of a subun gual exos-
tosis. In the early phase of development, areas of chondroid
metaplasia blend in to woven bon e an d a spin dle cell prolifera-
tion just beneath the nail bed.
F igu r e 2.19. Higher-power appearance of a subungual exos-
tosis showing a well-defi ned cartilage cap maturing into woven
bon e surroun ded by spin dle cells.
F igu r e 2.20. H igh -power appearan ce of cartilagin ous cap
in subungual exostosis. The cartilage is hypercellular and the
ch on drocytes show moderate atypia. Taken out of con text,
th is lesion may be mistaken for a ch on drosarcoma.
is a gradual maturation from spindle cell proliferation
to cartilage to bony trabecula. Such spindle cell prolifer-
ation is not seen in an osteochondroma. Furthermore,
the bony trabeculae lie embedded in a proliferation of
loosely arranged spindle cells ( Figs. 2.18–2.20) .
Simple excision is usually curative. However, Landon
and coauthors described recurrence in 11%.
Subungual osteogenic melanoma, a recently described
entity, must be included in the differential diagnosis. As
the name indicates, this melanoma produces metaplas-
tic bone and sometimes cartilage, and the combination
may resemble the appearance of subungual exostosis.
A melanoma on the overlying epithelium helps to dif-
ferentiate this lesion from subungual exostosis.
BIZARRE PAROSTEAL
OSTEOCH ON D ROMATOU S
PROLIFERATION S OF TH E
H AN D S AN D FEET
Nora and coworkers described a condition similar to
subungual exostosis but not occurring in the nail bed.
The lesions are much more common in the han ds than
in the feet. Although the lesions described in the origi-
nal article involved only the small bones of the hands
and feet, a more recent study showed that more than
 ■ Osteochondroma (Osteocartilaginous Exostosis) 19

25% of the lesions tended to involve the lon g bones. a bizarre parosteal osteochondromatous proliferation.
Most patients noted a swelling that was rarely associated Although the arrangement of the spindle cells, car-
with pain. Radiographs show a well-marginated mass of tilage, and bone suggests a reactive process, chromo-
heterotopic mineral arising from the cortical sur face of somal abnormalities have been described that suggest a
the affected bone. The cortex and spongiosa are not true neoplasm ( Figs. 2.21–2.26) .
continuous with the bone and the mass. There usually
is no unmineralized soft tissue mass. Microscopically,
bizarre parosteal osteochondromatous proliferations
consist of three components in different amounts: car-
tilage, bone, and spindle cells. The cartilage may form
a cap or be in lobules separated by dense fi brous tissue.
The cartilage matures into bone with spindle cells in
the background. The cartilage is usually hypercellular
and the chondrocytes are enlarged. The ossifi cation
is much more irregular than that in osteochondroma
and has a peculiar blue, tinctorial quality. Th e spindle
cells are arranged loosely between bony trabeculae. In
this series, more than half the patients with follow-up
information had recurrences, and 20% had more than
one recurrence. However, there was no instance of
malignant transformation in this series. There is one
case report of fi brosarcoma arising on the sur face of

F igu r e 2.21. Typical radiograph ic appearan ce of bizarre

parosteal osteochondromatous proliferation. A nodular- F igu r e 2.22. Recurren t lesion of bizarre parosteal osteo-
appearing mineralizing mass is attached to the cortex of the ch on dromatous proliferation in volvin g th e distal h umerus
phalanx. Cortical and medullary continuity ( as seen in osteo- of a youn g man. A: Th e lesion is un iformly min eralized an d
ch on droma) is lackin g. attached to the cortex. B: Gross appearan ce.
20 Chapter 2 ■
F igu r e 2.23. Resected specimen of recurren t bizarre
parosteal osteochondromatous proliferation involving the
distal ulna. Mineralization is seen on the sur face, and there is
no involvemen t of the marrow ( Courtesy of Dr. Real Legace,
L’H otel Dieu de Quebec, Quebec, Can ada.) .
F igu r e 2.25. Th e trabeculae of bon e in bizarre parosteal
osteoch on dromatous proliferation are deeply stain ed. Th ere
is spindle cell proliferation between the bony trabeculae.
F igu r e 2.24. Low-power appearan ce of bizarre parosteal
osteoch on dromatous proliferation . Hyperplastic cartilage is
maturin g in to bon e.
F igu r e 2.26. A distinctive blue tinctorial quality of matrix
in cartilage and bone is commonly seen in bizarre parosteal
osteoch on dromatous proliferation .
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BIBLIOGRAPH Y
1943 Jaffe, H. L.: Hereditary Multiple Exostosis. Arch Pathol,
36:335–357.
1954 Harsha, W. N.: The Natural History of Osteocartilaginous
Exostoses ( O steochondroma) . Am Surg, 20:65–72.
1962 Murphy, F. D., Jr. and Blount, W. P.: Cartilaginous Exos-
toses Following Irradiation . J Bone Joint Surg, 44A:662–668.
1963 Anastasi, G. W., Wertheimer, H. M., and Brown, J. R.: Popliteal
An eurysm With Osteoch on droma of th e Femur. Arch Surg,
87:636–639.
1971 Schweitzer, G. and Pirie, D.: Osteosarcoma Arising in a Soli-
tary Osteochon droma. S Afr Med J, 45:810–811.
1972 Hershey, S. L. and Lansden, F. T.: Osteochondromas as a
Cause of False Popliteal An eurysms: Review of th e Literature
and Report of Two Cases. J Bone Joint Surg, 54A:1765–1768.
1979 El-Khoury, G. Y. and Bassett, G. S.: Symptomatic Bursa Forma-
tion With Osteochondromas. Am J Roentgenol, 133:895–898.
1979 Landon, G. C., Johnson, K. A., and Dahlin, D. C.: Subun-
gual Exostoses. J Bone Joint Surg, 61A:256–259.
1979 Shapiro, F., Simon S., and Glimcher, M. J.: H ereditary
Multiple Exostoses: An th ropometric, Roen tgen ograph ic, an d
Clin ical Aspects. J Bone Joint Surg, 61A:815–824.
1981 Borges, A. M., Huvos, A. G., and Smith, J.: Bursa Formation
an d Syn ovial Ch on drometaplasia Associated With O steoch on -
dromas. Am J Clin Pathol, 75:648–653.
1982 Garrison, R. C., Unni, K. K., McLeod, R. A., Pritchard, D.
J., an d Dah lin , D. C.: Ch on drosarcoma Arisin g in O steoch on -
droma. Can cer, 49:1890–1897.
1982 Libshitz, H . I. and Cohen, M. A.: Radiation-Induced Osteo-
ch ondromas. Radiology, 142:643–647.
1983 Nora, F. E., Dahlin, D. C., and Beabout, J. W.: Bizarre
Parosteal Osteoch on dromatous Proliferation s of th e Han ds
and Feet. Am J Surg Pathol, 7:245–250.
■ Osteochondroma (Osteocartilaginous Exostosis) 21
1985 Copelan d, R. L., Meehan , P. L., an d Morrissy, R. T.: Spon -
taneous Regression of Osteochondromas: Two Case Reports.
J Bone Joint Surg, 67A:971–973.
1985 Josefczyk, M. A., Huvos, A. G., Smith, J., and Urmacher,
C.: Bursa Formation in Secondary Chondrosarcoma With Intra-
bursal Chondrosarcomatosis. Am J Surg Pathol, 9:309–314.
1989 Peterson , H. A.: Multiple Hereditary Osteoch on dromata.
Clin Orth op, 239:222–230.
1993 Lucas, D. R., Tazelaar, H. D., Un n i, K. K., Wold, L. E.,
Okada, K., Dimarzio, D. R., Jr., and Rolfe, B.: Osteogenic Mel-
an oma: A Rare Varian t of Malign an t Melan oma. Am J Surg
Path ol, 17:400–409.
1993 Meneses, M. F., Unn i, K. K., an d Swee, R. G.: Bizarre
Parosteal Osteoch on dromatous Proliferation of Bon e ( Nora’s
Lesion) . Am J Surg Pathol, 17:691–697.
2001 Choi, J. H., Gu, M. J., Kim, M. J., Ch oi, W. H., Sh in, D. S.,
an d Ch o, K. H.: Fibrosarcoma in Bizarre Parosteal Osteoch on -
dromatous Proliferation . Skeletal Radiol, 30:44–47.
2003 Ah med, A. R., Tan , T. S., Un ni, K. K., Collin s, M. S., Wen ger,
D. E., and Sim, F. H.: Secondary Chondrosarcoma in Osteo-
ch on droma: Report of 107 Patien ts. Clin Orth op Relat Res,
411:193–206.
2004 Zambrano, E., Nose, V., Perez-Atayde, A. R., Gebhardt, M.,
Heresko, M. T., Kleinman, P., Richkind, K. E., and Kozakewich,
H. P.: Distinct Chromosomal Rearrangements in Subungual
( Dupuytren) Exostosis and Bizarre Parosteal Osteochon-
dromatous Proliferation ( Nora Lesion). Am J Surg Pathol, 28:
1033–1039.
2007 Hameetman, L., Szuhai, K., Yavas, A., Knijn en burg, J., van
Duin, M., van Dekken, H., Taminiau, A.H., Cleton-Jansen,
A.M., Bovée, J.V., an d Hogendoorn , P.C.: Th e Role of EXT1 in
Non h ereditary Osteoch on droma: Iden tifi cation of Homozy-
gous Deletions. J Natl Can cer Inst, 99:396–406.
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 C H APT ER
3
Chondroma
Chondroma is a benign tumor composed of mature
hyalin e cartilage. Most commonly, chondromas are
centrally located in bone, and such tumors are called
enchondromas. Less often, they are distinctly eccentric
and cause the overlying periosteum to bulge. This type
has been called periosteal chondroma. In thin or fl at bones,
such as the ribs, scapula, or innominate bone, the exact
origin of the chondroma, that is, whether central or
subperiosteal, often cannot be determined because
the landmarks are destroyed by the tumor. Sometimes
a tumefactive but nonneoplastic proliferation of costal
cartilage simulates a chondroma. Such proliferation
can even be mistaken for chondrosarcoma; typically,
the radiograph shows no abnormality.
Multiple chondromas represent a dysplasia of bone
characterized by failure of normal enchondral ossifi -
cation and proliferation of tumefactive cartilaginous
masses in the metaphyseal and adjacent regions of the
shaft. A few or many bones may be affected. With wide-
spread involvement and a tendency to unilaterality, this
condition is often called Ollier disease. In addition to
tumefaction, this disease results in concomitant bowing
and shortening of bones. In fact, multiple chondro-
mas and fi brous dysplasia both result from a disorder
of ossifi cation, and this relationship is evident in the
lesions that contain histopathologic features of both.
Multiple chondromas should be differentiated from
skeletal osteochondromatosis ( multiple osteochon-
dromas) . When associated with angiomas of the soft
tissues, skeletal chondromatosis is referred to as Maf-
fucci syndrome. Other rare syndromes associated with the
skeletal chondromas have been recognized. Alth ough
completely reliable fi gures are not available, it has been
estimated that chondrosarcoma develops by age 40
in approximately 25% of patients with Ollier disease.
The incidence of malignancy in Maffucci syndrome is
considered to be higher, although in a large review of
reported cases, Lewis and coauthors estimated th at the
incidence of neoplasia in Maffucci syndrome was 23%.
Not in cluded in th e Mayo Clin ic series are carti-
lagin ous tumors arisin g in un usual sites, such as th e
22
laryn x an d th e syn ovial membranes. These tumors have
unusual ch aracteristics, th e most sign ifi can t of wh ich is
a less aggressive clin ical beh avior than th eir h istologic
appearan ce suggests. Th e same attribute applies to th e
n ot un common extraosseous cartilagin ous tumors of
the h an ds an d feet, most of wh ich are small an d man y
of wh ich are probably derived from th e synovium.
Fran kly malignan t extraosseous neoplasms th at are
defi n itely cartilagin ous are rare. Rarely ch on dromas,
occasion ally large, occur in th e dura mater, often in th e
falx cerebri.
IN CID EN CE
In the Mayo Clinic series, chondromas constituted
15.6% of benign tumors and 4.7% of all tumors. These
fi gures, however, do not refl ect the true incidence of
chondromas because they are generally asymptomatic.
SEX
In the overall group of chondromas, there was a distinct
female predominance, whereas for patients with mul-
tiple chondromas, the reverse was true.
AGE
Patients were fairly evenly distributed through out all
decades of life; approximately 50% were in the second,
third, and fourth decades. Patients with multiple lesions
required surgery, on average, at a younger age; approxi-
mately 71% were in the fi rst and second decades of life.
LOCALIZATION
More than 41% of the tumors were in the small bones
of the hands and feet, chiefl y in the phalanges, and 91%
of these were in the hands. Chondroma is by far the
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 ■ Chondroma 23

most common tumor of the small bones of the hands.
Four of the lesions of the innominate bone involved
the pubis and th ree the ilium. Chondroma does not
usually occur in the bones most commonly affected by
chondrosarcoma. There were only two chondromas of
the sternum. Almost all chondroid neoplasms of the
sternum are malignant. Two intracranial chondromas
of meningeal origin were excluded. There were no
benign cartilaginous tumors of the base of the skull in
the Mayo Clinic series, and some of these rare lesions
reported were probably chordomas or related to them
( Figs. 3.1 & 3.2) .
Eighteen of the periosteal chondromas in volved the
femur, and 14 involved the humerus. The proximal
metaphysis of the humerus was the most common loca-
tion for periosteal chondroma ( Fig. 3.3) .
Only one chondroma in the Mayo Clinic series was
defi nitely epiphyseal in location.
SYMPTOMS
Ch on dromas of th e lon g tubular an d fl at bon es are
gen erally asymptomatic. Ch on dromas are frequen tly

F igu r e 3.1. Distribution of

ch on dromas accordin g to age
and sex of the patient and site
of th e lesion .

F igu re 3.2. Distribution of

multiple chondromas according
to age and sex of the patient.

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24 Chapter 3 ■
“h ot” on isotope bon e scan s an d are discovered in
patien ts un dergoin g th e scan usually for eviden ce of
metastatic carcin oma. If th e radiograph ic features sug-
gest an en ch on droma, biopsy is n ot n ecessary. Th ree
ch on dromas were in ciden tal fi n din gs with oth er n eo-
plasms: on e myeloma, on e metastatic squamous cell
carcinoma, and one adamantinoma. One patient with
enchondroma of the femur had osteomalacia, but the
latter was caused by a typical phosphaturic mesenchymal
tumor of the fi rst cervical vertebra. Chondromas of the
small bones tend to become painful because they fre-
quently undergo pathologic fracture. It is unusual to see
a pathologic fracture in a chondroma of larger bones.
RAD IOGRAPH IC FEATU RES
Chondromas produce a localized, central region of rar-
efaction. Any portion of the bone may be involved, but
in the long bones, the tumors tend to be metaphyseal. In
the short tubular bones, chondromas tend to involve the
middle portion. The amount of calcifi cation varies from
slight to marked. Long-bone chondromas are gen erally
mineralized, whereas small-bone chondromas tend to
be less so. The pattern of mineralization is described as
popcornlike or ringlike. The mineralization is usually
distributed uniformly throughout the lesion. Uneven
mineralization should arouse suspicion of chondro-
sarcoma. The bony cortex overlying a long-bone chon-
droma is uninvolved. Scalloping of the endosteal aspect
of the cortex is evidence of growth but not necessarily
of malignancy ( Figs. 3.4–3.6) .
F igu r e 3.3. Distribution of
periosteal chondromas accord-
ing to age and sex of the patient
and site of the lesion.
Magnetic resonance images and computed tomo-
grams do not add signifi cantly to the diagnostic features
in enchondromas. However, computed tomograms
may show calcifi cation not appreciated on plain radio-
graphs. On magnetic resonance images, enchondromas
tend to be dark on T1-weighted images and bright on
T2-weighted images and have a characteristic lobulated
appearance. Magnetic resonance images and computed
tomograms may also be helpful in confi rming the lack of
permeation and cortical involvement ( Figs. 3.7 & 3.8) .
Th e cortex is th in n ed in small-bon e en ch on dromas.
Such in volvemen t of th e cortex sh ould n ot be con sid-
ered a sign of malign an cy in small bon es. Ch on dro-
sarcoma, wh ich is extremely un usual in th is location ,
permeates through the cortex into the soft tissues.
Periosteal chondromas tend to be small, usually 2 to
3 cm in greatest dimension. The lesion is situated on
the sur face of bone, with scalloping of the underlying
cortex. Usually, there is a rim of sclerosis in the underly-
ing bone, and the lesion is sharply marginated. The cor-
tex tends to overhang the lesion, giving rise to a buttress
effect ( Figs. 3.9 & 3.10) .
In several con dition s, multiple ch ondroid lesion s
may be seen in th e skeleton . Some almost surely rep-
resen t true ch on droid n eoplasms an d, h en ce, may
be called multiple chondromas. Ollier disease an d Maf-
fucci syndrome probably are dysplastic con dition s, so
the term chondrodysplasia may be used. H owever, th e
distin ction between multiple chon dromas an d chon -
drodysplasias may n ot always be possible. In Maffucci
syndrome an d O llier disease, th e n umber of bones
involved is variable. In some patien ts, the skeleton is
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 ■ Chondroma 25

F igu r e 3.4. Enchondroma involving the proximal tibial shaft in a 39-year-old woman. A: Positive
fi n ding on a bon e scan . B: Plain radiograph of th e lesion. There is a hazy den sity in th e midportion
of th e tibia. Th e lucen t area may represen t erosion of th e cortex. Oth erwise, th e lesion is well cir-
cumscribed and does n ot sh ow in volvemen t of th e cortex. C: MRI sh ows th at th e lesion is lobulated
and well circumscribed.

F igu r e 3.5. H eavily calcifi ed ch on droma in volvin g th e

proximal humerus. The lesion is well demarcated, and
min eralization is even ly distributed th rough out. Such a
lesion may be mistaken for an infarct, but calcifi cation in
an infarct tends to be peripheral.

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26 Chapter 3 ■
F igu r e 3.6. Enchondroma involving the proximal phalanx
of a fi n ger. The cortex is un iformly th in , but th ere is n o per-
meation in to soft tissues. Th is th in n in g of th e cortex leads to
frequent pathologic fractures in enchondromas of the small
bon es.
F igu r e 3.7. T1-weigh ted MRI of en ch on droma of th e dis-
tal femur in a 50-year-old man . Th e lobulated appearan ce
is typical ( Case provided by Dr. David Aldrich , Lafayette,
In diana.) .
F igu r e 3.8. T2-weighted MRI of enchondroma of the proxi-
mal tibia in a 42-year-old woman with a history of breast cancer.
Th e sign al is brigh t, an d th e typical lobulation is apparen t.
in volved exten sively, wh ereas in oth ers, only on e-half
of th e body, or even on e limb, is affected. It is possible
th at there are examples of O llier disease that in volve a
sin gle bone.
In ch on drodysplasias, th e radiograph s sh ow
massive calcifi ed ch on droid lesion s in volvin g th e
metadiaph yseal region s of lon g bon es. Flat bon es
also may be affected. Th e bon es in volved ten d to be
expan ded, an d th e calcifi cation may be popcorn like,
as in ch on droma, or, more ch aracteristically, h ave a
lin ear pattern . In addition to expan sile masses with in
th e marrow, lesion s may also occur on th e sur face of
bon e. Th is appearan ce may give rise to a false impres-
sion of a destructive tumor. In Maffucci syn drome,
soft tissue h eman giomas are presen t in addition to
th e bon y lesion an d may be visualized on plain radio-
graph s because of th e presen ce of ph lebolith s. Serial
radiograph s in affected patien ts h ave sh own “h eal-
in g” of th e lesion s. Th e bon es appear expan ded an d
deformed, but th e ch aracteristic calcifi cation is usually
absen t an d, h en ce, th e features may n ot be diagn ostic
in adult patien ts ( Fig. 3.11) .
Bone infarcts may resemble calcifying cartilaginous
neoplasms, but infarcts typically are lucent centrally and
well separated from surrounding normal bone by a zone
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F igu r e 3.9. Periosteal chondroma involving the sur face of
th e distal femoral metaph ysis, a typical location . Th e lesion
appears as a lucency involving the cortex, where it resides in
a saucer-shaped depression. A sclerotic margin surrounds the
lesion, and the medullary cavity is not involved.
F igu r e 3.10. Th e proximal h umerus is also common ly in vol-
ved with periosteal chondroma. The radiographic appearance
is that of a sur face lesion with marginal buttresses.
■ Chondroma 27
F igu r e 3.11. Multiple ch on dromas in volvin g both h an ds
of an 18-year-old man . Th e patien t h ad n o eviden ce of a dys-
plastic process elsewhere in the skeleton. Some of the lesions
expan d th e bone con siderably.
of calcifi cation or even ossifi cation at their periphery.
Enchondromas generally have mineralization in the
central regions.
GROSS PATH OLOGIC FEATU RES
Ch on droma is ch aracteristically composed of con fl u-
en t masses of bluish , semitran slucen t h yalin e cartilage
with a distin ctly lobular arran gemen t. Th e lobules may
var y from a few millimeters to a cen timeter or more in
diameter. Th e periph er y of th e lesion may be some-
wh at in distin ct because ramifi cation s of th e cartilagi-
n ous tumor sometimes pen etrate in to adjacen t marrow
spaces. Tumors ch aracterized by radiograph ic evi-
den ce of pun ctate areas of calcifi cation h ave calcifi ed
masses scattered th rough out, an d occasion ally th ese
lesion s are h eavily calcifi ed an d ossifi ed. Alth ough th e
gross ch aracteristics of th e solitar y tumor are similar
to th ose of multiple tumors, th e latter ten d to h ave
well-circumscribed n odules separated by apparen tly
n ormal marrow. Th is appearan ce, wh ich may give rise
to a false impression of permeation , represen ts multi-
focality ( Fig. 3.12) .
Periosteal chondromas produce a well-marginated
defect in the underlying cortex and a bulge in the con-
tour of the bone. They lie in a concavity in the bone,
and their internal aspect is marked by a thin sclerotic
zone. The outer sur faces are smooth and appear to be
demarcated by a fi brous capsule. Periosteal chondro-
mas tend to be small and rarely exceed 5 cm in greatest
dimension ( Fig. 3.13) .
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28 Chapter 3 ■
F igu r e 3.12. En chon droma of the proximal fi bula. Th ere is
exten sive cortical erosion, but th e fi bula is con sidered a small
bon e an d th e cortical erosion does n ot con n ote malign an cy.
F igu r e 3.13. Periosteal chondroma in the distal femur. The
lesion, involving the cortex and extending into soft tissue,
is small and well circumscribed. The medullary cavity is not
involved.
Chondroma is characteristically a small tumor, and
when a tumor of hyaline cartilage that is several centime-
ters in greatest dimension is seen, the lesion should be
examined carefully for evidence of malignancy. Erosion
or thickening of the overlying cortex is an ominous sign,
often evident on radiographs. Myxoid change in the
matrix, especially if it gives rise to cystifi cation, also is an
ominous sign. The rules are different in the small bones
because, as indicated above, the cortex may be paper
thin. Moderate myxoid change in the matrix can also be
seen in chondromas of the small bones and periosteal
chondromas.
H ISTOPATH OLOGIC FEATU RES
The histologic features of chondromas vary consider-
ably, depending on the location of the lesion. Hence,
it is important to have information about location,
radiographic features, and clinical features before a
defi nite diagnosis is made. It is reasonable to discuss the
features separately ( Figs. 3.14–3.26) .
Ch on drom as, excludin g th ose in volvin g th e
sm all bon es of th e h an ds an d feet, periosteal ch on -
drom a, an d ch on drom as in patien ts with m ultiple
ch on drom as can be described as follows: th e ch on -
drocytes always lie in lacun ae, are sm all, an d h ave a
roun d regular n ucleus th at is h ardly visible un der
low power. Th e lesion is relatively h ypocellular, an d
ch on drocytes are in clusters, with in ter ven in g blue-
stain in g ch on droid m atrix. Man y cells m ay be seen in
a lacun a, but truly double-n ucleated cells are un com -
m on . Necrotic foci are also un com m on . Th e lesion is
well circum scribed, an d th e ch on droid lobules m ay
be surroun ded by th in bon y trabeculae th at form
“rin gs” aroun d th e lobules, correspon din g to th e
rin gs seen on radiograph s. Even solitar y ch on drom as
m ay grow as m ultiple n odules with in ter ven in g bon y
trabeculae, but th is appearan ce does n ot con stitute
perm eation . Th e lobules lie in th e m arrow an d do
n ot destroy or en trap m edullar y bon e. Calcifi cation
m ay be seen as fi n e purple-stain ed gran ular precipi-
tate or even as large ch un ks. En ch on dral ossifi cation
m ay also be seen ( Figs. 3.14–3.20) .
Ch on dromas of th e small bon es of th e h an ds an d
feet are much more cellular th an th eir coun terparts
in large bon es. Sligh t myxoid ch an ge of th e matrix, in
th e form of foci of frayed matrix, may be seen . H ow-
ever, exten sive myxoid ch an ge is n ot seen in ch on -
dromas of small bon es. Th e ch on drocytes may be in
clusters or may even form sh eets. Th e ch on drocytes
sh ow en largemen t of th e n uclei, an d double-n ucleated
F igu r e 3.14. Low-power appearan ce of an en ch on droma of
the fi bula. The tumor abuts the cortex, but there is no destruc-
tive permeation.
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 ■ Chondroma 29

F igu r e 3.15. H ypocellular en ch on droma con tain in g small, Figu re 3.18. Enchondroma with focal dark blue calcification.
uniform chondrocytes within lacunar spaces.

F igu r e 3.19. Enchon droma with areas of degenerative myx-

F igu r e 3.16. En ch on droma con tain in g lobules of cartilage oid ch an ge. The tumor is h ypocellular an d sh ows n o cytologic
that are partially surrounded by a rim of lamellar bone. atypia. Myxoid change should not be a prominent component
of en ch on droma.

F igu r e 3.17. Lobules of enchondroma in the medullary cav- F igu r e 3.20. High-power appearance of an enchondroma.
ity partially separated by hematopoietic bone marrow. Th e n uclei are small, dark, an d regular.

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30 Chapter 3 ■

cells are common . Ch on dromas of small bon es grow

by expan sion , so th at en trapped medullary bon e is n ot
seen . If bon e is en trapped or if th e tumor permeates
th rough th e in terstices of th e cortex, th e diagn osis
sh ould be ch on drosarcoma. Wh en a ch on droid n eo-
plasm of th e small bon e is malign an t, th e diagn osis is
usually obvious on radiograph s. Rarely does on e make
a diagn osis of ch on drosarcoma wh en th e radiograph ic
appearan ce is th at of a ben ign lesion . For th is diagn o-
sis, th e lesion must be extremely h ypercellular an d th e
n uclei pleomorph ic or marked myxoid ch an ge sh ould
be presen t ( Figs. 3.21–3.23) .
The periosteal chondromas also tend to show
cytologic atypia and myxoid change in matrix. The
outer sur faces are well demarcated, and there is no
tendency for permeation. Nuclear atypia may be pro- F igu r e 3.21. En ch on droma of a ph alan x with diffuse in -
nounced. Nodules of well-circumscribed cartilage that crease in cellularity.
may be present in the underlying marrow should not be
taken as evidence of permeation ( Figs. 3.24–3.26) .
The cartilage in lesions of multiple chondromas also
is moderately hypercellular. The lesion has a distinct
lobulated architecture and a tendency for multifocal-
ity. The chondrocytes tend to have a characteristic oval
shape. Although the lesions tend to be hypercellular,
the chondrocytes are generally not characterized by
cytologic atypia. Slight myxoid change of the matrix may
be seen.
Large ch on droid n eoplasm s of an y sort n eed to
be exam in ed carefully to rule out m align an cy. Per-
m eation of surroun din g tissue is perh aps th e m ost
useful criterion in differen tiatin g ben ign from m alig-
n an t lesion s. Low-grade ch on drosarcom as m ay h ave
large areas th at h istologically appear ben ign . H ow- F igu re 3.22. Enchondroma of a small bone. The lesion is
ever, we do n ot believe th at th is appearan ce sh ould quite cellular, with focal myxoid change in the matrix and hyper-
be an in dication th at an en ch on drom a h as un der- chromasia of the nuclei. This appearance in a cartilage tumor
gon e m align an t ch an ge. Th e differen tiation of an of a large bone would be diagnostic of chondrosarcoma.
en ch on drom a from a low-grade ch on drosarcom a
depen ds so h eavily on th e radiograph ic appearan ce
th at we th in k it is virtually im possible to prove th at a
ben ign preexistin g ch on drom a was associated with a
low-grade ch on drosarcom a.
Areas of defi nite fi brous dysplasia in a central car-
tilagin ous lesion indicate fi brocartilaginous dysplasia.
Such benign chondroid masses can be several centi-
meters in diameter. Most dysplasias of this type involve
the upper part of the shaft or the neck of the femur. In
rare cases, features of both multiple chondromas and
fi brous dysplasia may coexist. This occurrence suggests
that most, if not all, examples of multiple chondromas
also represent some dysplastic process.
Fracture or recen t in jury, such as th at produced
by surger y, may cause active fi brocartilagin ous prolif-
F igu r e 3.23. High-power appearance of an enchondroma
eration , wh ich sh ould n ot be mistaken for malign an t of a ph alan x. The ch on drocytes are en larged an d h yperch ro-
disease. Th is appearan ce may simulate th at of dedif- matic. Th ese cytologic features can be ign ored if th e radio-
feren tiated ch on drosarcoma. graph ic features sh ow a ben ign process.

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F igu r e 3.24. Periosteal chondroma. The tumor shows mod-
erate cellularity, and th e chon drocytes are fairly un iform.
F igu r e 3.25. H igh -power appearan ce of periosteal ch on -
droma. There is increased cellularity with mild to moderate
nuclear h yperchromasia an d some myxoid ch an ge in the
stroma.
F igu r e 3.26. Periosteal ch on droma. Th ere are areas wh ere
the cells tend to cluster, as in synovial chondromatosis.
■ Chondroma 31
TREATMEN T
Solitary chondromas of long or fl at bones, which may be
incidental fi ndings, need no treatment. Because chon-
dromas, by defi nition, do not involve the cortex, patho-
logic fracture should not occur. If the lesion needs to
be removed for some reason, simple curettage should
be suffi cient. If a chondroid lesion appears benign
on radiographs or, at most, of very low malignancy, it
should be removed completely rather than having a
biopsy per formed.
Most of the chondromas of the small bones may require
treatment because of the possibility of pathologic fracture.
Simple curettage with bone grafting should suffice.
PROGN OSIS
Prognosis in chondroma is good and recurrence is
unusual, even after curettage. Occasionally, however, a
tumor that seemed to be completely benign recurs, and
the recurrent tumor is characterized, in rare instances,
by increased anaplasia with obvious evidence of malig-
nancy. Frequently, this apparent increase in cellular
activity is the result of incorrect interpretation of the
original specimen because microscopic sections were
inadequate.
MU LTIPLE CH ON D ROMAS
Fifty-four patien ts with ben ign multiple ch on dromas
are n ot in cluded in th e localization data in Fig. 3.1.
Th ese patien ts required surgical procedures for vari-
ous reason s. Deformin g tumors are frequen tly excised
from both lon g an d small bon es. O n e patien t in th is
group required disarticulation at th e sh oulder for a
h uge tumor of th e h umerus from wh ich tissue was n ot
available for study. O n e patien t required amputation
th rough th e femur because of severe an d disablin g tibial
deformity. An oth er patien t required amputation of an
affected arm because of an associated an giosarcoma of
th e soft tissues th at complicated ch ron ic lymph edema
an d caused death with in a year. Th e an giosarcoma
did n ot arise in association with Maffucci syn drome
( Figs. 3.27–3.32) .
Th e severity of skeletal ch on dromatosis varied greatly
in th is group. Th irteen patien ts h ad in volvemen t of
th e small bon es of th e h an d, an d th ree patien ts h ad
in volvemen t of th e toes on ly. Th e remain in g patien ts
h ad in volvemen t of oth er bon es, also to various
degrees. An attempt was made to divide th e lesion s
in to multiple ch on dromas an d ch on drodysplasias.
Th e division was arbitrary, depen din g predomin an tly
on th e ability of th e radiologist to recogn ize areas of
32 Chapter 3 ■
disease. O n ly th ree patien ts h ad th e combin ation of
skeletal ch on dromatosis an d soft-tissue h eman giomas
th at could be classifi ed as Maffucci syn drome. Twen ty-
eigh t oth er patien ts seemed to h ave th e stigmata of
O llier disease. Th e remain in g 23 patien ts h ad multi-
ple ch on dromas, but available data did n ot suggest a
F igu r e 3.27. O llier disease in volvin g multiple por-
tion s of th e skeleton of a 6-year-old girl. A: Th e proxi-
mal tibia an d fi bula sh ow lin ear masses of cartilage
extending from the ph ysis into the shaft. B: Appear-
ance of the pelvis. There is extensive involvement of
th e ilium an d the proximal femur. C: Appearan ce of
th e skeleton of th e h an d. Multiple bon es are in volved,
and even in the small bon es, the linear ch aracteristics
of min eralization are seen . Absen ce of th e cortex over
th e cartilage masses does n ot in dicate malign an cy.
ch on drodysplastic con dition . Wh eth er th is distin ction
h as an y clin ical or progn ostic sign ifi can ce is n ot yet
clear. O n e patien t previously listed as h avin g Maffucci
syn drome h ad to be removed from th e category of
ch on dromatosis with out malign an cy wh en ch on dro-
sarcoma of th e n ose developed.

F igu r e 3.28. “Ch on droma” of O llier disease in volving the
ilium in a 29-year-old man who had chondrosarcoma in the
ischium. The cartilaginous masses appear multicentric, and
there is no myxoid quality to the matrix.
F igu r e 3.29. Maffucci syn drome. Multiple cartilagin ous
masses in volve bon es of th e h an d. Th e calcifi c den sities in th e
soft tissues represen t ph lebolith s in soft-tissue h eman giomas.
■ Chondroma 33
F igu r e 3.30. Gross specimen of a thumb involved with
Maffucci syndrome. The dark areas in the soft tissues repre-
sen t h eman giomas. Th e ch on droid lesion s appear multilobu-
lar, with large areas of normal marrow separating the lesions
( Case provided by Dr. Tim Morgan, St. Joseph Hospital,
Den ver, Colorado.) .
F igu r e 3.31. Cartilaginous lesion in Ollier disease. The car-
tilage is in the form of lobules but is hypercellular and shows
moderate nuclear pleomorphism. Such changes are common
in the cartilaginous masses of Ollier disease.
F igu r e 3.32. H igh -power appearan ce of en ch on droma of
Ollier disease. Some of the nuclei within the lacunar spaces
are elongated.
34 Chapter 3 ■

disease. O n ly th ree patien ts h ad th e combin ation of

skeletal ch on dromatosis an d soft-tissue h eman giomas
th at could be classifi ed as Maffucci syn drome. Twen ty-
eigh t oth er patien ts seemed to h ave th e stigmata of
O llier disease. Th e remain in g 23 patien ts h ad multi-
ple ch on dromas, but available data did n ot suggest a
ch on drodysplastic con dition . Wh eth er th is distin ction
h as an y clin ical or progn ostic sign ifi can ce is n ot yet
clear. O n e patien t previously listed as h avin g Maffucci
syn drome h ad to be removed from th e category of
ch on dromatosis with out malign an cy wh en ch on dro-
sarcoma of th e n ose developed.

SARCOMAS AN D
MU LTIPLE CH ON D ROMAS

In addition to the previously mentioned 54 patients

with skeletal chondromatosis, 24 patients had the same
disease complicated by sarcoma. These patients were
included in the group with malignant tumors. Nine-
teen of the patients had chondrosarcoma, three had
dedifferentiated chondrosarcoma, one had an osteosar-
coma, an d one had chondroid chordoma. Two patients
had two separate chondrosarcomas each. Of the 24 F igu r e 3.33. Large, multin odular, min eralized soft-tissue
patients with complicating malignant lesions, 10 had ch on droma of th e h an d of a 19-year-old man ( Case provided
features of Ollier disease, 5 had features of Maffucci by Dr. Mark Pollock, MPL, Dallas, Texas.) .
syndrome, and the rest h ad what may be termed mul-
tiple chondromas. Two patients had chondromas limited
to the femur, whereas the others all had disseminated
involvement with cartilaginous masses.

CARTILAGIN OU S TU MORS
OF TH E SOFT TISSU ES
OF TH E H AN D S AN D FEET

Ch on drosarcoma of th e classic type occurs ver y rarely

in various soft tissues, in cludin g th e breast. In addition
to such malign an t tumors of distin ctly h yalin e cartilage
type, a n umber of “ch on droid” n eoplasms are foun d,
as described by Lich ten stein an d Bern stein , th at are
n ot defi n itely cartilagin ous. Th e latter lesion s are
often of debatable h istologic type an d clin ical capabil-
ity. Most of th e primary ch on drosarcomas of th e soft
tissue are of th e myxoid variety, th e so-called ch ordoid
sarcoma.
Most tumors of soft tissue that are un equivocally car-
tilagin ous occur in th e h an ds an d feet and are benign.
The radiographs may show an unmineralized soft-tissue
mass or a soft-tissue mass with calcifi cation typical of
cartilage tumors. Grossly, th e lesion s ten d to be well F igu r e 3.34. Soft-tissue ch on droma of th e great toe in
a 31-year-old man. The tumor has eroded bone where it is
circumscribed an d h ave an atypical ligh t blue chon -
surroun ded by a sclerotic rim. Th ere is a path ologic fracture
droid appearance. O ccasionally, the lesion s appear ( Case provided by Dr. Leonard Robinson, University of Ala-
multin odular ( Figs. 3.33–3.35) . bama, Birmin gham, Alabama.) .

F igu r e 3.35. Soft-tissue ch on droma con tain in g lobulated
blue-wh ite tissue periph erally th at correspon ds to cartilage.
Yellow areas of calcifi cation are in th e cen ter of th e lesion .
F igu r e 3.36. Soft-tissue ch on droma. Lobulated masses of
cartilage with a clustererin g arran gemen t of th e ch on dro-
cytes. Th e h istologic features are similar to syn ovial ch on dro-
matosis.
Microscopically, soft-tissue chondromas have lobu-
lated masses of cartilage and may have a fl attened layer
of cells at the periphery, suggesting synovial mem-
branes. Some soft-tissue chondromas have elongated,
grooved nuclei, suggesting chondroblastoma. About
15% of the tumors have mononuclear cells and giant
cells typical of giant cell tumor of tendon sheath. Calci-
fi cation tends to be fi ne and powdery. Within the chon-
droid nodules, the chondrocytes are in lacunae and
have a tendency to cluster, with large amounts of inter-
■ Chondroma 35
F igu r e 3.37. Soft-tissue ch on droma. Ch un ky an d/ or pow-
dery calcifi cation is typical of soft-tissue chondroma. It may be
focal or involve the lesion diffusely.
F igu r e 3.38. Soft-tissue chondroma. Occasionally, the
cartilage nodules are surrounded by plump cells with eosino-
philic cytoplasm, creating a resemblance to chondroblastoma.
Multinucleated giant cells are also frequently present in this
settin g.
vening chondroid matrix. This clustering arrangement
is typical of soft-tissue chondromas and synovial chon-
dromatosis but is not unique to them ( Figs. 3.36–3.38) .
Typically, the cartilage cells in soft-tissue chondroma
appear enlarged and contain hyperchromatic, irregular
nuclei. Double-nucleated cells are common. These fea-
tures taken out of context would be diagnostic of chon-
drosarcoma. However, the location and the character-
istic clustering arrangement should lead to the correct
diagnosis. Recurrences are not uncommon in soft-tissue
36 Chapter 3 ■

chondromas, but we have seen only two documented

examples of soft-tissue chondromas that underwent
malignant transformation to chondrosarcoma.

SYN OVIAL CH ON D ROMATOSIS

Synovial chondromatosis is an unusual nonneoplas-

tic condition of joints in which nodules of metaplastic
cartilage are present within the synovium. The lesion is
almost always monoarticular and tends to involve major
joints, such as the knee an d the hip. However, un usual
sites, such as the temporomandibular joint and the
facet join ts of the spine, may be involved. The patients,
usually young adults, complain of pain or limitation of
movement of the involved joints. The radiographs may
show on ly diffuse soft-tissue swelling in the joint or may
show discrete calcifi ed nodules. In the latter instance,
the diagnosis of synovial chondromatosis is suggested
by the radiologist ( Fig. 3.39) .
Grossly, syn ovial ch on dromatosis appears as multi-
ple well-circumscribed n odules of cartilage eith er lyin g
loose in th e join t cavity or embedded in th e syn ovium.
O ccasion ally, it produces marked th icken in g of syn -
ovial membran es. Th e un derlyin g bon e may be eroded,
an d occasion ally th e lesion exten ds outside th e join t
capsule. Erosion of th e un derlyin g bon e or exten sion
in to periarticular tissues can n ot be taken as eviden ce
of malign an cy. Microscopically, syn ovial ch on droma-
tosis is ch aracterized by n odules of cartilage lin ed by
syn ovial membran es con sistin g of a layer of fl atten ed
cells. Th e clusterin g pattern of th e cartilagin ous n od-
ules is very ch aracteristic: clusters of ch on drocytes with
large amoun ts of in terven in g solid ch on droid matrix.
Marked myxoid ch an ge of th e ch on droid matrix does
n ot occur in syn ovial ch on dromatosis. Th e ch on dro-
cytes ten d to sh ow moderate to marked cellular atypia.
Double-n ucleated cells are common ly foun d. Again ,
th ese features may lead to a mistaken diagn osis of
ch on drosarcoma if th e clin ical features are n ot taken
in to accoun t ( Figs. 3.40–3.44) .
F igu r e 3.39. Syn ovial ch on dromatosis in a 35-year-old
Synovial ch ondromatosis has to be differentiated man . A: Multiple min eralized masses are con tain ed in
from osteocartilaginous loose bodies that are secondary the joint space. B: MRI of the knee ( Case provided by Dr.
to a preexisting con dition, such as degen erative joint Michael A. McNutt, Laboratory of Pathology Seattle, Seattle,
disease. Grossly, loose bodies are white and fi rm. Wash in gton .) .
Th ey are found lying loose in th e join t cavity, alth ough
th ey may be embedded in the syn ovium. Microscopi- wh ich in turn may produce osteocartilaginous loose
cally, th e cartilage appears nonn eoplastic and lacks bodies, so that a joint may contain both types of carti-
th e clustering arran gemen t an d nuclear chan ges seen lagin ous n odules.
in syn ovial ch ondromatosis. Th e cartilage is arranged Synovial chondromatosis commonly recurs. It
in layers and on cross section h as a tree-bark effect. tends to be a diffuse involvement of the joint; hence,
Loose bodies lack th e aggressive clin ical characteristics recurrences probably represent regrowth of tumor left
of primary synovial chondromatosis, and man agement behind at the time of surgery.
is th at of the un derlying condition . Syn ovial chon dro- Juxta-articular chondromas are well-circumscribed,
matosis may give rise to degenerative join t disease, mineralized masses that occur close to a joint, usually

F igu r e 3.40. Syn ovial ch on dromatosis. Multiple discrete
cartilagin ous masses were removed from th e kn ee join t.
F igu r e 3.41. Syn ovial ch on dromatosis. Low-power appear-
ance showing multiple nodules of hyaline cartilage contining
ch on drocytes arran ged in clusters, with in terven in g matrix.
F igu r e 3.42. H igh -power appearan ce of syn ovial ch on dro-
matosis. Th e chon drocytes con tain en larged h yperch romatic
nuclei.
■ Chondroma 37
F igu r e 3.43. Syn ovial ch on dromatosis. O ccasion ally, th e
ch on droid matrix un dergoes myxoid degen eration .
F igu r e 3.44. Synovial chondromatosis. This lesion involving
a knee joint contains areas of coarse mineralization. The min-
eralization also can be more delicate and powdery.
the knee. Radiographs show a well-circumscribed uni-
formly mineralized mass that usually has the appear-
ance of an extra patella. Microscopically, proliferation
of cartilage focally may have the clustered appearance of
synovial chondromatosis. In other areas, the cartilage is
nonneoplastic and mimics the appearance of osteocar-
tilaginous loose bodies. Because of extensive trabecular
bone formations, the histologic appearance suggests a
mixture of synovial chondromatosis, osteocartilaginous
loose bodies, and osteochondroma. The lesion prob-
ably is reactive ( Figs. 3.45 & 3.46) .
Malign an t tran sformation of syn ovial ch on droma-
tosis h as been described. Th ere are th ree examples of
ch on drosarcoma secon dary to syn ovial ch on dromato-
sis in th e Mayo Clin ic fi les. Th e diagn osis is obviously
38 Chapter 3 ■

F igu r e 3.45. Juxta-articular chondroma. A: A well-circumscribed calcifi ed mass is located in the

knee joint just below the patella. This is the most common location for this reactive lesion. B: MRI
sh ows th at th e mass is extremely well circumscribed ( Case provided by Dr. Steph en G. Ruby, Hin s-
dale Hospital, Hinsdale, Illinois.) .

Figure 3.47. Ch on drosarcoma of th e syn ovium in a h ip

Figure 3.46. Juxta-articular chondroma. Plates of cartilage join t. Th e ch ondroid masses glisten because of marked myx-
with maturation into bony trabeculae are shown. oid ch an ge of the matrix.

Figure 3.48. Chondrosarcoma of the synovium. The cluster-
ing arrangement of the chondrocytes typical in synovial chon-
dromatosis is lost. The arrangement of the cells is more like
th at in con ven tion al ch on drosarcoma.
very diffi cult because of th e atypical cytologic features
of preexistin g syn ovial ch on dromatosis. Th e features
th at we fi n d useful are as follows: 1) Marked myx-
oid ch an ge of th e matrix. Th is usually gives rise to a
mucoid quality to th e n odules of cartilage grossly an d
sometimes even cyst formation . 2) Loss of th e cluster-
in g pattern typical of syn ovial ch on dromatosis. Sh eets
of ch on drocytes in a biopsy specimen from a ch on -
droid n odule th ough t to be syn ovial ch on dromatosis
suggest ch on drosarcoma. 3) Crowdin g an d spin dlin g
of n uclei at th e periph er y of lobules. Alth ough syn -
ovial ch on dromatosis may sh ow cytologic atypia, th ere
is n o spin dle cell proliferation at th e periph ery of th e
lobules ( Figs. 3.47 & 3.48) .
Even rarer is the occurrence of a chondrosarcoma
apparently primary in the synovium. Possibly, this is
a secondary chondrosarcoma in which the preexist-
ing synovial chondromatosis has been completely
destroyed.
BIBLIOGRAPH Y
1951 Pugh, D. G.: Roentgenologic Diagnosis of Diseases of
Bon es. New York, Th omas Nelson & Son s, 316 pp.
1952 Lichtenstein, L. and Hall, J. E.: Periosteal Chondroma:
A Distinctive Benign Cartilage Tumor. J Bone Joint Surg,
34A:691–697.
1958 Bean, W. B.: Dyschondroplasia and Hemangiomata ( Maf-
fucci’s Syndrome) . II. Arch Intern Med, 102:544–550.
1959 Lichtenstein, L. and Bernstein, D.: Unusual Benign and
Malign an t Ch on droid Tumors of Bon e: A Survey of Some
Mesen ch ymal Cartilage Tumors an d Malign an t Ch on dro-
blastic Tumors, In cludin g a Few Multicen tric On es, as Well as
Man y Atypical Ben ign Ch on droblastomas an d Ch on dromyx-
oid Fibromas. Cancer, 12:1142–1157.
■ Chondroma 39
1962 Murph y, F. P., Dah lin , D. C., and Sullivan, C. R.: Articular
Synovial Chon dromatosis. J Bon e Join t Surg, 44A:77–86.
1963 Gilmer, W. S., Jr., Kilgore, W., and Smith , H .: Cen tral
Cartilage Tumors of Bon e. Clin Orth op, 26:81–103.
1963 Goethals, P. L., Dahlin, D. C., and Devine, K. D.: Cartilaginous
Tumors of the Larynx. Surg Gynecol Obstet, 117:77–82.
1971 Takigawa, K.: Chondroma of th e Bones of th e Han d:
A Review of 110 Cases. J Bone Joint Surg, 53A:1591–1600.
1972 Rockwell, M. A., Saiter, E. T., an d En nekin g, W. F.: Periosteal
Chon droma. J Bon e Join t Surg, 54A:102–108.
1973 Lewis, R. J. an d Ketch am, A. S.: Maffucci’s Syn drome:
Functional and Neoplastic Signifi cance; Case Report and
Review of the Literature. J Bon e Join t Surg, 55A:1465–1479.
1974 Dahlin , D. C. an d Salvador, A. H.: Cartilaginous Tumors
of th e Soft Tissues of th e Han ds an d Feet. Mayo Clin Proc,
49:721–726.
1974 Dun n, E. J., McGavran , M. H ., Nelson , P., an d Greer, R. B. III:
Synovial Chondrosarcoma: Report of a Case. J Bone Joint
Surg, 56A:811–813.
1978 Chun g, E. B. an d Enzin ger, F. M.: Chondroma of Soft Parts.
Cancer, 41:1414–1424.
1978 Ron ald, J. B., Keller, E. E., and Weilan d, L. H.: Syn ovial
Ch on dromatosis of th e Temporoman dibular Join t. J Oral
Surg, 36:13–19.
1979 DeBenedetti, M. J. and Schwinn, C. P.: Tenosynovial
Chondromatosis in the Hand. J Bone Joint Surg, 61A:898–903.
1980 Kaiser, T. E., Ivins, J. C., an d Unn i, K. K.: Malign ant
Transformation of Extra-Articular Synovial Chondromatosis:
Report of a Case. Skeletal Radiol, 5:223–226.
1981 DeSantos, L. A. an d Spjut, H. J.: Periosteal Ch ondroma:
A Radiographic Spectrum. Skeletal Radiol, 6:15–20.
1982 Bauer, T. W., Dor fman , H. D., and Latham, J. T., Jr.:
Periosteal Ch on droma: A Clin icopath ologic Study of 23 Cases.
Am J Surg Path ol, 6:631–637.
1983 Borian i, S., Bacchini, P., Berton i, F., and Campanacci, M.:
Periosteal Ch on droma: A Review of Twen ty Cases. J Bon e Join t
Surg, 65A:205–212.
1985 Blan kestijn , J., Panders, A. K., Vermey, A., and Sch erpbier,
A. J.: Syn ovial Ch on dromatosis of th e Temporo-Man dibular
Joint: Report of Three Cases and a Review of the Literature.
Cancer, 55:479–485.
1985 Nojima, T., Unn i, K. K., McLeod, R. A., an d Pritch ard, D. J.:
Periosteal Ch on droma an d Periosteal Ch on drosarcoma. Am
J Surg Pathol, 9:666–677.
1985 Sun, T.-C., Swee, R. G., Shives, T. C., and Un n i, K. K.:
Ch on drosarcoma in Maffucci’s Syn drome. J Bon e Join t Surg,
67A:1214–1219.
1987 Liu, J., Hudkins, P. G., Swee, R. G., and Unni, K. K.: Bone
Sarcomas Associated With Ollier’s Disease. Cancer, 59 : 1376–1385.
1987 Mitchell, M. L. and Ackerman, L. V.: Case Report 405: Ollier
Disease ( Enchondromatosis) . Skeletal Radiol, 16 : 61–66.
1987 Sch wartz, H . S., Zimmerman, N. B., Simon , M. A., Wroble,
R. R., Millar, E. A., an d Bon fi glio, M.: Th e Malign an t Poten tial
of En chon dromatosis. J Bon e Join t Surg, 69A:269–274.
1988 Perry, B. E., McQueen, D. A., an d Lin , J. J.: Syn ovial
Ch on dromatosis With Malign an t Degen eration to Ch on dro-
sarcoma: Report of a Case. J Bone Joint Surg, 70A:1259–1261.
1989 Coolican , M. R. and Dan dy, D. J.: Arthroscopic Man age-
men t of Syn ovial Ch on dromatosis of th e Kn ee: Fin din gs an d
Results in 18 Cases. J Bon e Joint Surg, 71B:498–500.
1990 Lewis, M. M., Ken an , S., Yabut, S. M., Norman, A., and
Steiner, G.: Periosteal Chondroma: A Report of Ten Cases and
Review of the Literature. Clin Orth op, 256:185–192.
1991 Bertoni, F., Un n i, K. K., Beabout, J. W., and Sim, F. H.:
Chon drosarcomas of th e Syn ovium. Cancer, 67:155–162.
40 Chapter 3 ■

1995 Fanburg, J. C., Meis-Kindblom, J. M., and Rosenburg, A. E.: 2001 Cates, J. M., Rosen berg, A. E., O ’Con nell, J. X., and Nielsen ,
Multiple En ch on dromas Associated with Spin dle-Cell G. P.: Chondroblastoma-Like Chondroma of Soft Tissue: An
Hemangioendotheliomas: An Overlooked Variant of Maffuc- Un derrecogn ized Varian t an d Its Differen tial Diagn osis. Am J
ci’s Syn drome. Am J Surg Pathol, 19:1029–1038. Surg Pathol, 25:661–666.
1995 Yamada, T., Irisa, T., Nakano, S., and Tokunaga, O.: Extra-
skeletal Chondroma with Chondroblastic and Granuloma-Like
Elements. Clin Orthop Relat Res, 315:257–261.

Benign Chondroblastoma
Benign chondroblastoma is a neoplasm of bone that
has been separated from giant cell tumors because of
a ch ondroid matrix. The basic proliferating cells of
the neoplasm may be remarkably similar to those of a
true giant cell tumor, but these cells can produce foci
of ch ondroid matrix, so it is logical to include chon-
droblastoma among th e tumors of cartilaginous origin.
Because of the unusual cytologic characteristics of the
mononuclear cells, a reticulohistiocytic origin has been
suggested for chondroblastoma. Electron microscopic
and immunoperoxidase studies have supported a carti-
laginous derivation for this neoplasm.
Although some of the features of this neoplasm were
recognized earlier, it was not until 1942 that the term
benign chondroblastoma was introduced and distinctive clini-
copathologic features were delineated. The cellular zones
of these tumors ordinarily contain at least a few mitotic
figures. These, coupled with chondroid zones, have led to
the erroneous diagnosis of malignant giant cell tumor. In
fact, one of the main reasons for recognizing this entity is
that clinically it is relatively nonaggressive and readily cur-
able, even more so than ordinary giant cell tumor.
Most studies have indicated a close relationship
between benign chondroblastoma and chondromyxoid
fi broma. Although some authors have suggested the
possibility of a malignant chondroblastoma, there are
no such examples in the Mayo Clinic fi les. Some chon-
droblastomas have metastasized as benign tumors and
some have produced huge, occasionally leth al, local
recurrences. The term “aggressive” has been used for
these lesions. Cytologically, however, these aggressive
and metastasizing chondroblastomas are indistinguish-
able from the more common benign lesions; hence,
the terms aggressive and “malignant” do not appear to
be reasonable. These terms may be used for describing
clinical features but not pathologic entities. Some oste-
osarcomas have cytologic features remarkably similar to
those of chondroblastoma. Hence, these rare tumors
and clear cell chondrosarcomas have to be considered
when neoplasms behave aggressively.
C H APT ER
4
IN CID EN CE
The Mayo Clinic series contains 147 examples of chon-
droblastoma, which constitutes 4.79% of all benign
lesions and 1.45% of all neoplasms of bone ( Fig. 4.1) .
Chondroblastoma is approximately one-fi fth as com-
mon as a giant cell tumor.
SEX
In the Mayo Clinic series, just over 60% of the patients
with benign chondroblastomas were male. In a larger
series, including consultation cases, published from
Mayo Clinic, the male-to-female ratio was 2:1.
AGE
More th an 60% of all patients were in the second
decade of life. Th e youn gest patien t was 8 years old an d
th e oldest, 60.
LOCALIZATION
Ch on droblastom as are typically cen tered in an
epiph ysis ( Fig. 4.1) . Alth ough th ey occur most often
in th e en d of a major tubular bon e, th ey can appear
in an y cen ter of ossifi cation , such as th e greater tro-
ch an ter. Th e region of th e kn ee accoun ted for 34% of
all th e tumors; th e proximal tibia was in volved sligh tly
more often th an th e distal fem ur. Ch on droblastoma
in volved th e patella in four patien ts, accoun tin g for
50% of all ben ign tumors in th at bon e an d 28.6%
of all tum ors. Th e proximal h um erus was th e sin gle
most common site, accoun tin g for just less th an 20%
of all sites. Th e proxim al femur was in volved in 20
patien ts; of th ese ch on droblastomas, six in volved th e
greater troch an ter. Seven teen patien ts were older th an
41
42 Chapter 4 ■
40 years; fi ve of th em h ad in volvem en t of th e tempo-
ral bon e ( Kurt an d associates also foun d th at patien ts
with ch on droblastoma of th e skull bon es ten ded to be
older th an patien ts with ch on droblastoma of th e lon g
bon es) . O n e typical ch on droblastoma was cen tered
in th e metaph ysis. A diagn osis of ch on droblastoma-
like osteosarcoma h as to be ruled out wh en th is tumor
occurs in an atypical site. Th ere h as been on e docu-
men ted exam ple of two ch on droblastomas occurrin g
in on e patien t. Th ere are n o such examples in th e
Mayo Clin ic fi les.
SYMPTOMS
Local pain is the most important symptom of benign
chondroblastoma and affects most patients. Turcotte and
coauthors reported that 86% of patients had pain. The
average duration of symptoms was 20 months ( range,
5 weeks to 16 years) . The other symptoms reported
were swelling, a limp, and joint stiffness. Lesions in the
temporal bone were associated with progressive loss of
hearing and earache.
PH YSICAL FIN D IN GS
About 45% of patients have a tender area on palpa-
tion. The less common fi n dings are decreased range of
F igu r e 4.1. Distribution of
chondroblastomas according
to age and sex of the patient
and site of the lesion.
motion in a nearby joint, muscular atrophy, a palpable
mass, and soft-tissue swelling.
RAD IOGRAPH IC FEATU RES
Characteristically, benign chondroblastoma appears as
a central area of rarefaction. A typical feature of chon-
droblastoma is its location within the involved bone. In
the series reported on by Kurt and associates, 37% of
the lesions that involved the long bones were entirely
within the epiphysis, and 60% involved the epiphysis
and extended through the epiphyseal plate into the
adjacent metaphysis. Thus, 97% of chondroblastomas
of long bones were either entirely epiphyseal or had an
epiphyseal component. The fi nding of a lesion involving
both sides of an open epiphyseal plate is practically diag-
nostic of chondroblastoma. Only one chondroblastoma
recorded in the Mayo Clinic fi les was entirely metaphy-
seal. Most chondroblastomas involve the medullary cav-
ity, although rarely they may appear to involve the cortex.
There were no examples of chondroblastoma presenting
as a sur face or soft-tissue lesion ( Figs. 4.2–4.7) .
Approximately one-fourth of the lesions in long
bones in the report by Kurt and associates involved an
apophysis, either the greater trochanter of the femur or
the greater tuberosity of the humerus.
Chondroblastomas tend to form a round or an oval
defect in the involved bone. Nearly half the tumors
 ■ Benign Chondroblastoma 43

F igu r e 4.2. Chondroblastoma involving the proximal

humerus in a 14-year-old girl. Anteroposterior plain fi lm sh ows
a lucent lesion in the epiphysis, with associated periosteal
reaction.
F igu r e 4.3. Mineralized ch ondroblastoma involvin g an apo-
ph ysis—the greatest trochan ter of the femur—in a 28-year-
old man ( Case provided by Dr. David H . H oun , St. Bern ard’s
Region al Medical Cen ter, Jon esboro, Arkan sas) .

F igu r e 4.4. Computed tomograph ic appear-

ance of chondroblastoma in a 19-year-old
man . Th e lesion is well margin ated an d con -
tain s min eral ( Case provided by Dr. J. Adolph ,
St. Paul’s Hospital, Saskatch ewan , Can ada) .

have a surrounding thin sclerotic rim. Two-thirds of
chondroblastomas do not show mineralization. Com-
puted tomographic scans may show mineral not visualized
on plain radiographs. Approximately three-fourths of
chondroblastomas involve the adjacent cortex. Periosteal
new bone formation is seen rarely (Figs. 4.2–4.5).
Ch ondroblastomas of pelvic bones have a remark-
able tendency to originate near the triradiate carti-
lage. Lesions that arise in fl at bones, facial bones, or
other unusual sites often have nonspecifi c radiographic
features ( Figs. 4.6 & 4.7) .
Magnetic resonance images show a thin lobulated
rim. Peritumoral edema is characteristically seen and
should not be mistaken for permeation.
GROSS PATH OLOGIC FEATU RES
Chondroblastomas are ordinarily small. The primary
tumors in our series varied from 1 to 7 cm in greatest
dimension. The lesional tissue does not have pathogno-
monic features. It is grayish pink and may contain zones
44 Chapter 4 ■

F igu r e 4.5. A: An teropos-

terior plain radiograph of a
ch on droblastoma formin g a
well-circumscribed lesion with
a th ick sclerotic rim with in th e
distal left femur. B: Coron al
T2-weigh ted magn etic reso-
n ance image shows the epiphy-
seal location an d sign ifi can t
reactive edema around th e
lesion .

F igu r e 4.6. Computed tomogram of chondroblastoma

of th e temporal bon e in a 47-year-old man . Th e associa-
tion of th e lesion with a secon dary an eurysmal bon e cyst
explains th e expan sile quality of the mass ( Case provided
by Dr. Peter Robbin s, Th e Queen Elizabeth II Medical Cen -
ter, Nedlan d, Western Australia.) .
 ■ Benign Chondroblastoma 45

F igu re 4.7. A: Anteroposterior plain radiograph of a chondroblastoma forming a lytic lesion in the
righ t supra-acetabular ilium adjacent to the triradiate cartilage. B: Axial magnetic resonan ce image
shows bright cystic changes corresponding to a secondary aneurysmal bone cyst component.

F igu r e 4.8. Gross specimen of a chondroblastoma with a

heterogen eous mixture of tan -gray soft areas admixed with
fi rm, n odular foci of calcifi cation.

F igu re 4.9. “Aggressive” ch ondroblastoma involving the

of hemorrhage and calcifi cation. In rare instances, the
ch ondroid matrix is prominent. If the tumor is removed
intact, a thin sclerotic rim may be identifi ed. Cystic
ch ange, sometimes prominent, may occur; occasionally,
the tumor simulates an aneurysmal bone cyst. A chon-
droblastoma recurring in the soft tissues tends to be
well circumscribed and has a shell of ossifi cation, giving
rise to an eggshell appearance. In the Mayo Clinic fi les,
only two lesions were associated with soft-tissue recur-
rence ( Figs. 4.8 & 4.9) .
proximal h umerus in a 10-year-old boy. Th e lesion h ad
recurred twice previously. Th e humeral h ead is completely
destroyed, an d th e lesion exten ds in to soft tissue. H owever,
th e h istologic fi n din gs were th ose of an ordin ary ch on dro-
blastoma.
H ISTOPATH OLOGIC FEATU RES
As indicated by the name of the tumor, the basic prolif-
erating cell is considered to be a chondroblast. The typi-
cal cell is oval-shaped and has well-defi ned cytoplasmic
46 Chapter 4 ■

F igu r e 4.11. Th e n odular cartilage matrix in ch on droblas-

F igu r e 4.10. Typical appearance of chondroblastoma. The toma typically stains pink rather than blue.
left side of the fi eld shows chondroid differentiation, and
the right side shows calcifi cation. The stroma is composed of
mon on uclear cells with distin ct cytoplasmic boun daries an d
scattered ben ign gian t cells.

borders. The cytoplasm is indistinct or focally clear. It

may even stain pink. Characteristically, the nucleus is
oval and has a longitudinal groove in the middle that
gives rise to a coffee-bean appearance. In some oth-
erwise typical chondroblastomas, the tumor cells tend
to be somewhat epithelioid. These cells have vesicular
nuclei and abundant pink cytoplasm. Benign giant
cells are scattered throughout the lesion. These cells
may contain 5 to 40 nuclei. Although this description
F igu r e 4.12. The calcifi cation in chondroblastoma is seen
suggests that chondroblastomas can be recognized on between in dividual tumor cells. Large n odular masses of calci-
a clearly cytologic basis, to confi rm the diagnosis one fi cation with or without cartilage matrix can also be present.
must identify either chondroid foci or foci of calcifi ca-
tion ( Fig. 4.10) .
In the series reported by Kurt and associates, 95% of
the lesion showed chondroid differentiation. The chon-
droid foci may be small or may dominate the appear-
ance. The cartilage in chondroblastomas stains pink
rather than blue ( Fig. 4.11) . Ossifi cation may be seen
but rarely is it prominent enough to suggest a diagno-
sis of osteoblastoma. Calcifi c deposits occur in approxi-
mately one-third of the lesions. The calcifi cation tends
to be lacelike and appears to be deposited between
degenerating tumor cells ( Fig. 4.12) .
Mitotic fi gures are commonly seen in the mononu-
clear cells. However, they are usually not frequen t, and
atypical mitotic fi gures are almost never seen. Occa-
sionally, the tumor cells have some atypical cytologic
features, such as enlarged, irregular, and sometimes
F igu r e 4.13. Ch on droblastoma ( righ t) with secon dary an eu-
hyperchromatic nuclei. These are usually focal, how- rysmal bone cyst ( left) . O ccasionally, the aneurysmal bone cyst
ever, and do not suggest the possibility of malignant compon en t is so exten sive th at it masks th e un derlyin g ch on -
disease ( Figs. 4.13–4.16) . droblastoma.

F igu r e 4.14. High-power appearance of the mononuclear
cells of ch on droblastoma. Th e cytoplasm is well defi n ed, an d
some of th e n uclei h ave a cleaved appearan ce. Ch on droblas-
tomas typically contain several multinucleated giant cells.
F igu r e 4.15. Mitotic fi gures are not uncommon in chon-
droblastoma. Two mitotic fi gures are visible in this photo-
micrograph .
F igu r e 4.16. A mixture of pin k an d blue cartilage matrix in
a chondroblastoma.
■ Benign Chondroblastoma 47
F igu r e 4.17. Ch on droblastoma from th e temporal bon e.
Th e cells con tain abun dan t eosin oph ilic cytoplasm, an d th e
n ucleus tends to be pushed to on e side. These epithelioid-
like cells are seen most commonly in chondroblastoma of the
temporal bone.
F igu r e 4.18. Chondroblastoma of the temporal bone con-
tain in g abun dan t cytoplasmic deposition of golden -brown
h emosiderin .
Brown-yellow granular pigment, positive with iron
stain, is present in approximately one-fourth of all cases of
chondroblastoma. The pigment appears in the cytoplasm
of the tumor cells and in some macrophages. These pig-
mented cells are commonly seen in chondroblastomas
of the skull bones and may indeed be very prominent
(Figs. 4.17 & 4.18).
Small areas of necrosis, such as those in giant cell
tumors, may occur in one-fourth of all chondroblasto-
mas. Vascular invasion is rare but is more common in
lesions of fl at bones and of the skull.
Changes resembling secondary aneurysmal bone cyst
occur in more than one-third of all chondroblastomas.
48 Chapter 4 ■

These foci are usually microscopic and do not obscure

the un derlying lesion. In some chondroblastomas, how-
ever, the predominant feature may be an aneurysmal
bone cyst, with the neoplasm occurring as a mural nod-
ule. Although some authors have suggested that recur-
rences are more common when secondary aneurysmal
bone cyst is present, this has not been the experience at
Mayo Clinic.

TREATMEN T

Chondroblastomas are generally treated by curettage

with or without bone grafts. In the series reported by
Turcotte and coauthors, 64 patients had been treated
with curettage. There were nine local recurrences. Local F igu r e 4.19. Ch on droblastoma recurren t in th e soft tissues
recurrence was more likely to be in a fl at bone th an in in a 55-year-old man. The primary lesion was in the scapula.
Note sh ell of calcifi cation as seen also with recurren t gian t cell
a lon g bone. Most local recurrences can be treated by tumor in soft tissue.
repeat curettage and resection is rarely necessary. Occa-
sionally, a chondroblastoma recurs aggressively and
destroys the bone so that resection is required. Two
patients in the Mayo Clinic series developed soft-tissue
recurrences.
Radiation therapy is nearly always unnecessary and may
lead to a postradiation sarcoma. In one of the patients in
the Mayo Clinic series, a postradiation sarcoma of the dis-
tal femur developed 29 years after radiation for a chon-
droblastoma of the proximal tibia. Another patient, who
died with metastatic tumor, probably had postradiation
sarcoma.

PROGN OSIS

Nearly all ch on droblastomas can be eradicated by

proper treatmen t. Even th e rare tumor th at recurs or
produces implan tation in n earby soft tissues sh ould
be curable by total resection . As n oted, on ly two soft-
tissue recurren ces were foun d in th e Mayo Clin ic series
( Fig. 4.19) .
Several ben ign ch on droblastomas h ave metasta-
sized to th e lun gs as ben ign tumors. In th is respect,
th ey are similar to th e rare ben ign metastasizin g gian t
cell tumor. Th ey are quasimalign an t, an d th e meta-
static deposits usually are n on progressive. Kyriakos
an d associates presen ted on e well-documen ted exam-
ple of widespread metastasis developin g with ben ign
ch on droblastoma, an d th e patien t died of th e disease.
Pulmon ary metastasis developed in on ly four patien ts
in th e Mayo Clin ic series. O n e patien t h ad metastasis
at presen tation an d an oth er patien t h ad associated
acquired immun odefi cien cy syn drome. Not en ough
experien ce h as accrued to kn ow wh eth er ch emoth er-
apy is useful in th e rare patien t with progressive meta-
static ch on droblastoma ( Fig. 4.20) .
F igu r e 4.20. Computed tomogram of th e chest in a 24-year-
old woman with bilateral metastatic ben ign ch on droblastoma.
Th e primary tumor was in th e talus ( Case provided by Dr. Sub-
imal Roy, All India Institute of Medical Sciences, New Delhi,
In dia.) .
Several aggressive ch on droblastomas h ave been
reported in th e literature. Alth ough h istologically
similar to th e oth ers, th ese tumors h ave become
large an d usually locally aggressive. A related prob-
lem in volved a patien t in our series wh o h ad a lesion
of th e pelvis treated by h emipelvectomy. Th e tumor
recurred an d th e patien t ultimately died of local dis-
ease. An oth er lesion , origin ally coded as ch on droblas-
toma of th e scapula with a malign an t clin ical course,
h as been reclassifi ed as an osteosarcoma, resemblin g
ch on droblastoma.

BIBLIOGRAPH Y
1931 Codman, E. A.: Epiphyseal Chondromatous Giant Cell
Tumors of the Upper End of the Humerus. Surg Gynecol
Obstet, 52 :543–548.
1942 Jaffe, H. L. and Lichtenstein , L.: Benign Ch ondroblastoma
of Bon e: A Rein terpretation of th e So-Called Calcifyin g or
Ch ondromatous Giant Cell Tumor. Am J Pathol, 18:969–991.
1949 Copeland, M. M. and Geschickter, C. F.: Chondroblas-
tic Tumors of Bone: Benign and Malignant. Ann Surg, 129 :
724–733.
1951 Hatcher, C. H . and Campbell, J. C.: Benign Chondroblas-
toma of Bone: Its Histologic Variations and a Report of Late
Sarcoma in th e Site of O n e. Bull Hosp Jt Dis, 12 :411–430.
1956 Kunkel, M. G., Dahlin, D. C., and Young, H. H .: Benign
Ch ondroblastoma. J Bone Join t Surg, 38A:817–826.
1958 Plum, G. E. and Pugh, D. G.: Roentgenologic Aspects of
Ben ign Ch on droblastoma of Bon e. Am J Roen tgen ol, 79 :
584–591.
1965 Steiner, G. C.: Postradiation Sarcoma of Bone. Cancer,
18 :603–612.
1969 Kahn, L. B., Wood, F. M., and Ackerman, L. V.: Malignant
Ch on droblastoma: Report of Two Cases an d Review of th e
Literature. Arch Pathol, 88 :371–376.
1970 Schajowicz, F. and Gallardo, H.: Epiphysial Chondroblas-
toma of Bone: A Clinico-Pathological Study of Sixty-Nine
Cases. J Bone Join t Surg, 52B :205–226.
1970 Sirsat, M. V. and Doctor, V. M.: Benign Chondroblastoma
of Bon e: Report of a Case of Malign an t Tran sformation . J
Bone Joint Surg, 52B :741–745.
1973 McLeod, R. A. and Beabout, J. W.: The Roentgenographic
Features of Ch on droblastoma. Am J Roen tgen ol, 118: 464–
471.
1975 Green, P. and Whittaker, R. P.: Benign Chondroblastoma:
Case Report With Pulmon ary Metastasis. J Bon e Join t Surg,
57A:418–420.
1976 Aronsohn, R. S., Hart, W. R., and Martel, W.: Metaphyseal
Ch ondroblastoma of Bone. Am J Roen tgenol, 127:686–688.
1979 Harner, S. G., Cody, D. T. R., and Dahlin, D. C.: Benign
Ch on droblastoma of th e Temporal Bon e. Otolaryn gol Head
Neck Surg, 87:229–236.
■ Benign Chondroblastoma 49
1979 Reyes, C. V. and Kath uria, S.: Recurrent an d Aggressive
Ch on droblastoma of th e Pelvis With Late Malign an t Neoplas-
tic Chan ges. Am J Surg Path ol, 3:449–455.
1979 Wirman, J. A., Crissman, J. D., an d Aron , B. F.: Metastatic
Ch on droblastoma: Report of an Un usual Case Treated With
Radiotherapy. Cancer, 44:87–93.
1980 Roberts, P. F. an d Taylor, J. G.: Multifocal Benign Ch on dro-
blastomas: Report of a Case. Hum Pathol, 11:296–298.
1982 Spah r, J., Elzay, R. P., Kay, S., and Frable, W. J.: Ch on -
droblastoma of th e Temporoman dibular Join t Arisin g From
Articular Cartilage: A Previously Un reported Presen tation of
an Un common Neoplasm. Oral Surg Oral Med Oral Path ol,
54:430–435.
1984 Feely, M. an d Keoh ane, C.: Chon droblastoma of the Skull.
J Neurol Neurosurg Psych iatry, 47:1348–1350.
1984 Quint, L. E., Gross, B. H., Glazer, G. M., Braun stein , E. M.,
an d Wh ite, S. J.: CT Evaluation of Ch on droblastoma. J Com-
put Assist Tomogr, 8:907–910.
1985 Kyriakos, M., Land, V. J., Penning, H. L., and Parker, S. G.:
Metastatic Chondroblastoma: Report of a Fatal Case With a
Review of the Literature on Atypical, Aggressive, and Malignant
Chondroblastoma. Cancer, 55:1770–1789.
1987 Matsuno, T., Hasegawa, I., an d Masuda, T.: Ch on droblas-
toma Arising in the Triradiate Cartilage: Report of Two Cases
With Review of th e Literature. Skeletal Radiol, 16:216–222.
1989 Kurt, A. M., Un n i, K. K., Sim, F. H., an d McLeod, R. A.:
Chon droblastoma of Bon e. Hum Pathol, 20:965–976.
1990 Fanning, C. V., Sneige, N. S., Carrasco, C. H., Ayala, A. G.,
Murray, J. A., an d Raymond, A. K.: Fine Needle Aspiration
Cytology of Chondroblastoma of Bone. Can cer, 65:1847–1863.
1993 Turcotte, R. E., Kurt, A. M., Sim, F. H., Un ni, K. K., an d
McLeod, R. A.: Ch on droblastoma. Hum Path ol, 24:944–949.
1994 Weath erall, P. T., Maale, G. E., Mendelsohn , D. B., Sh erry,
C. S., Erdman , W. E., an d Pascoe, H. R.: Ch on droblastoma:
Classic an d Confusin g Appearan ce at MR Imagin g. Radiology,
190:467–474.
 C H APT ER

5
Chondromyxoid Fibroma

Chondromyxoid fi broma is a rare benign tumor, It accounted for less than 0.5% of all bone tumors.
apparently derived from cartilage-forming connective Chondroblastoma is almost three times as common as
tissue. Its name, which is cumbersome, has the merit chondromyxoid fi broma.
of being highly descriptive and has gained acceptance
for this distinctive tumor. The tumor was described
originally by Jaffee and Lichtenstein in 1948 when they SEX
presented eight cases and emphasized the danger of
mistaking this benign neoplasm for a malignant lesion, A defi nite male predilection was found in this series.
especially chondrosarcoma. Although chondromyxoid The literature indicates only a very slight male predomi-
fi broma characteristically contains variable amounts nance.
of chondroid, fi bromatoid, and myxoid components,
certain portions within at least some tumors resemble
hyalin e cartilage; therefore, it is logical to include this AGE
neoplasm among th ose of cartilaginous predilection.
The rationale of this classifi cation is enhanced by the Ch on dromyxoid fi broma h as a marked predilection
strikin g histologic similarity sometimes shared by chon- for patien ts in th e secon d an d th ird decades of life.
dromyxoid fi broma and benign chondroblastoma. Fifty-eigh t percen t of all patien ts were in th ese two
Many of the tumors described in the literature as myx- decades. Th e youn gest patien t was 6 years old an d th e
omas and fi bromyxomas are, no doubt, chondromyxoid oldest 75.
fi bromas. The distinctive myxoma ( fi bromyxoma) of a
jawbone lacks the lobulation and varied histologic spec-
trum of chondromyxoid fi broma. It has no exact coun-
terpart in the rest of the skeleton and is apparen tly of
LOCALIZATION
odontogenic derivation.
Typically, chondromyxoid fi broma is located in the
The earlier admonition to avoid overdiagnosing chon-
metaphyseal region of a long bone and may abut or be a
dromyxoid fi broma as chondrosarcoma has been taken
variable distance from the epiphyseal line. Rarely, the
too seriously by some pathologists. In several instances,
tumor involves both the metaphysis and the epiphysis.
errors have been made in the reverse direction, with
This localization suggests that, like benign chondroblas-
consequent inadequate treatment of chondrosarcoma.
toma, chondromyxoid fi broma may arise from the epi-
Chondromyxoid fi bromas can be expected to behave
physeal cartilaginous plate. In a large series reported by
in a benign fashion, except for the extremely rare lesion
Wu and coauthors, the tumor was diaphyseal in 11 cases
that undergoes malignan t transformation spontane-
and epiphyseal in only one. Approximately two-thirds of
ously and the lesion subject to the slight risk of malig-
the recorded examples of this tumor have been in the
nant change by radiation therapy.
long tubular bones, with approximately one-third of all
tumors occurring in the tibia. The proximal tibial meta-
physis was the most common location in the series. The
IN CID EN CE small bones of the foot are also commonly involved.
Chondromyxoid fi broma is uncommon in the vertebrae,
Chondromyxoid fi broma is one of the less common ribs, scapula, skull, and jawbones.
neoplasms of bone, accounting for only 1.6% of all Ten tumors in the series occurred in patients older
benign n eoplasms in the Mayo Clinic fi les ( Fig. 5.1) . than 40 years; three of these tumors involved the long
50

Figure 5.1. Distribution of
chondromyxoid fibroma accord-
ing to age and sex of the patient
and site of the lesion.
tubular bones. The seven others involved the pelvic
bones, the small bones of the foot, and the nasal sep-
tum.
SYMPTOMS
Pain is by far the most common presenting symptom in
chondromyxoid fibroma. Occasionally, pain is of several
years’ duration. Local swelling may be noticed by patients
whose tumors are not camoufl aged by a thick layer of
overlying tissue. Such tumefaction had been noted by
only six patients in this series. Swelling was more com-
mon in tumors of the small bones. Occasionally, these
tumors are asymptomatic incidental fi ndings on radio-
graphs. One patient had radiographic evidence of rickets,
which resolved after the lesion was removed. However,
although this lesion has been classifi ed as a chondromyx-
oid fi broma, it has some unusual histologic features.
PH YSICAL FIN D IN GS
Physical examination is of little diagnostic aid. Tender-
ness in the region of the tumor or a tender or nontender
mass help in the exact localization.
RAD IOGRAPH IC FEATU RES
Chondromyxoid fi broma characteristically appears as
an eccentric, sharply circumscribed zone of rarefaction
■ Chondromyxoid Fibroma 51
that occasionally expands the bone. Especially in a small
bone, this tumor can produce fusiform expansion of the
entire contour of the bone ( Figs. 5.2–5.4) .
In most cases, trabeculae appear to traverse th e
defect, but th ese are merely th e radiograph ic refl ec-
tion s of corrugation s on th e sur face of th e cavity th at
con tain s th e tumor. Th e defect may be roun ded or
oval. Frequen tly, th e lesion h as a scalloped appearan ce
similar to th at in metaph yseal fi brous defect ( Fig. 5.5) ;
th is lobulated appearan ce may be appreciated best
on magn etic reson an ce images. Sometimes th ere is a
th in lin e of sclerosis in th e surroun din g bon e. Radio-
graph ic eviden ce of calcifi cation is rare in ch on dro-
myxoid fi broma. It was reported in on ly 1 of 76 cases
described by Rah imi an d coauth ors. Path ologic frac-
ture was presen t in 4 of th e 30 cases described by th ese
auth ors. Alth ough th e lesion may destroy th e cortex
an d, especially in small bon es, expan d in to soft tissue,
th e radiograph ic features are con sisten tly th ose of a
ben ign process ( Figs. 5.6–5.9) .
Robinson and coauthors described 14 examples of
chondromyxoid fi broma involving the sur face of bone,
usually the femur and the tibia. In addition to the
unusual location, these lesions tended to show exten-
sive mineralization ( Fig. 5.10) .
GROSS PATH OLOGIC FEATU RES
The average chondromyxoid fi broma is small. In the Mayo
Clinic series, the greatest dimension of these tumors was
52 Chapter 5 ■

Figure 5.4. Ch on dromyxoid fi broma in th e proximal fi bula

in a 22-year-old man . Although the lateral cortex is destroyed,
the rest of the lesion is well marginated and purely lytic
( Case provided by Dr. Gordon P. Flake, Touro Infi rmary,
New Orlean s, Louisian a.) .

Figure 5.2. Chondromyxoid fi broma involving a metatar-

sal bon e. Th ere is fusiform expan sion in volvin g much of th e
bon e. Th e lesion is surroun ded by sclerotic bon e an d appears
ben ign .

Figure 5.5. Chondromyxoid fibroma of the proximal tibial

Figure 5.3. Purely lytic, well-delineated chondromyxoid metaphysis in a 47-year-old man. The irregular, scalloped border
fi broma at an unusual age an d in an un usual location . Th e is similar to that in metaphyseal fibrous defect (Case provided by
patient was a 75-year-old man. Dr. Phillip T. Stoffel, PSL Medical Center, Denver, Colorado.).
 ■ Chondromyxoid Fibroma 53

Figure 5.6. A: An teroposte-

rior radiograph of th e kn ee
sh ows a purely lytic lesion in
th e distal femoral metadiaph y-
sis th at abuts but does n ot cross
th e growth plate an d is associ-
ated with a benign buttress of
periosteal new bone forma-
tion . Alth ough th ere is evi-
dence of partial destruction of
th e lateral femoral cortex, th e
lesion has benign imaging fea-
tures. B: Coron al T2-weigh ted
magn etic reson an ce image
with fat saturation shows the
expan sile nature of th e lesion ,
with an intact shell of cortical
bon e an d exten sive associated
surroun din g bon e marrow
an d soft-tissue edema.

Figure 5.7. Computed tomogram of a large chondromyx-

oid fi broma of the ilium in a 27-year-old man. The lesion is
expansile and almost completely surrounded by a sclerotic rim.
Benign neoplasms such as chondromyxoid fi broma may destroy
the cortex by expansion ( Case provided by Dr. Donald J. Manz,
Holy Redeemer Hospital, Meadowbrook, Pennsylvania.).
Figure 5.8. Computed tomogram of chondromyxoid fibroma
in an unusual location—a rib—in a 71-year-old woman, who
was asymptomatic. The lesion has expanded through the cor-
tex to form a soft-tissue mass (Case provided by Dr. Anthony
M. Pireillo, Jr., Butler Memorial Hospital, Butler, Pennsylvania.).
54 Chapter 5 ■

up to 5 cm, although larger tumors have been reported.

Grossly, curetted fragments appear firm, somewhat
fi brous, and semitranslucent. The lesion rarely resembles
hyaline cartilage. If the lesion is removed intact, it appears
lobulated and sharply demarcated from the surrounding
bone. Although the lesion appears translucent, a frank
myxoid quality is not apparent grossly (Figs. 5.11–5.13).

Figure 5.9. Ch on dromyxoid fi broma in volvin g th e cortex

of th e distal fi bula in a 64-year-old man . Th e lesion is purely
lytic and has a sclerotic edge. Like many other neoplasms of
bon e, ch on dromyxoid fi bromas may be predomin an tly corti-
cal ( Case provided by Dr. Gary F. Neitzel, West Allis Memorial
Hospital, West Allis, Wisconsin.) .

Figure 5.11. Chondromyxoid fi broma of the tibia. The

lesion is extremely well circumscribed and appears as a mar-
ble set in bon e.

Figure 5.10. Chondromyxoid fi broma on the sur face of the

femur in a 27-year-old man . Th e lesion is h eavily min eralized, Figu re 5.12. Chondromyoid fibroma removed from the right
not un usual for a sur face lesion ( Case provided by Dr. Stan ethmoid sinus in a 54-year-old woman. The craniofacial bones
McCarth y, Royal Prince Alfred Hospital, Camperdown, New are not a common site for this tumor. It is well circumscribed and
South Wales, Australia.) . has a heterogeneous yellow, gray, and red-brown appearance.
 ■ Chondromyxoid Fibroma 55

Figure 5.13. Soft-tissue recurrence of a chondromyxoid Figure 5.14. Chondromyxoid fi broma involving the proxi-
fi broma. Th e primary tumor was removed from th e proxi- mal tibia in a 30-year-old man . Th e lesion h as a lobulated edge
mal tibia 1 year before removal of th e recurren t lesion . Both and is sharply demarcated from the bone.
tumors were glisten in g, lobulated, an d well circumscribed.

H ISTOPATH OLOGIC FEATU RES

The name of this tumor indicates a variation observed

microscopically in different fi elds of a given tumor and
from tumor to tumor. The gamut includes myxomatous
zones, fi brous zones, and fi elds with a distinctly chon-
droid appearance. The nuclei of the cells are round, oval,
eccentric, spindle-shaped, or stellate-shaped. Cytoplas-
mic extensions are often multipolar. Frank hyaline car-
tilaginous foci are unusual in chondromyxoid fi broma.
In a study from Mayo Clinic, Wu and coauthors found
hyaline cartilage in only 19% of the cases. Chondromyx-
oid fi broma ch aracteristically h as a lobular pattern of
growth . Th ese lobules vary in size, ran gin g from on es Figure 5.15. Low-power view of a macrolobular pattern in
easily visible un der low power to th ose small en ough ch on dromyxoid fi broma. Th e sh ape an d size of th e lobules
to be visible on ly on medium power. Ch aracteristically, vary. They have a hypocellular center, with condensation of
tumor cells toward the periphery.
th ese lobules h ave a h ypocellular cen ter an d a h yper-
cellular periph ery. All lobulated n eoplasms sh ow th is
growth pattern . H owever, in a lobulated ch on drosar-
coma, wh ich may be in th e differen tial diagn osis, th e
lesion is un iformly h ypercellular, alth ough with more
con den sation at th e periph ery of th e lobules. At th e
edge of th e lobules, approximately 50% of th e tumors
h ave scattered ben ign gian t cells. Th ere may be sh eets
of cells between lobules, an d in th ese cellular foci, th e
tumor cells frequen tly h ave th e microscopic features
of th e cells of ch on droblastoma. Mitotic fi gures may
be seen but are n ot common . Microscopic foci of calci-
fi cation are presen t in approximately on e-th ird of th e
lesion s. Th e calcifi cation may be in th e form of fi n e
lacelike deposits, as in ch on droblastomas, or more
common ly, plaquelike. Th is calcifi cation is very promi-
n en t in th e rare ch on dromyxoid fi broma th at occurs Figure 5.16. Oval- to spindle-shaped cells surround the
on th e sur face of bon e, impartin g un usual min eraliza- h ypocellular myxoid lobules. Benign giant cells are seen at
tion on radiograph s ( Figs. 5.14–5.21) . the periphery of the lobules.
56 Chapter 5 ■

Figure 5.17. High-power appearance of stellate tumor cells Figure 5.18. Occasionally, cells surrounding the lobules in
within hypocellular lobules. The cells contain round to oval ch on dromyxoid fi broma h ave th e appearan ce of cells seen in
nuclei an d eosin oph ilic cytoplasmic exten sion s. ch on droblastoma.

Figure 5.19. A an d B: Ch on dromyxoid fi broma with a microlobular pattern. Some of the lobules
h ave an eosin oph ilic appearance, wh ereas others are more myxoid.

Figure 5.20. O n ly rarely does ch on dromyxoid fi broma Figure 5.21. Chondromyxoid fi broma with chunky calcifi ca-
entrap fragmen ts of lamellar bon e. tion that differs from the lacelike pattern of calcifi cation seen
in chondroblastoma.
 ■ Chondromyxoid Fibroma 57

Figure 5.22. Ch on dromyxoid fi bromas may h ave cellular Figure 5.23. H igh-power view of pleomorphic cells in chon -
atypia. The cells within the peripheral areas of the lobules dromyxoid fi broma. Some nuclei show vacuolization resem-
have pleomorph ic n uclei. H owever, th ere is abundan t cyto- blin g th at seen in bizarre n uclei of oth er ben ign n eoplasms
plasm and no increase in the nucleus-to-cytoplasm ratio. with degenerative or pseudomalignant features.

As suggested by the radiographic features, chon- the matrix, clear-cut permeation of surroun ding bone,
dromyxoid fi bromas are sharply demarcated from the malignant radiographic features, and, most importantly,
surrounding bone. Indeed, in sections, the outermost hypercellularity throughout. Radiographic features are
lobules seem to pull away from the surrounding bone. extremely helpful in this distinction.
Rarely, however, separate nodules of chondromyxoid A rare neoplasm may have features of both chon-
fi broma are visible in surrounding bone. Even clear- droblastoma and chondromyxoid fi broma. In these, the
cut permeation, characterized by entrapped medullary diagnosis may depend entirely on the location within
bone, may be seen in rare instances, especially in small the bone, that is, whether epiphyseal or metaphyseal.
an d fl at bones.
The myxoid stroma in chondromyxoid fi broma is
TREATMEN T
somewhat different from myxoid foci of chondrosar-
coma. The matrix is uniformly stained and does not
Block excision of the affected area, when feasible, is the
show the liquefaction present in chondrosarcoma.
best treatment. Curettage, although ordinarily success-
However, small foci of liquefactive change occur in
ful, imposes perhaps a 25% risk of recurrence. Soft tis-
about one-third of chondromyxoid fi bromas. Necrosis
sue implantation may be a problem in rare instances.
also is apparent in approximately 12% of chondromyx-
Bone grafting after excisional curettage is often neces-
oid fi bromas. Foci of secondary aneurysmal bone cyst
sary. Indeed, it has been suggested that bone grafting
are rarely seen.
reduces the risk of recurrence. Radiation therapy is not
O n e of th e m ost im p ortan t h istologic features of
indicated except for the very rare surgically inaccessible
ch on d rom yxoid fibrom a is th at in som e portion s
lesion.
of th ese tum ors th e cells are large an d h ave n u clei
Three patients in the Mayo Clinic series underwent
of irregular sizes an d sh ap es, an d th e cells m ay even
amputation: one because of the large size of the tumor,
con tain m u ltiple n u clei. In th e stud y by Wu an d coau-
one because of a diagnosis of sarcoma, and one because
th ors, cellu lar atypia was foun d in approxim ately
a recurrent lesion treated elsewhere was similarly misin-
18% of th e cases. H owever, th e n u clei in th ese areas
terpreted. In addition, two of the patients with metatar-
are sim ilar to th e pseud om align an t n uclei seen in
sal tumors had ray amputations.
oth er ben ign n eoplasm s an d h ave a sm udgy ch rom a-
tin p attern ( Figs. 5.22 & 5.23) .
The most importan t differential diagnosis involves PROGN OSIS
a somewhat myxoid chondrosarcoma that may have
spindle cells and lobulated growth pattern. Most chon- The tumor recurred in 11 patients in the Mayo Clinic
drosarcomas that resemble chondromyxoid fi broma are series. One patient with a tumor of the distal fi bula
relatively high grade. They show liquefactive changes of had two recurrences in the soft tissues but has been
58 Chapter 5 ■

Figure 5.24. Ch on dromyxoid fi broma of th e ilium. A: Th e lesion h as features typical of ch on dro-

blastoma, in cludin g cytologic ch aracteristics an d lobulation . B: At autopsy, a h igh -grade, h istiocytic-
appearing sarcoma was seen to adjoin the chondromyxoid fi broma. Metastatic high-grade sarcomas
involving the right atrium ( C) and lungs ( D) were seen also at autopsy.

without further problems for approximately 10 years.
One patient with a sacral tumor died of the local
effects of an aggressive recurrence of chondromyxoid
fi broma.
Rahimi and coauthors found that the risk of recurrence
was higher if the tumors contained enlarged and irregu-
lar nuclei or had a prominent myxoid matrix, especially
in patients younger than 15 years. However, Gherlinzoni
and others could not confirm this finding.
Malignant transformation of chon dromyxoid
fi broma h as rarely been demon strated convincin gly in
th e literature, alth ough th ere h ave been many allusions
to th is problem. We know of one sarcoma th at developed
6 years after radiation to the area of a chon dromyxoid
fi broma. In one patien t in the Mayo Clin ic series, a
lethal sarcoma developed in a typical ch on dromyxoid
fi brom a, alth ough radiation h ad n ot been given . Th e
patien t died with dissem in ated m etastasis. At th e tim e
of autopsy, areas of both ch on dromyxoid fi broma an d
a h igh -grade sarcom a coexisted in th e pubis. Sarcoma-
tous ch an ge, h owever, rem ain s a path ologic curiosity
( Fig. 5.24) .
BIBLIOGRAPH Y
1948 Jaffe, H. L. and Lichtenstein, L.: Chondromyxoid Fibroma
of Bon e: A Distin ctive Ben ign Tumor Likely to be Mistaken
Especially for Ch ondrosarcoma. Arch Path ol, 45:541–551.
1953 Dahlin, D. C., Wells, A. H., and Henderson, E. D.: Chon-
dromyxoid Fibroma of Bon e: Report of Two Cases. J Bon e
Join t Surg, 35A:831–834.
1956 Dahlin, D. C.: Chondromyxoid Fibroma of Bone, With
Emphasis on Its Morphological Relationship to Benign Chon-
droblastoma. Can cer, 9:195–203.
1962 Turcotte, B., Pugh, D. G., and Dahlin, D. C.: The Roent-
genologic Aspects of Chondromyxoid Fibroma of Bone.
Am J Roen tgenol, 87:1085–1095.

1971 Schajowicz, F. and Gallardo, H.: Chondromyxoid Fibroma
( Fibromyxoid Chondroma) of Bone: A Clinico-Pathological
Study of Thirty-Two Cases. J Bone Joint Surg, 53B:198–216.
1972 Rahimi, A., Beabout, J. W., Ivins, J. C., and Dahlin, D.
C.: Ch on dromyxoid Fibroma: A Clin icopath ologic Study of
76 Cases. Cancer, 30:726–736.
1979 Kyriakos, M.: Soft Tissue Implantation of Chondromyxoid
Fibroma. Am J Surg Pathol, 3:363–372.
1983 Gherlinzoni, F., Rock, M., and Picci, P.: Chondromyxoid
Fibroma: Th e Experien ce at th e Istituto O rtopedico Rizzoli.
J Bone Joint Surg, 65A:198–204.
1989 Zillmer, D. A. and Dor fman, H . D.: Chondromyxoid
Fibroma of Bon e: Th irty-Six Cases With Clin icopath ologic
Correlation . Hum Path ol, 20:952–964.
■ Chondromyxoid Fibroma 59
1994 Robin son, L. H ., Un ni, K. K., O’Laugh lin , S., Beabout,
J. W., and Siegal, G. P.: Sur face Chondromyxoid Fibroma of
Bone ( abstract) . Mod Pathol, 7:10A.
1998 Wu, C. T., Inwards, C. Y., O’Laughlin, S., Rock, M. G.,
Beabout, J. W., and Unni, K. K.: Chondromyxoid Fibroma of
Bone. A Clinicopathologic Review of 278 Cases. Hum Pathol, 29:
438–446.
2007 Baker, A. C., Rezeanu, L., Unni, K., Klein, M. J., and
Siegal, G. P.: Juxtacortical Chondromyxoid Fibroma of Bone: A
Unique Variant: A Case Study of 20 Patients. Am J Surg Pathol,
31:1662–1668.
 C H APT ER
6
Chondrosarcoma (Primary,
Secondary, D edifferentiated,
and Clear Cell)
CH ON D ROSARCOMA
Chon drosarcoma sh ould be differen tiated from
osteosarcoma because of basic path ologic differen ces
that are refl ected in vastly differen t clin ical, th era-
peutic, an d progn ostic features. Th e exact origin of
chon drosarcoma is obscure, but th e salien t path o-
logic fact is th at its basic proliferatin g tissue is carti-
lagin ous th rough out. Large portion s of these tumors
may become myxomatous, calcifi ed, or even ossifi ed.
Sometimes at th e periph ery of lobules of h igh -grade
chon drosarcoma, a few fi brosarcoma-like spin dlin g
tumor cells occur. Osseous trabeculae, when presen t,
are seen at th e periph ery of lobules an d appear to be
rimmed with osteoblasts. H owever, wh en th e malignan t
cells directly produce an osteoid lacework or osteoid
trabeculae even in small foci, th e n eoplasm h as clin i-
cal ch aracteristics of osteosarcoma and belon gs in th at
category ( Table 6.1) .
Chondrosarcoma usually has a slow clinical evolu-
tion. Metastasis is relatively rare and often occurs late.
Therefore, the basic therapeutic goal is local control;
however, in osteosarcoma, systemic spread has also to
be addressed because of early hematogenous dissemi-
nation. Attainment of this goal demands adequate, fre-
quently radical, early surgical treatment but generally
not chemotherapy.
Chondrosarcomas can arise de novo in extraskeletal
tissues or in teratomas and other mixed tumors. Chon-
drosarcomas composed of hyaline cartilage are extremely
rare in somatic soft tissues.
Secondary chondrosarcomas arise most commonly in
osteochondromas ( osteocartilaginous exostosis) , espe-
cially in the multiple, familial type. Whether a solitary
60
enchondroma can give rise to a chondrosarcoma is a
diffi cult question to answer.
The distinction between an enchondroma and an
extremely well-differentiated chondrosarcoma depends
so much on the radiographic fi ndings that a pure his-
tologic interpretation is hazardous. It is possible that
enchondromas undergo change to chondrosarcoma,
but this is hard to prove one way or the other. In the
Mayo Clinic series of 158 defi nite secondary chon-
drosarcomas ( in 155 patients) , 82 occurred in patients
with solitary exostoses, 44 in patients with multiple
hereditary exostoses, and 19 in patients with multiple
chondromas ( 8 with Ollier disease, 5 with Maffucci syn-
drome, and 6 with multiple chondromas) . The remain-
ing 10 occurred in miscellaneous conditions such as
fi brous dysplasia and previous radiation. Some of the
details of these secondary chondrosarcomas are given
in Chapters 2 and 3.
In addition to the 1,223 primary and secondary
chondrosarcomas ( in 1,228 patients) , 145 had given
rise to more highly malignant tumors—osteosarcomas,
fi brosarcomas, or malignant fi brous histiocytomas—
and these are called dedifferentiated chondrosarcomas.
Among the primary chondrosarcomas were 26 of the
clear cell type. The 46 mesenchymal chondrosarcomas,
not included in this list, are discussed in Chapter 7.
IN CID EN CE
Chondrosarcomas constituted just over 20.4% of the
malignant tumors in our series, and approximately
75% were of the primary type. Dedifferentiation has
occurred in both primary and secondary chondrosar-
comas. Osteosarcoma was approximately 1.5 times as
common as chondrosarcoma.
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 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell) 61

LOCALIZATION
Classifi cation of
TABL E 6.1.
Chondrosarcoma More than two-thirds of the tumors were in the trunk
( including the shoulder girdle) and the upper ends of
Type Number of Cases
the femora and humeri ( Fig. 6.1) . Most of the lesions in
Con ven tion al 829 the maxillary region seemed to arise from th e cartilage
Secondary 158 of the walls of the nasal cavity. There were 23 tumors
Respiratory tract 27
in the nose, whereas only 6 tumors were considered to
Small bones 36
Periph eral 24 arise primarily in the maxilla and only 2 in the man-
In join ts 2 dible. Three tumors arose from the hyoid bone; one
Clear cell 26 of the patients also had Gardner syndrome. Five chon-
Dedifferen tiated 145 drosarcomas involved the synovium. Two of these were
Mesen ch ymal 46
considered to be primary chondrosarcoma of the
1,293 synovium: one in the hip and the other in the knee.
Three were considered to be secondary to preexisting
synovial chondromatosis: one each involved the knee,
ankle, and elbow. In addition, fi ve chondrosarcomas
SEX
arose after radiation therapy; one of the patients had
Approximately 57% of the patients were males. fi brous dysplasia. One of the postradiation chondrosar-
comas was a clear cell variant. Three patients had chon-
drosarcoma arising in preexisting fi brous dysplasia.
AGE
One of these patients previously had radiation, and that
Chondrosarcoma is primarily a tumor of adulthood tumor is included among the fi ve arising after radiation.
and old age. Approximately 60% of the patients were One of the other two tumors was a clear cell chondrosar-
in the fourth, fi fth, and sixth decades of life. Only seven coma. The remarkable rarity of chondrosarcoma in the
patients were in the fi rst decade of life. The youngest distal portions of the extremities, with only 36 occurring
patient was a 3-year-old boy with a lesion of the mid distal to the ankle and wrist joints, is noteworthy. Some
right humerus, and the oldest was a 91-year-old woman of the few lesions reported as juxtacortical chondrosar-
with a lesion of the tenth thoracic vertebra. Patients with comas in the literature are classed with chondroblas-
secon dary chondrosarcoma were somewhat younger, tic osteosarcomas because component malignant cells
with approximately 52% being in the third an d fourth produce osteoid; these are described in a later chapter
decades of life. Only 5.21% of the total group of patients as periosteal osteosarcomas. However, 24 chondrosar-
was in the second decade of life. Any series with a rela- comas were situated peripherally. Seventeen of these
tively large number of patients in the fi rst two decades were termed periosteal chondrosarcomas because their
of life probably includes patients with chondroblastic radiographic features suggested a relation to periosteal
osteosarcoma, a tumor with biologic capabilities similar chondroma. The remaining seven were classifi ed as
to that of the overall osteosarcoma group. peripheral chondrosarcomas because they did not show

F igu r e 6.1. Distribution of chondrosarco-

mas accordin g to age an d sex of th e patien t
and site of the lesion.

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62 Chapter 6 ■
features similar to those of periosteal chondromas and
did not appear to have a preexisting osteochondroma.
Localization data on the 158 chondrosarcomas sec-
ondary to exostoses and multiple chondromas are given
in Figure 6.2. As in dicated previously, the 44 patients
with chondrosarcomas complicating multiple exostoses
were from a group of 184 patients who required surgery
for the latter condition. Of the 966 patients requiring
surgery for solitary exostoses, 82 had complicating chon-
drosarcomas. Nineteen of the 73 patients operated on
for multiple chondromas of the skeleton had secondary
chondrosarcomas. These data should not be construed
to represent the true incidence of sarcomatous change
in the three conditions. Continued follow-up of the
total groups should alter the data, and factors of selec-
tion probably increase the likelihood that the patients
with sarcoma will seek help at a large medical center.
Figure 6.1 shows that patients with secondary chondro-
sarcoma tend to be younger than the average patient
with primary chondrosarcoma.
Information concerning various subtypes of chon-
drosarcoma is given in Table 6.1.
SYMPTOMS
Local swellin g an d pain , eith er alon e or in combi-
n ation , are sign ifi can t presen tin g symptoms. Pain
stron gly suggests active growth of a cen tral cartilagi-
n ous tumor. Except for some tumors of th e pelvic
girdle or spin al column , in wh ich referred pain may
precede local pain or discern ible ph ysical or radio-
graph ic fi n din gs, localization of th ese tumors is easy.
As in oth er tumors of bon e, th e ch aracteristics of
th e pain or swellin g offer little aid in th e differen tial
F igu r e 6.2. Distribution of secondary chon-
drosarcomas according to age and sex of the
patien t and site of th e lesion. A: Solitary exos-
tosis. B: Multiple exostoses.
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 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell)
F igu r e 6.2. Continued. C: Ch on drodysplasias.
D: Total.
diagn osis. Path ologic fracture may be th e presen tin g
symptom. Th e prolon ged clin ical course so often
obser ved affords a clue. A tumor th at gradually
en larges for on e to two decades ( or even lon ger) may
h ave been n oted by patien ts wh o h ave an osteoch on -
droma th at un dergoes malign an t ch an ge. Such tran s-
formation often produces pain an d rapid in crease in
th e size of a tumor of lon g duration . Patien ts with pri-
mar y ch on drosarcoma also may h ave h ad symptoms
for several years before seekin g defi n itive th erapy.
In adequately treated tumors h ave a typical h istor y of
man y recurren ces an d, fi n ally, of in operable exten -
sion or metastasis leadin g to death . A few ch on drosar-
comas h ave a rapid clin ical course because of a h igh er
degree of malign an cy in itially or because of in creased
activity with recurren ces.
63
The slow clinical evolution of chondrosarcoma is
emphasized by the fi nding that in approximately 10%
of chondrosarcomas that recurred in the Mayo Clinic
series, the interval between treatment and recurrence
was 5 to 10 years. A recurrence may even become mani-
fest more than 10 years after initial treatment. Because
recurrence may be so delayed, conclusions about the
effi cacy of any treatment must be based not only on a
sizeable series of cases but also on follow-up of 10 years
or more. In a selected series of patients treated at Mayo
Clinic, Bjornsson and coauthors found that the recur-
rence rate was approximately 20%. The cumulative
probability of local recurrence was 20.1% at 5 years,
22.4% at 10 years, and 26.5% at 20 years. This study
emphasizes the possibility of local recurrence even up
to 20 years.
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64 Chapter 6 ■

F igu r e 6.3. Proximal femoral ch on drosarcoma in a 77-year-old woman . A: Plain radiograph sh ows
th at th e lesion is focally min eralized. Th e combin ation of cortical expan sion an d cortical th icken -
ing suggests the diagnosis. B: Corresponding gross specimen. There is marked thickening of the
cortex, an d the tumor erodes th e cortex at several places. ( Figure 6.3A is from Un n i, K. K., an d
In wards, C. Y.: Tumours of Osteoarticular System. In : Fletch er, C. D. M. [ ed] . Diagn ostic Histopa-
th ology of Tumors. Edin burgh , Ch urch ill Livin gston e, 1995. By permission of th e publish er.)

PH YSICAL FIN D IN GS

Many chondrosarcomas can be palpated, but a sizeable

number of those affecting the trunk, or even th e long
bones of the extremities if they have not breached
the cortex, cause pain alone to signal their presence.
A palpable mass is characteristically hard and may be
painful. When a mass cannot be palpated, the diagno-
sis may be diffi cult, especially for chondrosarcomas of
the innominate bone, which may lack defi nite radio-
graphic changes. The region of the acetabulum, where
many chondrosarcomas originate, is notorious for such
“hidden” malignant tumors. In our series, one chondro-
sarcoma of the hyoid bone was associated with Gardner
syndrome.

RAD IOGRAPH IC FEATU RES

Th e radiograph is n early always h elpful and often affords

F igu r e 6.4. Ch on drosarcoma arisin g in th e proximal femur.
The plain radiograph sh ows a lytic lesion with min eralization,
cortical th icken in g, an d en dosteal scallopin g.
almost pathognomonic eviden ce of ch on drosarcoma
( Figs. 6.3–6.7) . Ch ondrosarcomas ten d to be large. In
a study by Bjornsson an d coworkers, the mean size of
th e tumors of th e 180 cases for which radiograph s were
available was 9.5 cm. Small lesion s tended to be round
or oval. Large lesion s, once th ey reach ed the adjacent

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 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell) 65

F igu r e 6.6. Magn etic reson an ce image of a grade 1 ch on dro-

sarcoma in volvin g th e distal femur with a soft-tissue mass. Th is
imaging modality can be helpful in evaluating the extent and
ch aracter of intramedullary disease an d soft tissue exten sion .
F igu r e 6.5. Plain radiograph of a chondrosarcoma in the
mid-tibia in a 71-year-old woman . Th e lesion is expan sile with
focal mineralization and a pathologic fracture ( Case provided
by Dr. Van dana Kumar, Lon don , Ken tucky) .

F igu r e 6.7. Huge chondrosarcoma apparently arising from the vertebral column in a 74-year-old
man was man ifested by an abdomin al mass. A: Focal calcifi cation is apparen t on computed tomog-
raph y. B: Gross specimen of th e chondrosarcoma. The tumor sh ows focal calcifi cation and pro-
noun ced cystifi cation because of th e myxoid chan ge in th e matrix. The size of the lesion and th e
cystifi cation alon e are suffi cien t to diagn ose ch on drosarcoma.

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66 Chapter 6 ■
cortex, h ad a pron ounced tenden cy to con form to the
sh ape of the bon e. In this study, approximately 79% of
the tumors had poor margination, 17% had intermedi-
ate margin s, and 4% were sh arply circumscribed. An al-
ysis of margin ation was diffi cult in several intramed-
ullary tumors because on ly matrix calcifi cation was
visualized. A clear-cut sclerotic rim was present in only
two tumors. Approximately three-fourths of th e lesion s
sh owed min eral, wh ich was con sidered to be slight in
39% of tumors, moderate in 47% and marked in 14%.
In some lesion s, calcifi cation not visible on oth er stud-
ies was clearly demonstrable on computed tomograms.
Areas of lucency within an oth erwise calcifi ed tumor
were common an d con sidered suggestive of ch on dro-
sarcoma. Approximately one-fourth of th e tumors did
not sh ow calcifi cation . H owever, these were con sid-
ered to have malign an t ch aracteristics on th e basis of
oth er features. Approximately 84% of th e tumors h ad
caused cortical abn ormalities. More than h alf of th ese
con sisted of en dosteal erosion , an d th e rest showed
frank cortical destruction. En dosteal scallopin g is a
sign of growth but n ot n ecessarily of chondrosarcoma.
En chondromas of small bones always sh ow erosion of
cortex; permeation of th e tumor th rough the cortex
in to soft tissue has to be iden tifi ed before a diagn osis
of ch on drosarcoma is entertain ed in the small bon es.
More th an one-third of th e lesions sh owed widenin g or
expan sion of th e bon e. O f th ese, approximately one-
half h ad cortical thinn in g. Approximately 20% of th e
tumors sh owed th e combination of expan sion of bon e
an d cortical th icken ing. Periosteal new bone formation
was unusual and, when present, scant. Forty percent of
th e lesion s had a soft-tissue mass. Magnetic resonance
images and computed tomograms detected a soft-tissue
mass and delin eated its exten t more accurately th an
con vention al radiograph s ( Figs. 6.8–6.10) .
In an osteochondroma that has undergone malig-
nant change, the radiographic fi ndings may be similar
to those of the benign lesion from which it originated,
but the sur face ordinarily is indistinct and fuzzy, and the
clear demarcation from the adjacent soft tissue may be
lost. A large soft-tissue mass, if associated with irregular
deposits of bone or calcifi cation, is especially charac-
teristic. Areas of lysis instead of the uniform calcifi ca-
tion of osteochondroma is also suggestive of secondary
chondrosarcoma. Computed tomograms and magnetic
resonance images help in delineating the true thickness
of the cartilage cap ( Figs. 6.11 & 6.12) .
GROSS PATH OLOGIC FEATU RES
Ch on drosarcomas may be divided in to cen tral an d
periph eral types. In lon g bon es, this separation in type
is usually obvious, with a rare periph eral sarcoma aris-
in g eith er on an osteoch on droma or directly from th e
sur face of a bon e. Th e latter, a periosteal ch on drosar-
coma, is exceedin gly rare, with on ly 17 examples in th e
Mayo Clin ic fi les. Seven oth ers were situated periph er-
ally an d did n ot h ave features of periosteal ch on dro-
sarcoma. Th ey may h ave arisen in exostoses, but th is
could n ot be proven . Th e size of th e lesion is most
h elpful in differen tiatin g periosteal ch on droma from
ch on drosarcoma. Th e former is almost always less th an
3 cm in greatest dimen sion , wh ereas th e latter is rarely
less than 5 cm. If exostosis is presen t, th e fi n din g of a
cartilagin ous cap, irregularly th icken ed to more th an
1 cm, must be viewed with th e suspicion of malign an cy;
cartilagin ous masses of 3 or 4 cm usually are in dicative
of a ch on drosarcoma. In th in or fl at bon es, as in th e pel-
vic girdle or th oracic cage, lan dmarks are so destroyed
by th e time th e average tumor is diagn osed th at th e
exact site of origin can on ly be surmised, but most of
th e tumors apparen tly begin cen trally. As seen radio-
graph ically, a cen tral ch on drosarcoma often produces
expan sion an d con comitan t th icken in g of th e cortex of
lon g bon es. In such cases, th e region of in volved mar-
row is usually distin ctly demarcated. Th e th icken ed
cortex is in vaded by tumor, an d breakth rough even tu-
ally occurs ( Figs. 6.13 & 6.14) .
Ch on drosarcomas are ch aracteristically composed of
lobules th at vary from a few millimeters to several cen -
timeters in greatest dimen sion . Except at th e periph -
ery of th e tumor, th ese lobules are usually completely
coalesced. Th e cen ters of th e lobules often become
n ecrotic, liquefi ed, an d cystic. Th e liquefaction an d
cystifi cation are secon dary to marked myxoid ch an ge
of th e matrix. Th e myxoid ch an ge may also give rise
to a gelatin ous appearan ce of th e n eoplasm. Necrotic
foci often calcify in an irregular fash ion . Some of th e
calcifi c zon es observed grossly are actually osseous
masses ( Figs. 6.15–6.20) .
Chondrosarcomas produce a matrix substance that
varies in consistency from that of fi rm hyaline carti-
lage to that of mucus. A myxoid quality is an ominous
sign, strongly suggestive of malignancy. Sometimes
the periphery of the recurrent form of a cartilaginous
tumor is opaque and fi brous, resembling a fi brosar-
coma or even an osteosarcoma grossly and microscopi-
cally ( Fig. 6.21) .
It is extremely unusual to see a multicentric chon-
drosarcoma. There were only eight examples in the
Mayo Clinic fi les. One patient had separate chondrosar-
comas involving the rib and the sphenoid bone 2 years
apart. One patient had a lesion of one distal femur and
one distal fi bula 5 years apart. Two patients had Ollier
disease: one of them had a lesion of the ischium and
13 years later a chondrosarcoma of the proximal tibia,
and the other had a chondrosarcoma of the humerus
7 years after an above-knee amputation for chondrosar-
coma of the proximal tibia. One patient with multiple
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 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell) 67

F igu re 6.8. Anteroposterior radiograph ( A) and

two-dimen sional coron al computed tomogram ( B) of
th e pelvis in a 70-year-old man sh ows an aggressive
destructive mixed lytic and sclerotic lesion in the
right acetabulum an d isch ium, with scattered foci
of ch on droid matrix an d an associated path ologic
fracture. Th e coron al T1- ( C) an d T2- ( D) weigh ted
magn etic reson an ce images sh ow th at th e lesion is
associated with a large extraosseous component. The
gadolin ium-enh an ced image ( E) sh ows th at th ere are
large regions with little to no enhancement within
th e lesion , suggestive of myxoid ch an ge. Th e con stel-
lation of fi ndings is most consistent with chondrosar-
coma. Because of th e large un min eralized soft-tissue
mass, th e differen tial diagn osis would also in clude
dedifferentiated chondrosarcoma.

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68 Chapter 6 ■

F igu r e 6.9. Chondrosarcoma arising in the setting of Ollier disease. A: Anteroposterior radiograph
of the left hand shows multiple lytic lesions in the phalanges, with varying degrees of expansion
typical of multiple en ch on dromas in a patient with Ollier disease. B: Sagittal T2-weighted magnetic
reson ance imaging with fat suppression sh ows cortical destruction an d a large soft-tissue mass asso-
ciated with one of the cartilage lesions in the fi fth middle phalanx, consistent with chondrosarcoma
arising in an enchondroma. The soft-tissue extension is not detectable in the radiograph.

F igu r e 6.11. O steoch on droma of th e distal tibia in an

18-year-old woman . A: Th e sur face is smooth , an d th e cartilage
cap is th in . B: Three years later, th e cap is irregular an d n odu-
lar, a change supporting the diagnosis of secondary chondro-
sarcoma. ( Case provided by Dr. Cyn th ia Flessn er, Memorial
Medical Center, Springfi eld, Illinois.)

F igu r e 6.10. Chondrosarcoma of the fi rst metatarsal in a

32-year-old man. The tumor extends into soft tissues.

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 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell) 69

F igu r e 6.12. A: An teroposterior radiograph sh ows multiple osteoch on dromas in volvin g th e bon es
of th e kn ee, with associated developmen tal deformity compatible with multiple h ereditary osteo-
ch on dromatosis. B: Lateral radiograph sh ows malign an t destruction of on e of th e lesion s in volvin g
the proximal tibia posteriorly, with a large associated soft-tissue mass that contains fl ecks of cartilagi-
nous matrix. Sagittal T1- ( C) an d axial T2- ( D) weigh ted images sh ow the large soft-tissue mass sur-
roun din g a remnant of th e stalk of the osteochon droma. These imaging features are characteristic
of malign an t degen eration of an osteoch on droma to ch on drosarcoma.

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70 Chapter 6 ■

F igu r e 6.13. Secon dary ch on drosarcoma arisin g from a sessile osteoch on droma in th e righ t ilium
of a 21-year-old man. A: Computed tomography shows a large mineralized mass. B: The lesion con-
sists almost entirely of cartilage. There is gross cystic change. The cystic cavities contain gelatinous
material representing myxoid change.

F igu r e 6.14. Secondary chondrosarcoma involving the F igu r e 6.15. Grade 1 ch on drosarcoma in volvin g th e righ t
ilium. The top portion of the fi eld shows features of osteo- anterior lower seven th rib in a 48-year-old man . He presented
ch on droma. Th e lower portion sh ows pure cartilagin ous with right upper quadrant pain, likely from this large chest
growth with marked myxoid ch an ge. wall mass that was abutting the right colon.

exostoses developed a chondrosarcoma of the sacrum
4 years after undergoing internal hemipelvectomy for
a chondrosarcoma of the pubis. One patient had two
chondrosarcomas involving the femur, and another
patient had two chondrosarcomas involving the proxi-
mal and distal tibia.
Metastasis to regional lymph nodes is distinctly rare.
In chondrosarcoma, hematogenous dissemination to
the lungs is much less common than in osteosarcoma
or fi brosarcoma.
Chondrosarcoma has a pronounced propensity for
local recurrence, even when the surgeon has apparently
removed the tumor completely.
H ISTOPATH OLOGIC FEATU RES
Chondrosarcoma may be diffi cult to diagnose purely on
the basis of histologic features. The criteria that differ-
entiate low-grade chondrosarcoma from a chondroma
are very subtle. Experience has shown that different

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 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell)
F igu r e 6.16. Grade 1 chondrosarcoma involving the pelvis.
Th e tumor h as gray-wh ite lobulated areas correspon din g to
cartilagin ous differen tiation . Yellow areas of n ecrosis an d
degenerative myxoid change are also present.
F igu r e 6.17. Chondrosarcoma involving the distal humerus.
On radiographs, a large soft-tissue mass suggested a diagno-
sis of dedifferen tiation . Microscopically, h owever, th e en tire
tumor was a grade 2 chondrosarcoma.
rules apply in different clinical situations. Almost
without exception, cartilaginous tumors of the sternum
are malignant, regardless of the histologic appearance.
However, some lesions may appear to be “malignant”
by conventional criteria but are benign: chondromas of
the small bones of the hands and feet, periosteal chon-
dromas, chondromas of Ollier disease and Maffucci syn-
drome, synovial chondromatosis, and chondromas of
the soft tissues of the hands and feet are examples. The
71
F igu r e 6.18. Exten sive recurren ce of a grade 2 ch on drosar-
coma in th e thigh , a site of previous resection , in a patien t
who had declined an amputation.
features proposed by Lichtenstein and Jaffe are very
helpful when viable fi elds are studied. These include
many cells with plump nuclei, more than an occa-
sional cell with two such nuclei, and, especially, giant
cells with large single or multiple nuclei or clumps of
chromatin. The correct diagnosis depends on the cor-
rect interpretation of the subtle qualitative characteris-
tics. Furthermore, malignant foci may be obscured by
necrotic regions or by zones with insuffi cient cytologic
evidence for diagnosis of sarcoma, further complicating
the pathologist’s task.
Generous material for biopsy is mandatory, and the
use of clinical and radiographic evidence is extremely
helpful. A microscopic diagnosis cannot be made on
the basis of clinical and radiographic evidence, but such
evidence guides the search for pathognomonic micro-
scopic fi elds.
As indicated above, differentiation of a low-grade
chondrosarcoma from an enchondroma can be diffi cult
on a purely histologic basis. Mirra and coauthors pro-
posed several histologic criteria for making this distinc-
tion. Enchondromas tend to form well-circumscribed
nodules that may be surrounded by bony trabeculae.
Chondrosarcomas tend to permeate, fi lling the marrow
cavity and entrapping bony trabeculae. This perme-
ative quality is probably the most important feature that
differentiates chondrosarcoma from enchondroma.
Here, two caveats apply. First, chondrosarcomas grow
72 Chapter 6 ■

F igu r e 6.19. A: Grade 1 ch on drosarcoma in volvin g a

metacarpal in a 65-year-old woman . Th e tumor in vades soft
tissues. B: Gross specimen of ch on drosarcoma metastatic
to th e lun g. Pulmon ary metastatic lesion s developed with in
2 years.

F igu r e 6.21. Chondrosarcoma arising in the proximal fi bula

in a 37-year-old woman with Maffucci syndrome. In addition
Figu re 6.20. Chondrosarcoma of the first metatarsal invading to the central benign-appearing fi rm, gray-white nodules of
soft tissues extensively. ( Case provided by Dr. Paul R. Wilson, cartilage, th ere are large, cystic, myxoid nodules of malignant
Hackley H ospital, Muskegon, Michigan.) cartilage permeatin g beyon d th e con fi n es of th e bon e.
 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell)
in lobules and some of them may have rings of reactive
bone around them. Second, the lack of permeation does
not always mean that the lesion is benign. Permeation
may not be seen on limited biopsy samples. Enchon-
dromas tend to be relatively hypocellular, especially in
the large bones. As indicated above, enchondromas
of the small bones tend to be quite cellular. However,
even in the small bon es, en chondromas tend to grow
by expansion, rather than by permeation. Hence, one
does not ordinarily fi nd entrapped bony trabeculae in
ench ondromas of small bones. Grossly, chondrosarco-
mas of the small bon es tend to permeate through the
in terstices of the cortex into soft tissue. Formation of a
soft-tissue mass has to be considered defi nite evidence
of malign ancy in a cartilage tumor arising in the medul-
lary cavity ( Fig. 6.22) .
Chondromas tend to have a solid chondroid matrix.
The matrix stains blue and has a smooth, unbroken
appearance under low power. Chondrosarcomas tend
to show a myxoid change in the matrix ( Fig. 6.23) . This
is manifested as partial dissolution of the matrix into
F igu r e 6.22. Grade 2 chondrosarcoma involving a meta-
carpal. Th e tumor in vades preexistin g bon e ( A) an d exten ds
into surrounding soft tissue ( B) . Within 2 years, the tumor
had metastasized to th e lun g ( C) .
73
strings or chords. Marked myxoid change is manifested
by lack of nuclei, and sometimes the matrix is lost, so
that the fi eld appears empty. A mucinous material with
no cells has to be considered evidence of chondrosar-
coma in the proper clinical setting. Chondromas of
small bones and periosteal chondromas may show con-
siderable myxoid change.
Foci of necrosis are also a worrisome feature in a car-
tilage tumor. Necrosis is manifested by lacunae contain-
ing pink-staining cells without blue-staining nuclei.
Most chondrosarcomas have sheets of chondrocytes,
which may have a lobulated growth pattern when viewed
under low power. Some chondrosarcomas, however,
have pronounced clustering of the chondrocytes, simi-
lar to the classic appearance in synovial chondromato-
sis. Chondrosarcoma is not a spindle cell neoplasm,
because chondrocytes lie within lacunae. Occasionally,
however, the nuclei appear oval shaped ( Fig. 6.24) .
Radiograph ic features an d gross appearan ce, as
already in dicated, are very importan t in distin guish -
in g between an osteoch on droma an d a secon dary
74 Chapter 6 ■
F igu r e 6.23. Typical appearance of a grade 1 chondrosar-
coma with extensive myxoid ch an ge of th e matrix.
F igu r e 6.24. Grade 1 chondrosarcoma with a nodular
growth pattern, hyperchromatic nuclei, and elongated cyto-
plasmic extensions. The cytologic features are similar to those
seen in ch on dromyxoid fi broma. H owever, th e n uclear atypia
supports th e diagn osis of ch on drosarcoma.
F igu r e 6.25. Grade 1 chondrosarcoma arising in an osteo-
chondroma. Usually extremely well differentiated, these lesions
are difficult to diagnose cytologically. Invasion at the periphery,
as seen in this low-power photomicrograph, is a helpful feature.
ch on drosarcoma arisin g in an osteoch on droma. Most
of th ese secon dary ch on drosarcomas are extremely
well differen tiated, so th at a clear-cut h istologic diag-
n osis of ch on drosarcoma is usually n ot possible. O n e
gen erally can form an idea about th e th ickn ess of th e
cartilage cap by th e amoun t of cartilage seen on th e
microscopic section . In osteoch on droma, th ere is a
column ar arran gemen t of th e ch on drocytes toward
th e base. Th is orderly arran gemen t is lost wh en ch on -
drosarcoma super ven es. Nodules of cartilage appar-
en tly permeatin g soft tissues an d separated from th e
main mass of th e tumor are also eviden ce of ch on dro-
sarcoma ( Fig. 6.25) .
Mitotic fi gures are uncommon in chondrosarcoma.
In a study by Bjornsson and colleagues, approximately
6% of the lesions contained an occasional mitotic fi g-
ure, and only seven lesions showed numerous mitotic
fi gures. The rest of the tumors did not show any mitotic
activity whatsoever.
Several studies have indicated the importance of
grading chondrosarcomas. Chondrosarcomas are
graded mainly on the cellularity of the neoplasm and
the cytologic atypia. Because mitotic activity is uncom-
mon in chondrosarcomas, it is not used in grading
these tumors. Grade 1 chondrosarcomas are relatively
hypercellular compared with enchondromas and have
moderate cytologic atypia ( Figs. 6.26–6.28) . Grade 2
chondrosarcomas are even more cellular than grade
1, and cytologic atypia is more pronounced. Grade 3
chondrosarcomas are extremely uncommon. They
are characterized by extreme cellularity, large bizarre
nuclei, and small foci of spindling at the periphery of
the lobule. Sheets of spindled cells are not seen in chon-
drosarcoma. In a study by Bjornsson and associates,
61% of the tumors were grade 1, 36% were grade 2, and
only 3% were grade 3 chondrosarcoma ( Figs. 6.23, 6.26,
6.29 & 6.30) .
An addition al h istopath ologic feature of ch on d-
rosarcom a requires com m en t. Approxim ately 10%
of th e tum ors th at recur h ave an in crease in degree
of m align an cy. Som etim es th is is in th e form of a
m ore active pure ch on drosarcom a; at oth er tim es,
th e recurren ce is in th e form of a h igh ly m align an t
fi brosarcom a or osteosarcom a. Th is dedifferen tia-
tion of ch on drosarcom a is con sidered in detail later
in th is ch apter.
The histopathologist should use all available evidence
to support the diagnosis of chondrosarcoma, including
large size, pain, invasiveness, extraosseous extension,
myxoid quality, radiographic signs of aggressiveness,
and rapid growth. Cartilaginous tumors in the distal
parts of the skeleton, in a circumscribed subperiosteal
location, or in the lining of capsules of joints are almost
certain to be clinically benign.
 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell) 75

F igu r e 6.26. Low-power appearance of a grade 1 chondro- F igu r e 6.27. Grade 1 ch on drosarcoma en trappin g can cel-
sarcoma th at diffusely permeates marrow spaces. lous bone. The tumor is closely juxtaposed to the bone.

F igu r e 6.28. Grade 1 chondrosarcoma. A: Increased cellularity and modest hyperchromasia are
apparent. B: High-power view shows nuclear details.

F igu r e 6.29. Grade 2 ch on drosarcoma. A: Low-power appearan ce. The lesion is more cellular
than grade 1 chondrosarcoma, and there is more nuclear enlargement and hyperchromasia. Com-
pare with Figure 6.28A. B: High-power appearance. Doubly nucleated cells are seen in the fi eld.
There is more cytologic atypia than seen in grade 1 chondrosarcoma. Compare with Figure 6.28B.
76 Chapter 6 ■

F igu re 6.30. Grade 3 chondrosarcoma. A: There is a marked increase in cellularity and pronounced
nuclear atypia compared with grades 1 and 2. B: High-power view highlights pleomorphic nuclei.

PERIOSTEAL CH ON D ROSARCOMA

Twenty-four of the chondrosarcomas were considered

to be “peripheral.” Seventeen of them fulfi lled the crite-
ria for periosteal chondrosarcoma. The others seemed
to be on the sur face of bone but were otherwise non-
specifi c.
Periosteal ch on drosarcomas can be diffi cult to dif-
feren tiate from periosteal ch on droma. As in dicated
above, periosteal ch on dromas ten d to sh ow cytologic
atypia. H owever, periosteal ch on dromas are usually
small, less th an 5 cm in greatest dimen sion , wh ereas
periosteal ch on drosarcomas ten d to be larger lesion s.
Radiograph s sh ow an extremely well-demarcated
lesion in a periosteal ch on droma, wh ereas th e lesion s
are ill-defi n ed in a periosteal ch on drosarcoma. H is-
tologically, th e distin ction is based primarily on evi-
den ce of in vasion in a periosteal ch on drosarcoma
( Figs. 6.31 & 6.32) .
Periosteal chondrosarcoma can present a serious
therapeutic problem. Five of the seventeen patients
have died with disease.

D ED IFFEREN TIATED
CH ON D ROSARCOMA

IN CID EN CE

In addition to th e 1,080 ch on drosarcomas ( in 1,073 F igu r e 6.31. Periosteal ch on drosarcoma. A: Lesion in th e

patien ts) , 145 lesion s h ad region s of sign ifi can tly m ore
an aplastic sarcoma ( usually Broders grade 3 or 4) . O f
th e 145 lesion s, 80 h ad th e microscopic quality of an
osteosarcoma in th e dedifferen tiated portion , 53 h ad
proximal humerus appears to involve the cortex but is not well
defi ned as a periosteal chondroma. The lesion is large and
merges in to soft tissue. B: Gross specimen . Th e lesion in volves
th e cortex but not th e medullary cavity. Alth ough th ere are n o
obvious in vasive n odules, th e lesion is large.
 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell)
features of fi brosarcom a, an d 7 h ad h istologic features
of malign an t fi brous h istiocytom a. Th e rest could n ot
be evaluated ( Fig. 6.33) . Th e problem of dedifferen -
tiation h as been alluded to in several publication s.
Recen t papers h ave accepted th is en tity, alth ough th e
term dedifferentiation h as been question ed by som e
auth ors, wh o prefer th e term chondrosarcoma with
additional mesenchymal component. Dedifferentiation can
occur in either primary or secondary chondrosarcoma,
F igu r e 6.32. Periosteal grade 1 ch on drosarcoma. Th e lesion
does not show circumscription.
F igu r e 6.33. Distribution of dedifferen tiated ch on drosarcomas accordin g to age an d sex of
th e patien t an d site of th e lesion .
77
an d, in con sultation m aterial, it h as been seen in a
ch on drosarcoma of th e lar yn x. Th ree dedifferen -
tiated ch on drosarcomas occurred in patien ts with
multiple ch on dromas. O n e patien t with a dediffer-
en tiated ch on drosarcoma of th e distal fem ur h ad a
con ven tion al ch on drosarcom a of th e proxim al fem u r
on th e sam e side. Eigh t dedifferen tiated ch on dro-
sarcom as were perip h eral. Fou r of th ese were con -
sidered to arise from solitar y exostosis an d on e in a
patien t with m ultiple exostoses. Th ree d ed ifferen ti-
ated ch on drosarcom as were situated periph erally but
did n ot seem to arise from exostoses. Th ey m ay h ave
arisen from preexistin g periosteal ch on drom as. Two
of th e d edifferen tiated ch on d rosarcom as were associ-
ated with preexistin g clear cell ch on d rosarcom a. In a
study of 79 cases of d edifferen tiated ch on drosarcom a
from th e Mayo Clin ic files, Frassica an d coauth ors
foun d th at 68 of th e tum ors sh owed dedifferen tiation
at th e tim e of diagn osis, wh ereas 11 d edifferen tiated
ch on d rosarcom as arose in recurren t low-grad e ch on -
drosarcom a.
SYMPTOMS
Clinically, these sarcomas are like the other chondro-
sarcomas; a few long-standing indolent tumors have
changed into aggressive lesions. Occasionally, recurrence
is the fi rst indication of this increasing malignancy.
78 Chapter 6 ■

SEX
There is a slight male predilection.

AGE

Dedifferentiated chondrosarcoma is a disease of older

adults. Only two patients were younger than 20 years.

RAD IOGRAPH IC FEATU RES

Dedifferen tiated ch on drosarcomas ten d to be large

an d to show aggressive, destructive ch anges, in dicat-
in g th eir malignan t n ature ( Figs. 6.34–6.38) . Beabout
an d associates described th e radiographic fi ndin gs in
57 of th e 79 patien ts reported by Frassica and coau-
th ors. Calcifi cation was found in approximately 50% of
th e lesions an d an extraosseous mass in approximately
55%. Ch aracteristically, the lesion s h ad a bimorphic
pattern , with an area of a low-grade tumor juxtaposed
to an area of more aggressive destructive ch an ge. Th is
bimorph ic appearan ce usually suggested a diagn osis of
dedifferen tiated ch ondrosarcoma but was present in
on ly about three-fourth s of th e patien ts. In th e rest, th e
radiograph ic features were those of well-differentiated F igu re 6.34. Dedifferentiated chondrosarcoma involving the
ch ondrosarcoma. Rarely, the radiograph ic features distal femur in a 69-year-old woman. Much of the lesion has the
mineralizing appearance of enchondroma or low-grade chond-
suggest an en ch on droma. In th e more recen t cases, rosarcoma. The lucent zone, lacking mineral and destroying cor-
tex, represents dedifferentiation. (Case provided by Dr. David
Hicks, University of Rochester, Rochester, New York.)

F igu r e 6 .3 5 . Ded ifferen tiated ch on d rosarcom a

involving the proximal femur in a 44-year-old man.
A: Th e appearan ce on a plain radiograph suggests
an ordinary chondrosarcoma. B: On magnetic reso-
nance imaging, th e in traosseous portion is large,
as shown on the plain radiograph. In addition,
however, a large soft-tissue mass medially suggests
a diagnosis of dedifferentiated chondrosarcoma.
C: Central portion of the gross specimen is chondro-
sarcoma with myxoid ch an ge. Th e dedifferen tiated
portion is fl eshy appearing and involves predomi-
nantly th e soft tissues. This juxtaposition is typical of
dedifferentiated chon drosarcoma. ( Figure 6.35B and
C are from Unni, K. K., and Inwards, C. Y.: Tumours
of O steoarticular System. In : Fletch er, C. D. M. [ ed] .
Diagnostic Histopathology of Tumors. Edinburgh,
Churchill Livingstone, 1995. By permission of the
publisher.)
 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell)
F igu r e 6.36. Dedifferentiated chondrosarcoma of the
humeral sh aft. Th e patien t h ad un dergon e two previous
surgical procedures for ordin ary ch on drosarcoma at th is
site. Th e dedifferen tiation occurred at th e secon d recur-
rence. ( From Frassica, F. J., Unni, K. K., Beabout, J. W., and
Sim, F. H.: Dedifferentiated Chondrosarcoma: A Report of
the Clinicopathological Features and Treatment of Seventy-
Eight Cases. J Bone Joint Surg, 68A:1197–1205, 1986. By
permission of the publisher.)
computed tomograms an d magn etic reson ance images
were obtain ed. These disclosed a large soft-tissue mass in
some in stances in which th e plain radiograph s showed
on ly features of a ch ondrosarcoma. This dich otomy
suggested the diagnosis of dedifferentiated ch ondro-
sarcoma in th ese cases.
GROSS PATH OLOGIC FEATU RES
Typically, th e cartilagin ous precursor is cen trally
located. It may be so small th at it is overlooked. Th e
more an aplastic, fl esh y tumor frequen tly destroys th e
ch on droid precursor. Th e ch aracteristic semitran slu-
cen t, sometimes calcifi ed an d lobulated, cartilagin ous
tumor abuts th e grayer, fl esh y an aplastic tumor. Cor-
tical destruction an d extraosseous exten sion are seen
n ear th e latter compon en t. Alth ough th e sarcomatous
compon en t is usually obvious grossly, some dedifferen -
tiated ch on drosarcomas h ave on ly small foci of fl esh y
tumor. An occasion al dedifferen tiated ch on drosar-
coma h as th e radiograph ic an d gross appearan ce of
ordin ary ch on drosarcoma, an d th e dedifferen tiated
features are appreciated on ly microscopically ( Figs.
6.39 & 6.40) .
79
H ISTOPATH OLOGIC FEATU RES
Typically, there is an abrupt zone in which low-grade
chondrosarcoma changes to highly anaplastic tumor.
Under low power, the appearance is that of two sepa-
rate tumors without a gradual transition from one to
the other. Occasionally, one sees lobules of extremely
well-differentiated chondrosarcoma in several intermin-
gling areas of high-grade anaplastic sarcoma. Classically,
the chondrosarcomatous portion is extremely well dif-
ferentiated; however, in the study by Frassica and coau-
thors, only about three-fourths of the dedifferentiated
chondrosarcomas were considered to be a combination
of grade 1 chondrosarcoma and high-grade spindle cell
sarcoma. The rest of the cases showed areas of grade 2
chondrosarcoma with high-grade spindle cell sarcoma.
At least three lesions were considered to be borderline
cartilaginous tumors. One dedifferentiated chondrosar-
coma may have arisen in a chondroma, but this was dif-
fi cult to prove ( Figs. 6.41–6.46) .
As indicated above, the dedifferentiated portion is
almost always very malignant appearing. It may show an
osteosarcoma, a fi brosarcoma, or a malignant fi brous
histiocytoma. One that was classifi ed as a fi brosarcoma
had features of angiosarcoma. Occasionally, the spindle
80 Chapter 6 ■

F igu r e 6.37. Dedifferentiated chondrosarcoma involving the right pelvis in a 72-year-old woman.
A: An teroposterior radiograph of th e pelvis sh ows a subtle destructive lesion in th e righ t acetabu-
lum medially, with th e suggestion of matrix calcifi cation . Also, a soft-tissue mass projects over th e
pelvic sidewall, obturator foramen , an d isch ium. B: Coron al computed tomogram sh ows th e lytic
lesion with associated osseous expan sion an d cartilage matrix typical of ch on drosarcoma. C an d
D: Coronal and axial T2-weighted magnetic resonance images with fat suppression show fi ndings
typical of ch ondrosarcoma in th e roof an d medial wall of th e acetabulum. In addition , magn etic
resonance imagin g shows a massive associated soft-tissue mass in the superior pubic ramus. This
con stellation of fi n din gs is h igh ly suggestive of dedifferen tiated ch on drosarcoma.
 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell)
F igu r e 6.38. Dedifferentiated chondrosarcoma of the prox-
imal h umerus. Th ere is extensive in tramedullary involvement
by low-grade chon drosarcoma, but th e bulk of th e dedifferen -
tiated tumor forms a soft-tissue mass.
F igu r e 6.39. Dedifferentiated chondro-
sarcoma of th e femur arisin g in a 64-year-
old man with Ollier disease. A: Plain radio-
graph shows an area of lucen cy with in th e
cen tral part of th e min eralized tumor th at
suggests th e possibility of dedifferen tia-
tion . B: Th e dedifferen tiated part of th e
tumor in th e gross specimen h as a red-
brown fl esh y appearan ce th at is distin ctly
different from the gray-white cartilaginous
compon en t proximally an d distally.
81
cell sarcoma may have abundant pink cytoplasm, sug-
gesting the diagnosis of rhabdomyosarcoma. Not
uncommonly, these cells are large, with vesicular nuclei
and prominent nucleoli. The cells may even cluster,
suggesting the diagnosis of metastatic carcinoma. An
epithelial-appearing neoplasm, especially in an older
adult, may suggest the diagnosis of metastatic carci-
noma. However, if radiographs suggest calcifi cation
within the lesion, the possibility of a dedifferentiated
chondrosarcoma should be considered.
TREATMEN T
Treatment must be radical and should be predicated on
the dedifferentiated portion. In the few cases treated
with preoperative chemotherapy at Mayo Clinic, the
results have not been encouraging. The tumors have
not shown much response to chemotherapy.
PROGN OSIS
The prognosis for dedifferentiated chondrosarcoma is
poor. In the report by Frassica and coauthors, the 5-year
survival rate was 10.5%.
82 Chapter 6 ■

F igu r e 6.40. Dedifferen tiated ch on drosarcoma in volvin g

th e proximal h umerus. Th e distal portion of th e tumor h as
th e typical gray-blue appearan ce of h yalin e cartilage. Th e
h igh -grade sarcoma compon en t correspon ds to th e proxi- F igu r e 6.41. A an d B: Dedifferen tiated ch on drosarcoma
mal solid, tan -wh ite part of th e tumor. Most common ly, th e sh owin g th e classic abrupt zon e between low-grade ch on dro-
h igh -grade sarcoma compon en t is extraosseous; h owever, sarcoma an d h igh -grade sarcoma.
occasion ally it is admixed with th e cen trally located precur-
sor lesion .

F igu r e 6.43. Dedifferentiated chondrosarcoma that has

undergone degenerative change. The low-grade chondrosar-
F igu r e 6.42. Dedifferentiated chondrosarcoma involving coma contains areas of necrosis with loss of nuclei, leading to
th e pelvis. Th e cartilage compon en t is usually low grade. H ow- the possibility that this portion of the tumor may be overlooked
ever, in th is tumor, it was grade 2 ch ondrosarcoma. in the background of a high-grade spindle cell sarcoma.
 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell)
F igu re 6.44. Dedifferentiated chondrosarcoma. A: At high
magnifi cation, the epithelioid appearance of the tumor cells
in the high-grade sarcoma component resembles metastatic
carcinoma. B: At low magnifi cation, other parts of the biopsy
specimen include the low-grade chondrosarcoma component.
F igu r e 6.45. Dedifferentiated chondrosarcoma in which the
high-grade malign an cy con tains several multinucleated giant
cells, wh ich may suggest th e diagn osis of gian t cell tumor.
However, other areas of the noncartilaginous component
sh owed more pron oun ced cytologic atypia.
83
F igu r e 6.46. Biopsy specimen of dedifferentiated chondro-
sarcoma. Because th e biopsy tissue was submitted in fragmen ts,
the low-grade chondrosarcoma and high-grade malignancy
are not immediately juxtaposed. This emphasizes the impor-
tance of examining all fragments of tissue within a biopsy of
presumed chondrosarcoma in order to avoid overlooking a
dedifferentiated component.
CLEAR CELL CH ON D ROSARCOMA
Clear cell chondrosarcoma has unusual clinical and
histologic features. The tumor has frequently been
mistaken for chondroblastoma or even osteoblastoma
because of its unusual histologic features and tendency
to occur in the ends of long bones.
IN CID EN CE
Clear cell chondrosarcomas are rare tumors, account-
ing for only 26 of the 1,290 chondrosarcomas in the
Mayo Clinic fi les ( Fig. 6.47) .
SEX
The male predominance noted in other reports is pres-
ent in the Mayo Clinic series. The 26 patients included
18 males and 8 females.
AGE
The ages of the 26 patients ranged from 18 to 65 years.
More than one-half of the patients were in the fourth
and fi fth decades of life.
LOCALIZATION
Clear cell chondrosarcomas tend to involve the ends of
bones, extending to the articular cartilage. Ten tumors
were situated in the proximal femur, and fi ve were in the
proximal humerus. One involved the proximal ulna. Six
tumors had an unusual location: three involved the verte-
bral column, two the pubis, and one the nasal septum.
84 Chapter 6 ■

F igu r e 6.47. Distribution of

clear cell ch on drosarcomas
according to age and sex of the
patient and site of the lesion.

SYMPTOMS

Clinically, these tumors are slow growing. Patients usu-

ally have symptoms of long duration. In the report
by Bjornsson and coauthors, 18% of the patients had
symptoms for more than 5 years.

RAD IOGRAPH IC FEATU RES

Clear cell chondrosarcomas usually produce osteolytic

expansion in the end of a long bone. Most of the tumors
involved the epiphyseal region, and metaphyseal and
diaphyseal lesions are extremely uncommon. Radio-
graphically, small lesions resemble chondroblastoma.
The lesion tends to be purely lytic, may appear well cir-
cumscribed, and may even have a sclerotic rim. In larger
lesions, radiographs show that the lesion has destroyed
the cortex and extended into soft tissue. Mottled min-
eralization suggestive of a cartilaginous tumor may be
seen within the lesion ( Figs. 6.48–6.50) .

GROSS PATH OLOGIC FEATU RES

Th e tumors often are n ot recogn izable as cartilagi-

n ous. Min ute cystic spaces are sometimes presen t. O n e
tumor h ad promin en t cystic ch an ge an d on ly a mural
n odule in wh at oth erwise would h ave been an an eurys-
mal bon e cyst. Approximately on e-h alf of th e lesion s
h ave areas th at appear to be ordin ary ch on drosarcoma,
ch aracteristically pale blue. Th e rest h ave a fl eshy, gray
appearan ce. Rarely, a lesion is h eavily min eralized
grossly ( Fig. 6.51) .
F igu r e 6.48. Clear cell chondrosarcoma involving the
femoral h ead in a 59-year-old woman . A: Th e lesion is well
demarcated and shows focal mineralization. Even though the
patient is older than usual, chondroblastoma still would be
con sidered in the differen tial diagn osis. B: Magn etic reso-
n an ce imaging emphasizes the benign appearance.
 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell) 85

F igu r e 6.49. Clear cell chondrosarcoma in the proximal femur in a 28-year-old man.
A: Plain radiograph of the hip shows a partially well-defi ned lesion with punctate mineraliza-
tion. B: Axial computed tomogram shows more clearly the mineralization and intramedullary
extent of th e tumor.

H ISTOPATH OLOGIC FEATU RES PROGN OSIS

Clear cell chondrosarcomas are different from the aver-
age chondrosarcoma, which contains no benign giant cells
except perhaps in reactive zones adjacent to the tumor.
In clear cell chondrosarcoma, benign giant cells are usu-
ally found throughout the tumor, either in small clusters
or singly. This feature helps explain why several of these
tumors have been considered to be “atypical” chondro-
blastoma. Under low power, clear cell chondrosarcomas
tend to show a lobulated growth pattern (Figs. 6.52–6.57).
Between the lobules of cartilage, one may see capillary
proliferation and clusters of benign giant cells. Typically,
new bone formation is present in the center of the lobule,
so that under low power, a bone-forming neoplasm may be
suspected. The tumor cells have well-defined cytoplasmic
borders and a single vesicular nucleus, which may have a
prominent nucleolus. The cytoplasm is clear or pink stain-
ing. About one-half of the tumors contain areas of con-
ventional low-grade chondrosarcoma. Benign giant cells
are not observed in such zones. A few cases of dedifferen-
tiated clear cell chondrosarcoma have been reported.
TREATMEN T
Generally, treatment of these lesions has been too con-
servative, because of their having been mistaken for
benign conditions. Evidence indicates that complete
total resection is necessary for hope of cure. Radiation
therapy has not been effi cacious.
The prognosis has been worse than it probably should
have been, because many tumors have been treated by
less than early radical resection. Clear cell chondrosar-
coma may recur 10 to 15 years after initial surgery. Clear
cell chondrosarcomas may also metastasize to other
bones and to the lungs. Of the 48 patients reported by
Bjornsson and associates, 7 are known to have died of
tumor ( Figs. 6.58–6.60) .
TREATMEN T OF ORD IN ARY
CH ON D ROSARCOMA
Surgery is th e main stay in th erapy of th is radioresis-
tan t tumor. At best, irradiation is a palliative measure
for tumors n ot amen able to surgical removal. Ch emo-
th erapy also seems to h ave n o role in th e treatmen t of
ch on drosarcoma. Surgeon s with much experien ce in
th e treatmen t of bon e tumors h ave learn ed th at th e
optimal treatmen t for ch on drosarcoma is early radical
removal with as wide a margin of un in volved tissue as
possible. Th e exact surgical procedure depen ds on th e
location of th e tumor, th e exten t of th e disease, an d th e
grade of th e lesion . Th e term “borderlin e ch on drosar-
coma” was popularized man y years ago. Th is diagn osis
was ren dered if th e radiograph s sh owed an y degree of
en dosteal scallopin g in th e large bon e. Th e h istologic
features were in suffi cien t to con fi rm th e diagn osis of
86 Chapter 6 ■

F igu r e 6.50. Clear cell ch on -

drosarcoma with an aggressive
radiograph ic appearance. A: Plain
radiograph shows the tumor
exten ding to the end of the bone.
B and C: Magnetic resonance
imaging shows more clearly the
extraosseous extension in to sur-
roundin g soft tissue. ( Case pro-
vided by Dr. David Bylund, Scripps
Mercy Hospital, San Diego,
California.)

ch on drosarcoma in th ese cases. We h ave n ot used th is

F igu r e 6.51. Clear cell ch on drosarcoma involving the prox-
imal femur. The lesion extends up to the articular cartilage.
Th e ch alky white areas represen t min eralization . Th ere is
focal cystic ch ange.
term for man y years. We make a diagn osis of grade 1
ch on drosarcoma on ly if th e cytologic features are con -
vin cin g or if th e radiograph s sh ow more th an min imal
scallopin g. Th e so-called borderlin e ch on drosarcomas
were treated less th an radically—with th orough curet-
tage. We see an alarmin g ten den cy amon g orth opedic
on cologists to use th e same meth od to treat grade 1
ch on drosarcomas. We fear th at th is attitude is born e
out of th e con fusion cause by th e term “borderlin e
ch on drosarcoma.” Surgeon s feel satisfi ed with th e
results of curettage of grade 1 ch on drosarcomas. H ow-
ever, on ly lon g-term follow-up will validate or in vali-
date th is approach .
Advances in surgical techniques allow a major resec-
tion with limb salvage even for bulky tumors. Sometimes
a major amputation is necessary because of th e location
 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell) 87

F igu r e 6.52. Low-power appearan ce of clear cell ch on dro- F igu r e 6.55. Clear cell ch on drosarcoma with ch on droid
sarcoma. Th e righ t portion of th e fi eld sh ows a con ven tion al matrix an d several multin ucleated gian t cells.
ch on drosarcoma. Th e surroun din g tumor h as a clear cell
appearance. Small trabeculae of woven bone are scattered in
between th e clear cells.

F igu r e 6.56. High-power view of clear cell chondrosarcoma

F igu re 6.53. Low-power appearance of clear cell chondrosar- sh ows well-defi n ed cytoplasmic borders, clear or gran ular
coma shows numerous trabeculae of woven bone. The presence cytoplasm, an d promin en t n ucleoli.
of bone may lead to a mistaken diagnosis of osteosarcoma.

F igu r e 6.54. View of clear cell chondrosarcoma highlight- F igu r e 6.57. Clear cell chondrosarcoma containing some
ing clear cells surrounding trabeculae of woven bone. cells with cytoplasmic vacuoles.
88 Chapter 6 ■

F igu r e 6.58. Large recurren ce of clear cell ch on drosarcoma

in soft tissues 12 years after resection of the primary tumor in
th e femur.

F igu r e 6.59. Dedifferentiated clear cell chondrosarcoma of

the proximal femur in a 42-year-old man. The primary tumor
had been resected 4 years previously. Th ere is a fl eshy area
correspon din g to dedifferen tiation . Th e patien t died 4 years
later with widespread metastasis.

or size of the tumor. For chondrosarcomas secondary to

exostosis, experience indicates that wide local excision is
likely to succeed. Equivocal pathologic or radiograph ic
evidence is an indication for a conservative attitude.
Ideally, as with any of the surgically managed malign ant
tumors of bone, defi n itive treatmen t sh ould be admin-
istered at the time of biopsy, but delay is doubtless of
less importance in therapy for chondrosarcoma th an in
that for more anaplastic sarcomas. A radiograph may
indicate the most aggressive and in fi ltrative portion of
F igu r e 6.60. Dedifferentiated clear cell chondrosarcoma
( corresponds to Figure 6.59) . A: Low-power view shows a high-
grade spindle cell sarcoma in the left half of the fi eld and a
con ven tion al clear cell ch on drosarcoma occupyin g th e righ t
side. H igh -power view of th e h igh -grade sarcoma portion ( B)
and the conventional clear cell chondrosarcoma ( C) .
 ■ Chondrosarcoma (Primary, Secondary, Dedifferentiated, and Clear Cell)
the tumor, which is the best location for taking a biopsy
specimen. The biopsy wound sh ould be plan ned so that
the defi nitive operation can include it as part of the
tissue to be completely removed or ablated, because of
the notorious capability of chondrosarcomas to recur by
implantation. The tumor should be completely excised
with an adequate zone of surrounding tissue so that the
surgeon does not break into or see the tumor at any
time.
PROGN OSIS IN CH ON D ROSARCOMA
Because chondrosarcomas occasionally recur after
5 years and sometimes even after 10 years, 5-year sur-
vival is not very signifi cant as a criterion for cure. Actu-
ally, because of the common error of underdiagnosis
and consequent inadequate treatment in th e earlier
part of the series, the overall rate for cure of chond-
rosarcoma was less than that of osteosarcoma in those
years. Thoracic surgeons learned decades ago that wide
local excision was mandatory if cure was to be expected
in the treatment of malignant cartilage tumors of the
thoracic cage. Accordingly, many of the long-term sur-
vivors in this series were patients who had chondrosar-
coma in that location. During the past several years,
when more radical surgery became common therapy
for tumors around the pelvis and shoulder girdles, an
increasing number of patients with chondrosarcoma in
these locations have been cured.
Several factors affect the prognosis in chondrosar-
coma. Malignant tumors of the axial skeleton are dif-
fi cult to cure. The study by Pritchard and coauthors of
280 patients showed that the size of the lesion and the
histologic grade were the most signifi cant prognostic
features. A more recent study by Bjornsson and coau-
thors confi rmed the importance of histologic grade
in prognosis in chondrosarcoma. The 5-year survival
rate was 77% overall. In this study, local recurrence was
approximately 20%. Distant metastasis developed in
approximately 14% of cases. High-grade tumors were
statistically signifi cantly more likely to produce dis-
tant metastasis. Recent studies have suggested that a
high DNA content of the tumor cells may indicate the
patients who have a poorer prognosis.
Experience at Mayo Clinic indicates that the rare
ch ondrosarcoma in ch ildhood has the same prognosis
as its counterpart in adults. Reports indicating a worse
prognosis in childhood chondrosaroma probably
refl ect the inclusion of chondroblastic osteosarcoma in
the series.
Lesion s with th e h istologic appearan ce of ch on dro-
sarcoma but in un usual sites, such as th e laryn x an d
th e n asal cavities, h ave a differen t biologic beh avior
th an do th e typical skeletal examples. Tumors in th e
89
laryn x metastasize on ly very rarely, an d th ose in th e
n asal cavities, probably arisin g from th e cartilage of
th e upper respiratory tract, h ave a relatively slow clini-
cal evolution .
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 C H APT ER
7
Mesenchymal Chondrosarcoma
Mesenchymal chondrosarcoma was fi rst described by
Lichtenstein and Bernstein in 1959. The other unusual
chondroid tumors described by these authors do not
have counterparts th at we have recognized in the mate-
rial available for study. If any lesions are present, they
have been classed with chondrosarcoma, chondromyx-
oid fi broma, and chondroblastoma.
Primitive multipotential primary sarcoma of bone, as
described in 1966, includes lesions that fi t the descrip-
tions of mesenchymal chondrosarcoma. Polyhistioma of
bone and soft tissue is a more recently suggested term for
malignant tumors that have areas of small round-to-oval
cells. In such zones, the tumors bear a striking similarity
to Ewing sarcoma, but they differ from Ewing sarcoma
in that the other areas show various types of differen-
tiation, especially chondroid, osteoid, or fi bromatoid,
and with corresponding matrices. Hence, mesenchymal
chondrosarcoma may artifi cially exclude some related
tumors. Unfortunately, the exact delimitations of these
other varieties of so-called polyhistioma are not yet well
defi ned.
IN CID EN CE
The total of 48 ( 46 patients) mesenchymal chondrosar-
comas in the Mayo Clinic series indicates the rarity of
this lesion ( Fig. 7.1) . They accounted for about 0.7% of
malignant tumors. Included in this total were 11 lesions
primary in soft tissue and 1 in the meninges.
SEX
Th ere was a sligh t m ale predom in an ce in th e series.
In a series of patien ts reported by Nakash im a
an d associates, in cludin g cases from th e con sulta-
tion fi les at Mayo Clin ic, th ere was a sligh t fem ale
predom in an ce.
92
AGE
Mesenchymal chondrosarcoma tends to affect young
adults and teenagers. Approximately two-thirds of all
patients were in the third and fourth decades of life.
The youngest patient was 12 years old, and the oldest
was 74. In the series of 111 cases reported by Nakashima
and colleagues, the youngest patient was 5 years old
and the oldest was 74. Approximately one-half of these
patients were in the second and third decades of life.
LOCALIZATION
As mentioned above, 11 of the 48 lesions occurred in the
soft tissues and 1 in the meninges. The other 36 involved
multiple skeletal sites. One patient had involvement of
three different skeletal sites at the time of presentation.
Another patient had involvement of mediastinal soft tis-
sues that was followed several years later by involvement
of the sacrum. Nine patients had involvement of the jaw-
bones and six of the spine. Four patients had involve-
ment of the ilium and four of the ribs. In the series
reported by Nakashima and coauthors, the mandible,
ribs, vertebrae, pelvic bones, and femur were the most
commonly involved. Approximately one-fourth of all
lesions arose in the somatic soft tissues. Several cases of
involvement of the orbit have been described. There are
also single case reports of primary mesenchymal chond-
rosarcoma involving the lung and the kidney.
SYMPTOMS
Pain and sometimes swelling are the usual symptoms
and are not unlike those of any other malignant tumor.
In the series reported by Nakashima and associates, the
duration of symptoms varied from 4 days to 7 years, and
in 16 cases, the duration was for more than 2 years. Seven
of the tumors were incidental fi ndings on radiographs.

F igu r e 7.1. Distribution of
mesen ch ymal ch on drosarco-
mas accordin g to age an d sex
of th e patien t an d site of th e
lesion.
RAD IOGRAPH IC FEATU RES
Radiograph s sh ow a lytic destructive process.
Alth ough a few of th e lesion s are purely lytic, m ost
con tain m in eral. Man y lesion s h ave th e radiograph ic
features of con ven tion al ch on drosarcom a: in tram ed-
ullar y tum or with calcifi cation , expan sion of th e
bon e, an d cortical th icken in g. Th e tum ors gen erally
h ave poor m argin ation , wh ich suggests a m align an t
tum or. Mesen ch ym al ch on drosarcom as th at occur in
th e soft tissues typically con tain stippled areas of cal-
cifi cation ( Figs. 7.2 & 7.3) .
Th e radiograph ic features of mesen ch ymal ch on -
drosarcoma are n ot specifi c; h owever, th ey usually
suggest a malign an t tumor, probably of cartilagin ous
derivation .
GROSS PATH OLOGIC FEATU RES
The tumor is typically gray-to-pink, fi rm or soft, and usu-
ally well defi ned. In rare instances, it is lobulated. The
tumors vary in size, up to 14 cm in greatest dimension,
and most contain hard, mineralized material that var-
ies in amount from scattered foci to prominent zones.
Some are cartilaginous, at least in part. Zones of necrosis
and hemorrhage may be seen. Tumors of the soft tissue
tend to be sharply circumscribed. Part of the lesion may
appear soft and fl eshy, similar to most sarcomas. How-
ever, most of them contain calcifi c foci ( Fig. 7.4) .
■ Mesenchymal Chondrosarcoma 93
H ISTOPATH OLOGIC FEATU RES
Mesenchymal chondrosarcoma shows the paradoxical
histologic combination of highly cellular zones composed
of anaplastic small cells and islands of relatively hypocel-
lular chondroid areas that may be calcifi ed and even
ossifi ed. The chondroid islands vary in size from small
nodules to large islands. The relative amounts of chon-
droid matrix and small cells vary from tumor to tumor.
Some tumors have large islands of cartilage juxtaposed
to large sheets of small malignant cells. Others have only
small foci of chondroid differentiation in what appears
to be a small-cell malignant lesion. Rarely, the cartilage
is the predominant pattern, with lobules of cartilage and
condensation of small malignant cells between the lob-
ules. With this pattern, the tumor may be easily mistaken
for a conventional chondrosarcoma (Figs. 7.5–7.8) .
The cartilaginous matrix appears hypocellular and,
under low power, may even suggest a benign tumor.
However, high-power examination shows that the
tumor cells in the lacunae have small and hyperchro-
matic nuclei and resemble the cells of the highly cellu-
lar areas. The small cells are round to oval or may show
frank spindling. The nuclei are extremely dark, and
there is little cytoplasm. In the areas with spindle cells, a
herringbone pattern may be found. Very typically, there
is vascular proliferation with a hemangiopericytomatous
pattern. In other areas, the small round cells tend
to form an alveolar pattern. The spindle cell pat-
tern, hemangiopericytomatous pattern, and alveolar
94 Chapter 7 ■

F igu re 7.2. Mesenchymal chondrosarcoma involving the proximal femoral shaft in a 19-year-old
man. A: The intraosseous component is purely lytic, whereas the sur face lesion is heavily mineral-
ized. B: On computed tomography, the tumor completely fi lls the marrow cavity and forms a large
soft-tissue mass that is only partly mineralized. C: The patient began but did not complete chemo-
therapy. A disarticulation of the hip was per formed. Mineralized areas are clearly seen in both the
intraosseous and the extraosseous components of the tumor. The patient died with metastatic disease
within 18 months.

F igu r e 7.3. Mesen ch ymal ch on drosarcoma in volvin g th e man dible in a 12-year-old girl. A: Th e
lesion is purely lytic and is well circumscribed. The lesion had been present for at least 5 years
before th is radiograph was taken . B: In th e gross specimen , th e lesion appears soft an d lobulated
and has broken through the cortex at several places. However, the lesion is still quite small and well
demarcated. The patient was alive without evidence of disease 7 years after this resection.
 ■ Mesenchymal Chondrosarcoma 95

F igu r e 7.6. Th e lobules of cartilage matrix in th is mesen ch y-

mal chon drosarcoma are less well formed th an in Fig. 7.5 and
partially eosinophilic.

F igu r e 7.4. Mesenchymal chondrosarcoma involving the

distal femur in a 27-year-old man. The lesion has destroyed
the bone completely and forms a large soft-tissue mass. Nod-
ules of cartilage are clearly visible ( Case provided by Dr. Sarah
Milchgrub, Parkland Hospital, Dallas, Texas.) .

F igu r e 7.7. Mesench ymal ch ondrosarcoma with ossifi cation

of a cartilaginous lobule.

F igu r e 7.5. Mesenchymal chondrosarcoma with a lobule of F igu r e 7.8. Mesen ch ymal ch on drosarcoma with coarse cal-
cartilage surroun ded by malign an t small cells. cifi cation of the cartilagin ous lobule.
96 Chapter 7 ■
pattern are all intermingled, and subclassifi cation is not
possible ( Figs. 7.9 & 7.10) .
The chondroid islands frequently undergo calci-
fi cation and even ossifi cation. Trabecular-appearing
bone may be seen between the small malignant cells.
Even fi n e, wispy, pin k material suggesting osteoid may
be seen between the small cells. It may suggest a diag-
nosis of small cell osteosarcoma. However, the very
characteristic low-grade–appearing cartilaginous foci
and the typical nuclear morphology should suggest the
correct diagnosis. Dedifferentiated chondrosarcomas
also have juxtaposition of low-grade cartilage with high-
grade malignancy. In this tumor, however, the high-
F igu r e 7.9. Typical vascular pattern in mesenchymal chon-
drosarcoma. The vessels are surrounded by small malignant
cells, wh ich compress an d deform th e vessels, producin g th e
typical staghorn appearance. No chondroid differentiation is
seen in th is fi eld.
F igu r e 7.10. H igh -power appearan ce of th e tumor cells in
mesen ch ymal ch on drosarcoma. Th e cells are quite un iform
in appearance and have a round to oval shape. They are
arranged around vascular spaces.
grade malignancy portion is composed of large cells
rather than small cells.
TREATMEN T
Mesenchymal chondrosarcoma is probably best treated
by radical surgery, with the goal of complete removal
of the tumor. Work at Memorial Hospital in New York
has suggested that the tumors with “Ewing-like” cells
are much more sensitive to combination chemotherapy
than are those with “hemangiopericytoma-like” areas.
PROGN OSIS
Too few cases h ave been followed up lon g en ough
to provide completely convin cin g data on progn osis.
Th e progn osis in mesen ch ymal ch on drosarcoma is
completely un predictable. Some patien ts presen t with
widespread metastasis an d die soon . O th er patien ts
h ave a prolon ged clin ical course, alth ough most even -
tually die of th e effects of tumor. H uvos an d coauth ors
reported a 10-year survival rate of 28%. Nakash ima
an d coauth ors, reportin g on 23 cases from th e Mayo
Clin ic fi les, foun d a 5-year survival rate of 54.6% an d
a 10-year survival rate of 27.3%. O n e patien t from th e
Mayo Clin ic fi les h as h ad a remarkable clin ical course.
Th e patien t was 16 years old in 1972 wh en sh e un der-
wen t h emiman dibulectomy for mesen ch ymal ch on -
drosarcoma. In 1981, a sin gle metastatic n odule in th e
scalp was excised. Sh e was alive with out disease in 1999,
27 years after th e origin al operation an d 18 years after
th e scalp metastasis. An oth er youn g girl with a man dib-
ular tumor h ad kn own disease for at least 5 years before
resection was per formed. Sh e is alive with out disease
7 years after th e resection . In a study of 19 cases of mes-
en ch ymal ch on drosarcoma of th e jawbon es, Ven cio
an d coauth ors foun d a 5-year survival rate of 82% an d
a 10-year survival rate of 56%. Th e h istologic features
of th e tumors associated with an in dolen t course are
n o differen t from th ose of th e tumors associated with a
rapid clin ical course.
BIBLIOGRAPH Y
1959 Lichtenstein, L. and Bernstein, D.: Unusual Benign and
Malign an t Ch on droid Tumors of Bon e: A Survey of Some
Mesen ch ymal Cartilage Tumors an d Malign an t Ch on dro-
blastic Tumors, In cludin g a Few Multicen tric On es, as Well as
Man y Atypical Ben ign Ch on droblastomas an d Ch on dromyx-
oid Fibromas. Cancer, 12:1142–1157.
1962 Dah lin , D. C. an d H en d erson , E. D.: Mesen ch ym al
Chondrosarcoma: Further Observations on a New Entity. Cancer,
15:410–417.

1966 Hutter, R. V. P., Foote, F. W., Jr., Francis, K. C., and
Sherman, R. S.: Primitive Multipotential Primary Sarcoma of
Bone. Cancer, 19:1–25.
1967 Goldman, R. L.: “Mesenchymal” Chondrosarcoma, a Rare
Malignant Chondroid Tumor Usually Primary in Bone: Report
of a Case Arising in Extraskeletal Soft Tissue. Cancer, 20:1494–
1498.
1971 Salvador, A. H., Beabout, J. W., and Dahlin, D. C.:
Mesen ch ymal Ch on drosarcoma: Observation s on 30 New
Cases. Cancer, 28:605–615.
1973 Guccion, J. G., Font, R. L., Enzinger, F. M., and
Zimmerman, L. E.: Extraskeletal Mesench ymal Ch on drosar-
coma. Arch Pathol, 95:336–340.
1977 Jacobson, S. A.: Polyhistioma: A Malignant Tumor of Bone
and Extraskeletal Tissues. Cancer, 40:2116–2130.
1978 Scheithauer, B. W. and Rubinstein, L. J.: Meningeal
Mesen ch ymal Ch on drosarcoma: Report of 8 Cases With
Review of th e Literature. Cancer, 42:2744–2752.
1979 Rollo, J. L., Green, W. R., and Kahn, L. B.: Primary
Men in geal Mesen ch ymal Ch on drosarcoma. Arch Path ol Lab
Med, 103:239–243.
1981 Harwood, A. R., Krajbich, J. I., and Fornasier, V. L.:
Mesen ch ymal Ch on drosarcoma: A Report of 17 Cases. Clin
Orthop, 158:144–148.
1983 Bertoni, F., Picci, P., Bacchini, P., Capanna, R., Innao, V.,
Bacci, G., an d Campan acci, M.: Mesen ch ymal Ch on drosar-
coma of Bone an d Soft Tissue. Cancer, 52:533–541.
1983 Dabska, M. and Huvos, A. G.: Mesenchymal Chondrosar-
coma in th e Youn g. Virch ows Arch [ A] Path ol An at Histo-
path ol, 399:89–104.
■ Mesenchymal Chondrosarcoma 97
1983 Huvos, A. G., Rosen, G., Dabska, M., and Marcove, R. C.:
Mesen ch ymal Ch on drosarcoma: A Clin icopath ologic An aly-
sis of 35 Patien ts With Emph asis on Treatmen t. Can cer,
51:1230–1237.
1984 Harsh, G. R. IV an d Wilson , C. B.: Cen tral Nervous System
Mesen ch ymal Ch on drosarcoma: Case Report. J Neurosurg,
61:375–381.
1984 Malhotra, C. M., Doolittle, C. H ., Rodil, J. V., an d Verzeri-
dis, M. P.: Mesen ch ymal Ch on drosarcoma of th e Kidn ey. Can -
cer, 54:2495–2499.
1986 Nakashima, Y., Unni, K. K., Sh ives, T. C., Swee, R. G., and
Dahlin, D. C.: Mesenchymal Chondrosarcoma of Bone and
Soft Tissue: A Review of 111 Cases. Can cer, 57:2444–2453.
1992 Kurotaki, H., Takeoka, H., Takeuch i, M., Yagih ash i, S.,
Kamata, Y., an d Nagai, K.: Primary Mesen ch ymal Ch on drosar-
coma of th e Lun g: A Case Report With Immun oh istoch emical
and Ultrastructural Studies. Acta Path ol Jpn, 42:364–371.
1993 Bagchi, M., Husain, N., Goel, M. M., Agrawal, P. K., an d
Bhatt, S.: Extraskeletal Mesenchymal Chondrosarcoma of the
Orbit. Can cer, 72:2224–2226.
1993 Shapeero, L. G., Vanel, D., Couan et, D., Contesso, G., an d
Ackerman , L. V.: Extraskeletal Mesen ch ymal Ch on drosar-
coma. Radiology, 186:819–826.
1994 Jacobs, J. L., Merriam, J. C., Chadburn, A., Garvin ,
J., Houspian, E., and Hilal, S. K.: Mesenchymal Chondrosar-
coma of th e Orbit: Report of Th ree New Cases an d Review of
th e Literature. Cancer, 73:399–405.
1998 Ven cio, E. F., Reeve, C. M., Unn i, K. K., and Nascimento,
A. G.: Mesen ch ymal Ch on drosarcoma of th e Jaw Bon es:
Clin icopath ologic Study of 19 Cases. Can cer, 82:2350–2355.
 C H APT ER
8
Osteoma
The actual occurrence of true osteoma is so debatable
that this tumor is n ot included in the overall statisti-
cal data. Reactive ch anges from trauma, infection, or
an invading tumor such as a meningioma can cause
osseous overgrowth. Some bony outgrowths may repre-
sent an ancient osteochondroma, the cartilaginous cap
of which is completely involuted. Because these tume-
factions produce th e clinical manifestations of a neo-
plasm, they are often erroneously called “osteomas.”
Occasional tumors of the skull, especially those
involving the paranasal sinuses, are the most nearly
bona fi de osteomas, and yet there is room for conjec-
ture regarding these. The gamut of fi bro-osseous dys-
plastic lesions that affect these bones runs from soft,
purely fi brous lesions to lesions that are heavily ossifi ed.
A few of the dense “ivory” osteomas contain softer zones
of fi bro-osseous dysplasia. Hence, there is no clear line
of distin ction between obviously dysplastic lesions and
completely osseous tumors that one wants to call “true
osteomas” ( Figs. 8.1–8.4) .
Rarely, a sessile ossifi ed neoplasm found on the sur-
face of a bone has the radiographic and pathologic
features that relate it closely to the malignant tumor
called parosteal osteosarcoma. This benign counterpart is
regarded as a parosteal osteoma.
Skeletal osteomas of various bones, but predomi-
nantly involving the skull and jaws, are associated with
intestinal polyps, fi bromatous and other lesions of
connective tissue, and epidermal cysts in Gardner syn-
drome.
The appearance of some lesions regarded as “solid”
odontomas is such that th ey may be osteomas, because
formed elements of tooth structure cannot be absolutely
identifi ed. It seems probable that dentin can become
ossifi ed.
The dense body overgrowths of the torus palatinus
and the torus mandibularis are of unknown cause but
can hardly be considered neoplastic, because they have
very restricted growth potential. Similar reasoning
applies to hyperostosis cranii.
98
Th e list of osteomas seen at Mayo Clin ic is n ot
complete. H owever, 147 cases were coded as such
th rough 2003. O f th ese, on ly four in volved th e lon g
bon es. Th e rest in volved th e skull, th e jawbon es, an d
th e sin uses. Th ese lesion s of th e h ead may produce
symptom s th rough deformity or even proptosis or
may be in ciden tal fi n din gs on radiograph s. As in di-
cated above, some of th ese lesion s may be related to
fi brous dysplasia.
Parosteal osteoma of a long bone is extremely unusual
( Fig. 8.5) . Bertoni and associates, in reviewing the Mayo
Clinic fi les, found only 14 parosteal osteomas of extrag-
nathic location out of approximately 40,000 recorded
bone lesions. Ten cases originally coded as parosteal
osteoma were excluded and reclassifi ed as parosteal
osteosarcoma ( three) , reactive new bone associated
with soft-tissue angiomas ( two) , and end-stage reac-
tive lesions, such as myositis ossifi cans ( fi ve) . Parosteal
osteoma of the long bone may be an asymptomatic inci-
dental fi nding, or the patient may have noted a mass
lesion that may have enlarged gradually. Two of the
14 patients reported by Bertoni and coworkers com-
plained of pain. Radiographs show a very heavily ossifi ed
mass attached to the underlying cortex. There are no
areas of lucency, and underlying bone is not in volved.
No unmineralized soft-tissue mass is present. Histologi-
cally, osteomas consist of dense sclerotic lamellar bone
similar to that in cortical bone. Appreciable spindle cell
proliferation should not be present ( Fig. 8.6) .
Follow-up information suggests that these lesions
are, indeed, benign. The differential diagnosis includes,
most importantly, parosteal osteosarcoma. Any lucency
or unmineralized soft tissue mass seen on imaging
studies should rule out the consideration of parosteal
osteoma. Parosteal osteoma should have only dense cor-
tical-appearing bone. Parosteal osteosarcoma generally
has parallel arrays of bone with a hypocellular spindle
cell stroma. Any spindle cell proliferation should rule
out the diagnosis of a parosteal osteoma. Despite these
rules, this differentiation is sometimes arbitrary.

Figu re 8.1. Osteoma in the frontal sinus of a 19-year-old man
produced local tumefaction. Such lesions can produce symp-
toms by blocking drainage from the sinus or by penetrating into
neighboring structures, including the cranial cavity.
F igu r e 8.2. Gross specimen removed from the patient whose
radiograph is shown in Fig. 8.1.
■ Osteoma 99
F igu r e 8.3. Gross specimen of a fi rm, well-circumscribed
osteoma th at was located in th e eth moid sin us. Th e wh ite
color produces th e appearan ce of an “ivory” osteoma.
F igu r e 8.4. Gross specimen of a recurrent osteoma removed
from the left frontal skull of a 48-year-old woman. An osteoma
was removed from the same site 25 years earlier, after head
pain had developed.
Some soft-tissue lesions adjacent to bone, hemangioma
in the soft tissues, lipoma, and meningioma of the dura
mater invading skull bones can give rise to an osteomatous
reaction. An apparent osteoma of long bone may turn out
to be reactive bone to an underlying osteoid osteoma in
which the nidus is not apparent on radiographs.
100 Chapter 8 ■

F igu r e 8.5. Parosteal osteoma involving the proximal femur

in a 45-year-old man wh o presen ted with dull, ach in g h ip pain .
An teroposterior ( A) an d lateral ( B) radiograph s sh ow a large
h eavily min eralized mass intimately associated with the cortex
alon g th e posterior aspect of th e proximal femoral diaph ysis.
Computed tomograph y an d magn etic reson an ce imagin g con -
fi rmed th at the lesion was periosteal in origin , with n o eviden ce
of medullary in volvemen t. Computed tomograph y ( C) sh ows a
pattern of mineralization ch aracteristic of den se osteoid matrix.
Th e marked homogen eous low-sign al in ten sity th rough out th e
lesion on th e T1- ( D) an d T2- ( E) weigh ted images con fi rms th at
th e lesion is composed en tirely of min eralized matrix, with n o
evidence of a soft-tissue componen t.

F igu r e 8.6. O steoma. Low-power ( A) an d h igh -power ( B) appearan ce. Th e tumor is composed
en tirely of dense compact bon e.
BIBLIOGRAPH Y
1950 Hallberg, O. E. and Begley, J. W., Jr.: O rigin and Treatment
of O steomas of th e Paran asal Sin uses. Arch Otolaryn gol, 51:
750–760.
1958 Caughey, J. E.: The Etiology of Hyperostosis Cranii
( Metabolic Craniopathy) : A Clinical Study. J Bone Joint Surg,
40B:701–721.
1962 Gardner, E. J.: Follow-up Study of a Family Group Exhib-
itin g Domin an t In h eritan ce for a Syn drome In cludin g
In testin al Polyps, Osteomas, Fibromas an d Epidermal Cysts.
Am J Hum Genet, 14:376–390.
■ Osteoma 101
1965 Bullough, P. G.: Ivory Exostosis of the Skull. Postgrad Med J,
41:277–281.
1966 Colcock, B. P. and Zomorodian, A. A.: Gardner’s Syn-
drome: Multiple Polyposis of Colon , Bon e Tumors an d Soft-
Tissue Tumors. Postgrad Med, 40:29–34.
1993 O’Connell, J. X., Rosenthal, D. I., Mankin, H . J., and
Rosen berg, A. E.: Solitary Osteoma of a Lon g Bon e: A Case
Report. J Bone Joint Surg, 75A:1830–1834.
1995 Bertoni, F., Unni, K. K., Beabout, J. W., and Sim, F. H.:
Parosteal O steoma of Bon es Oth er Th an of Skull an d Face.
Cancer, 75:2466–2473.
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 C H APT ER

9
Osteoid Osteoma

It is generally accepted that osteoid osteoma is a neoplasm actual incidence, because this type of tumor was recog-
and not the result of some obscure infection or other nized only rarely before 1940.
known specific etiologic agent. This distinctive benign
osteoblastic lesion consists of a small oval or round mass
commonly called a nidus. The nidus is often associated SEX
with a surrounding zone of sclerotic bone, especially
when the lesion develops in a cortical portion of bone. Male predominance was pronounced by a ratio of
The nidus is the essential part of the tumor; the surround- almost 3:1. Male and female age and localization distri-
ing sclerosis is a reversible change that disappears after butions were similar.
the nidus is removed. The major component of the tumor
is a meshwork of osteoid trabeculae of various degrees of
mineralization in a background of usually vascular fibrous
AGE
connective tissue.
Approximately 76% of patients in the Mayo Clinic series
In certain instances, focal subacute or chronic
were 5 to 24 years old. Twelve patients were younger
osteomyelitis ( Brodie abscess) produces a clinical and
than 5 years; the youngest was 21 months old, and the
radiographic pattern that has been confused with that
oldest was 72 years old.
of osteoid osteoma, especially when the infl ammatory
lesion is associated with a small, discrete, central rarefi ed
focus. Histologically, the lesion produced by infl amma-
LOCALIZATION
tion is readily differentiated from an osteoid osteoma
when appropriate sections are made. An osteoid osteoma
More th an h alf of osteoid osteom as occur in th e
located immediately beneath articular cartilage can be
fem ur an d th e tibia. Th e proximal femur, in cludin g
mistaken for osteochondritis dissecans radiographically.
th e fem oral n eck, is by far th e sin gle m ost com mon
Although focal islan ds of idiopathic medullary sclerosis
location . In lon g bon es, th e lesion is usually n ear th e
may be the size of a nidus of sclerotic osteoid osteoma,
en d of th e sh aft or in th e middle portion . In verte-
they do not produce clinical symptoms.
brae, th e arch is m ost comm on ly in volved. Som e of
For a neoplasm, osteoid osteoma has a strangely limited
th e vertebral an d n on vertebral exam ples described in
growth potential, and tumors more than 1.5 cm in largest
th e literature are un doubtedly ben ign osteoblastom as.
dimension are unusual. The tumor may have a remark-
In th e Mayo Clin ic series, on ly two lesion s in volved
able histologic similarity to osteoblastoma, as described in
th e skull, an d n on e in volved th e clavicle or stern um .
Chapter 10. All lesions less than 1 cm in greatest dimen-
Th e ph alan ges of th e h an ds were th e fi fth m ost com -
sion were arbitrarily called osteoid osteoma by McLeod and
mon location , but th ere were n o examples in th e ph a-
coauthors; they called lesions more than 2 cm in diam-
lan ges of th e feet. Th e tarsal bon es, h owever, were
eter osteoblastomas. They used an arbitrary dividing line of
relatively comm on ly in volved. O n ly on e patien t h ad
1.5 cm for lesions indistinguishable by all other criteria.
lesion s in volvin g m ore th an on e bon e. Th is patien t
h ad an osteoid osteom a of th e distal ph alan x of th e
IN CID EN CE in dex fi n ger rem oved in 1967 an d presen ted with a
lesion of th e fem oral n eck in 1981. Two patien ts h ad
The 396 cases of osteoid osteoma in the Mayo Clinic wh at appeared to be m ulticen tric disease in volvin g
series accounted for 12.9% of all benign tumors on e site. Th ree oth er patien ts h ad question able m ul-
( Fig. 9.1) . This percentage is probably lower than the tiple n iduses in on e bon e.
102
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F igu r e 9.1. Distribution of osteoid
osteomas accordin g to age an d sex of th e
patien t an d site of th e lesion .
SYMPTOMS
By far the most important complaint is pain of gradu-
ally progressive severity. The duration of pain before
the patient seeks medical care may vary from weeks to
several years. Typically, salicylates relieve the pain dra-
matically. The pain is usually described as being worse at
night, inter fering with sleep. The pain is often referred
to th e adjacent joint region and occasionally to a site
so distant from the lesion that radiographic studies are
misdirected. In a report of 38 patients with bone tumors
who had a preoperative diagnosis of lumbar disk syn-
drome, Sim and coauthors found that osteoid osteoma
was the most common bone tumor simulating disk pro-
lapse clinically. In some instances, especially when the
involved bone is near the skin, painful local swelling
may become evident. Growth disturbances, including
increased bone length, may occur. Osteoid osteoma
may produce scoliosis and fl exion contractures. Tumors
located near a joint may simulate arthritis. Kattapuram
and coauthors h ighlighted the delay caused in making
the correct diagnosis in these patients because they are
treated as if they had arthritis.
Only six lesions in the series were painless. Some
lesion s of fi brous dysplasia, especially in the ribs and
jawbones, may have areas simulating the appearance
of osteoid osteoma. Hence, reports of painless osteoid
osteomas have to be interpreted with some skepticism.
The cause of the very typical pain associated with osteoid
osteoma is still not clear. Nerves, identifi ed by special
axon stains, within the nidus may be causally related
to the pain. High levels of prostaglandins in the lesion
have also been implicated and may explain why aspirin
relieves the pain.
■ Osteoid Osteoma 103
PH YSICAL FIN D IN GS
Dysfunction, often resulting in a limp, is commonly
produced by an osteoid osteoma. Atrophy of some of
the muscles of the affected extremity is common. When
added to the character of the pain and the decreased
muscle stretch refl exes, the atrophy may suggest a neu-
rologic disorder. This combination resulted in a clinical
suspicion of lumbar disk prolapse in seven patients in
the series; three had undergone a laminectomy. One
other patient had been operated on for a suspected glo-
mus tumor of soft tissue.
RAD IOGRAPH IC FEATU RES
Typically, the nidus of an osteoid osteoma appears as
a small, relatively radiolucent zone. The nidus may
undergo various amounts of sclerosis and, hence, may
appear as a rounded area of sclerosis with a halo of
lucency around it. A variable, sometimes extensive, scle-
rotic zone ordinarily surrounds the nidus and may mask
it, necessitating special radiographic techniques for its
demonstration. In a study of 100 cases of histologically
proven osteoid osteoma, Swee and coauthors found
that in 75 cases, the plain radiographs were diagnostic
of osteoid osteoma. Seventeen patients had equivocal
radiographic fi ndings, and 14 of these patients had
tomography. Eleven of the tomograms demonstrated
a nidus. Eight patients had normal plain radiographs.
Seven of them had tomography, and in three, the tomo-
grams showed a nidus. When fi ndings were positive on
plain radiographs, tomograms did not add to the pre-
operative diagnosis, although they tended to help in
localizing the lesion ( Figs. 9.2– 9.5) .
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104 Chapter 9 ■

F igu r e 9.2. O steoid osteoma in an 18-year-old man with kn ee pain . A: An teroposterior radiograph
shows a region of marked cortical th icken in g and ben ign periosteal new bone formation alon g th e
medial aspect of th e femoral diaphysis, with a very subtle round lucency in th e cortex near the epi-
cen ter of th e process. B: Computed tomograph y sh ows better delin eation of th e lytic in tracortical
lesion that contains a tiny focus of central calcifi cation characteristic of an osteoid osteoma. C: A
bon e scan sh ows th e typical appearan ce of an osteoid osteoma, with a small focus of h yperin ten se
activity surrounded by a larger region of less intense activity that correlates with the reactive change
around the tumor. D: Axial computed tomogram obtained during computed tomographic-guided
radiofrequen cy ablation of th e osteoid osteoma shows th e tip of the ablation probe transversin g
the tumor. Computed tomographic-guided radiofrequency ablation has become the treatment of
ch oice for th e majority of osteoid osteomas occurrin g in th e appen dicular skeleton .

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F igu r e 9.3. O steoid osteoma of th e proximal ph alan x of
the index fi nger. The lesion was painless, and the patient pre-
sen ted with swellin g. Th e tomogram sh ows a lucen t defect
with central mineralization. Dense sclerosis surrounds the
lesion. ( Case provided by Dr. Michael Waldron, St. Paul Medi-
cal Cen ter, Dallas, Texas.)
The exact localization of a nidus of osteoid osteoma
may be diffi cult because of either the anatomy of the
location, such as in the spine, or extensive new bone
formation. Osteoid osteoma always tends to give posi-
tive results on a bone scan. Although the entire area
of sclerosis is positive, the nidus shows a focal area of
increased activity. This sign has been suggested to be
of help in localizing an osteoid osteoma. Computed
tomography is the preferred method for localization of
the nidus, especially in the spine.
Sometimes the reactive periosteal laminations of
new bone mimic those of Ewing tumor. One patient in
the series had been treated with radiation elsewhere
because of a mistaken diagnosis made on the basis of
the radiographic fi ndings. More often, the periosteal
bone formation is thick and benign appearing and may
be mistaken for an osteoma.
In some patien ts, th e typical clin ical symptoms
precede th e on set of recogn izable radiograph ic
ch an ges. Some osteoid osteomas, especially th ose in
■ Osteoid Osteoma 105
th e can cellous bon e, sh ow little or n o perifocal sclero-
sis. Th is absen ce of sclerosis makes th e radiograph ic
appearan ce of osteoid osteoma merge with th at of
osteo blastoma.
Absence of signifi cant sclerosis is usual for an osteoid
osteoma located near the end of a bone, especially if it
abuts articular cartilage, and for tumors in superfi cial
subperiosteal locations. Tumors near a joint may show
osteoporosis only; those near the elbow may be espe-
cially diffi cult to localize. Computed tomography may
be helpful in this location.
Previous surgery or a multifocal nidus may obscure
details of the lesion.
GROSS PATH OLOGIC FEATU RES
Whether an osteoid osteoma is found in relatively non-
sclerotic cancellous bone or buried in a large region
of cortical sclerosis, the nidus, upon exposure, usually
stands out as a discrete round or oval mass of tissue. The
nidus is ordinarily red, whereas the surrounding bone is
white and can be lifted from its bed. The nidus varies in
consistency from soft granular to densely sclerotic, but
the degree of sclerosis does not correlate with the dura-
tion of symptoms. Sclerosis, when present, is usually
most pronounced in the central portion of the nidus.
Osteoid osteoma has, as previously noted, a peculiarly
limited growth potential, which is an unusual feature of
true neoplasms. Even when symptoms have been pres-
ent for several years, the nidus rarely exceeds 1 cm in
greatest dimension ( Figs. 9.6–9.9) .
If th e sclerotic zon e, in cludin g th e n idus, is ch is-
eled in discrimin ately from an affected bon e, it may be
diffi cult for th e path ologist to fi n d th e all-importan t
cen tral mass of tumor tissue, with out wh ich th e diag-
n osis can n ot be establish ed. Th erefore, for satisfac-
tory path ologic appraisal, th e surgeon must remove
th e n idus in tact. If large fragmen ts of cortical bon e
are received in th e laboratory, th ey sh ould be carefully
examin ed grossly for th e red, gran ular n idus; a radio-
graph of th e specimen may be useful. If th e n idus is n ot
foun d, th in slices of th e sclerotic bon e sh ould be made
an d examin ed. If th e path ologist is still un successful,
th e surgeon sh ould be so in formed, an d an oth er radio-
graph of th e bon e sh ould be taken to con fi rm th at th e
affected area h as been removed. Th e relatively rare
multifocal n idus th at may be presen t, especially after
previous un successful operation , may be particularly
diffi cult to localize.
H ISTOPATH OLOGIC FEATU RES
Microscopic examination shows a distinct demarca-
tion between the nidus and the surrounding bone.
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106 Chapter 9 ■

F igu r e 9.4. Osteoid osteoma in a 16-year-old boy. Anteroposterior radiograph of the pelvis ( A)
and computed tomogram of the proximal right femur ( B) show a small intracortical lytic lesion
in the proximal right femoral cortex medially at the level of the lesser trochanter that has marked
associated cortical thickening and thick chronic benign periosteal new bone formation. The fi nd-
ings are characteristic of osteoid osteoma. C: The intracortical tumor nidus is evident on a coronal
T1-weigh ted magn etic reson an ce image. D: Th e coron al T2-weigh ted magn etic reson an ce image
with fat suppression illustrates th e extensive soft-tissue and bone marrow edema typically seen with
an osteoid osteoma.

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 ■ Osteoid Osteoma 107

F igu r e 9.5. O steoid osteoma. A: An teroposterior radiograph of th e lower th oracic spin e. B: Select
axial computed tomogram at the level of the spine of the tenth thoracic vertebra. These images
sh ow a lytic lesion in the left pedicle of th is vertebra that is less th an 1 cm in diameter and contains
a large focus of central calcifi cation. The lesion is typical of osteoid osteoma and is surrounded by
sign ifi can t medullary sclerosis.

F igu r e 9.6. Gross specimen of osteoid osteoma from the

calcan eus contain ed a well-circumscribed n idus th at, like a F igu r e 9.7. Th e n idus of th is osteoid osteoma is situated
marble, fell out of th e surroun din g bon e. within the cortex.

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108 Chapter 9 ■

F igu r e 9.8. Th e n idus of th is osteoid osteoma forms a cir-

cumscribed pale red n odule surroun ded by a th ick sh ell of
bon e. Th e lesion was excised from th e femur.

F igu r e 9.10. A: Low-power view of an osteoid osteoma sh ow-

ing a well-circumscribed central nidus surrounded by reac-
tive, partially sclerotic bon e. Th e bon y trabeculae of th e n idus
sh ow variable min eralization . B: H igh -power view of th e n idus
sh ows an astomosin g trabeculae surroun ded by loose fi brovas-
cular proliferation .

F igu r e 9.9. Typical appearance of a nidus of an osteoid

osteoma. Th e lesion is soft an d fl esh y. It was removed from
th e cuboid in a 39-year-old woman .

Surrounding bone may be densely sclerotic, but other-

wise it shows no typical features (Figs. 9.10 & 9.11).
The nidus consists of an interlacing network of
osteoid and bony trabeculae having a variable amount
of mineralization. The trabeculae are usually thin and F igu r e 9.11. A rim of th ick, sclerotic bon e on th e righ t
arran ged in a meaningless tangle of numerous an asto- side of th e ph otograph surroun ds th e n idus of th is osteoid
moses. The central part of the nidus ordinarily is the osteoma.

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F igu r e 9.12. Occasionally, a lacelike pattern of osteoid simi-
lar to that seen in osteosarcoma can be found in the nidus of
an osteoid osteoma.
F igu r e 9.13. A sclerotic n idus with con fl uen t areas of osteoid
in an osteoid osteoma.
F igu r e 9.14. Numerous osteoblasts surroun d th e trabeculae
of woven bon e in th is osteoid osteoma. Multin ucleated gian t
cells are scattered with in th e surroun din g fi brous tissue.
■ Osteoid Osteoma 109
F igu r e 9.15. H ypocellular loose fi brovascular tissue occu-
pies the intratrabecular spaces of this osteoid osteoma.
F igu r e 9.16. Occasionally, the bony trabeculae in the
osteoid osteoma n idus can be wide, with promin en t cemen t
lines producing a pagetoid appearance.
site of the most mineralization and may be converted
into bone. Instead of bone marrow elements within the
trabecular framework, there is a somewhat vascular,
fi brous connective tissue that contains various numbers
of benign giant cells. The osteoblasts that mantle the
osteoid trabeculae in the zones of proliferation are too
well differentiated to suggest osteosarcoma, except in
rare instances; in these cases, the total pattern of osteoid
osteoma, including the small size of the nidus, indicates
the benignity of the cells. The size of the trabeculae
of these lesions varies from extremely small to rather
broad bone beams. Cement lines may be prominent in
the larger trabeculae. Clear-cut cartilage is unusual in
this tumor ( Figs. 9.12–9.16) .
Osteoblastoma typically contains broader and longer
osteoid trabeculae. Further, the lesion is, on average,
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110 Chapter 9 ■
more vascular than osteoid osteoma. The nidus of an
osteoblastoma appears to be less tightly woven than that
of an osteoid osteoma. A clear distinction, however, does
not exist between these two tumors, and occasional bor-
derline lesions may be classed in either group.
The bone adjacent to the nidus may contain scat-
tered lymphocytes and plasma cells. Nearby synovium
sometimes is thicken ed and shows a prominent infi ltra-
tion, at times similar to that of rheumatoid synovitis, of
similar chronic infl ammatory elements.
TREATMEN T
The management of patients with osteoid osteoma has
changed dramatically in th e last decade. Whereas exci-
sion of the nidus was standard treatment, it is rarely per-
formed n ow.
The majority of patients undergo thermablation
under computed tomographic guidance in which a
needle is introduced into the nidus and the lesion is
aspirated. Smears and histologic sections are per formed
before ablation. In the last 30 cases at Mayo Clinic, a
nidus was identifi ed histologically in about 50%. Symp-
tomatic relief has been obtained in most cases.
However, surgical removal may be necessary in some
cases when thermablation is not feasible for technical
reasons, such as proximity to a nerve. At the time of
surgery, the nidus may be diffi cult to localize, especially
in areas such as the femoral neck and the spine. Sim
and coauthors studied 54 patients who had features
of osteoid osteoma but in whom no nidus was found.
Thirty-on e patients had relief of symptoms. A Brodie
abscess was found in 2 of 31 patients. Eighteen patients
underwent a second surgical procedure, which relieved
pain in 13; a nidus was found in 7. A parosteal osteo-
sarcoma was found in one of the patients, who h ad no
relief of symptoms. Three patients underwent a third
surgical procedure and had relief of symptoms; a nidus
was found in two. Thirty-six patients had relief of symp-
toms without a nidus being found. It is possible that
the nidus was small and lost either at surgery or in the
laboratory. However, at least some of these patients with
symptoms suggestive of osteoid osteoma probably had
no pathologic processes.
Th e n otorious diffi culty in localization of a n idus
h as led to several suggestion s to h elp iden tify th e
n idus. Vigorita an d Gh elman advocated preoperative
in jection of tech n etium Tc 99 meth ylen e diph osph o-
n ate an d in traoperative probin g to localize th e n idus.
Ayala an d coauth ors suggested in jection of tetracy-
clin e preoperatively an d examin ation of th e resected
specimen un der ultraviolet ligh t. In th eir study, reac-
tive an d n ormal bon e did n ot fl uoresce. Marcove an d
coauth ors suggested preoperative in sertion of a n eedle
with computed tomograph ic guidan ce un der local
an esth esia to localize th e n idus.
If the nidus is removed, the patient is relieved of pain
almost immediately and may notice it in the immediate
postoperative period. All the thickened bone around
the osteoid osteoma need not be removed; this zone
resolves spontaneously once the entire nidus is gone.
Mazoyer and coauthors treated patients with percuta-
neous destruction or drilled resection under computed
tomographic guidance. All patients thus treated were
asymptomatic during follow-up. Histologic examina-
tion, however, is not always possible with this technique.
Kneisl and Simon treated some patients with nonsteroi-
dal antiinfl ammatory medications. They reported com-
plete relief of pain and thus suggested that this therapy
may be an alternative wh en surgery is diffi cult because
of location.
PROGN OSIS
Complete removal of the focus of tumor tissue results
in cure, whereas incomplete removal may lead to recur-
rence of symptoms and the necessity for reoperation.
In the series of 396 patients in the Mayo Clinic fi les,
10 have had recurrences. These recurrences are usually
simply managed by reexcision of the lesion. There was
no instance of malignant change in osteoid osteoma in
this series.
BIBLIOGRAPH Y
1935 Jaffe, H. L.: “Osteoid-Osteoma”: A Benign Osteoblastic
Tumor Composed of Osteoid and Atypical Bone. Arch Surg,
31:709–728.
1940 Jaffe, H. L. and Lichtenstein, L.: Osteoid-Osteoma: Further
Experience With This Benign Tumor of Bone; With Special
Referen ce to Cases Sh owin g th e Lesion in Relation to Sh aft
Cortices an d Common ly Misclassifi ed as In stan ces of Scleros-
in g Non -suppurative Osteomyelitis or Cortical-Bon e Abscess.
J Bone Join t Surg, n .s. 22:645–682.
1955 Rushton, J. G., Mulder, D. W., and Lipscomb, P. R.: Neu-
rologic Symptoms With Osteoid Osteoma. Neurology ( Min -
neap) , 5:794–797.
1956 Flaherty, R. A., Pugh, D. G., and Dockerty, M. B.: O steoid
Osteoma. Am J Roen tgenol, 76:1041–1051.
1959 Freiberger, R. H., Loitman, B. S., Helpern, M., and Thompson,
T. C.: Osteoid Osteoma: A Report on 80 Cases. Am J Roentgenol,
82:194–205.
1960 Lindbom, A., Lindvall, N., Söderberg, G., and Spjut, H.: Angiog-
raphy in Osteoid Osteoma. Acta Radiol (Stockh), 54:327–333.
1970 Giustra, P. E. and Freiberger, R. H.: Severe Growth Distur-
ban ce With O steoid Osteoma: A Report of Two Cases In volv-
ing th e Femoral Neck. Radiology, 96:285–288.
1970 Lawrie, T. R., Aterman, K., and Sinclair, A. M.: Painless
Osteoid Osteoma: A Report of Two Cases. J Bone Joint Surg,
52A:1357–1363.
1970 Schulman, L. and Dor fman, H. D.: Nerve Fibers in O steoid
Osteoma. J Bone Join t Surg, 52A:1351–1356.
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1973 Sn arr, J. W., Abell, M. R., and Martel, W.: Lymph ofollicular
Syn ovitis With Osteoid O steoma. Radiology, 106:557–560.
1974 Corbett, J. M., Wilde, A. H., McCormack, L. J., and Evarts,
C. M.: Intra-Articular Osteoid Osteoma: A Diagnostic Problem.
Clin Orth op, 98:225–230.
1974 Greenspan, A., Elguezabel, A., and Bryk, D.: Multifocal
Osteoid Osteoma: A Case Report and Review of the Literature.
Am J Roentgenol, 121:103–106.
1975 Keim, H. A. and Reina, E. G.: Osteoid-Osteoma as a Cause
of Scoliosis. J Bone Join t Surg, 57A:159–163.
1975 Norman, A. and Dor fman, H. D.: Osteoid-O steoma Induc-
in g Pron oun ced Overgrowth an d Deformity of Bon e. Clin
Orthop, 110:233–238.
1975 Sim, F. H., Dahlin, D. C., and Beabout, J. W.: Osteoid-Osteoma:
Diagnostic Problems. J Bone Join t Surg, 57A:154–159.
1976 McLeod, R. A., Dahlin, D. C., and Beabout, J. W.: The Spec-
trum of Osteoblastoma. Am J Roentgenol, 126:321–335.
1977 Sim, F. H ., Dahlin, D. C., Stauffer, R. N., and Laws, E. R., Jr.:
Primary Bone Tumors Simulatin g Lumbar Disc Syndrome.
Spin e, 2:65–74.
1979 Swee, R. G., McLeod, R. A., and Beabout, J. W.: Osteoid
Osteoma: Detection, Diagnosis, and Localization. Radiology,
130:117–123.
1982 Makley, J. T. and Dunn, M. J.: Prostaglandin Synthesis by
Osteoid O steoma ( letter) . Lancet, 2:42.
1983 Kattapuram, S. V., Kushner, D. C., Phillips, W. C., and
Rosen th al, D. I.: O steoid Osteoma: An Un usual Cause of Artic-
ular Pain . Radiology, 147:383–387.
1983 Vigorita, V. J. and Ghelman, B.: Localization of Osteoid
Osteomas—Use of Radionuclide Scanning and Autoimagin g
in Identifying th e Nidus. Am J Clin Pathol, 79:223–225.
■ Osteoid Osteoma 111
1986 Ayala, A. G., Murray, J. A., Erling, M. A., and Raymond, A. K.:
Osteoid-Osteoma: Intraoperative Tetracycline-Fluorescence
Demon stration of the Nidus. J Bone Joint Surg, 68A:747–751.
1986 Brabants, K., Geens, S., and van Damme, B.: Subperiosteal
Juxta-Articular Osteoid Osteoma. J Bon e Join t Surg, 68B:
320–324.
1987 Helms, C. A.: Osteoid Osteoma: The Double Density Sign.
Clin Orth op, 222:167–173.
1991 Marcove, R. C., Heelan, R. T., Huvos, A. G., Healey, J., and
Lindeque, B. G.: Osteoid Osteoma: Diagnosis, Localization,
and Treatmen t. Clin O rthop, 267:197–201.
1991 Mazoyer, J. F., Kohler, R., and Bossard, D.: Osteoid O steoma:
CT-Guided Percutan eous Treatmen t. Radiology, 181:269–271.
1992 Klein, M. H. and Shankman, S.: Osteoid Osteoma: Radio-
logic and Path ologic Correlation . Skeletal Radiol, 21:23–31.
1992 Kneisl, J. S. and Simon, M. A.: Medical Management Com-
pared With O perative Treatmen t for O steoid-Osteoma. J Bon e
Joint Surg, 74A:179–185.
1993 Kaweblum, M., Lehman, W. B., Bash, J., Strongwater, A.,
an d Gran t, A. D.: Osteoid O steoma Un der th e Age of Five
Years: Th e Diffi culty of Diagn osis. Clin O rth op, 296:218–224.
1995 Rosenthal, D. I., Springfi eld, D. S., Gebhardt, M. C.,
Rosenberg, A. E., and Manken, H. J.: Osteoid Osteoma: Percu-
taneous Radio-Frequency Ablation. Radiology, 197:451–454.
1998 O’Connell, J. X., Nanthakumar, S. S., Nielsen, G. P., and
Rosenberg, A. E.: Osteoid Osteoma: The Uniquely Innervated
Bone Tumor. Mod Pathol, 11:175–180.
2006 Rosenthal, D. I.: Radiofrequency Treatment. Orthop Clin
North Am, 37:475–484.
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 C H APT ER
10
Osteoblastoma
(Giant Osteoid Osteoma)
The literature on this rare benign tumor is especially
confusing. The osteoblastic nature of the tumor often
results in zones similar to those of an osteoid osteoma,
producing a histologic kinship that cannot be ignored.
Osteoblastoma differs, however, in not sharing the mark-
edly limited growth potential of the average osteoid
osteoma. Further, osteoblastoma frequently lacks the
characteristic pain and the halo of sclerotic bone associ-
ated with osteoid osteoma. Even so, occasionally a lesion
has composite features th at place it midway between
the two lesions under discussion. McLeod and cowork-
ers resolved this problem by arbitrarily regarding an
equivocal lesion as an osteoblastoma when the lesion
was more than 1.5 cm in greatest dimension.
The term giant osteoid osteoma, introduced several years
ago, was an attempt to recognize the pathologic similar-
ity of this lesion to osteoid osteoma, at the same time
indicating a difference, especially in the size of the aver-
age tumor. Benign osteoblastoma nevertheless has become
the most widely accepted designation for this tumor.
In the literature on neoplasms, osteoblastoma
is foun d under various diagnoses, including giant
cell tumor, osteoid osteoma, osteogenic (or ossifying)
fi broma, and sarcoma. An important reason for recog-
nizing this entity is th at it commonly has been mistaken
for the much more aggressive giant cell tumor or even
for osteosarcoma.
One may logically question whether osteoblastoma
is correctly classed with true neoplasms because some
osteoblastomas regress or become arrested after incom-
plete surgical removal. Fields within some of these tumors
resemble portions of an aneurysmal bone cyst. This
resemblance, coupled with the pronounced clinical simi-
larity, suggests that both tumors may be different mani-
festations of a reaction to some as yet unknown agent.
However, some osteoblastomas are locally aggres-
sive. Osteoblastomas have even led to the death of
the patient, especially wh en in such locations as the
112
spine. The terms aggressive osteoblastoma and malignant
osteoblastoma in the literature emphasize this problem.
There are rare well-documented examples of osteoblas-
toma undergoing malignant change to osteosarcoma.
The problem is compounded by the fi nding that some
osteosarcomas have microscopic fi elds indistinguish-
able from those of osteoblastoma. Hence, at least some
reported examples of osteosarcoma arising from an
osteoblastoma may actually be examples of osteosarco-
mas that were underdiagnosed. These features suggest
that osteoblastoma should be considered a neoplasm
and not a reactive process. Perhaps the terminology
should be osteoblastoma, not benign osteoblastoma, to
emphasize the rare aggressive lesion.
The lesion called cementoblastoma at or around the
root of a tooth is very similar, too, and has been included
with osteoblastoma in this series.
IN CID EN CE
Osteoblastoma accounted for approximately 3.5% of
all benign primary tumors of bone in the Mayo Clinic
series and 1% of all bone neoplasms ( Fig. 10.1) .
SEX
Male patients accounted for approximately 72% of all
cases. The marked male predominance also occurred in a
large series of tumors reported by Lucas and coauthors.
AGE
The younger age group was predominantly affected,
and more than 80% of the patients were in the fi rst
3 decades of life. The youngest patient was 4 years old,
and the oldest was 75.

F igu r e 10.1. Distribution of
osteoblastomas accordin g to
age and sex of the patient and
site of th e lesion.
LOCALIZATION
Osteoblastoma, in contrast to most other neoplasms of
bone, has a distinct predilection for the vertebral col-
umn. The spinal column and sacrum were involved in
more than 40% of all lesions. The rest were in the long
bones, except for 11 in the mandible ( several of these
might be called cementoblastoma) , 9 in the innominate
bone, 2 each in the ribs and the maxilla, 5 in the tarsal
bones, and 1 each in the carpals, phalanges of the hand,
and clavicle.
Osteoblastomas in the vertebral column tend to
involve the posterior elements. In the series reported
by Lucas and coauthors, 55% of the lesions were con-
tained entirely within the dorsal element, whereas 42%
affected both the dorsal element and the adjacent verte-
bral body. Rarely was an osteoblastoma confi ned to the
body of a vertebra.
SYMPTOMS
Pain, often progressive, was the most frequent com-
plaint, identifi ed in 87% of the patients. Local swell-
ing, tenderness, warmth, and gait disturbances were
also mentioned frequently. Ten patients had neurologic
disorders secondary to spinal tumors at presentation,
ranging from numbness and tingling to paraparesis
and paraplegia. The average duration of symptoms
■ Osteoblastoma (Giant Osteoid Osteoma) 113
was 2 years. Mirra and coauthors described a case of
osteoblastoma associated with severe systemic toxic-
ity. Symptoms included massive weight loss, chronic
fever, anemia, and systemic periostitis. The symptoms
abated after amputation. Yoshikawa and coauthors
reported two examples of osteoblastoma associated with
osteomalacia.
PH YSICAL FIN D IN GS
Physical examination is of little value in the defi nitive
diagnosis of this lesion, but it may show a tender mass at
the site of the tumor. Atrophy of the adjacent muscles
sometimes occurs. Various neurologic defi cits may be
noted, depending on the degree of involvement of the
spinal cord or emerging nerves.
RAD IOGRAPH IC FEATU RES
The radiographic features of osteoblastoma are often
nonspecifi c, and the radiographs may not suggest the
true diagnosis. In reviewing the radiographs of 116
cases of appendicular osteoblastoma, Lucas and coau-
thors found that 65% of the tumors were located within
the cortex and the other 35% in the medullary canal.
Included in those involving the cortex were six tumors
that arose on the sur face of bone. Of the 116 lesions,
114 Chapter 10 ■

42% were metaphyseal, 36% were diaphyseal, and 22%
were epiphyseal. The lesions were from 1 to 11 cm in
greatest dimension, with an average of 3.18 cm. Only
eight lesions had a calcifi ed central nidus with a lucent
halo suggestive of the diagnosis. Reactive sclerosis was
found in more than 50% of the cases. Periosteal new
bone formation was also frequent. The lesions had
large areas of destruction of the bone and variable scle-
rosis. The margins were well defi ned, poorly defi ned,
or indefi nite. On the basis of the radiographic fea-
tures, 72% of the lesions were thought to be benign,
10% to be malignant, and the rest to be indeterminate
( Figs. 10.2–10.9) .
There were 66 vertebral osteoblastomas in this series.
Sizes ranged from 1 to 15 cm, with an average size of
3.55 cm. Margination could be good, intermediate, or
poor, and each of th ese three types occurred with equal
frequency. Osteoblastomas of the jawbones usually show
heavily mineralized well-demarcated lesions at the base
of a tooth.
In summary, the radiographic features of osteoblas-
toma may be quite specifi c but usually are not and may
suggest malignancy.
the trabeculae of neoplastic bone tend to merge with
those of a host bone, giving rise to an appearance of
maturation ( Fig. 10.13) .
The matrix is variably calcifi ed. Some osteoblasto-
mas have abundant thick, pink osteoid seams without
mineralization, whereas others have much calcifi cation
with the appearance of bony trabeculae. The osteoid
seams and the bony trabeculae are lined with a single
layer of osteoblasts. The osteoblasts may have small
inconspicuous nuclei with abundant cytoplasm or large
vesicular nuclei with prominent nucleoli. The intertra-
becular stroma is composed of capillary proliferation
and loosely arranged spindle cells without atypia ( Figs.
10.14–10.21)

GROSS PATH OLOGIC FEATU RES

Whole gross specimens are rarely seen because the

average lesion is removed with curettage. The lesions
are reasonably well circumscribed. The tumor tissue is F igu r e 10.2. Osteoblastoma of the fourth lumbar verte-
hemorrhagic, granular, and friable because of its vascu- bra in a 10-year-old girl. Th e lesion is n ot seen well on plain
larity and osteoid component, which shows variable cal- radiographs but is shown clearly by computed tomography to
cifi cation . In some of the older lesions, the consistency involve the dorsal element.
resembles that of cancellous bone and decalcifi cation
is necessary before microscopic sections can be made.
When the tumor bulges from and distorts the contour of
the affected bone, the margins of the tumor are sharply
defi ned ( Figs. 10.10–10.12) .
As previously indicated, the bone adjacent to a
benign osteoblastoma often is not sclerosed. Some of
the tumors have a thin sclerotic rim, whereas others,
especially those in the long bones of the extremities,
have a zone of increased density as prominent as that of
the ordinary osteoid osteoma.
In some tumors, the greatest dimension has extended
to 10 cm. Sometimes the vascularity of the osteoblastoma
is so great that hemostasis may be a problem for the
surgeon.

H ISTOPATH OLOGIC FEATU RES

Osteoblastomas are composed of anastomosing bony
trabeculae in a loose fi brovascular stroma. The lesion
is extremely well circumscribed, and toward the edges,
F igu r e 10.3. An teroposterior radiograph of th e righ t pubic
bon e sh ows a mixed lytic an d sclerotic lesion in th e body an d
inferior ramus of the bone, with associated expansion of the
bon e, scattered foci of matrix min eralization , an d an associ-
ated soft-tissue mass in the adjacent obturator foramen.
 ■ Osteoblastoma (Giant Osteoid Osteoma) 115

F igu r e 10.4. Radiograph of th e pelvis ( A) an d computed tomograph ic images of th e lower pelvis

( B) show an expansile mass in the lower sacrum with matrix mineralization. The sagittal T1- ( C)
and axial T2- ( D) weighted magnetic resonance images with fat suppression show the anatomical
exten t of th e lesion . Foci with in th e lesion have low-sign al in ten sity on both th e T1- and T2-weigh ted
images that correlate with the mineral seen on the radiograph and computed tomograms. The
imaging features are indicative of a benign mineralizing lesion with osteoid matrix and, given the
anatomical location, are most consistent with an osteoblastoma.

Mitotic activity may be found within the osteoblasts.
It is not promin ent, however, and atypical mitotic fi g-
ures are not present. Areas resembling secondary aneu-
rysmal bone cysts may be seen in up to 10% of the cases.
Occasionally, osteoblastoma-like areas may be found
in an otherwise typical aneurysmal bone cyst, and this
distinction sometimes is arbitrary. Although classically
the bony trabeculae are thick and well formed, fi ne
lacelike osteoid, a feature of classic osteosarcoma,
may be seen focally. Such areas were found in 20% of
the cases studied by Lucas and coauthors. Necrosis is
unusual in osteoblastoma without pathologic fracture.
116 Chapter 10 ■
F igu r e 10.5. Osteoblastoma, with an aggressive radiographic
appearance, arising in a proximal phalanx.
F igu re 10.6. Anteroposterior radiograph of the left hip shows
a lytic lesion in the subtrochanteric region of the femur, with
extensive surrounding medullary sclerosis, cortical thickening,
and chronic periosteal new bone formation. The differential
diagnosis would include osteoblastoma and Brodie abscess.
F igu r e 10.7. Heavily mineralized osteoblastoma surround-
ing the root of a tooth. The term “cementoblastoma” has been
applied to this lesion.
F igu r e 10.8. Multicentric osteoblastoma of the distal femur
simulating an osteosarcoma. ( From McLeod, R. A., Dahlin,
D. C., and Beabout, J. W.: The Spectrum of Osteoblastoma.
Am J Roentgenol, 126:321–335, 1976. By permission of the
American Roentgen Ray Society.)

F igu r e 10.9. O steoblastoma of th e sacrum in a 41-year-old
man . A: H eavily min eralized lesion exten ded in to soft tissue
and suggested a diagnosis of osteosarcoma. B: In this com-
puted tomographic image, the lesion is well circumscribed, is
heavily min eralized, an d protrudes in to th e soft tissues. Th e
lesion was resected, and the patient was well 9 years later.
It used to be dogma th at cartilage differen tiation is
n ot seen in osteoblastoma. H owever, clear-cut ch on -
droid areas or islan ds of cartilage maturin g in to bon e
an d givin g rise to a ch on dro-osteoid appearan ce occur
in approximately 6% of all osteoblastomas. Th ey h ave
n o clin ical sign ifi can ce. Five of th e lesion s in th e Mayo
Clin ic series h ad a multifocal growth pattern . Th ese
lesion s ten d to sh ow multiple small foci of typical osteo-
blastoma separated by proliferatin g bon e an d fi brous
tissue. Th is appearan ce sh ould n ot be mistaken for
■ Osteoblastoma (Giant Osteoid Osteoma) 117
F igu r e 10.10. O steoblastoma arisin g with in th e clavicle. Th e
tumor was removed after a misdiagn osis of osteosarcoma.
F igu r e 10.11. Osteoblastoma of the proximal femur. The
tumor has a friable, hemorrhagic appearance that is seen
common ly in osteoblastoma.
true permeation , wh ich is accompan ied by destruction
of bon e. A few multifocal osteoblastomas h ave a pre-
domin an t proliferation of epith elioid cells. Some of
th e n odules are composed solely of cells an d migh t be
mistaken for metastatic carcin oma. Mirra an d associ-
ates poin ted out bizarre, pleomorph ic n uclei in oth er-
wise typical osteoblastomas. Th ese n uclei are en larged
an d h yperch romatic but do n ot h ave crisp n uclear fea-
tures. H en ce, th ey are similar to th e degen erated cells
in n eurilemmoma or after radiation . Th ey are also
associated with fi brosis in th e in tertrabecular spaces.
Lucas an d coauth ors foun d such features in 11% of
th eir cases ( Figs. 10.22–10.24) .
As mentioned previously, conventional osteosarcomas
may have areas identical to those in osteoblastoma. We
think the distinction between osteoblastoma and osteo-
sarcoma can be almost impossible to make with limited
material. The features favoring an osteoblastoma are the
118 Chapter 10 ■

F igu r e 10.14. O steoblastoma. Den se compact areas of

osteoid production in th e top h alf of th e ph otomicrograph
merge with better-formed trabeculae of woven bon e in lower
part of the photomicrograph.

F igu r e 10.12. Osteoblastoma of the distal femur in a

13-year-old boy. The lesion involves the cortex and is expan-
sile. Reactive sclerosis surroun ds th e lesion . ( Case provided
by Dr. J. L. Myers, Un iversity of Alabama, Birmin gh am,
Alabama.)

F igu r e 10.15. Partially min eralized trabeculae of bon e in

an osteoblastoma are surrounded by a single layer of osteo-
blasts an d loose fi brous tissue.

F igu r e 10.13. O steoblastoma sh owin g sh arp circumscrip-

tion in relation to the surrounding bone.

following: sharp circumscription with no permeation of

surrounding bone; loose arrangement of the tissue, with
the bony trabeculae appearing to be embedded in loose
connective tissue; and a single layer of osteoblasts sur-
rounding bony trabeculae. The most important single F igu r e 10.16. Dilated vascular spaces within the intertrabe-
feature, in our opinion, for the diagnosis of osteosarcoma cular tissue of an osteoblastoma.
 ■ Osteoblastoma (Giant Osteoid Osteoma) 119

F igu r e 10.17. A compact population of osteoblasts fi lls th e F igu r e 10.20. O steoblastoma con tain in g abun dan t sh eets
intertrabecular spaces of this osteoblastoma. of epith elioid osteoblasts.

F igu r e 10.18. Secondary aneurysmal bone cyst formation F igu r e 10.21. Uneven mineralization within the central
arising in association with osteoblastoma. portion of an osteoblastoma.

F igu r e 10.19. Abundant hemorrhage fi lls the intertrabe- F igu r e 10.22. Multicentric osteoblastoma. Multiple ( three)
cular spaces in th is osteoblastoma. Oth er areas with in th e small foci of bone formation an d proliferation of osteoblasts
tumor con tain ed more compact sh eets of osteoblasts in stead are present. The separate foci appear embedded in a loose
of blood. fi brovascular tissue.
120 Chapter 10 ■
F igu r e 10.23. Focus of cartilagin ous differen tiation in
an oth er wise typical osteoblastoma. Th is is an un common
fi n din g.
F igu r e 10.24. Pseudomalign an t osteoblastoma. Th ere are
man y h yperch romatic en larged n uclei. However, th e n uclei
have a smudgy appearan ce, an d th e n ucleus-to-cytoplasm
ratio is n ot in creased. Th e backgroun d stroma is fi brotic.
Th ese fi n din gs likely represen t degen erative ch an ges.
is permeation of surrounding tissue with entrapment of
host bon e. Sheets of osteoblasts without bone produc-
tion also favor osteosarcoma ( with the exception of the
rare multifocal epithelioid osteoblastoma) .
Th is ackn owledged diffi culty in separatin g osteo-
blastoma from osteosarcoma h as led to th e con cepts
of malign an t osteoblastoma proposed by Sch ajowicz
an d Lemos, an d aggressive osteoblastoma, proposed
by Dor fman an d Weiss. Sch ajowicz an d Lemos foun d
n o eviden ce of metastatic tumor in th eir group of
eigh t cases. Dor fman an d Weiss suggested th at epith e-
lioid osteoblasts, trabecular or sh eetlike osteoid, an d
osteoclastic resorption in dicate a diagn osis of aggres-
sive osteoblastoma. Th ey th ough t th at th ese features
porten d a more aggressive clin ical beh avior. Berton i
an d coauth ors in Italy stated th at epith elioid osteo-
blasts suggest a more aggressive lesion an d, h en ce,
agreed with th e con cept of aggressive osteoblastoma.
Della Rocca an d H uvos at Memorial Sloan -Ketterin g
Can cer Cen ter in New York, h owever, could n ot fi n d
an y correlation between th e morph ologic appearan ce
of an osteoblastoma an d its clin ical beh avior. Lucas
an d coauth ors also could n ot separate out a group of
aggressive osteoblastomas.
TREATMEN T
The benign nature of osteoblastoma dictates that con-
servative surgical treatment be used. Usually, the entire
lesion, or as much of it as possible, is removed by curet-
tage, with bone grafting of the defect if indicated. It is
still doubtful whether radiation therapy is useful. Some
of the patients in our series had incomplete surgical
removal of the lesional part and were cured. The clini-
cal course suggests that until surgical intervention, the
tumefaction usually increases. However, a 14-year-old
girl with an osteoblastoma involving the right half of
the sacrum was not treated after biopsy, and she was
asymptomatic 15 years later. The tumor was not surgi-
cally accessible, and irradiation of her pelvic region was
considered unwise.
PROGN OSIS
Perhaps the main reasons for recognizing this rare
pathologic entity are that it is not malignant and that,
as indicated, the response to treatment is nearly always
good. Occasionally, incompletely removed tumors of
this type require more than one surgical procedure.
The most likely major problem is involement of the spi-
nal column by a lesion; if this occurs, therapy must be
directed to preserving the integrity of the spinal cord
and the emerging nerve roots. In the Mayo Clin ic fi les,
there are fi ve instances of recurrence.
Malignant change occurs in a very few lesions consid-
ered to be correctly diagnosed as benign osteoblastoma.
This happened in a 16-year-old boy in the Mayo Clinic
series who had what appeared to be an osteoblastoma of
the proximal tibia. Forty months later, recurrent tumor
was clearly an osteosarcoma. We have reviewed this case
several times, and it appears that the original diagnosis
is correct. This is the only example in the Mayo Clinic
fi les of this apparent transformation. In a somewhat sim-
ilar case, a 59-year-old woman presented in 1987 with a
lesion of the third thoracic vertebra. Histologically, it
appeared to be an osteoblastoma. It recurred multiple

times, however, and clearly was an osteosarcoma 7 years
later. We have not kept this as an example of malignant
transformation, preferring to think that the original
diagnosis was incorrect.
Th e poten tial h azard of radiation therapy is in di-
cated by one case in th is series in wh ich a fatal fi bro-
sarcoma developed in th e same region 10 years after
radiation th erapy for osteoblastoma of the fi fth cervical
vertebra.
Despite the problem occasionally associated with the
histologic diagnosis, osteoblastoma is a useful designa-
tion, and the lesion can nearly always be cured by rela-
tively conservative surgical procedures.
BIBLIOGRAPH Y
1924 Lewis, D.: Primary Giant Cell Tumors of the Vertebrae:
An alysis of a Group of Cases, With Report of Case in Wh ich
Patien t is Well Two Years an d Nin e Mon th s After Operation .
JAMA, 83:1224–1229.
1954 Dahlin, D. C. and Johnson, E. W., Jr.: Giant Osteoid
Osteoma. J Bone Joint Surg, 36A:559–572.
1956 Jaffe, H . L.: Benign Osteoblastoma. Bull Hosp Joint Dis,
17:141–151.
1963 Marcove, R. C. and Alpert, M.: A Pathologic Study of
Benign Osteoblastoma. Clin Orthop, 30:175–181.
1967 Mayer, L.: Malignant Degeneration of So-called Benign
Osteoblastoma. Bull Hosp Joint Dis, 28:4–13.
1970 Schajowicz, F. and Lemos, C.: Osteoid O steoma an d Osteo-
blastoma: Closely Related En tities of Osteoblastic Derivation .
Acta Orthop Scan d, 41:272–291.
1974 Abrams, A. M., Kirby, J. W., and Melrose, R. J.: Cemento-
blastoma: A Clin ical-Path ologic Study of Seven New Cases.
Oral Surg, 38:394–403.
1974 Dias, L. S. and Frost, H. M.: Osteoid Osteoma—Osteoblas-
toma. Cancer, 33:1075–1081.
1974 Yip, W.-K. and Lee, H. T. L.: Benign Osteoblastoma of the
Maxilla. Oral Surg, 38:259–263.
1975 Seki, T., Fukuda, H., Ishii, Y., Hanaoka, H., Yatabe, S.,
Takano, M., and Koide, O.: Malignant Transformation of
Ben ign Osteoblastoma: A Case Report. J Bon e Join t Surg,
57A:424–426.
1976 McLeod, R. A., Dahlin, D. C., and Beabout, J. W.: The Spec-
trum of O steoblastoma. Am J Roentgen ol, 126:321–335.
1976 Mirra, J. M., Kendrick, R. A., and Kendrick, R. E.: Pseudo-
malign an t Osteoblastoma Versus Arrested O steosarcoma:
A Case Report. Cancer, 37:2005–2014.
1976 Schajowicz, F. and Lemos, C.: Malignant Osteoblastoma.
J Bone Joint Surg, 58B:202–211.
■ Osteoblastoma (Giant Osteoid Osteoma) 121
1977 Jackson , R. P., Recklin g, F. W., an d Man ts, F. A.: Osteoid
Osteoma and O steoblastoma: Similar Histologic Lesions With
Differen t Natural Histories. Clin Orthop, 128:303–313.
1977 Yosh ikawa, S., Nakamura, T., Takagi, M., Imamura,
T., Okan o, K., an d Sasaki, S.: Ben ign O steoblastoma as a Cause
of Osteomalacia: A Report of Two Cases. J Bon e Join t Surg,
59B:279–286.
1979 Mirra, J. M., Th eros, E., Smasson , J., Cove, K., an d
Paladugu, R.: A Case of O steoblastoma Associated With Severe
Systemic Toxicity. Am J Surg Path ol, 3:463–471.
1979 Sung, H. W. and Liu, C. C.: Can Osteoid Osteoma Become
Osteoblastoma? A Case Report. Arch Orthop Trauma Surg,
95:217–219.
1980 Merryweath er, R., Middlemiss, J. H., and San erkin, N. G.:
Malign an t Tran sformation of Osteoblastoma. J Bon e Join t
Surg, 62B:381–384.
1982 Tonai, M., Campbell, C. J., Ahn , G. H., Sch iller, A. L., an d
Man kin , H. J.: Osteoblastoma: Classifi cation an d Report of
16 Patients. Clin Orth op, 167:222–235.
1983 Pieterse, A. S., Vernon-Roberts, B., Paterson, D. C., Cornish,
B. L., and Lewis, P. R.: Osteoid O steoma Transforming to
Aggressive ( Low Grade Malign an t) Osteoblastoma: A Case
Report an d Literature Review. Histopathology, 7:789–800.
1984 Dor fman, H. D., an d Weiss, S. W.: Borderline Osteoblastic
Tumors: Problems in the Differential Diagnosis of Aggressive
Osteoblastoma and Low-Grade Osteosarcoma. Semin Diagn
Path ol, 1:215–234.
1985 Bertoni, F., Unni, K. K., McLeod, R. A., and Dahlin, D. C.:
Osteosarcoma Resembling Osteoblastoma. Cancer, 55:416–426.
1985 Beyer, W. F. and Küh n , H.: Can an Osteoblastoma Become
Malign an t? Virch ows Arch A Path ol An at Histopath ol,
408:297–305.
1990 Kroon, H. M. and Schurman s, J.: Osteoblastoma: Clin i-
cal an d Radiologic Fin din gs in 98 New Cases. Radiology,
175:783–790.
1993 Bertoni, F., Don ati, D., Bacch ini, P., Martini, A., Picci, P.,
an d Campan acci, M.: Th e Morph ologic Spectrum of Osteo-
blastoma ( O BL) : Is Its “Aggressive” Nature Predictable
( abstract) ? Mod Pathol, 6:3A.
1994 Della Rocca, C. an d Huvos, A. G.: Osteoblastoma: Do Histo-
logic Features Predict Clin ical Beh avior? A Study of 55 Patien ts
( abstract) . Mod Pathol, 7:6A.
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an d Sim, F. H.: Osteoblastoma: Clin icopath ologic Study of 306
Cases. Hum Path ol, 25:117–134.
1994 Ulman sky, M., Hjørting-Han sen , E., Praetorius, F., an d
Haque, M. F.: Benign Cementoblastoma: A Review and Five
New Cases. Oral Surg Oral Med Oral Pathol, 77:48–55.
2007 Filippi, R. Z., Swee, R. G., an d Unn i, K. K.: Epithelioid Mul-
tinodular O steoblastoma: A Clinicopathologic Analysis of 26
Cases. Am J Surg Path ol, 31:1265–1268.
 C H APT ER
11
Osteosarcoma
To qualify as an osteosarcoma, a neoplasm should have
proliferating malignant cells that produce either osteoid
substance or material histologically indistinguishable
from it at least in small foci. Although the production
of osteoid matrix is implicit in a diagnosis of osteosar-
coma, this production may be quite focal and, hence,
may not be recognized in limited tissue sampling. Thus,
the diagnosis of osteosarcoma may be reasonable, even
when no defi nite osteoid matrix is recognized if the neo-
plasm in question has features that in all respects are
classic for osteosarcoma. In a qualifying tumor that is
sampled throughout, elements with osteoid, chondroid,
or fi bromatoid differentiation may be predominant.
Accordingly, in this series, osteosarcomas are divided
into osteoblastic, chondroblastic, and fi broblastic types,
depending on the dominant element. The implica-
tion is that what appears to be a chondroblastic osteo-
sarcoma on biopsy may turn out to be an osteoblastic
osteosarcoma when more tissue is sampled. This classi-
fi cation merely highlights the wide variation seen in the
histopathology of osteosarcoma. It almost surely has no
prognostic signifi cance. All these tumors, however, are
similar in the characteristics of bones of predilection,
age of affected patients, pronounced tendency to early
hematogenous dissemination, and necessity for prompt
ablative surgical therapy. Malignant fi broblastic tumors
with no defi nite osteoid production by neoplastic cells,
regardless of their degree of anaplasia, are classifi ed as
fi brosarcomas or malignan t fi brous histiocytomas. Simi-
larly, chondroblastic malignant tumors with no defi nite
sheets of spindle cells or osteoid production are desig-
nated chondrosarcomas. Sometimes exact designation
is diffi cult and must be arbitrary because there is no spe-
cial stain for osteoid and its qualities merge with those
of collagen and cartilaginous matrix.
It has not seemed practical to divide the osteosar-
comas into sclerotic and lytic subtypes, but some special
types, such as periosteal, telangiectatic, and low-grade central,
have special features that will be elaborated. Alth ough
most osteosarcomas are of unknown cause, some sarco-
mas have Paget disease as a precursor, especially those
122
in older patients. Of the 1,952 osteosarcomas in the
Mayo Clinic series, 61 arose in pagetic bone, as did 7 fi -
brosarcomas, 3 malignant fi brous histiocytomas, 1 giant
cell tumor, and 1 malignant lymphoma.
An increasing number of sarcomas occurrin g after
radiation therapy of bone are being recognized. There
were 110 postradiation osteosarcomas in this series.
Other lesions that arose in irradiated bone were 48
fi brosarcomas, 12 malignant fi brous histiocytomas,
5 chondrosarcomas, 2 angiosarcomas, 1 malignant lym-
phoma, and 1 Ewing tumor.
Dedifferentiated chondrosarcoma with foci of osteo-
sarcoma are described in Chapter 6. Of the 145 dedif-
ferentiated chondrosarcomas, 80 had a dedifferentiated
component that was considered to be an osteosarcoma.
Osteosarcoma of the jaw has special features to be
described.
A special type of osteosarcoma that grows slowly,
metastasizes late ( if at all) , and is characteristically jux-
tacortical or parosteal in location is known as parosteal
osteosarcoma. It is discussed in Chapter 12.
Extraskeletal osteosarcomas occur in older adults,
are almost always high grade, and are associated with a
poor prognosis. They are excluded from the series dis-
cussed here.
The cause of osteosarcoma is unknown. As indicated
above, Paget disease and previous irradiation are known
to be associated with a higher incidence of osteosar-
coma. It has been suggested that preceding trauma may
contribute to the causation of bone tumors. In th e Mayo
Clinic series, there was only a single well-documented
example of previous trauma associated with later devel-
opment of osteosarcoma. This case involved a 37-year-
old man who incurred a bullet wound to the leg 11 years
before an osteosarcoma developed at exactly the same
site. Whether the trauma or the fragments of lead were
related to the later development of osteosarcoma is
unknown. Brien and coauthors reported an example of
an osteosarcoma arising in the site of previous total hip
arthroplasty. This case also suggests that metallic ions
may predispose to the development of osteosarcoma.

Evidence has been accumulating that at least some
cases of osteosarcoma may be related to a genetic abnor-
mality. It has been well recognized that patients with the
hereditary form of bilateral retinoblastoma are at high
risk for the development of osteosarcoma. In the Mayo
Clinic series, there were only two such patients. Benedict
an d coauthors found that a suppressor gene ( located on
chromosome 13) is lost in patients with retinoblastoma
an d osteosarcoma. Beigel and coauthors studied the
karyotypes of several osteosarcomas and found complex
abnormalities, but there was a consistent loss of normal
chromosome 13 homologue in all cases studied. This,
again, suggests a relation with the retinoblastoma gene.
In the Mayo Clinic series, multicentric osteosarcoma
developed in two brothers with Bloom syndrome. Two
siblings with Roth mun d-Thomson syndrome had osteo-
sarcoma. One had multicentric osteosarcoma, and the
other had a solitary lesion. A third patient probably had
the syndrome. One patient had Li-Fraumeni syndrome.
Another patient had multiple metachronous osteo-
sarcoma, which she survived, but she died later with
bilateral breast carcinoma. This patient’s daughter had
a rhabdomyosarcoma of the temporal region , suggest-
in g that this patient may also have a genetic syndrome.
One patient with multiple osteosarcomas had preexist-
in g osteopoikilosis. In one patient with osteosarcoma,
Ewing sarcoma had been diagnosed 6 years previously
at the same site treated only with chemotherapy.
IN CID EN CE
The 1,952 osteosarcomas ( excluding the parosteal
variety) accounted for 27.5% of all malignant tumors
and 19.2% of all bone tumors. Osteosarcoma is by far
Figu re 11.1. Distribution of osteosar-
comas according to age and sex of the
patient and site of the lesion.
■ Osteosarcoma 123
the most common malignant bone tumor ( excluding
myelomas diagnosed with bone marrow biopsy) .
SEX
Approximately 58% of the patients with osteosarcoma
were male. Of the 137 patients with osteosarcoma of the
jaws, 55% were male.
AGE
Although a few patients with osteosarcomas are in the
fi rst decade of life, the peak incidence is in the sec-
ond decade ( 44.77%) , and there is a steady, gradual
decrease thereafter ( Figs. 11.1 & 11.2) . Eight patients
were younger than 5 years, and the youngest patient
was 2 years 11 months old. Six of these eight very young
patients were girls. One hundred ninety-two patients
were older than 60 years ( Fig. 11.3) . Of these, 99 were
male and 93 were female. Of the 192 older patients, 59
had a preexisting condition: Paget disease ( 32) , previ-
ous radiation ( 24) , infarct ( 1) , chronic osteomyelitis
( 1) , and cyst of degenerative joint disease ( 1) . The last
condition probably should be considered coincidental.
Data from Memorial Sloan-Kettering Cancer Center in
New York also pointed to the high likelihood of a sec-
ondary osteosarcoma in an older age group.
LOCALIZATION
The metaphyseal part of the long bones is the site of
predilection, and almost one-half of the osteosarcomas
in the Mayo Clinic series were in the region of the knee.
124 Chapter 11 ■
Of the total number of osteosarcomas, only 24 were dis-
tal to the ankle and wrist joints. One patient developed
an osteosarcoma in a phalanx of the hand; non e had
a tumor of the phalanges of the foot. Mirra and coau-
thors found only one example of an osteosarcoma of the
phalanx of a toe in 4,214 cases of conventional osteosar-
coma. Sarcomas that did not extend to within 5 cm of an
articular sur face of a long bone were considered to be in
its midportion. Of the 1,430 osteosarcomas involving the
long bones, 152 ( 10.62%) were considered diaphyseal.
Excluding osteosarcoma of the jaws, 77.4% of the
tumors arose in the long tubular bones. However, in
patients older than 60, only 39% of the tumors arose
in long tubular bones. Huvos also noted that in the
F igu r e 11.2. Age distribution of patien ts with
ch on drosarcoma compared with th e distribution s in
ch on droblastic, fi broblastic, an d osteoblastic osteo-
sarcoma. Note that all types of osteosarcomas ten d to
occur in th e fi rst two decades of life, wh ereas ch on -
drosarcomas occur predominantly in adults.
F igu r e 11.3. Distribution of osteosar-
comas in patients 60 and older according
to age and sex of the patient and site of
the lesion. PR, postradiation.
Memorial Sloan-Kettering Cancer Center group of
older patients with osteosarcoma, the axial skeleton was
the most common site.
SYMPTOMS
Pain, which initially may be intermittent, and swelling
are the cardinal symptoms. Because they are nonspe-
cifi c, one should not ignore the possible seriousness
of these complaints, especially when they occur in
children, adolescents, or young adults. It is extremely
uncommon for patients with osteosarcoma to be asymp-
tomatic. One patient with osteosarcoma of the femur
 ■ Osteosarcoma 125

presented after a football injury. He had no symptoms

before the injury. Pathologic fracture is uncommon.
In th e Mayo Clinic series, two osteosarcomas of the
femur were associated with old infarcts, and two tumors
developed in chronic osteomyelitis: one in the femur
and one in the tibia. One patient with osteosarcoma
had associated myasthenia gravis, and one patient with
osteosarcoma of the tibia had radiographic evidence of
rickets ( oncogenic osteomalacia) . Cheng and coauthors
also reported on a patient with osteosarcoma associated
with oncogenic osteomalacia. The duration of symptoms
preceding defi nitive th erapy varies from a few weeks to
several months. A history of trouble for more than 1
year is uncommon in patients with conventional osteo-
sarcoma. Swellin g or an increase in pain suggests malig-
nant change in Paget disease. Similarly, a fl are-up of
symptoms in a patient who had irradiation for a benign
condition of bone should arouse suspicion. Also, rapid
progression of disease is an ominous sign in a patient
with known or suspected cartilaginous tumors.
An increased level of alkaline phosphatase, which
occurs in about half the patients, refl ects osteoblastic
activity.

PH YSICAL FIN D IN GS

A painful mass in the affected region is usually appar-

ent. If the mass is very large, it may be associated with
overlying prominent veins and even edema distal to the
lesion. Physical examination is noncontributory in some
patients with tumors covered by a thick layer of tissue.
Evidence of pathologic fracture is distinctly uncommon.
Some osteosarcomas are familial, an d some are asso-
ciated with gen eralized skeletal disease, such as osteo-
gen esis imper fecta.

RAD IOGRAPH IC FEATU RES

The radiographic appearance varies greatly depending

on the amount of ossifi cation and calcifi cation in the
osteosarcoma. Tumors may be completely lytic or pre-
dominantly sclerotic, but they usually have a combina-
tion of these features. The destructive process may be
limited to the medulla, but it usually involves the cortex
as well, and the cortex is nearly always per forated by the
growing tumor. Because of a gradual transition from
zones of pronounced lysis to zones of uninvolved bone,
the borders of the lesion are indistinct. Nonneoplastic
bone is deposited, sometimes in layers, when the perios-
teum is elevated by the per forating tumor ( Codman tri-
angle) . With con tinued development of the neoplasm,
a large soft-tissue mass is frequently seen contiguous to
the bone ( Figs. 11.4–11.12) .
F igu r e 11.4. Primary h igh -grade osteosarcoma. Lateral
radiograph ( A) an d axial T1-weigh ted magnetic resonan ce
image ( B) of the distal femur sh ow th e classic features of a
primary h igh -grade osteosarcoma with a large mixed lytic
an d sclerotic destructive lesion in volvin g th e distal femoral
metadiaph ysis, with cortical destruction , exten sive malign an t
periosteal n ew bon e formation , an d a large soft-tissue mass.
As seen in ( B) , th e popliteal artery an d vein are displaced but
n ot encased by th e mass.
126 Chapter 11 ■

F igu r e 11.5. Anteroposterior ( left) an d lateral ( right) views

of an osteosarcoma in volvin g th e sh aft of th e femur. Approxi-
mately 10% of osteosarcomas in volve th e sh aft. Th e tumor h as
an aggressive radiographic appearance, with cortical destruc-
tion and periosteal reaction with Codman triangle.

F igu r e 11.6. O steosarcoma formin g a den sely sclerotic mass

in the distal femur.

F igu r e 11.7. Axial ( A) an d two-dimen sion al sagittal ( B) com-

When the osteosarcoma produces calcifying and
ossifying osteoid substance, various degrees of density
are seen within the affected portion of the bone. These
densities often extend into the contiguous soft tissues.
The proliferated bone produced by the neoplastic cells
characteristically has a “cloudlike” appearance and ill-
defi ned margins. Usually, the radiographic diagnosis is
puted tomographic images of the lumbar spine show a large
destructive lytic lesion involving the body and posterior ele-
men ts of th e third lumbar vertebra, with associated cortical
destruction and a soft-tissue mass. Although the lesion is pre-
dominantly lytic, there is suggestion on the axial images of
subtle h azy matrix production with in th e posterior aspect of
the lesion. There is an expansile component to the lesion in
the posterior elements.

F igu r e 11.8. Extensive osteosarcoma involv-
ing almost the entire femur in a 14-year-old girl.
A: Th e patien t was completely asymptomatic
until a pathologic fracture developed. B: The
gross specimen after disarticulation at th e h ip
sh ows th at th e tumor grows from n ear th e
greater troch anter almost down to th e articular
cartilage of th e distal femur.
easily made when destruction of bone is combined with
proliferation of new bone, but defi nitive therapy should
never be initiated without confi rmation by biopsy. Some
osteosarcomas may be deceptively benign-appearing;
some even resemble cysts of bone.
Osteoid substance, even if present in large amounts
as in an osteoblastic osteosarcoma, does not produce
radiodensity if it is completely uncalcifi ed. Generally,
however, a very sclerotic osteosarcoma is usually, but
not necessarily, osteoblastic.
The use of plain radiographs is the most effective
way of localizing and suggesting a diagnosis of osteo-
sarcoma. A radioactive isotope bone scan may be
helpful in demonstrating multicentric osteosarcoma.
Modern imaging techniques, such as computed tomog-
raphy and magnetic resonance imaging, are routinely
used for a preoperative staging study in patients with
■ Osteosarcoma 127
osteosarcoma. With the widespread use of limb-sparing
surgery, accurate pretreatment staging of th ese tumors
has become even more important. McLeod an d Berquist
emphasized that although the use of plain radiographs
is the standard means for diagnosing osteosarcoma,
computed tomograms and magnetic resonance images
are far superior in delineating the extent of the disease.
Computed tomograms may be superior in axial loca-
tions, but magnetic resonance images are superior in
the extremities. Both T1- and T2-weighted sequences are
necessary to accurately delineate the intramedullary and
extraosseous extent of osteosarcomas on magnetic reso-
nance imaging sequences. Normal marrow is “bright” on
T1-weighted images and “dark” on T2-weighted images.
In contrast, osteosarcomas are “dark” on T1-weighted
images and “bright” on T2-weighted images. These con-
trasting signals help to accurately delineate the extent
128 Chapter 11 ■

F igu r e 11.9. O steosarcoma. An teroposterior radiograph

( A) and axial computed tomogram ( B) of the pelvis in a 33-year-
old woman show a mixed lytic and sclerotic destructive lesion
involving the left pubic bone with a large associated unmineral-
ized soft-tissue mass. Axial ( C and D) and coron al ( E) T2-weigh ted
magnetic resonance images show the anatomical extent of the
soft-tissue mass, which has both an intrapelvic and extrapelvic
component. The soft-tissue mass fi lls the left hemipelvis, where it
causes signifi cant mass effect on the bladder and extends along
the pelvic sidewall through the obturator foramen to the adduc-
tor region of the proximal thigh.
 ■ Osteosarcoma 129

F igu r e 11.10. O steoblastic grade 4 osteosarcoma

involving the proximal tibia. A: Anteroposterior radio-
graph shows a tumor with indeterminate fi ndings. B
an d C: Magn etic reson an ce imagin g is h elpful in dem-
onstrating more clearly the aggressive features that
suggest malignancy.

F igu r e 11.11. O steosarcoma formin g a sclerotic mass in

th e patella, a very un common location for osteosarcoma.
130 Chapter 11 ■

F igu r e 11.12. O steosarcoma in volvin g th e proximal tibia

in a young girl. The lesion was associated with hyperphos-
phatemic osteomalacia, as manifested by the widened epi-
physeal plates. This appearan ce ch an ged after the patien t was
treated with chemotherapy.

of the tumor. These images also help in determining

if the neurovascular bundle is involved. Redmond and
coauthors and Gillespy and coauthors also emphasized
the superiority of magnetic resonance imaging studies F igu r e 11.13. Typical gross appearan ce of osteosarcoma
for preoperative staging of osteosarcoma. involving the distal femoral metaphysis. The tumor has
Pulmonary metastasis is sometimes found when the destroyed the epiphyseal plate and extends almost down to
articular cartilage. There is also a soft-tissue mass.
patient fi rst seeks medical advice. Computed tomog-
raphy aids in demonstrating pulmonary metastasis. In
a small percentage of patients, computed tomograms
reveal pulmonary metastasis when plain radiographs
are negative, and they may show more disease th an is
obvious on radiographs.

GROSS PATH OLOGIC FEATU RES

By the time a patient receives defi nitive therapy, the

osteosarcoma has generally breached the cortex. The
extraosseous mass may even completely encircle the
bone. The periosteum presents a barrier that often
becomes greatly distended before it is per forated. Sim-
ilarly, the epiphyseal plate acts as a relative barrier to
F igu r e 11.14. Osteosarcoma arising from the second rib
the growth of osteosarcoma. Cortical destruction that in a 21-year-old woman, who complained of chest pain for
is slight to complete is found at the site of per foration 3 years. Th e tumor extends beyon d th e bone to create a large
( Figs. 11.13 & 11.14) . soft-tissue mass.
 ■ Osteosarcoma 131

Some of the tumors spread in the marrow cavity for

unexpectedly great distances, occasionally beyond the
area visible on the radiograph, and this spread must be
considered during therapy. In nearly all instances, the
extent of marrow involvement is readily apparent grossly
when the bone is sawed longitudinally, and most tumors do
not spread in the marrow beyond their gross extraosseous
limits. Skip areas of medullary involvement are extremely
rare, although Enneking and Kagan stressed their impor-
tance. With modern imaging techniques, the clinician is
unlikely to miss a rare skip metastatic lesion.
Nearly all osteosarcomas have such a prominent
central component that a central origin is logically
assumed. In the Mayo Clinic series, none of the oste-
osarcomas seemed to arise within the cortex. Rarely,
however, highly malign ant tumors were located mainly
outside the bone and involved only the outer portion of
the cortex, fi ndin gs suggestive of a periosteal origin.
As indicated by the radiographic fi ndings, osteosar-
comas vary from extremely soft, fl eshy masses through
a fi rm, fi brous tumor with foci of irregular ossifi cation
an d various amounts of chondroid material to a densely
sclerotic type ( Figs. 11.15–11.17) . Sclerosis, when
present, is invariably most pronounced in the central F igu re 11.16. No gross features suggest that this osteosar-
regions. Nearly all osteosarcomas, however sclerotic, coma has a cartilaginous component. However, the microscopic
features were those of a chondroblastic grade 3 osteosarcoma.

F igu r e 11.15. Fibroblastic grade 4 osteosarcoma involving

the proximal humerus in a 13-year-old boy. The tumor forms
a massive, partially hemorrhagic, and necrotic soft-tissue mass.
Treatment included amputation without adjuvant therapy.
Th e osteosarcoma was cured; h owever, 17 years later an oli-
godendroglioma developed. The patient died 7 years later of
recurrent glioma.
F igu r e 11.17. Amputation specimen after chemotherapy
for an extensive osteosarcoma involving the proximal tibia.
Tumor involves the distal femur and the proximal tibia,
and there are extensive soft-tissue masses. All the tumor was
n ecrotic.
132 Chapter 11 ■
have soft peripheral zones that can be sectioned without
prelimin ary decalcifi cation. Most osteosarcomas have a
soft tissue component by the time a diagnosis is made,
so that the surgeon need not breach the cortex to get
tissue from within the medullary cavity for diagnostic
purposes. Areas of necrosis, cyst formation, telangiecta-
sis, an d hemorrhage are most likely to occur in th e soft
tumors.
Metastasis is predominantly hematogenous, with
the production of pulmonary deposits. Metastasis to
other bones may be early and widespread, suggesting a
multifocal origin of the sarcoma, or delayed and local-
ized, suggesting that a new tumor has developed. In
42 patients in the Mayo Clinic series, more than one
bone was involved with osteosarcoma. Twenty-six of the
42 patients had metachronous osteosarcoma. The inter-
val between the two sarcomas ranged from 9 months to
14 years. The interval was less than 1 year in 5 patients,
between 1 and 2 years in 7, between 2 and 5 years in 9,
between 5 and 10 years in 3, and more than 10 years
in 2. One of the patients had Paget disease, and one
other patient probably had Rothmund-Thomson syn-
drome but the evidence was not conclusive. Five patients
were cured of their tumor; one of these patients died of
bilateral breast carcinoma 15 years later. This patient’s
daughter developed embryonal rhabdomyosarcoma of
the temporal region.
Sixteen patients had synchronous osteosarcoma,
four of whom had multiple skeletal sites of involvement.
Five of the 16 patients had preexisting conditions:
Rothmund-Thomson syndrome ( 1) , Bloom syndrome
( 1) , Li-Fraumeni syndrome ( 1) , Paget disease ( 1) , and
osteopoikilosis ( 1) . Only one patient survived the sarco-
mas, but this patient developed another osteosarcoma
at 10 years and died of that tumor.
Most patients with osteosarcoma receive preopera-
tive chemotherapy. The material sent to the laboratory
usually is a resection specimen rather than an amputa-
tion specimen. However, the handling of the specimen
is essentially the same. At Mayo Clinic, the surgeon usu-
ally sends a specimen of the marrow from the resection
margin so it can be checked on frozen section. The
gross specimen then should be stripped of all extrane-
ous soft tissue, so that only the affected bone and tumor
remain. Raymond and Ayala described the techniques
for the gross examination of postchemotherapy speci-
mens. They attempt to cut the specimen where preop-
erative angiograms suggest the most viable tumor will
be. How many sections of the specimen should be taken
is a question that is still not settled. At Mayo Clinic, we
make one longitudinal section through the middle of
the specimen. Using a band saw, we then obtain a thin
slice of the entire specimen. This specimen is put in
a plastic bag and “photographed” with a xerographic
copier. The copy serves as a template for mapping of
the specimen. The entire slab is decalcifi ed, a process
requiring several days because of cortical bone. After
decalcifi cation is complete, the entire specimen is cut
into blocks and labeled according to the xerographic
fi gure of the gross specimen.
H ISTOPATH OLOGIC FEATU RES
The histopathologic features of osteosarcoma vary
greatly, as mentioned above. Lichtenstein tersely stated
the essential criteria as “( 1) the presence of a frankly sar-
comatous stroma and ( 2) the direct formation of tumor
osteoid and bone by this malignant connective tissue.”
Although osteosarcomas can be divided rather conve-
niently into osteoblastic, chondroblastic, and fi broblastic
groups, depending on the dominant histologic pattern,
it is necessary to be arbitrary in some cases. Occasion-
ally, a highly anaplastic tumor contains no osteoid but
is otherwise so similar to an osteoid-producing tumor
in histologic appearance that it logically must be clas-
sifi ed as an osteoblastic sarcoma. Some such tumors
have features that qualify them to be malignant fi brous
histiocytomas. However, some of these tumors show
production of matrix in foci or occasionally in meta-
static tumors. This problem has been highlighted by
Balance and coauthors, who use the term osteogenic sar-
coma, malignant fi brous histiocytoma subtype. Other tumors
that seem to be nearly pure fi brosarcomas contain foci
of homogeneous, afi brillar, eosinophilic material that
resembles hyalinized collagen. When such foci can-
not be differentiated with certainty from osteoid tis-
sue, the tumor containing these foci is best classifi ed
as fi broblastic osteosarcoma. An occasional fi broblastic
tumor with only questionable osteoid production pro-
duces very sclerotic metastases. The usual member of
this group, however, contains obvious osteoid material
( Figs. 11.18–11.34) .
F igu re 11.18. Osteoblastic grade 4 osteosarcoma. The tumor
contains abundant osteoid intimately associated with anaplastic
tumor cells.
 ■ Osteosarcoma 133

F igu r e 11.21. An example of osteoblastic osteosarcoma

F igu r e 11.19. O steosarcoma with h igh ly atypical spin dle with a hemangiopericytomatous vascular pattern.
cells. Matrix is presen t between th e tumor cells.

Figu re 11.22. Sclerotic osteosarcoma. The tumor has pro-

duced so much matrix that the tumor cells have been markedly
compressed. A diagnostic feature of malignancy is that the tumor
permeates between preexisting trabeculae of medullary bone.

F igu r e 11.23. Typical chondroblastic osteosarcoma. The

cartilage h as malign an t-appearin g cells in lacunae, an d th ere
F igu r e 11.20. Low- ( A) an d h igh - ( B) power views of an is crowding at the periphery of the lobule where sheets of
osteoblastic grade 4 osteosarcoma sh ow a lacelike pattern of spin dle cells are formed. Islan ds of osteoid are seen with in
osteoid production . the cartilage.
134 Chapter 11 ■
F igu r e 11.24. Th is ch on droblastic osteosarcoma con tain s
sh eets of grade 3 cartilage th at merge in to large areas of min -
eralized osteoid.
F igu r e 11.25. An example of ch on droblastic grade 4 oste-
osarcoma con tain in g malign an t cartilage, bon e, an d h igh -
grade spin dle cells.
Approximately 56% of osteosarcomas in the Mayo
Clin ic series can be classifi ed as osteoblastic. Most
common ly in this group, osteoid is present as a fi ne
lacelike n etwork between individual tumor cells. The
tumor cells have obvious features of malignancy, such as
nuclear hyperchromasia and abun dant mitotic activity,
including atypical mitotic f igures. The matrix may
undergo calcifi cation focally ( Figs. 11.18–11.21) . Occa-
sion ally, the matrix is produced in the form of bony
trabeculae rather than osteoid. The trabeculae are usu-
ally th in and anastomosin g. Rarely, th ick, well-formed
bony trabeculae are seen in an oth erwise high-grade
osteosarcoma. Some osteoblastic osteosarcomas are
extremely sclerotic. The sclerosis may be so promin ent
that the tumor cells are not visible. In this instan ce, the
matrix completely fi lls up the marrow cavity and entraps
F igu r e 11.26. Fibroblastic grade 3 osteosarcoma. Irregu-
larly shaped nodules of osteoid are surrounded by malignant
spin dle cells.
F igu r e 11.27. Fibroblastic grade 4 osteosarcoma. Malignant
osteoid production is presen t with in fascicles of atypical spin -
dle cells.
preexisting bony trabeculae. The diagnosis of th ese
extremely sclerotic osteosarcomas may have to be made
only on the basis of permeation an d without iden tifying
malignant cells ( Fig. 11.22) .
Approximately 20% of the osteosarcomas in this series
were classifi ed as chondroblastic osteosarcoma. The cells lie
in lacunae and form lobules. The cytologic features of the
cells in lacunae are very similar to the cytologic features
of spindling tumors seen elsewhere in the neoplasm.
The center of the chondroid lobule frequently has bony
trabeculae that produce a feathery appearance. Toward
the periphery of the lobule, the tumor becomes hyper-
cellular and sheets of spindle cells are seen. Osteoid
matrix is usually present between the tumor cells in
the spindling areas ( Figs. 11.23–11.25) . Occasionally, a
chondroblastic tumor has extensive spindling without

F igu r e 11.28. A: Areas of th is osteoblastic osteosarcoma
involving the transverse process of the fi rst thoracic vertebra
simulate th e appearan ce of osteoblastoma. Th e radiograph ic
images showed the features typical of osteoblastoma. B: How-
ever, obvious cytologic atypia was evident in oth er microscopic
fi elds. C: Destructive permeation of preexistin g trabeculae of
bon e was also presen t.
■ Osteosarcoma 135
F igu r e 11.29. A: At low magn ifi cation , th is osteosarcoma
resembles giant cell tumor because of the presence of sev-
eral multinucleated gian t cells. B: The cytologic atypia that
supports a diagn osis of osteosarcoma is better appreciated at
h igher magnifi cation .
F igu r e 11.30. This osteosarcoma formed a destructive mass
in the ischium in a 53-year-old woman. Histologically, the
tumor h as features th at resemble ch on droblastoma, an d it
invades into surrounding soft tissue.
136 Chapter 11 ■
F igu r e 11.31. Osteosarcoma in the femur in an 11-year-old
boy. Th e epith elioid cytologic features an d clusterin g of th e
tumor cells in this osteosarcoma suggest a diagn osis of meta-
static carcin oma. Th ese h istologic features are particularly dif-
fi cult to in terpret wh en en coun tered in an adult patient.
F igu r e 11.32. An epith elioid-appearin g osteosarcoma
involving the tibia in a 56-year-old man. Immunostains may be
helpful in ruling out metastatic carcinoma.
clear-cut osteoid production. These tumors are logically
classifi ed as chondroblastic osteosarcoma. The lack of
osteoid is assumed to be a function of sampling.
Approximately 24% of the osteosarcomas can be
called fi broblastic osteosarcomas. The tumor cells are
spindle-shaped and may be arranged in a herringbone
pattern. Matrix production is seen only focally. Some
of these fi broblastic osteosarcomas have a rich vascular
pattern and may even resemble a hemangiopericytoma
( Figs. 11.26 & 11.27) .
The above description can be considered to be for
a classic, conventional high-grade osteosarcoma. How-
ever, even in th e group of tumors that can be called con-
ventional osteosarcomas, histologic variations exist.
F igu r e 11.33. Small cell osteosarcoma. Lacelike osteoid pro-
duction is associated with small cells resembling lymphoma or
Ewing sarcoma.
F igu r e 11.34. Small cell osteosarcoma. Th e tumor cells
sh ow more variability in n uclear size an d sh ape th an typically
seen in Ewin g sarcoma.
Many osteosarcomas contain benign giant cells that
have the appearance of osteoclasts. However, this resem-
blance does not create a diagnostic problem unless the
osteosarcoma is so rich in giant cells that the malignant
nature of the tumor may be overlooked ( Fig. 11.29) . The
giant cells may have the confi guration of those in classic
giant cell tumors, and the mononuclear cells may show
only subtle cytologic atypia. Differentiating an osteoclast-
rich osteosarcoma from a true giant cell tumor is one of
the more diffi cult problems in bone tumor pathology.
If one encounters a tumor that has all the features of a
giant cell tumor but occurs in an unusual location, such
as in the metaphysis of a growing child, serious consid-
eration should be given to osteosarcoma. Unfortunately,
 ■ Osteosarcoma 137

however, such osteosarcomas can occur in the end

TABL E 11.1. Types of Osteosarcoma
of the bone and may even have the radiographic fea-
tures of a giant cell tumor. Only 12 tumors in the Mayo Type Number of Cases
Clinic series were considered to be rich in giant cells. As
already mentioned, some osteoblastic sarcomas produce Conventional osteosarcoma 1,449
Others 503
bony trabeculae. These bony trabeculae may be lined by
Osteosarcoma of jaw 137
osteoblasts, simulating the appearance of an osteoblas- Osteosarcoma in Paget disease 61
toma. The term osteoblastoma-like osteosarcoma has been Postradiation osteosarcoma 110
applied to this lesion. Permeation of preexisting bony Osteosarcoma in benign conditions 20
trabeculae and the presence of sheets of cells without Telan giectatic osteosarcoma 67
Low-grade central osteosarcoma 21
matrix production are the two most important charac-
Multicen tric osteosarcoma 42
teristics that help to differentiate an osteosarcoma from Periosteal osteosarcoma 31
an osteoblastoma ( Fig. 11.28) . High-grade sur face osteosarcoma 14
Four of the osteosarcomas in this series had tumor Parosteal osteosarcoma 75
cells with cytologic features of those in chondroblastoma Osteosarcoma in dedifferentiated 78
chondrosarcoma
( Fig. 11.30) . Indeed, one postradiation sarcoma, which
is now classifi ed as an osteosarcoma, was previously clas- Total 2,105
sifi ed as a malignant chondroblastoma. Anoth er tumor,
occurring in a metatarsal of an older man, had benign
radiographic features and was originally misdiagnosed
There is no good rule about how small the tumor cells
as chondroblastoma. The malignant quality of the tumor
have to be for a diagnosis of small cell osteosarcoma to
was recognized only at the time of recurrence. The
be made. Hence, it is diffi cult to obtain exact numbers
third tumor occurred in the spine of an older woman
regarding the prevalence of small cell osteosarcoma. The
and invaded the lung. Chondroblastomas usually have
term was used when the cytologic features suggest Ewing
a loose arrangement of the cells. When the cells form
sarcoma or malignant lymphoma. Only nine tumors
sh eets, a diagnosis of osteosarcoma should be suspected.
were classifi ed as small cell osteosarcoma in this series.
Prominent permeation of preexisting bone also is a wor-
Exuberant callus, especially in some patients with
risome feature. The cytologic atypia is very subtle and
fractures secondary to osteogenesis imper fecta, has been
cannot be depen ded on in making a diagnosis.
mistaken for osteosarcoma. This error can be avoided if
Some osteosarcomas have epithelioid-appearing cells
one insists on cytologic evidence of malignancy in the
( Figs. 11.32 & 11.33) . It is well known that osteoblasts
diagnosis of sarcoma. The orderly maturation in a frac-
may appear epithelioid; hence, epithelioid-appearing
ture callus from cartilage to bone is lacking in osteosar-
osteosarcoma is not surprising. Kramer and coauthors
coma. In addition, the reactive subperiosteal new bone
and Hasegawa and coauthors reported on epithelioid-
in the Codman triangle is nonneoplastic and worthless
appearing osteosarcoma in which the immunohis-
for biopsy. The cells in pseudosarcomatous myositis ossi-
tochemical profi le also showed epithelial differentiation.
fi cans lack anaplasia, even in the zones wh ere mitotic
Glan d formation is un usual in osteosarcoma, but the
figures are numerous; the rather orderly production
osteoblasts may have a rosette confi guration, with pro-
of bone in these lesions, especially peripherally, as they
duction of matrix in the center simulating the appear-
mature also helps one to recognize the benign process.
an ce of glands. Frequently, one sees only sheets of
Osteosarcoma is often considered a diagnosis that
epithelioid cells with pink cytoplasm, vesicular nuclei,
indicates a stereotyped and standard disease with a
an d prominent central nucleoli. Osteoid production
relatively predictable clinical behavior. To the contrary,
may occur only focally. The diagnosis of osteosarcoma
however, any sizable series contains a wide variety of
should be suspected when a biopsy specimen from a
subtypes, each of which has its own, often signifi cantly
bone tumor in a young person has the histologic char-
different, clinical features and prognostic implications.
acteristics of carcinoma. However, such epithelioid oste-
Table 11.1 indicates the varieties that need to be rec-
osarcomas may occur even in older patients, especially
ognized. Some of the features of each are noted in the
in association with dedifferentiated chondrosarcoma.
remarks that follow.
Rarely, an osteosarcoma has extremely small cells
resembling those in Ewing sarcoma or malignant lym-
phoma ( Figs. 11.33 & 11.34) . The cells may be round, OSTEOSARCOMA OF TH E JAWS
oval, or frankly spindle-shaped. The problem is com-
pounded because a fi brin-like material may be seen in Several peculiarities of osteosarcoma of th e jawbon es
Ewing sarcoma. One good rule is to diagnose small cell deser ve special commen t. Th e average age of th e
osteosarcoma only if mineralized osteoid matrix is seen. patients is signifi cantly greater than that of patients
138 Chapter 11 ■
with tumors in conventional sites. In the Mayo Clinic
series, 137 osteosarcomas involved the jawbones. Of
these, 74 affected the maxilla and 63 the mandible
( Figs. 11.35–11.37) . Wh ereas patien ts in th e secon d
decade of life predomin ate in con ven tion al osteo-
sarcoma, patien ts in th e secon d, th ird, an d fourth
decades of life predomin ate in osteosarcoma of th e
jaws. Approximately 50% of osteosarcomas of th e jaws
sh ow ch on droblastic differen tiation ( Figs. 11.38 &
11.39) . O steoid production may be min imal an d dif-
fi cult to recogn ize. In fact, some obser vers believe
th at some of th e ch on droblastic tumors in our series
sh ould be called chondrosarcomas. Th is distin ction may
be of more th an academic in terest. In a recen t study,
Saito an d coauth ors foun d th at, at least in th e sh ort
term, patien ts with ch on drosarcomas of th e jawbon es
do better th an patien ts with osteosarcoma. Th is differ-
en ce is n ot apparen t after 20 years.
Grading by the Broders method indicates that cellu-
lar anaplasia is less evident in osteosarcoma of the jaws.
Approximately half of the tumors are graded 2. One
result is that occasional tumors are differentiated from
benign processes with diffi culty. Regardless of relatively
little anaplasia, chon droid differentiation in a lesion of
the jaws should be viewed with alarm because it is almost
never found in benign processes, exclusive of callus, in
these bones.
F igu r e 11.35. A: Radiograph of a mandible showing a poorly demarcated lesion with destruction
of the cortex. Areas of sclerosis are mixed with areas of lysis. B: Computed tomogram shows a min-
eralizin g mass extending in to soft tissues.
In this series, 14 of the 137 patients had a precursor
lesion. Ten patients had previous radiation, and four
had Paget disease; one of the latter also had fi brous dys-
plasia. Six of the 10 patients with postradiation sarcoma
had radiation for fi brous dysplasia.
Historically, the prognosis for patients with osteosar-
comas of the jaw has been surprisingly good. The over-
all 5-year survival rate in the series reported by Clark
and coauthors was nearly 40%. For patients with radical
surgery initially, the survival was 80%. However, Bertoni
and coauthors, reporting from Bologna, Italy, did not
fi nd that osteosarcoma of the jaws was associated with a
better prognosis.
Hematogenous spread is unusual in osteosarcoma of
the jaw, and in the series reported by Clark and coau-
thors, there were only four documented examples of
pulmonary metastasis. Patients who die do so from
uncontrolled local disease.
Th ere is a ten den cy to group osteosarcomas of th e
skull with th ose of th e jawbon es. H owever, patien ts
with osteosarcoma of th e skull h ave an extremely poor
progn osis. In a series of 21 patien ts reported by Nora
an d oth ers, th ere was on ly on e lon g-term sur vivor.
H owever, H uvos an d coauth ors foun d th at wh ereas
patien ts with secon dary osteosarcoma of th e skull h ad
a poor progn osis, th ose with primary osteosarcoma did
much better.

Figure 11.36. Ch on droblastic osteosarcoma of th e man di-
ble. Th e gross appearan ce suggests cartilage.
F igu r e 11.37. Fibroblastic osteosarcoma of the mandible.
Th ere is destruction of th e root of a tooth .
F igu r e 11.38. Chondroblastic osteosarcoma of the mandi-
ble. H igh -grade malign an t cartilage blen ds in to eosin oph ilic
osteoid an d h yperch romatic oval to spin dle-sh aped stromal
cells.
■ Osteosarcoma 139
F igu r e 11.39. O ccasion ally, ch on droblastic osteosarcomas
of th e jaw bon es are composed predomin ately of cartilagin ous
n odules surrounded by h igh-grade stromal cells without abun -
dan t osteoid. Some pathologists prefer to classify such tumors
as chondrosarcoma.
OSTEOSARCOMA IN PAGET D ISEASE
Sixty-one ( 3.12%) of the 1,952 osteosarcomas were
complications of Paget disease. Although th e humerus
is not commonly involved with Paget disease, 10 of the
pagetic sarcomas arose in the humerus ( Fig. 11.40) .
The ilium was the most commonly involved bone, with
22 examples. Three patients had involvement of the
pubis and 13 of the femur. Six tumors were in the skull
and four in the jawbones ( Fig. 11.41) . Fifty-two of the
seventy-three patients with tumor arising in Paget dis-
ease were older than 60 years. Long-term survival is rare
for patients with this type of sarcoma, but four patients
have survived longer than 10 years.
The exact in ciden ce of sarcoma arising in Paget
disease is un kn own . H owever, it is considered to be
less th an 1%. Fibrosarcoma, chon drosarcoma, an d
even gian t cell tumor can complicate Paget disease,
and this series in cludes 7 fi brosarcomas, 3 malig-
n an t fi brous h istiocytomas, 1 giant cell tumor, and 1
malign an t lymph oma in addition to th e 61 osteosarco-
mas ( Figs. 11.42 & 11.43) .
The prognosis for patients with Paget sarcoma con-
tinues to be poor.
POSTRAD IATION OSTEOSARCOMA
One hundred ten osteosarcomas in this series devel-
oped in bones that had been exposed to radiation.
The total of 179 postradiation sarcomas of bone included
48 fi brosarcomas, 12 malignant fi brous histiocytomas,
5 chondrosarcomas, 2 angiosarcomas, 1 Ewing tumor,
140 Chapter 11 ■

F igu r e 11.40. An teroposterior radiograph ( A) of th e left h umerus an d coron al T2-weigh ted

magn etic reson ance image ( B) sh ow ch an ges of Paget disease in th e humerus that exten d to the
articular sur face of the humeral head. In addition, a large, heavily mineralized destructive lesion
involves a long segment of the mid and proximal humeral diaphysis, with an associated circumfer-
ential soft-tissue mass th at h as exten sive osteoid matrix. The soft-tissue mass has imagin g features
typical of osteosarcoma arising in Paget disease.

F igu re 11.42. Osteoblastic osteosarcoma arising in Paget dis-

F igu r e 11.41. Computed tomogram of th e skull in a 74-year-
old man sh ows marked widen in g of bon e an d osteosarcoma
involving the frontal bone.
ease. The tan-white sarcoma with cystic necrosis broke through
the cortex and extends into soft tissue. The thickened cortical
and medullary bone is a characteristic feature of Paget disease.
( From Unni, K. K. and Inwards, C. Y.: Tumors of the Osteoartic-
ular System. In Fletcher, C. D. M. [ ed] . Diagnostic Histopathol-
ogy of Tumors, ed 3. Philadelphia, PA, Churchill Livingstone
Elsevier, 2007, pp 1593–1652. By permission of Elsevier.)
 ■ Osteosarcoma 141

F igu r e 11.43. Osteoblastic osteosarcoma in vadin g pagetoid

bon e. Th e broad trabeculae an d mosaic pattern of th e pag-
etoid bon e ( left) contrasts with the more delicate complex
pattern of malignant osteoid ( right) .

and 1 malignant lymphoma ( Figs. 11.44 & 11.45) .

The interval between irradiation and the diagnosis of
sarcoma varied from 1 year to 55 years; it was less than
5 years in only 13 patients and more than 20 years in 51
patients. The average interval was 12.9 years. The interval
between radiation and development of the sarcoma in
5-year segments is given in Table 11.2. The conditions for
which radiation had been used are listed in Table 11.3.
In this series of 179 patients, female predominance
was defi nite. Most patients were older, with more than
two-thirds of them 40 years or older. There was also a
tendency for unusual sites to be involved, such as the
clavicle, scapula, ribs, sacrum, and innominate bone.
The location of these tumors in unresectable loca-
tions, such as the skull, clavicle, scapula, and spine,
explains the traditionally poor prognosis. In a study
from Mayo Clinic of 136 patients with postradiation sar-
coma, Inoue and coauthors found that if only tumors
involving the peripheral portions of the skeleton are
included, the prognosis is no different from that of
conventional osteosarcoma. Hence, it is important that
these patients have aggressive treatment.
Figu re 11.44. Postradiation sarcoma involving the humerus
OSTEOSARCOMA IN OTH ER BEN IGN in an 88-year-old woman who received radiation to the area
18 years earlier for lymph oma. A: Plain radiograph sh ows a
CON D ITION S destructive-appearing mixed lytic and sclerotic lesion involv-
ing the head, neck, and proximal shaft of the humerus.
Th e importance of these 20 lesions relative to the 1,952 B: Magnetic resonance image of the shoulder shows a patho-
osteosarcomas is unknown, but it should be noted that logic fracture involving the neck of the humerus. The tumor
2 osteosarcomas arose in osteochondromas ( one had extends into the soft tissue of the axilla.
multiple exostoses) , 4 in lesions of fi brous dysplasia
without a history of radiation, 2 in old infarcts of bone, TELAN GIECTATIC OSTEOSARCOMA
2 in osteomyelitis, and 1 each in Ollier disease, in osteo-
blastoma, and in osteopoikilosis. In one patient, a high- The criteria for diagnosing telangiectatic osteosarcoma
grade osteosarcoma was associated with heterotopic are as follows: one, the radiograph shows a purely lytic
ossifi cation and dermatomyositis. However, it was a soft- lesion ( Fig. 11.46) . Any appreciable sclerosis rules out a
tissue osteosarcoma and is not included in this series. diagnosis of telangiectatic osteosarcoma. However, not
142 Chapter 11 ■

Postradiation Sarcoma:
TABL E 1 1.3. Condition for Which
Radiation Was Given

Condition Number of Cases

Bone lesions
Gian t cell tumor 23
Fibrous dysplasia 12
Bon e tumor, un verifi ed 11
Ewing tumor 6
An eurysmal bon e cyst 3
An giosarcoma 3
Ch ordoma 2
Lymph oma 2
Other 8
Total 70
Soft tissue tumors
Rh abdomyosarcoma 5
Hemangiopericytoma 3
Liposarcoma 3
Malign an t fi brous h istiocytoma 2
Desmoid tumor 1
Fibroxan th oma 1
Total 15
Malignancies of other organs
F igu r e 11.45. Extensive postradiation osteosarcoma involv- Carcin oma of breast 20
ing the pelvis and the proximal femur in a 14-year-old girl. She Malign an t lymph oma 17
had treatmen t for Ewin g sarcoma 5 years earlier. Carcin oma of cervix 12
Brain tumor 9
Uterin e can cer ( in cludes on e 5
Interval Between Radiation and leiomyosarcoma)
TABL E 11 .2 . Others 24
D evelopment of Sarcoma
Total 87
Cases Miscellaneous benign conditions
Number Percentage Birth mark 2
Interval (Years)
Burn scar 1
0–1 1 0.55 “Eosin oph ilic cyst” 1
1–4 12 6.70 Eczema 1
5–9 61 34.07 Pain 1
10–14 29 16.20 Un kn own 1
15–19 25 13.96 Total 7
20–24 20 11.17
25–29 14 7.82
30–34 8 4.46
35–39 1 0.55
40–44 5 2.79
45–49 1 0.55 pleomorphic cells appear in a bloody background with-
50–54 1 0.55 out any pattern. Osteoid production is minimal, and in
“Several years” 1 0.55 rare instances, no osteoid is seen. However, if the tumor
Total 179 99.92 produces septa, it should be classifi ed as a telangiectatic
osteosarcoma if the cells are malignant. Such tumors,
when they metastasize, commonly produce matrix.
Because benign giant cells are always present, they may
all lytic osteosarcomas are telangiectatic. Two, grossly, lead to a mistaken diagnosis of benign or even malig-
the tumor looks like a bag of blood ( Figs. 11.47 & 11.48) . nant giant cell tumor.
Fleshlike tumor tissue or sclerotic sarcoma is not seen. When the criteria above are used for diagnosis,
Three, microscopically, two patterns may be seen. Com- telangiectatic osteosarcoma is a rare subtype in our expe-
monly, spaces are separated by septa, as in aneurysmal rience, accounting for only 3.46% of all osteosarcomas
bone cyst. However, the cells that line the septa are ( Fig. 11.50) . A report from Memorial Sloan-Kettering
cytologically malignant ( Fig. 11.49) . Rarely, only very Cancer Center in New York gave an incidence of 12%.
 ■ Osteosarcoma 143

F igu r e 11.46. Telan giectatic osteosarcoma in volvin g th e

proximal humerus in a 7-year-old girl. A: The small lytic lesion
is confi ned to the bone associated with fracture. B: Seven
weeks later, the purely lytic lesion has completely destroyed
th e bon e, an d th ere is a large soft-tissue mass ( Case provided
by Dr. James R. Thompson , O ran ge, Californ ia.) .

The difference in incidences may be related to different

criteria used for diagnosing the same entity.
In 1976, Matsuno and coauthors reported on
25 patients with telangiectatic osteosarcoma whose
records are in the Mayo Clinic fi les. Of these 25 patients,
23 were dead, 1 was alive with pulmonary and rib metas-
tases, and 1 was a survivor at 76 months. This last patient
died with pulmonary and mediastinal metastases
8.5 years after diagnosis. The patient who was alive with
metastasis is still alive about 25 years after the original
diagn osis. These results have led us to believe that the
prognosis in telangiectatic osteosarcoma is worse than
that for conventional osteosarcoma.
In a study from Memorial Sloan-Kettering Cancer
Center of 124 patients with telangiectatic osteosarcoma,
Huvos and coauthors found no signifi cant difference in
prognosis from that of patients with conventional osteo-
sarcoma. Berton i and coauthors from Bologna, report-
F igu r e 11.47. A: Plain radiograph of a recurren t telan giec-
tatic osteosarcoma of the proximal humerus. Flecks of mineral
are from a previous operation. B: The corresponding gross
specimen sh ows cystic spaces con tain in g blood separated by
delicate septae.
ing on 41 patients with telangiectatic osteosarcoma, also
found no difference in prognosis. Mervak and coauthors
updated the Mayo Clinic experience with telangiectatic
osteosarcoma in 1991. In the patients evaluated at Mayo
Clinic after the previous report, the prognosis was similar
to that of conventional osteosarcoma. Hence, the prog-
nosis in telangiectatic osteosarcoma appears to be the
144 Chapter 11 ■
F igu r e 11.48. Telan giectatic osteosarcoma formin g a cystic
and hemorrhagic mass in the metaphysis of the distal femur.
Th ere is n o eviden ce th at th e tumor h as a solid compon en t.
same as that for conventional osteosarcoma. Indeed, it
appears that telangiectatic osteosarcoma is particularly
sensitive to preoperative chemotherapy and may indeed
be an osteosarcoma with a good prognosis if treated
with chemotherapy. However, it is still important to
recognize the tumor as a special variant because of the
peculiar radiographic, gross, and microscopic features
and the frequency with which it is underdiagnosed.
LOW-GRAD E CEN TRAL
(IN TRAMED U LLARY) OSTEOSARCOMA
O f th e 1,952 osteosarcomas in th e Mayo Clin ic fi les,
21 were very diffi cult to diagn ose because th ey were
so well differen tiated. Ten of th e patien ts were male
an d 11 were female ( Fig. 11.51) , an d th ey ten ded to
be somewh at older th an patien ts with con ven tion al
osteosarcoma. Fifty-two percen t of th e patien ts were in
th e th ird decade of life. Th e distal femur was in volved
in 10 of th ese patien ts an d th e upper tibia in 5. All
tumors in volved th e larger bon es of th e leg or th e pel-
vis. In a study of 80 well-differen tiated osteosarcomas
from Mayo Clin ic, in cludin g th ose in patien ts seen
in con sultation , Kurt an d coauth ors foun d th at 81%
in volved th e lon g tubular bon es. Twelve in volved th e
F igu r e 11.49. Telan giectatic osteosarcoma. A: At low power,
th e lesion can n ot be differen tiated from an an eurysmal bon e
cyst. B: At h igh power, th e pleomorph ic appearan ce of th e
tumor cells with in th e septa is obvious.
fl at bon es, an d th ree were foun d in th e bon es of th e
h an ds an d feet.
The radiographs showed large lesions involving the
metadiasphyseal region of a long bone. Most lesions had
poor margination, a sign of an aggressive process. How-
ever, a fair number had sharp, well-defi ned margins sug-
gestive of a benign lesion. Defi nite cortical destruction
was identifi ed in more than half the cases ( Fig. 11.52) .
Many of the lesions had a trabeculated appearance.
Grossly, low-grade osteosarcoma is generally well
demarcated and lacks the fi sh-fl esh appearance of a
high-grade sarcoma. Rather, it has a fi rm, whorled,
fi brous appearance suggestive of a desmoid tumor of
soft tissues ( Fig. 11.53) .
As the name indicates, low-grade osteosarcoma
consists of spindle cells with little cytologic atypia. Mitotic
fi gures are uncommon. Spindle cells are arranged in an
interlacing pattern and always show permeation of sur-
rounding structures, either fatty marrow or preexisting
 ■ Osteosarcoma 145

F igu r e 11.50. Distribution of

telean giectatic osteosarcomas
according to age and sex of the
patient and site of the lesion.

F igu r e 11.51. Distribution

of low grade osteosarcomas
accordin g to age an d sex of th e
patien t an d site of th e lesion .

bony trabeculae. The matrix produced is frequently in
the pattern of regular bony trabeculae, simulating the
appearance of a parosteal osteosarcoma ( Fig. 11.54 &
11.55) . One-third of the tumors have scanty osteoid and
a desmoid-type appearance. In rare cases, the bone has
the classic “Chinese character” appearance of fi brous
dysplasia.
The prognosis in low-grade osteosarcoma is excel-
lent. Metastasis is rare; however, 4 of the 21 patients had
dedifferentiation at the time of recurrence. Five patients
have died, three of metastatic disease. Two of the patients
with metastatic disease had dedifferentiation.
PERIOSTEAL OSTEOSARCOMA
Among the 1,952 osteosarcomas, 31 fulfi lled the
criteria for what has been termed periosteal osteosarcoma
( Fig. 11.56) . Schajowicz called this tumor juxtacorti-
cal chondrosarcoma, and Jaffe referred to it as cortical
146 Chapter 11 ■

F igu r e 11.52. Low-grade osteosarcoma in a 44-year-old man . A: Plain radiograph sh ows a well-
demarcated lesion with a scalloped appearance. This appearance may suggest a diagnosis of chon-
dromyxoid fi broma. B: Magnetic resonance image shows that the tumor has clearly broken through
the cortex to form a soft-tissue mass ( Case provided by Dr. Anna Elisabeth Stenwig, Institute for
Cancer Research, Oslo, Norway.) .

osteosarcoma. The cortical osteosarcomas described

F igu r e 11.53. Low-grade osteosarcoma extending to the end
of the distal femur. The tumor breaks through the cortex.
by Kyriakos and Vigorita and coauthors are different.
Although chondroid differentiation usually domi-
nates the histologic pattern of these lesions, condensa-
tion of the nuclei at the periphery of the lobules and
production of trabeculae of bone in center of the lobules
support the diagnosis of osteosarcoma. Furthermore,
typical spicules of new bone, sometimes numerous, are
nearly always found near the underlying cortex. Any
tumor of this type involving cancellous bone beneath
the extraosseous mass has been excluded because of its
similarity to the remainder of the chondroblastic osteo-
sarcomas; it then merges into the overall spectrum of
that disease. Whether periosteal osteosarcoma begins in
the periosteum or in the outer portion of the cortex is
not known, but its appearance suggests that th e term
periosteal osteosarcoma is appropriate.
The slightly greater than 1.5% incidence of this tumor
indicates its rarity in the Mayo Clinic experience. There
was a distinct female predominance in this small group.
The skeletal and age distribution are similar to those of
conventional osteosarcoma except for the tendency of
the tumor to involve the diaphysis of the femur and the
tibia. The most common location was the midportion of
the femur, followed by the midportion of the tibia.

F igu r e 11.54. Grade 1 fi broblastic osteosarcoma. The tumor in volved th e distal femoral meta-
physis and epiphysis with focal areas of cortical destruction. A: At low-power, the pattern of bone
formation is similar to that seen in parosteal osteosarcoma. B: H igh magnifi cation highlights the
lack of signifi cant cytologic atypia.
F igu r e 11.55. Grade 1 central fi broblastic osteosarcoma
exten ding in to surroun din g soft tissue.
The radiographic appearance of periosteal osteosar-
coma is virtually diagnostic. The lesion is radiolucent,
havin g a sunburst appearance merging into the sur-
rounding soft tissues. The lesion appears to be situated
in a saucer-shaped depression in the cortex, but the
endosteal aspect is uninvolved ( Figs. 11.57–11.59) .
Grossly, th e tumor is lobulated an d h as a ch on droid
appearan ce ( Figs. 11.60 & 11.61) . Microscopically,
periosteal osteosarcoma is a moderately differen tiated
ch on droblastic osteosarcoma. Th e appearan ce is very
similar to th at of oth er ch on droblastic osteosarcomas
of th e skeleton . Th e cartilage appears to be in lobules,
an d th ere is con den sation an d spin dlin g of cells at th e
periph ery of th e lobules ( Figs. 11.62 & 11.63) . Very typ-
ically, well-formed bon y trabeculae are seen in th e cen -
■ Osteosarcoma 147
ter of th e lobules an d give rise to a feath ery appearan ce
un der low power. A very pleomorph ic tumor ( grade 4
accordin g to Broders meth od of gradin g) n egates th e
diagn osis of periosteal osteosarcoma.
Of the 31 patients recorded in the Mayo Clinic fi les,
10 have died: 5 of tumor and 5 of other causes. Seven-
teen patients are alive, from 4.10 to 32.5 years. ( Two
other patients had no follow-up and another two are
recent patients without follow-up.) The prognosis in
periosteal osteosarcoma appears to be excellent with
surgical therapy alone.
H IGH -GRAD E SU RFACE
OSTEOSARCOMA
Very rarely, a h igh ly an aplastic osteosarcoma occurs
predomin an tly on th e sur face of a bon e. Th is tumor
h as to be differen tiated from th e very well-differen ti-
ated parosteal osteosarcoma an d th e moderately dif-
feren tiated periosteal osteosarcoma. Fourteen of th e
1,952 osteosarcomas were con sidered to belon g to
th is group of tumors ( Fig. 11.64) . Th ere was a defi -
n ite male predomin an ce, an d most patien ts were in
th e secon d decade of life. Th e distal femur was th e
most common ly in volved bon e. Radiograph s usually
sh ow th e tumor con fi n ed to th e sur face of th e bon e.
Th e lesion s are poorly defi n ed an d suggest malig-
n an cy. Frequen tly, h owever, th e appearan ce is similar
to th at of periosteal osteosarcoma ( Figs. 11.65–11.67) .
Some of th ese tumors h ave microscopic foci of med-
ullary in volvemen t. H owever, large areas of medullary
tumor are again st th e diagn osis of h igh -grade sur face
osteosarcoma. Ten of th e 14 patien ts h ave died of th e
148 Chapter 11 ■

F igu r e 11.56. Distribution of periosteal osteosarcoma according to age and sex of the patient
and site of the lesion.

F igu r e 11.57. Periosteal osteosarcoma involving the proxi-

mal femoral sh aft is min eralized more h eavily th an usual. Th e
sun burst pattern is apparen t. Th e medullary cavity appears to
be un in volved.
 ■ Osteosarcoma 149

F igu r e 11.58. Periosteal osteosarcoma of the proximal tibia in an

11-year-old girl. A: Anteroposterior radiograph shows a subtle defect on
the periosteal sur face of the proximal tibia. B an d C: Coronal an d axial
T1-weigh ted images better defi n e th e soft-tissue mass an d con fi rm th e
lack of intramedullary involvement.

Figure 11.59. A: Anteroposterior radio-

graph of the proximal tibia in an 11-year-old
girl sh ows a min eralized mass in volvin g
th e sur face of th e proximal tibial diaph ysis
medially th at is associated with malign an t
periosteal n ew bon e formation in feriorly
in th e form of a Codman trian gle. Th e
mass is min eralized more h eavily n ear th e
base, with an ill-defi n ed spiculated margin
periph erally. B: Axial T2-weigh ted magn etic
reson an ce image confi rms that th e lesion is
sur face based, with n o sign ifi can t medullary
in volvemen t. Th ese imagin g fi n din gs could
be foun d in a periosteal or h igh -grade sur-
face osteosarcoma.
150 Chapter 11 ■

F igu r e 11.60. Periosteal osteosarcoma in volvin g a typical

site, th e proximal femoral sh aft, in a 30-year-old woman .

F igu r e 11.62. Periosteal osteosarcoma. A: Low-power

appearance of chondroblastic osteosarcoma shows lobules
of cartilage with periph eral con den sation an d spin dlin g
of tumor cells. B: Th is example con tain s partially calcifi ed
osteoid an d spin dle cells periph erally.

disease, from 10 mon th s to 3.3 years after treatmen t.

Four patien ts are alive 2, 17, 26, an d 30 years after
treatmen t. Th ese data suggest th at th e progn osis for
h igh -grade osteosarcoma of th e sur face of bon e is simi-
lar to th at of con ven tion al osteosarcoma.

D ED IFFEREN TIATED
CH ON D ROSARCOMA

This subject is discussed in Chapter 6.

TREATMEN T AN D PROGN OSIS—ALL

OSTEOSARCOMAS

F igu r e 11.61. Periosteal osteosarcoma formin g a broad- Th e prin ciples of treatmen t of osteosarcoma h ave
based attach men t to th e sur face to th e bon e. Th ere is n o evi- un dergon e dramatic ch an ges in th e past 20 years. Un til
dence of medullary involvement. recen tly, 5-year sur vival of 20% with surgical treatmen t
 ■ Osteosarcoma 151

F igu re 11.63. Periosteal osteosarcoma. A: High-power view of chondroblastic grade 3 lesion with
obvious cytologic atypia of the cartilaginous component. B: The spindle cell component of this chon-
droblastic osteosarcoma contains myxoid change.

F igu r e 11.64. Distribution of high-grade sur face osteosarcoma according to age and sex of
the patient and site of the lesion.

alon e was con sidered acceptable. Th is outcome
suggested th at 80% of th e patien ts h ad pulmon ary
metastasis ( perh aps un detectable) at th e time of pre-
sen tation . H en ce, it follows th at refi n emen t of th e
surgical treatmen t of osteosarcoma will h ave little, if
an y, effect on improvin g sur vival in patien ts with oste-
osarcoma. Th e adven t of ch emoth erapy h as improved
th e progn osis con siderably, an d perh aps 75% of th e
patien ts can be expected to be lon g-term sur vivors.
Th e use of preoperative ch emoth erapy h as also led to
th e use of more limb-sparin g surgery in patien ts with
osteosarcoma ( Fig. 11.68) . O rth opedic on cologists
believe th at a margin th at is con sidered in adequate
un der oth er circumstan ces may be suffi cien t if th e
patien t h as been treated with preoperative ch emo-
th erapy. Simon an d coauth ors an d Sprin gfi eld an d
coauth ors reported th at limb-salvage surger y did n ot
adversely affect progn osis.
Curren tly, most specimen s received in th e surgical
path ology laboratory are altered by preoperative
152 Chapter 11 ■

F igu r e 11.65. H igh -grade sur face osteosarcoma in volvin g

th e sh aft of th e radius in a 14-year-old boy. Th e radiograph ic
appearance is that of a benign process. The patient had pul-
mon ary metastasis at th e time of presen tation ( Case provided
by Dr. Mich ael Klin e, Moun t Sin ai H ospital, New York City,
New York.) .

ch emoth erapy. Th e surgical path ologist is expected

to provide an accurate assessmen t of th e n ecrosis
apparen tly caused by ch emoth erapy, because th is in for-
mation h as been con sidered to be of great progn os-
tic sign ifi can ce. As in dicated above, th ere is n o good
rule for h ow much of th e tumor h as to be examin ed
microscopically. At Mayo Clin ic, h owever, we routin ely
examin e on e en tire slab of th e tumor. Th e effect of
ch emoth erapy is usually man ifested by marked scle-
rosis of th e bon e with wh at Raymon d an d Ayala h ave
called cell dropout. Th e en tire tumor may be replaced
with den se bon e with out tumor cells between th e bon y
trabeculae. Less common ly, on e may fi n d coagulative
n ecrosis of th e tumor. Ch on droblastic osteosarcomas
are gen erally con sidered to be more resistan t to th e
effect of ch emoth erapy. Th e tumor may disappear
completely an d may be replaced by gran ulation tissue.
Un der th ese circumstan ces, th e estimation of tumor
n ecrosis is fairly straigh tfor ward. In man y in stan ces, F igu r e 11.66. Sur face osteosarcoma of th e proximal
h owever, th is estimation is n ot clear-cut. O n e fi n ds h umerus in a 20-year-old man . A: Th e lesion is h eavily min -
eralized an d surroun ds th e in volved bon e. B: Magn etic reso-
occasion al bizarre cells with in th e matrix, an d it is dif- n an ce imagin g sh ows th at th e tumor surroun ds th e h umerus
fi cult to kn ow wh eth er th ese tumors are viable. It is but does n ot in volve th e medullar y cavity ( Case provided
also diffi cult to kn ow wh eth er an en tire area wh ere by Dr. Suzan n e Span ier, Un iversity of Florida, Gain esville,
tumor cells are foun d sh ould be con sidered viable or Florida.) .
wh eth er on e sh ould try to calculate th e area occupied
by th ese viable cells alon e. Despite th ese limitation s, it
 ■ Osteosarcoma 153

F igu r e 11.67. H igh -grade sur face osteosarcoma in volvin g

th e femoral sh aft in a 16-year-old boy.

is importan t to try to quan tify th e amoun t of n ecrosis

because th is calculation may h ave sign ifi can t progn os-
tic an d th erapeutic implication s ( Fig. 11.69) .
The 5-year survival rate for the 408 eligible patients
reported from Mayo Clinic by Dahlin and Coventry in
1967 was 20.3%, and the 10-year rate for 359 patients
was 17.3%. In that study, the prognosis for patients
with tumors in the tibia was almost twice as good as
the prognosis for patients with tumors in th e femur.
Current survival rates for patients with tumors of the
extremities treated with neoadjuvant chemotherapy
have been reported to range from 45% to 80%. Patients
with tumors involving the axial skeleton have a poorer
prognosis.
Several studies h ave tried to an alyze progn ostic fac- F igu r e 11.68. A: Magn etic reson an ce image of an osteo-
tors in osteosarcoma. Taylor an d coauth ors reported sarcoma th at in volved th e proximal h umerus at diagn osis.
B: Magnetic resonance image after completion of neoadju-
on 336 patien ts with con ven tion al osteosarcoma eval-
van t ch emoth erapy. Th e marked reduction in th e size of th e
uated at Mayo Clin ic from 1963 th rough 1981. Th ey tumor made it easier for th e surgeon to resect th e tumor.
foun d several un favorable ch aracteristics, such as
youn g age, large tumor, location toward th e cen ter ph osph atase levels, site, an d poor respon se to ch emo-
of th e body, sh ort period of symptoms, an d male sex. th erapy suggested a poor progn osis. Th e un favorable
Th ey also foun d th at patien ts with th e osteoblastic an d progn osis associated with h igh alkalin e ph osph atase
ch on droblastic h istologic pattern s h ad a worse progn o- values was also corroborated by Bacci an d coauth ors
sis. Un expectedly, th ey also foun d th at with th e same from Bologn a. In a study from Den mark, Ben tzen an d
treatmen t, sur vival h as greatly in creased sin ce 1969. coauth ors foun d th at youn g age an d old age, sh ort
H owever, in a study from Memorial Sloan -Ketterin g period of symptoms, an d location all were associated
Can cer Cen ter, Meyers an d coauth ors foun d th at age with a differen t progn osis. Taylor an d coauth ors, in a
an d sex did n ot affect progn osis but th at h igh alkalin e multi-in stitution al study, foun d th at site, size, grade,
154 Chapter 11 ■

F igu r e 11.69. Low- ( A) and high- ( B) power views

sh ow 100% n ecrosis of th e osteosarcoma after ch emo-
th erapy. Th ere are n o viable tumor cells with in th e
osteoid or stromal compon en ts of th e tumor. C: A few
viable pleomorphic tumor cells with in an area of fi bro-
sis h ave been affected by ch emoth erapy, but th ey are
n ot completely necrotic.

morph ology, duration of symptoms, an d weigh t loss all
were associated with a differen ce in progn osis. H ow-
ever, they found that treatment did n ot affect prognosis.
Mankin an d coauthors, in a study of 648 patients with
osteosarcoma treated at Massachusetts General Hospi-
tal, found that the Muskuloskeletal Tumor Society stage
of th e tumor, the chemotherapy, anatomic location,
presence of metastasis, and percentage of tumor necro-
sis after n eoadjuvant ch emoth erapy all had an effect on
outcome. Björnsson and coauthors studied th e effect
of spon taneous tumor necrosis on prognosis in osteo-
sarcoma and foun d th at all patien ts whose tumors had
more than 20% n ecrosis died of tumor.
As indicated above, different studies have suggested
that several factors have prognostic signifi cance in osteo-
sarcoma. It is now generally accepted that response to
chemotherapy is the single most important prognostic
criterion in osteosarcoma. However, this conclusion
should be considered in the context of previous studies.
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1993 Bacci, G., Picci, P., Ferrari, S., Orlandi, M., Ruggieri, P., Cas-
adei, R., Ferraro, A., Biagini, R., and Battistini, A.: Progn ostic
Signifi cance of Serum Alkanline Phosphatase Measurements
in Patients With Osteosarcoma Treated With Adjuvan t or Neo-
adjuvant Ch emotherapy. Can cer, 71:1224–1230.
1993 Björnsson, J., Inwards, C. Y., Wold, L. E., Sim, F. H., and
Taylor, W. F.: Prognostic Significance of Spontaneous Tumour
Necrosis in Osteosarcoma. Virch ows Arch A path ol An at H is-
topath ol, 423:195–199.
1993 H asegawa T, Shibata, T., Hirose, T., Seki, K., and Hizawa,
K.: Osteosarcoma With Epith elioid Features: An Immun oh is-
tochemical Study. Arch Path ol Lab Med, 177:295–298.
■ Osteosarcoma 157
1993 Kramer, K., Hicks, D. G., Palis, J., Rosier, R. N., Oppen-
heimer, J., Fallon , M. D., an d Coh en , H. J.: Epith elioid Osteo-
sarcoma of Bon e: Immun ocytoch emical Eviden ce Suggestin g
Divergen t Epith elial an d Mesen ch ymal Differen tiation in a
Primary Osseous Neoplasm. Can cer, 71( 10) :2977-2982.
1993 Okada, K., Wold, L. E., Beabout, J. W., and Shives, T. C.:
Osteosarcoma of the Hand: A Clinicopathological Study of 12
Cases. Can cer, 72:719–725.
1994 Davis, A. M., Bell, R. S., and Goodwin , P. J.: Progn ostic
Factors in Osteosarcoma: A Critical Review. J Clin On col, 12:
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1994 Ruggieri, P., Sim, F. H., Bond, J. R., and Unni, K. K.: Malig-
nan cies in Fibrous Dysplasia. Can cer, 73:1411–1424.
1996 Onikul, E., Fletcher, B. D., Parham, D. M., and Chen, G.:
Accuracy of MR Imagin g for Estimatin g In traosseous Exten t of
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1999 Okada, K., Unni, K. K., Swee, R. G., and Sim, F. H.: High
Grade Sur face O steosarcoma: A Clin icopath ologic Study of 46
Cases. Can cer, 85:1044–1054.
2000 In oue, Y. Z., Frassica, F. J., Sim, F. H., Un ni, K. K., Petersen ,
I. A., an d McLeod, R. A.: Clin icopath ologic Features an d Treat-
men t of Postirradiation Sarcoma of Bon e an d Soft Tissue.
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2002 Bielack, S. S., Kempf-Bielack, B., Delling, G., Exner, G. U.,
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 C H APT ER
12
Parosteal Osteosarcoma
(Juxtacortical Osteosarcoma)
Parosteal osteosarcoma is considered separately from
the rest of the osteosarcomas because it is distinctly less
malignant and, therefore, has a vastly different clinical
behavior. As the name implies, this tumor is located on
the outer sur face of the cortex of a bone, and some pre-
fer to call it juxtacortical osteosarcoma. The validity of the
concept of parosteal osteosarcoma as a distinct clinico-
pathologic entity demands that the tumor be well dif-
ferentiated ( low grade by Broders method) and that it
arise on the sur face of bone. Although occasional typical
cases had been documented in the literature, it was not
until the description of a collected series by Geschickter
and Copeland in 1951 that the entity was established.
Gradations exist from the even more uncommon com-
pletely benign parosteal osteoma through the lesion
with min imal evidence of malignancy to the frankly
malignant but fairly well-differentiated parosteal tumor.
When the diagnosis of sarcoma depends on such subtle
changes as are found in some of these tumors, the prob-
lem is often diffi cult.
Osteogenic tumors of a high degree of malignancy
histologically ( i.e., of high grade by the method of
Broders) are occasionally seen predominantly on the
sur face of a bone, but they do not belong in the cat-
egory under discussion. Inclusion of tumors that are
h istologically like th e ordin ar y osteosarcom a or fi b-
rosarcom a will decrease th e usefuln ess of th e term
parosteal osteosarcoma. Th ese h igh -grade sur face osteo-
sarcom as are discussed in Ch apter 11. Periosteal
osteosarcoma, as described in Chapter 11, is distinctly
different from parosteal osteosarcoma radiographically
and histologically.
Ah uja and coauthors and, more recently, Ritsch l and
coauthors have tended to consider all sur face osteosar-
comas to be parosteal and have distinguished them by
the histologic grade. All authors agree that sarcomas
with a high-grade malignancy have a much worse prog-
nosis than is seen with classic parosteal osteosarcoma.
158
Campanacci and coauthors from Bologna, Italy, also
considered all sur face osteosarcomas to be parosteal,
and they graded them and showed prognostic signifi -
cance of grading. Schajowicz and coauthors agreed with
the concept that has been used at Mayo Clinic an d have
divided the sur face tumors into parosteal, periosteal,
and high-grade sur face type. The terminology used is
probably not important so long as the clinical signifi -
cance of the different types is recognized. We believe
that it is best to reserve the term parosteal osteosarcoma
for the well-differentiated variety.
Some very rare, extremely well-differentiated osteo-
sarcomas begin within bone. These low-grade central
( intramedullary) osteosarcomas are described in
Chapter 11. Reference to the radiograph or to the
gross specimen is required in differentiating them from
parosteal osteosarcomas. In a rare case, it may be diffi -
cult or impossible to know whether a low-grade sarcoma
started as a parosteal osteosarcoma and invaded bone
or was a low-grade intramedullary osteosarcoma from
inception. This question is of only academic interest
because the prognosis in either case is excellent.
IN CID EN CE
Parosteal osteosarcoma is a distinctly rare neoplasm,
comprising just over 1% of malignant tumors in our
series and just 3.7% of all osteosarcomas ( Fig. 12.1) .
SEX
In this series, approximately 63% of the patients with
parosteal osteosarcomas were females, although males
have predominated in some series. Of the 1,952 patients
with other types of osteosarcomas in the Mayo Clinic
series, approximately 58% were males.

F igu re 12.1. Distribution of
parosteal osteosarcomas accord-
ing to age and sex of the patient
and site of the lesion.
AGE
The average age of patients with this tumor is greater
than that of those with ordinary osteosarcoma, a dif-
ference that can be explained, at least in part, by the
slow growth of parosteal osteosarcoma. Approximately
two-thirds of all patients were in the third an d fourth
decades of life. No patient was in the fi rst decade of life
or older than 55 years.
LOCALIZATION
Practically all the recorded parosteal osteosarcomas have
involved the femur, the humerus, or the tibia. Other
bones, however, may be affected. By far, the most common
site for its development is the posterior distal portion of
the shaft of the femur, accounting for approximately two-
thirds of all the cases in the Mayo Clinic files. In a large
series of parosteal osteosarcomas reported by Okada and
coauthors, there were rare tumors in unusual sites such as
the mandible, the clavicle, and the tarsal bones. When the
tumor involves a small or fl at bone, it may be impossible to
know whether the tumor is truly on the surface of bone.
SYMPTOMS
Swellin g is th e most importan t symptom. Frequen tly,
th e swelling is pain less an d may h ave been presen t for
several years. Because of th e location in th e popliteal
■ Parosteal Osteosarcoma ( Juxtacortical Osteosarcoma) 159
fossa, th e patien t may n ote in ability to fl ex th e kn ee.
Pain is th e secon d most importan t symptom, an d
patien ts may presen t with pain with out h avin g n oted
a lump.
A common and practically pathognomonic his-
tory is as follows: several years previously, the patient
underwent excision of a tumor that had been consid-
ered, radiographically, to be atypical osteochondroma.
The pathologists regarded it as an unusual osteochon-
droma and perhaps described it as being cellular. In
the interim, the tumor may or may not have required
excision because of recurrences. When seen now, the
patient has a recurrent, ossifi ed, juxtacortical mass in
one of the sites of predilection.
PH YSICAL FIN D IN GS
A mass at the lesional site, which is sometimes painful
to pressure, is the only signifi cant physical fi nding. The
mass may be very large.
RAD IOGRAPH IC FEATU RES
Parosteal osteosarcoma h as a pron oun ced ten den cy
to in volve th e posterior aspect of th e distal femoral
sh aft. Th e majority of th e tumors in volve th e meta-
ph ysis or metadiaph yseal region . H owever, a sm all
percen tage of tum ors in volves on ly th e diaph ysis of a
lon g bon e.
160 Chapter 12 ■
F igu r e 12.2. An teroposterior ( A) radiograph an d computed
tomogram ( B) of a dedifferen tiated parosteal osteosarcoma
involving the distal femur in a 43-year-old man.
The tumor tends to be densely mineralized and the
predominant pattern is amorphous, but occasionally, the
tumor may show osseous trabeculation. The lesion tends
to be lobulated at the periphery, and the outermost
F igu r e 12.3. Large dedifferen tiated parosteal osteosarcoma
in volvin g th e proximal h umerus in a 24-year-old man . Much
of th e lesion h as th e typical den sely min eralized, lobulated
appearan ce of a parosteal osteosarcoma. H owever, an area
of lytic destruction in th e proximal h umerus is typical of
h igh -grade sarcoma ( Case provided by Dr. Fran co Berton i,
Bologn a, Italy.) .
portions generally are the least mineralized. However,
lucencies may be seen within the substance of the lesion
also. Bertoni and coauthors compared the radiographs
with macrosections of a series of parosteal osteosarcoma.
Their study indicated that the presence of lucency within
the substance of the lesion is closely associated with areas
of dedifferentiation ( Figs. 12.2 & 12.3) .
Th e lesion is attach ed to th e un derlyin g cortex with
a broad base. As th e lesion en larges, it ten ds to grow
periph erally an d, h en ce, n ot attach to th e un derly-
in g cortex. Th is usually gives rise to a lucen t zon e
between th e growin g tumor an d th e un derlyin g bon e.
Parosteal osteosarcoma h as a remarkable ten den cy
to en circle th e un derlyin g bon e. Th e presen ce of a
 ■ Parosteal Osteosarcoma ( Juxtacortical Osteosarcoma) 161

F igu r e 12.4. Parosteal osteosarcoma involving the distal femur in a 41-year-old man. Anteropos-
terior ( A) and lateral ( B) radiographs suggest that this is a sur face tumor. C and D: Magnetic reso-
nan ce imaging con fi rms th at th ere is n o in volvement of the medullary can al.

ver y h eavily ossifi ed mass en circlin g a bon e may make
it diffi cult to kn ow th e exact site of origin . Cross-sec-
tion al imagin g is ver y h elpful in th ese sur face lesion s
( Figs. 12.4 –12.7) .
In the study by Okada and coauthors, the underlying
cortex was considered to be normal in approximately
50% of the cases. In approximately 25%, the cortex was
thickened, and in the rest, it was destroyed.
Parosteal osteosarcoma is considered to be a tumor of
the sur face of bone. However, the tumor can and does
invade the medullary cavity. Medullary involvement
is most clearly shown on computed tomography and
magnetic resonance imaging. In the study by Okada
and coauthors, 22% of the 37 patients who had cross-
sectional studies showed medullary involvement. This
medullary involvement was usually slight, and at most,
the involvement was no more than 25% of the width of
the medullary cavity.
Th e radiograph is importan t in th e differen tial
diagn osis. Th e h eterotopic bon e seen in myositis
162 Chapter 12 ■

F igu r e 12.5. Large parosteal osteosarcoma in th e

most common location, the distal femur, in a 21-year-
old man. A: The lesion is attached to the underlying
bone with a broad base and has a lobulated appearance.
B: Cross-sectional magnetic resonance image shows lack
of involvement of the marrow by the neoplasm( Case
provided by Dr. Jordan L. Mann , Memorial Medical
Cen ter, Sprin gfi eld, Illinois.) .

F igu r e 12.6. Parosteal osteosarcoma in the most common location, the posterior aspect of the
distal femoral metaphysis, in a 37-year-old woman. Anteroposterior ( A) and lateral ( B) radiographs
sh ow a large, h eavily min eralized mass in th e distal femur. It is n ot clear from th e plain radiograph s
whether the tumor arises from within the bone or on the sur face. C: Axial T2-weighted magnetic
reson ance image with fat saturation clearly demonstrates that th is is a sur face lesion an d there is no
intramedullary involvement.

F igu r e 12.7. An teroposterior ( A) an d lateral ( B) radiograph s of a parosteal osteosarcoma arisin g
in th e distal radius, a less common location for this tumor. C: Computed tomography sh ows lack of
intramedullary involvement.
ossifi can s gen erally sh ows a well-organ ized an d clear-
cut trabecular pattern , usually most pron oun ced in th e
periph eral portion of th e lesion , in con trast to wh at is
seen in parosteal osteosarcoma. Alth ough th e lesion of
myositis ossifi can s may abut a bon e an d may overlap it
wh en seen on ly on on e radiograph ic projection , care-
ful study, especially with cross-section al images, sh ows
th at it does n ot h ave broad-based attach men t to th e
cortex, as seen in parosteal osteosarcoma. O steoch on -
droma ( osteocartilagin ous exostosis) ordin arily can be
differen tiated radiograph ically from parosteal osteo-
sarcoma with assuran ce on th e basis of radiograph ic
fi n din gs. Th e con tin uity of th e bon y cortex with th e
pedun culated or sessile base of an osteoch on droma, as
well as th e con tin uity of th e can cellous bon e with th e
core of an osteoch on droma, is absen t in a parosteal
osteosarcoma. O ccasion ally, a con ven tion al h igh -grade
osteosarcoma with a large soft-tissue mass may simulate
th e appearan ce of a parosteal osteosarcoma. H owever,
th e exten sive in volvemen t of th e marrow, th e pres-
en ce of Codman trian gle, an d exten sive destruction
of th e cortex all are again st a diagn osis of parosteal
osteosarcoma. A ben ign parosteal osteoma, wh ich is
much less common th an th e malign an t coun terpart
un der discussion , may be impossible to differen tiate
radiograph ically. Th is fact is n ot un expected wh en on e
realizes th at th e differen tiation is so subtle th at it can
■ Parosteal Osteosarcoma ( Juxtacortical Osteosarcoma) 163
sometimes be made with n o real assuran ce, even by th e
h istopath ologist.
The radiographic features are usually so characteris-
tic that the correct diagnosis of parosteal osteosarcoma,
especially in advanced disease, is practically certain on
this basis alone.
GROSS PATH OLOGIC FEATU RES
Parosteal osteosarcoma tends to be a very heavily ossi-
fi ed, hard, white, somewhat lobulated mass. The lesion
is usually attached to the underlying cortex, which may
be thickened ( Figs. 12.8–12.10) . The outer aspect may
show plates of cartilage, which may have the appearance
of that seen in an osteochondroma. Islands of cartilage
may be seen within the substance of the tumor also. The
outer aspect of the tumor is frequently softer and may
merge into surrounding skeletal muscle. Gross evidence
of medullary involvement was seen in 16 tumors, and
3 others had only microscopic evidence of medullary
involvement ( Figs. 12.9–12.12) .
Although most parosteal osteosarcomas are heavily
ossifi ed, others may show dense fi brous tissue. Fleshy ( sar-
comatous) areas should not be seen in parosteal osteo-
sarcoma. If they are seen, dedifferentiation has probably
taken place. Such areas should be sampled carefully.
164 Chapter 12 ■

F igu r e 12.9. Grade 2 parosteal osteosarcoma in volvin g th e

distal femur. The tumor has the “fi brous” appearance of a
low-grade sarcoma ( Case provided by Dr. Rebecca C. Hankin,
William Beaumont Hospital, Royal Oak, Michigan .) .

F igu r e 12.8. Radiograph ( A) an d gross ( B) specimen of a

parosteal osteosarcoma of the distal femur. The gray-white
areas in the gross specimen represent cartilage, and the darker
areas represent the trabeculae of bone and fi brous tissue.

The presence of a cartilage cap may cause confusion

with an osteochondroma. Osteochondromas show mar-
row between the bony trabeculae, whereas fi brous tis-
sue is present in parosteal osteosarcoma. Myositis ossi-
fi cans is well circumscribed and is not attached to the
underlying bone.
F igu r e 12.10. Grade 1 parosteal osteosarcoma involving the
distal femur. The tumor forms a broad-based attach ment with
the underlying bone.

F igu r e 12.11. Large dedifferen tiated parosteal
osteosarcoma involvin g th e distal femur in a
21-year-old woman. The lesion had been excised
6 years previously, at wh ich time th e diagn osis was
classic parosteal osteosarcoma. Pulmon ary metas-
tasis developed 6 years after this amputation.
F igu r e 12.12. Dedifferen tiated parosteal osteosarcoma sur-
roun ding the femoral sh aft in a 30-year-old man. Th e patient
had pulmon ary metastatic lesion s ( Case provided by Dr. Real
Legace, L’H otel Dieu de Quebec, Quebec, Can ada.) .
H ISTOPATH OLOGIC FEATU RES
Th e most promin en t feature of parosteal osteosarcoma
is its compon en t of rath er regularly arran ged osseous
trabeculae. Apparen tly, th e more immature trabeculae
un dergo maturation in th is slowly developin g tumor
an d become “n ormalized.” Between th ese n early n or-
mal trabeculae are sligh tly atypical, proliferatin g spin -
dle cells in wh ich on ly occasion al mitotic fi gures are
foun d. Th e cellular proliferation is h ypocellular, with
■ Parosteal Osteosarcoma ( Juxtacortical Osteosarcoma) 165
F igu r e 12.13. Typical low-power appearance of parosteal
osteosarcoma. Relatively well-developed tumor bon e trabecu-
lae are surrounded by hypocellular spindle cell stroma.
abun dan t collagen between in dividual tumor cells. Th e
spin dle cells on ly sh ow sligh t cytologic atypia, an d on
th e basis of n uclear ch aracteristics, the tumor would
be grade 1 ( Figs. 12.13–12.16) . Th e periph ery of th e
lesion usually sh ows more spin dle cell proliferation
with out matrix production an d th e cells ten d to per-
meate surroun din g skeletal muscle. A small n umber of
lesion s h ave th e clin ical, gross, an d radiograph ic fea-
tures of parosteal osteosarcoma but sh ow somewh at
more pron oun ced cytologic atypia of th e spin dle cells.
Although mitotic fi gures are still rare, the increased cel-
lularity and cytologic atypia support a diagnosis of grade
2 osteosarcoma. In the study by Okada and coauthors,
82% of the tumors were graded 1 and 18% were graded
2. In this study, a cartilaginous component was identi-
fi ed in 55%. In 27% of these lesions, the cartilage was
166 Chapter 12 ■

at the periphery and tended to have a platelike arrange-

ment with formation of bony trabeculae, simulatin g
th e appearan ce of an osteoch on droma ( Fig. 12.17) .
H owever, un like th e column ar arran gemen t seen in
th e cap of an osteoch on droma, th e ch on drocytes ten d
to be irregularly arranged. Wh ereas th ere is fatty or
h ematopoietic marrow between bon y trabeculae in
osteoch on droma, th ere is spin dle cell proliferation in
parosteal osteosarcoma ( Figs. 12.13–12.20) .
Approximately 15% of th e tumors sh ow fatty mar-
row with in th e lesion , suggestin g th at th e tumor h as
been presen t for a lon g time an d the bon y trabe-
culae h ave matured. Some tumors sh ow cemen t lin es
in th e bon y trabeculae, such as seen in Paget disease
( Fig. 12.18) . Ben ign gian t cells are rarely seen in
parosteal osteosarcoma.
F igu r e 12.14. H ypocellular spin dle cell stroma separates
trabeculae of bone.

F igu r e 12.17. This parosteal osteosarcoma had cartilage

arranged in the form of a cap, giving rise to the low-power
F igu r e 12.15. H igh -power appearan ce of th e spin dle cells appearance of osteochondroma.
in parosteal osteosarcoma. The cells are separated by collagen
fi bers and do not show signifi can t cytologic atypia.

F igu r e 12.18. Low-power pattern of parosteal osteosar-

F igu r e 12.16. Parosteal osteosarcoma con tain in g areas of coma sh ows an anastomosing pattern of bone with a pagetoid
fat with in th e spindle cell stroma. appearance.

F igu r e 12.19. Metastatic parosteal osteosarcoma in volvin g
the lung. Pulmonary metastasis without dedifferentiation in
the primary tumor is unusual.
F igu re 12.20. Dedifferentiated parosteal osteosarcoma. A: At
low-power, the pattern of bone production is similar to that of
low-grade parosteal osteosarcoma. B: However, as seen at high
power, the stromal cells are markedly atypical.
■ Parosteal Osteosarcoma ( Juxtacortical Osteosarcoma) 167
Twenty-one tumors in the Mayo Clinic series under-
went dedifferentiation ( Figs. 12.2, 12.3, 12.11, & 12.12) .
In these tumors, in addition to the classic low-grade
osteosarcomas, there were areas of high-grade spindle
cell sarcoma ( Fig. 12.20) . Seven of these tumors were
dedifferentiated at presentation and 14 at the time of
recurrence, 2 to 15 years after the initial surgery. In two
tumors, the high-grade sarcoma was in the medullary
cavity and it was impossible to tell if there were two sepa-
rate tumors. One was diagnosed at presentation and the
second at the time of recurrence 14 years after surgery.
Differentiation of parosteal osteosarcoma from myo-
sitis ossifi cans usually is not diffi cult. Myositis ossifi cans
is much more cellular than a lesion of parosteal osteo-
sarcoma and shows more pronounced mitotic activity.
There is no maturation in parosteal osteosarcoma, as
seen in myositis ossifi cans.
TREATMEN T
Several studies support the following conclusions: sim-
ple excision almost invariably leads to recurrence; wide
resection with a sleeve of normal surrounding tissue is
the treatment of choice; in large or recurrent tumors,
this may entail amputation. Campanacci and coauthors
found no incidence of local recurrence when surgical
margins were considered adequate. The experience
from Gainsville reported by Enneking and coauthors
also supports this approach.
PROGN OSIS
In the Mayo Clinic series, 15 of the 75 patients, including
those with dedifferentiated sarcomas, have died; 10 of
them died with metastatic sarcoma. Eight of the patients
who developed pulmonary metastasis had dedifferentia-
tion. The other two patients with metastatic sarcoma orig-
inally had a grade 2 parosteal osteosarcoma ( Fig. 12.19) .
Although one parosteal osteosarcoma in the original
series was thought to have metastasized with classic his-
tology, this tumor has now been reclassifi ed as a central
low-grade osteosarcoma. Hence, there are no examples
of classic grade 1 parosteal osteosarcoma in this series
that produced metastatic sarcoma. One patient died
in the immediate postoperative period after multiple
recurrences. Five patients died of unrelated causes. Ten
of the patients with dedifferentiated parosteal osteosar-
coma are alive and free of disease from 0 to 32 years after
treatment. Two patients with dedifferentiated parosteal
osteosarcoma are alive with pulmonary metastasis at 6
and 27 years. One patient with typical parosteal osteo-
sarcoma developed a conventional osteosarcoma of the
scapula 5 years after surgery.
168 Chapter 12 ■
Early adequate treatment should cure most patients.
A long-term survival rate of 80% to 90% is to be expected
for parosteal osteosarcomas without dedifferentiation.
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1951 Geschickter, C. F. and Copeland, M. M.: Parosteal Osteoma
of Bone: A New Entity. Ann Surg, 133:790–806.
1954 Dwinnell, L. A., Dahlin, D. C., and Ghormley, R. K.:
Parosteal ( Juxtacortical) Osteogen ic Sarcoma. J Bon e Join t
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1957 Stevens, G. M., Pugh, D. G., and Dahlin, D. C.: Roentgeno-
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1968 Campanacci, M., Giunti, A., and Grandesso, F.: Sarcoma
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57:3–28.
1971 Edeiken, J., Farrell, C., Ackerman, L. V., and Spjut, H . J.:
Parosteal Sarcoma. Am J Roentgenol, 111:579–583.
1976 Unni, K. K., Dahlin, D. C., and Beabout, J. W.: Periosteal
Osteogenic Sarcoma. Cancer, 37:2476–2485.
1976 Unni, K. K., Dahlin, D. C., Beabout, J. W., and Ivins, J. C.:
Parosteal Osteogen ic Sarcoma. Cancer, 37:2466–2475.
1977 Ahuja, S. C., Villacin, A. B., Smith, J., Bullough, P. G.,
Huvos, A. G., and Marcove, R. C.: Juxtacortical ( Parosteal)
Osteogenic Sarcoma: Histological Grading and Prognosis. J
Bone Joint Surg, 59A:632–647.
1979 Dunham, W. K., Wilborn, W. H., and Zarzour, R. J.: A Large
Parosteal Osteosarcoma With Tran sformation to High -Grade
Osteosarcoma: A Case Report. Cancer, 44:1495–1500.
1984 Campanacci, M., Picci, P., Gherlinzoni, F., Guerra, A.,
Berton i, F., and Neff, J. R.: Parosteal O steosarcoma. J Bone
Joint Surg, 66B:313–321.
1984 Wold, L. E., Un ni, K. K., Beabout, J. W., Sim, F. H., an d
Dahlin, D. C.: Dedifferentiated Parosteal Osteosarcoma.
J Bone Joint Surg, 66A:53–59.
1985 Berton i, F., Presen t, D., Hudson , T., an d En nekin g, W. F.:
Th e Mean in g of Radiolucen cies in Parosteal Osteosarcoma.
J Bone Joint Surg, 67A:901–910.
1985 Copelan d, R. L., Meehan , P. L., an d Morrissy, R. T.: Spon -
taneous Regression of Osteochondromas: Two Case Reports.
J Bone Joint Surg, 67A:971–973.
1985 Enneking, W. F., Springfi eld, D., and Gross, M.: The Surgical
Treatment of Parosteal Osteosarcoma in Long Bones. J Bone
Joint Surg, 67A:125–135.
1987 Lindell, M. M., Jr., Shirkhoda, A., Raymond, A. K., Murray,
J. A., and Harle, T. S.: Parosteal Osteosarcoma: Radiologic-
Path ologic Correlation with Emph asis on CT. Am J Roen t-
gen ol, 148:323–328.
1987 Picci, P., Campanacci, M., Bacci, G., Capanna, R., and Ayala,
A.: Medullary In volvemen t in Parosteal Osteosarcoma: A Case
Report. J Bon e Joint Surg, 69A:131–136.
1988 Sch ajowicz, F., McQuire, M. H., San tin i Araujo, E., Muscolo,
D. L., and Gitelis, S.: Osteosarcomas Arising on the Sur faces of
Long Bon es. J Bon e Join t Surg, 70A:555–564.
1989 Hinton, C. E., Turnbull, A. E., O’Donnell, H. D., and Harvey,
L.: Parosteal Osteosarcoma of the Skull. Histopathology, 14:
322–323.
1989 Pin tado, S. O., Lan e, J., an d Huvos, A. G.: Parosteal Osteo-
genic Sarcoma of Bone With Coexistent Low- and H igh-Grade
Sarcomatous Compon ents. Hum Pathol, 20:488–491.
1989 van Oven , M. W., Molen aar, W. M., Frelin g, N. J., Sch raffordt
Koops, H ., Muis, N., Dam-Meirin g, A., an d Oosterh uis, J. W.:
Dedifferen tiated Parosteal Osteosarcoma of th e Femur with
An euploidy and Lun g Metastases. Can cer, 63:807–811.
1990 Kavanagh, T. G., Cannon, S. R., Pringle, J., Stoker, D. J., and
Kemp, H. B.: Parosteal Osteosarcoma: Treatmen t by Wide
Resection an d Prosth etic Replacemen t. J Bon e Join t Surg,
72B:959–965.
1990 Kumar, R., Moser, R. P., Jr., Madewell, J. E., and Edeiken,
J.: Parosteal Osteogen ic Sarcoma Arisin g in Cran ial Bon es:
Clin ical an d Radiologic Features in Eigh t Patien ts. Am J Roen t-
gen ol, 155:113–117.
1991 Ritschl, P., Wurnig, C., Lechner, G., and Roessner, A.:
Parosteal O steosarcoma: 2–23-Year Follow-up of 33 Patien ts.
Acta Orthop Scan d, 62:195–200.
1994 Okada, K., Frassica, F. J., Sim, F. H., Beabout, J. W., Bond,
J. R., an d Un n i, K. K.: Parosteal Osteosarcoma: A Clin icopath o-
logic Study. J Bon e Joint Surg, 76A:366–378.

Fibrosarcoma and
D esmoplastic Fibroma
FIBROSARCOMA
Fibrosarcoma in bone is a malignant tumor of spindle-
shaped cells that does not produce osteoid material in
either the primary lesion or the secondary deposits.
Collagen production varies from abundant to none,
tending to be less in the highly malignant examples.
Fibrosarcoma may be so well differentiated that dif-
ferentiating it from benign conditions such as fi brous
dysplasia is diffi cult. The differentiation of fi brosarcoma
from fi broblastic osteosarcoma and malignant fi brous
histiocytoma may be somewhat arbitrary. Occasionally,
matrix material is found only after a long search through
many sections of the tumor that is predominantly fi bro-
blastic, indicating that the distinction may be artifi cial.
After tumors that merely abutted on bone were
excluded on the premise that they were probably of soft
tissue origin, our series contained no distinct group of
tumors that might logically be called “periosteal fi brosar-
coma.” This manner of selection perhaps excludes some
sarcomas of periosteal origin. From the gross pathologic
features, it is apparent that most fi brosarcomas of bone
arise in the medullary or the cortical regions, although
a few undoubtedly begin in the periosteum.
“Secondary” fi brosarcoma accounted for just over
23% of the 286 fi brosarcomas in the Mayo Clinic fi les.
( Table 13.1) Forty-eigh t occurred after radiation, four
arose in giant cell tumors that had not been treated
with radiation, seven occurred in Paget disease, and
seven occurred in other conditions, including two
ameloblastic fi bromas, three bone infarcts, one fi brous
dysplasia, and one odontogenic myxoma.
Three patients apparently had multicentric disease,
but in only one patient was there histologic proof of
involvement of more than one bone.
Some fi brosarcomas have a myxoid matrix. Such
myxosarcoma-like foci may be prominent in some fi bro-
sarcomas. Rarely, the entire tumor has an appearance
C H APT ER
13
that tempts one to designate it as a “myxosarcoma.”
Transitional types between these and obvious fi brosar-
comas make it reasonable to include such types with
fi brosarcomas. Leiomyosarcoma has been described
in several publications as occurring primarily in bone.
Electron microscopic and immunoperoxidase studies
seem to support this diagnosis.
IN CID EN CE
The 286 fi brosarcomas comprised just over 4% of the
total primary malignant bone tumors. Osteosarcoma is
more than six times as common as fi brosarcoma in the
Mayo Clinic fi les ( Fig. 13.1) .
SEX
There was a slight male predominance.
AGE
Fibrosarcoma does n ot sh ow th e marked propen -
sity for patien ts in th e secon d decade of life th at
osteosarcoma does. In stead, th e tumors were m ore
or less even ly distributed in patien ts in th e secon d
th rough seven th decades of life. O n ly on e patien t was
youn ger th an 5 years. Th e ten den cy of fi brosarcoma
to occur am on g older person s as com mon ly as amon g
youn ger on es is th e major clin ical differen ce between
fi brosarcoma an d osteosarcoma; 64 tumors occurred
as late complication s of preexistin g con dition s.
LOCALIZATION
The sites involved by fi brosarcoma do not differ remark-
ably from those involved by osteosarcoma. The region
around the knee involving the distal femur and the
proximal tibia was the most common location. Just over
50% of the tumors were located in the long bones, where
the tumor is usually found in the metaphyseal region.
169
170 Chapter 13 ■

PH YSICAL FIN D IN GS
Predisposing Conditions
TABL E 13.1. in 64 Patients with Painful swelling in the region of the tumor is usually found
“Secondary Fibrosarcoma”* unless the tumor is covered by a thick layer of uninvolved
Condition No. of Patients
tissue. Spindle cell sarcoma, and even carcinomas with
spindle-shaped cells, may metastasize to the skeleton and
Previous radiation th erapy 46 mimic primary fi brosarcoma, so evidence for such hid-
Paget disease 7
Giant cell tumor without radiation therapy 4
den lesions should be sought. Four patients with fibrosar-
In farct of bon e 3 coma of bone had von Recklinghausen disease. Some of
Fibrous dysplasia 1 these sarcomas are pleomorphic and may be classified as
Ameloblastic fi broma 2 malignant fi brous histiocytoma. None of the patients had
Odontogenic myxoma 1 evidence of neurofibromatous involvement of the bone.
Total 64 The symptoms and physical examination are some-
*Four patients with stigmata of von Recklinghausen disease are times different in patients with fi brosarcoma secondarily
n ot included. to other conditions listed in Table 13.1. Fibrosarcomas
that result from dedifferentiation of chondrosarcomas, as
described in Chapter 6, are not included in these data.
Several tumors that affected the maxillary antrum,
including its bony walls, were excluded because they RAD IOGRAPH IC FEATU RES
lacked evidence of an osseous origin. Three patients in
the Mayo Clinic series had multifocal skeletal disease at Fibrosarcomas of bone do not have radiographic fea-
presentation. tures that differentiate them from lytic osteosarcomas.
The lesions are purely lucent geographic areas of bone
destruction and generally have features of malignancy,
SYMPTOMS
with cortical destruction and ill-defi ned borders. The
Fibrosarcoma produces th e usual symptoms of malig- radiographic appearance generally correlates with
n an t tumor in bon e, n amely, pain an d swellin g. Gen - the histologic grade of the tumor. Well-differentiated
erally, th ese are of sh ort duration . Patien ts wh ose tumors ten d to be more sharply defi ned th an poorly
fi brosarcomas arise secon darily give an appropriate differen tiated tumors. Tacon is an d van Rijssel foun d
h istory of th e origin al con dition an d often h ad h ad th at th e radiograph ic features of fi brosarcoma an d
radiation th erapy man y years before th e malign an t malign ant fi brous histiocytoma are essentially identical
tumor appeared. ( Figs. 13.2–13.5) .

F igu r e 13.1. Distribution of fi bro-

sarcomas accordin g to age an d sex
of th e patien t an d site of th e lesion .

F igu r e 13.2. Grade 1 fi brosarcoma formin g a well-
demarcated, purely lytic lesion in th e proximal tibia in a
47-year-old woman. The lesion has a sclerotic margin, sug-
gesting a benign process. ( Case provided by Dr. Alexander
Templeton, Rush -Presbyterian -St. Luke’s Medical Cen ter,
Ch icago, Illin ois.)
F igu r e 13.3. Computed tomogram of a grade 2 fi brosar-
coma in volvin g th e distal femur in a 50-year-old man . Th e
tumor has broken through the cortex to form a soft-tissue
mass, suggestin g a malign an t process.
■ Fibrosarcoma and Desmoplastic Fibroma 171
F igu r e 13.4. Grade 3 fi brosarcoma arisin g in th e ilium in a
59-year-old woman. The tumor was resected without any neo-
adjuvant chemotherapy. There was no matrix production in
the resected specimen.
F igu r e 13.5. Leiomyosarcoma in volvin g th e proximal tibia
in a 70-year-old woman. There was no primary tumor else-
where. A: Th e radiographic appearance is th at of a malignant
tumor but is otherwise nonspecifi c. B: Magnetic resonance
imaging shows destruction of cortex with involvement of soft
tissue. ( B, From Young, C. L., Wold, L. E., McLeod, R. A., and
Sim, F. H .: Primary Leiomyosarcoma of Bone. O rthopedics,
11:615–618, 1988. By permission of publish er.)
172 Chapter 13 ■

GROSS PATH OLOGIC FEATU RES

Th e gross appearan ce of fi brosarcoma also varies

accordin g to th e h istologic grade. Low-grade sarcomas
ten d to be fi rm an d fi brous an d may h ave a wh orled
appearan ce. H igh -grade sarcomas ten d to be soft an d
fl esh y. Th e tumor may h ave a glisten in g appearan ce
because of th e presen ce of a myxoid matrix. Th e bon e
is in vaded in an irregular fash ion an d th e margin s
may be in distin ct. At presen tation , almost all th e fi bro-
sarcomas of cen tral origin h ave broken th rough th e
cortex an d h ave a large or small extraosseous compo-
n en t. Th e gross specimen may sh ow eviden ce of a pre-
existin g con dition such as Paget disease or an in farct
( Figs. 13.6–13.9) .
Fibrosarcoma, like osteosarcoma, metastasizes pri-
marily by the hematogenous route, producing second-
ary deposits most commonly in the lung but also in
various sites, including other bones.

H ISTOPATH OLOGIC FEATU RES

Fibrosarcoma in bon e h as th e same h istologic features

as its soft tissue coun terpart. H owever, section s may
sh ow th at it h as in vaded an d destroyed bon e, espe-
cially n ear th e periph er y of th e tumor. Th ere is wide
variation in th e degree of differen tiation in th e com-
pon en t fi broblasts an d in th e amoun t of collagen pro-
duced. Th e sh ape of th e n uclei var y from lon g an d F igu r e 13.6. Large fi brosarcoma with myxoid change involv-
slen der to oval. Some fi brosarcomas h ave extremely ing the distal femur. The glistening appearance is caused by
small cells an d may mimic Ewin g tumor. H owever, in the myxoid matrix within the lesion.

Figu re 13.7. Recurrent grade 3 fi -

brosarcoma involving the shaft of the
fi bula. The tumor was curetted 1 year
earlier and then recurred locally.
 ■ Fibrosarcoma and Desmoplastic Fibroma 173

most fi brosarcomas, th e cells are organ ized, usually

in a “h errin gbon e” pattern . In lower grade tumors,
th e collagen is arran ged in rath er orderly ban ds an d
wh orls ( Figs. 13.10 & 13.11) .
Fibrosarcomas can be graded on th e basis of th e
cytologic features of th e tumor cells an d the cellularity
of the lesion. The cellularity of the lesion is in versely
proportion al to the collagen produced by th e neo-
plasm. Low-grade tumors tend to show marked colla-
gen production so that the spindle cells are separated.
Th e nuclei are usually elongated an d have tapered
en ds. Mitotic fi gures are uncommon . Grade 2 sarco-
mas show increased cellularity compared with a grade
1 tumor. Th e n uclei are somewh at more atypical appear-
in g, an d mitotic fi gures are usually more prominent.
Grade 3 sarcomas have darkly stained spindle cells in

F igu r e 13.8. Fibrosarcoma with small cells involving the

proximal femur. The original diagnosis was Ewing sarcoma.
Th e tumor did not respon d to ch emoth erapy.

F igu r e 13.10. Grade 4 fi brosarcoma. A: Low-power appear-

ance shows a cellular neoplasm composed of spindle cells
F igu r e 13.9. Fibrosarcoma with small cells involving the arranged in fascicles. B: High-power appearance shows signifi -
proximal femur. The Original diagnosis was Ewing sarcoma. can t cytologic atypia an d n umerous mitotic fi gures. Immun o-
Th e tumor did not respon d to ch emoth erapy. stain s are h elpful in rulin g out leiomyosarcoma.
174 Chapter 13 ■
F igu r e 13.11. Fibrosarcoma with variability in its cellularity.
Th is variability is similar to th at of myxoid spin dle cell sarco-
mas arisin g in soft tissue.
F igu r e 13.12. Myxoid grade 2 fi brosarcoma. A: Low-power
appearance shows a hypocellular to moderately cellular spin-
dle cell tumor with myxoid change. The tumor has entrapped
a preexisting fragment of bone. B: High magnifi cation high-
lights the myxoid change within the stroma.
a h errin gbon e pattern with little collagen production .
Mitotic fi gures are abun dan t, an d n ecrotic areas may be
seen . In grade 4 sarcomas, the cells are packed closely
togeth er with n o matrix production . Mitotic fi gures are
promin en t, an d n ecrotic areas may be seen. Some high -
grade fi brosarcomas h ave very small cells. Berton i an d
coauth ors reported on 80 fi brosarcomas of bon e. On ly
2 were con sidered grade 1, 11 were grade 2, 42 were
grade 3, an d 25 were grade 4. Th ese auth ors also foun d
that mitotic activity was prominen t only in h igh er grade
tumors. In 1969, Dah lin an d Ivins reported on 114 fi -
brosarcomas of bon e from the Mayo Clin ic fi les. Th ey
foun d only one grade 1 fi brosarcoma. O f th e oth er 113,
35 were grade 2, 48 were grade 3, an d 30 were con sid-
ered grade 4.
Some fi brosarcomas have a prominent myxoid com-
ponent. Because the myxoid matrix may separate the
spindle cells, the lesion may appear hypocellular and
be mistaken for a benign tumor. However, the tumor is
usually composed of cytologically very malignant cells
that show prominent permeation between preexisting
bony trabeculae ( Fig. 13.12) .
A few fi brosarcomas are so low-grade that they may
be mistaken for benign lesions such as fi brous dysplasia
and metaphyseal fi brous defect. This error can be
avoided by paying attention to signs of aggressiveness, as
may be indicated by the radiograph, by permeation of
the tumor among preexisting trabeculae, or by destruc-
tion of the overlying bony cortex.
Metastatic spin dle cell sarcoma can mimic pri-
mar y fi brosarcoma of bon e. O n th e on e h an d, it is
extremely un usual for a sarcoma to be occult an d to
presen t as a bon e lesion . O n th e oth er h an d, meta-
static sarcomatoid carcin oma can be ver y diffi cult to
differen tiate from primar y sarcoma. Metastatic sarco-
matoid ren al cell carcin oma is probably th e most com-
mon n eoplasm with th is propen sity. An y “clusterin g”
of th e tumor cells or th e presen ce of clear cells in th e
tumor is suggestive of ren al cell carcin oma, especially
in older patien ts. Appropriate radiograph ic studies
will usually resolve th e problem. Immun operoxidase
stain s may also be h elpful in demon stratin g epith elial
differen tiation .
Some sarcomas of bone have plump cells with eosino-
philic cytoplasm. These have a distinct myogenic qual-
ity. Immunoperoxidase and electron microscopic stud-
ies have supported the diagnosis of leiomyosarcoma in
some of these cases ( Fig. 13.13) . Several cases in this
series of fi brosarcoma probably would show myogenic
differentiation if studied appropriately. It is important
to remember the possibility of a metastatic leiomyo-
sarcoma when a spindling neoplasm of bone has an
obvious myogenic quality. In this clinical situation, the
gastrointestinal tract and the uterus should be consid-
ered possible primary sites.

F igu r e 13.13. Leiomyosarcoma ( from th e tumor seen in th e
radiographs in Figure 13.5) . A: The tumor cells are arran ged
in interlacing fascicles. B: High-power view shows cytologic
atypia and blunt-ended nuclei commonly seen in smooth mus-
cle n eoplasms. C: Th e tumor is immun oreactive with smooth
muscle actin .
■ Fibrosarcoma and Desmoplastic Fibroma 175
TREATMEN T
Ablative surgical treatment is usually indicated for fi bro-
sarcoma of bone. There is not enough experience to
know whether chemotherapy is effi cacious in the man-
agement of fi brosarcoma.
PROGN OSIS
The prognosis in fi brosarcoma of bone is similar to that
of osteosarcoma and malignant fibrous histiocytoma.
Taconis and van Rijssel found no difference in prognosis
between fi brosarcoma and malignant fibrous histiocytoma
of bone. They found that the grade of the neoplasm cor-
related well with the prognosis, with 5-year survival rates
of 64% for grade 1 fibrosarcomas, 41% for grade 2, and
23% for grade 3. The overall 5-year survival rate in their
series was 34%. Bertoni and coauthors reported a 42%
5-year survival rate in their series from Bologna, Italy. The
5-year survival was 83% for low-grade sarcomas and 34%
for high-grade sarcomas. They also found that local recur-
rence adversely affected the long-term prognosis.
D ESMOPLASTIC FIBROMA
Desmoplastic fi broma is one of the rarest of bone tumors
and may be considered to be an intraosseous counter-
part of the much more common desmoid tumor of soft
tissues.
IN CID EN CE
There were only 16 examples of desmoplastic fi broma
in the Mayo Clinic fi les ( Fig. 13.14) . Gebhardt and
coauthors found 85 cases in their review of the litera-
ture. However, Kwon and coauthors found 47 cases of
desmoplastic fi broma of the jawbones reported in the
literature.
SEX
In this small series of patients, males outnumbered
females 3:1.
AGE
The majority of the patients with desmoplastic fi broma
are in the second and third decades of life. This is simi-
lar to what has been reported in the literature.
LOCALIZATION
An y portion of th e skeleton may be in volved with desmo-
plastic fi broma. O n ly th ree examples of desmoplastic
fi broma in volvin g th e man dible were in th e Mayo
Clin ic fi les.
176 Chapter 13 ■
F igu r e 13.14. Distribution of desmoplastic fi bromas according to age and sex of the patient and
site of th e lesion .
SYMPTOMS
Pain and swelling are the usual symptoms. In the series
reported by Inwards and coauthors, approximately 20%
of the patients presented with a pathologic fracture.
PH YSICAL FIN D IN GS
Physical fi ndings are nonspecifi c, but some patients may
present with swelling.
RAD IOGRAPH IC FEATU RES
The radiographs show a purely lucent defect in bone.
Slight to moderate expansion of the bone may be seen.
The margins are usually lobulated and well defi ned.
Occasionally, the bone adjacent to the tumor may show
reactive sclerosis. Periosteal new bone formation is rare
even wh en the tumor breaks through the cortex into
soft tissue. As described by Crim and coauthors, there
is a striking tendency for uneven bone destruction,
leavin g behind intact ridges of bone and producing a
pseudotrabecular appearance ( Fig. 13.15) .
GROSS PATH OLOGIC FEATU RES
Desmoplastic fi broma is fi rm and has a whorled appear-
ance similar to that seen in desmoid tumors of soft tissue
( Figs. 13.16 & 13.17) .
H ISTOPATH OLOGIC FEATU RES
Desmoplastic fi bromas are composed of spindle cells,
with abundant production of collagen. The low-power
appearance is that of a hypocellular neoplasm, which
may show permeation of preexisting structures at the
periphery. The nuclei show no cytologic atypia, and
mitotic fi gures are unusual. Very typically, there are
gaping vascular spaces similar to those seen in desmoid
tumors ( Figs. 13.18 & 13.19) .
TREATMEN T
Desmoplastic fi broma is a locally aggressive neoplasm
with no potential for metastasis. Hence, en bloc resec-
tion of the neoplasm is the treatment of choice.
PROGN OSIS
Curettage of th e lesion is almost in variably followed
by recurren ces. H owever, wide resection is associated
with cure. Th ere h ave been n o reports in th e litera-
ture of a h igh -grade sarcoma developin g in to a desmo-
plastic fi broma. H owever, recen tly, th ere h as been on e
case in th e Mayo Clin ic con sultation fi les in wh ich a
h igh -grade sarcoma developed at th e site of a recur-
ren t desmoplastic fi broma 15 years after th e origin al
diagn osis.
 ■ Fibrosarcoma and Desmoplastic Fibroma 177

Figu re 13.15. Desmoplastic fibroma

involving the disal femur in a 30-year-
old man. A: The lesion extends to the
end of the bone, has a “trabeculated”
appearance, and has destroyed the
cortex focally. B: Magnetic resonance
imaging shows destruction of the
cortex with formation of a soft-tissue
mass. (Case provided by Dr. Anthony
G. Montag, University of Chicago Hos-
pital, Chicago, Illinois.)

F igu r e 13.16. Desmoplastic fi broma involving the ischium

in a 54-year-old man. The patient had pain for 10 years.
Th e tumor h as th e wh orled appearan ce seen with desmoid
tumors.

F igu r e 13.18. Desmoplastic fi broma. A: Hypocellular spin-

dle cell proliferation and large dilated vascular channels are
F igu r e 13.17. Desmoplastic fi broma that destroyed the scap- present. B: High-power view shows no evidence of cytologic
ula. The lesion lacks the fl eshy appearance of a true sarcoma. atypia.
178 Chapter 13 ■
F igu r e 13.19. Desmoplastic fi broma with abundant produc-
tion of collagen . Th e tumor is h ypocellular, an d th e slen der
nuclei do n ot show atypia.
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blasts. Can cer, 1:30–63.
1951 Pugh, D. G.: Roentgenologic Diagnosis of Diseases of
Bon es. New York, Th omas Nelson & Son s.
1957 McLeod, J. J., Dahlin, D. C., and Ivins, J. C.: Fibrosarcoma
of Bone. Am J Surg, 94:431–437.
1958 Gilmer, W. S., Jr., and MacEwen, G. D.: Central ( Medul-
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1958 Jaffe, H. L.: Tumors and Tumorous Conditions of the
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rosarcoma Arisin g at th e Site of Bone Infarcts: A Report of
Two Cases. J Bone Joint Surg, 42A:802–810.
1960 Whitesides, T. E., Jr., and Ackerman, L. V.: Desmoplastic
Fibroma: A Report of Th ree Cases. J Bon e Join t Surg,
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sarcom ata of th e Bon es. Acta Path ol Microbiol Scan d , 55:
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1964 Dahlin, D. C., and H oover, N. W.: Desmoplastic Fibroma of
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1966 Dor fman, H. D., Norman, A., and Wolff, H.: Fibrosarcoma
Complicatin g Bon e In farction in a Caisson Worker: A Case
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1968 Rabhan, W. N., and Rosai, J.: Desmoplastic Fibroma: Report
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50A:487–502.
1969 Dahlin, D. C., and Ivins, J. C.: Fibrosarcoma of Bone: A Study
of 114 Cases. Cancer, 23:35–41.
1969 Eyre-Brook, A. L., and Price, C. H. G.: Fibrosarcoma of
Bone: Review of Fifty Consecutive Cases From the Bristol Bone
Tumour Registry. J Bone Joint Surg, 51B:20–37.
1974 Mirra, J. M., and Marcove, R. C.: Fibrosarcomatous Dedif-
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Review of Five Cases. J Bon e Joint Surg, 56A:285–296.
1974 Nilsonne, W., and Mazabraud, A.: Les Fibrosarcomes de
l’os. Rev Ch ir Orthop, 60:109–122.
1975 Cunningham, C. D., Smith, R. O., Enriquez, P., and
Singleton, G. T.: Desmoplastic Fibroma of the Mandible:
A Case Report. Ann Otol Rh in ol Laryn gol, 84:125–129.
1976 Hernandez, F. J., and Fernandez, B. B.: Multiple Diffuse
Fibrosarcoma of Bone. Can cer, 37:939–945.
1976 Jeffree, G. M., and Price, C. H. G.: Metastatic Spread of Fib-
rosarcoma of Bone: A Report on Forty-Nine Cases, and a Com-
parison With Osteosarcoma. J Bon e Join t Surg, 58B:418–425.
1976 Larsson, S.-E., Lorentzon, R., and Boquist, L.: Fibrosar-
coma of Bon e: A Demograph ic, Clin ical an d Histopath ologi-
cal Study of All Cases Recorded in th e Swedish Can cer Registry
From 1958 to 1968. J Bone Join t Surg, 58B:412–417.
1976 Sugiura, I.: Desmoplastic Fibroma: Case Report and Review
of the Literature. J Bon e Join t Surg, 58A:126–130.
1979 Sanerkin, N. G.: Primary Leiomyosarcoma of the Bone and
Its Comparison With Fibrosarcoma: A Cytological, Histologi-
cal, an d Ultrastructural Study. Can cer, 44:1375–1387.
1980 Angervall, L., Berlin, Ö., Kindblom, L.-G., and Stener,
B.: Primary Leiomyosarcoma of Bon e: A Study of Five Cases.
Cancer, 46:1270–1279.
1980 Wang, T.-Y., Erlandson, R. A., Marcove, R. C., and Huvos,
A. G.: Primary Leiomyosarcoma of Bon e. Arch Path ol Lab
Med, 104:100–104.
1983 Ducatman, B. S., Scheithauer, B. W., and Dahlin, D. C.:
Malign an t Bon e Tumors Associated With Neurofi bromatosis.
Mayo Clin Proc, 58:578–582.
1984 Bertoni, F., Calderoni, P., Bacchini, P., and Campanacci, M.:
Desmoplastic Fibroma of Bon e: A Report of Six Cases. J Bon e
Joint Surg, 66B:265–268.
1984 Bertoni, F., Capanna, R., Calderoni, P., Patrizia, B., and
Campan acci, M.: Primary Cen tral ( Medullary) Fibrosarcoma
of Bon e. Semin Diagn Pathol, 1:185–198.
1984 Von Hochstetter, A. R., Eberle, H., and Rüttner, J. R.: Pri-
mary Leiomyosarcoma of Extragn ath ic Bon es: Case Report
and Review of Literature. Cancer, 53:2194–2200.
1985 Gebhardt, M. C., Campbell, C. J., Schiller, A. L., and
Man kin , H. J.: Desmoplastic Fibroma of Bon e: A Report of
Eight Cases and Review of th e Literature. J Bone Joint Surg,
67A:732–747.
1985 Taconis, W. K., and van Rijssel, T. G.: Fibrosarcoma of
Long Bones: A Study of the Signifi cance of Areas of Malignant
Fibrous H istiocytoma. J Bon e Join t Surg, 67B:111–116.
1986 Hadjipavlou, A., Lander, P. H., Begin, L. R., and Eibel, P.:
Desmoplastic Fibroma of a Metatarsal: Case Report. J Bon e
Joint Surg, 68A:459–461.
1988 Young, C. L., Wold, L. E., McLeod, R. A., and Sim, F. H.:
Primary Leiomyosarcoma of Bone. Orthopedics, 11:615–618.
1989 Crim, J. R., Gold, R. H., Mirra, J. M., Eckardt, J. J., and
Bassett, L. W.: Desmoplastic Fibroma of Bon e: Radiograph ic
An alysis. Radiology, 172:827–832.
1989 Kwon , P. H., H orswell, B. B., an d Gatto, D. J.: Desmoplastic
Fibroma of th e Jaws: Surgical Man agemen t an d Review of th e
Literature. Head Neck, 11:67–75.
1991 Inwards, C. Y., Unni, K. K., Beabout, J. W., and Sim, F. H .:
Desmoplastic Fibroma of Bone. Can cer, 68:1978–1983.
1991 Myers, J. L., Arocho, J., Bernreuter, W., Dunham, W., and
Mazur, M. T.: Leiomyosarcoma of Bon e: A Clin icopath ologic,
Immun oh istoch emical, an d Ultrastructural Study of Five
Cases. Can cer, 67:1051–1056.
1991 Young, M. P. and Freemont, A. J.: Primary Leiomyosarcoma
of Bon e. Histopathology, 19:257–262.
 C H APT ER

14
Benign Fibrous H istiocytoma

A variety of ben ign an d malign an t n eoplasms in th e some giant cell tumors show spindling of the mononu-
soft tissues are con sidered to be of h istiocytic origin . clear cells and even a storiform pattern. A radiographi-
Man y of th ese lesion s are n ot h istiocytic in origin . Nev- cally typical giant cell tumor may be so altered that only
erth eless, th ey do h ave some common h istologic fea- small and insignifi cant appearing zones of classic giant
tures an d fall in to distin ct clin icopath ologic en tities. cell tumor may be found. We have added only one addi-
Th e followin g features are common ly used to diagn ose tional example of benign fi brous histiocytoma in the
a fi broh istiocytic n eoplasm in soft tissue: a spin dle cell intervening 10 years.
lesion with a storiform pattern an d th e presen ce of
h istiocytic-appearin g cells, gian t cells, foam cells, an d
a polymorph ic-appearin g in fi ltrate. Th ese are also th e
features used to diagn ose fi broh istiocytic n eoplasms in IN CID EN CE
bon e.
The concept of benign fi brous histiocytoma of Only 10 of the 10,139 tumors in the Mayo Clinic series
bone is complicated by the fact that authors have ( Fig. 14.1) were considered to be benign fi brous
included several different entities in this terminology. histiocytoma.
Schajowicz, for instance, preferred the term histiocytic
xanthogranuloma for the more commonly known meta-
physeal fi brous defect, suggesting that this lesion is of SEX
histiocytic origin. However, he mentioned that it prob-
ably does not represen t a true neoplasm. Fech ner and There were four males and six females in this small
Mills included xanthomas of bone under the rubric series.
fi brohistiocytic neoplasm. They thought that a lesion con-
taining cholesterol crystals and lipid-laden h istiocytes
and commonly called xanthoma probably represents
an end stage of a fi brohistiocytic lesion.
AGE
In the fourth edition of this book, there were 10 exam-
All patients were adults, with ages ranging from 17 to 60
ples called benign and atypical fi brous histiocytomas. There
years at the time of diagnosis.
were only nine examples in the tabulations prepared
for the fi fth edition. One case that was previously con-
sidered a benign fi brous histiocytoma of the thoracic
spine had been reclassifi ed as a giant cell tumor. The LOCALIZATION
patient developed a recurrence 12 years later, and at
this time, the histology examination showed an osteosar- Four tumors involved the ilium and one th e sacrum.
coma. Matsuno has also referred to the problem of dif- Two tumors involved the femur: one the mid portion
ferentiating benign fi brous histiocytoma from giant cell and one th e lower end. O ne tumor each involved
tumor when the lesions occur at the ends of long bones. the distal portion of the tibia, th e mid portion of the
As mentioned in the description of giant cell tumors, humerus, and a metatarsal.

179
180 Chapter 14 ■

F igu r e 14.1. Distribution of atypical fi brous histiocytoma accordin g to age an d sex of the patien t
and site of the lesion.

SYMPTOMS

Local pain was the primary symptom of 8 of the 10

patients. One patient presented with osteomala-
cia, which was apparently related to this tumor. The
osteomalacia recurred when the patient developed
metastasis in the lung. The patient is alive and recently
had a pulmonary metastasis, approximately 26 years
after the original diagnosis was made.

PH YSICAL FIN D IN GS

Most of the patients had n o fi ndings attributed to their

tumors.

RAD IOGRAPH IC FEATU RES

Gen erally, th ese tumors produced a well-defi n ed zon e

of rarefaction . In two cases, th e somewh at irregular
edges were suggestive of a malign an t tumor. Th ere
was eviden ce of calcifi cation in th e lesion in volvin g
th e femur wh ich produced on cogen ic osteomalacia
( Figs. 14.2–14.5) .
F igu r e 14.2. Benign fi brous histiocytoma producing a well-
circumscribed rarefaction in th e righ t side of th e sacrum an d
adjacent ilium in a 23-year-old woman, who had noted sciatica
for 1 year. Sh e h as remain ed well for 36 years after curettage
of th e lesion , wh ich weigh ed 100 g.

F igu r e 14.3. Fibrous h istiocytoma in a 28-year-old woman is
well defi ned. Involvement of the epiphysis and the patient’s
age would both be unusual for nonosteogenic fi broma. The
patient was well 42 months after curettage and grafting ( Case
con tributed by Dr. J. B. Wilks of Cin cin n ati, O h io.) .
F igu r e 14.4. Fibrous histiocytoma in a 49-year-old man.
Th is tumor h ad produced pain for 8 mon th s. Two years after
biopsy, amputation was n ecessary, but details of th is operation
are unknown and the patient was lost to follow-up.
■ Benign Fibrous Histiocytoma 181
F igu r e 14.5. Fibrous histiocytoma located in the ilium in a
31-year-old woman. A: Computed tomography shows that the
tumor has a benign radiographic appearance. B: Gross speci-
men of th e curetted tumor sh ows a mixture of colors, in clud-
ing yellow, red, dark brown, and tan.
GROSS PATH OLOGIC FEATU RES
The usual tissue was in irregular fragments. Sometimes
the tissue was slightly fi brous, and occasionally it was yel-
lowish because of its lipid content.
H ISTOPATH OLOGIC FEATU RES
The similarity of this lesion to nonossifying fi broma has
been pointed out in the literature. The fi brogenic qual-
ity may be manifested by interlacing bundles of cells.
Benign giant cells are present in variable numbers, but
they may be sparse. Some of the nuclei are indented
or grooved, and this histiocytic quality may be associ-
ated with lipid, which is sometimes abundant, within the
cells. One tumor contained peculiar matrix calcifi cation
similar to that seen in at least some lesions associated
with oncogenic osteomalacia ( phosphaturic mesenchy-
mal tumor) ( Figs. 14.6–14.8) .
182 Chapter 14 ■

F igu r e 14.7. Th is fi brous h istiocytoma con tain s several

multin ucleated gian t cells an d, th us, resembles gian t cell
tumor. The tumor was located in the ilium.

F igu r e 14.6. Fibrous histiocytoma. A: Plump spindle cells

are arranged in a storiform pattern. B: High-power view shows F igu r e 14.8. Fibrous histiocytoma containing numerous
no eviden ce of cytologic atypia. C: Some areas of th e tumor h emosiderin -laden macrophages, lymph ocytes, an d plasma
con tain ed n umerous foamy h istiocytes. cells. Low- ( A) an d h igh - ( B) power views.

TREATMEN T AN D PROGN OSIS
The few cases allow no fi rm conclusions. If the tumor
is removed completely and no features of malignancy
are recognized, a good result can be expected. As men-
tioned above, one patient developed a metastatic tumor
but h as been a long-term survivor. Another required
amputation for a recurrent tumor of the humerus.
BIBLIOGRAPH Y
1981 Schajowicz, F.: Tumors and Tumor-Like Lesions of Bone
and Joints. New York, Springer-Verlag, pp. 449–463.
1985 Clarke, B. E., Xipell, J. M., and Thomas, D. P.: Benign
Fibrous Histiocytoma of Bon e. Am J Surg Path ol, 9:806–815.
■ Benign Fibrous Histiocytoma 183
1985 Fech ner, R. E.: Ben ign Fibrous Histiocytoma of Bon e
[ abstract] . Lab Invest, 52:21A.
1986 Bertoni, F., Calderon i, P., Bacchin i, P., Sudan ese, A.,
Baldini, N., Presen t, D., and Campanacci, M.: Ben ign Fibrous
Histiocytoma of Bone. J Bone Joint Surg, 68A:1225–1230.
1990 Matsuno, T.: Benign Fibrous H istiocytoma In volvin g th e
Ends of Long Bones. Skeletal Radiol, 19:561–566.
1993 Fech n er, R. E. an d Mills, S. E.: Atlas of Tumor Path ology:
Tumors of th e Bon es an d Join ts. Armed Forces In stitute of
Path ology, pp. 161–163.
 C H APT ER

15
Malignant Fibrous H istiocytoma

Numerous reports of malignant fi brous histiocytoma It is possible that the entity of malignant fi brous histio-
of bone have been reported. A typical neoplasm is one cytoma encompasses a variety of very pleomorphic sar-
that shows fi brogenic differentiation, often in a “stori- comas of bone and soft tissue.
form” pattern, and has other areas of cells with nuclei
that are similar but appear to be histiocytic. The nuclei
are often indented, the cytoplasm is usually abundant IN CID EN CE
and may be slightly foamy, the nucleoli are often large,
and multinucleated malignant giant cells are usually a Only 98 examples of malignant fi brous histiocytoma
prominent feature. were found among the total of 7,098 primary malignant
Many osteosarcomas, fi brosarcomas, and dediffer- tumors ( Fig. 15.1) .
entiated chondrosarcomas contain areas that resemble
what is regarded as malignant fi brous histiocytoma.
When sections of all parts of a malignant tumor fi t the
SEX
histologic pattern, the designation of malignant fi brous
histiocytoma seems appropriate. The fi nding of even
There was only a slight male predominance, with
minute foci of defi nite chondroid or osteoid matrix
57 males and 41 females. In a report of the largest series
excludes the tumor from the group of malignant fi brous
of malignant fi brous histiocytomas of bone to date,
histiocytomas.
Huvos and coauthors found that males constituted
In 1977, a series of 35 exam ples of malign an t
approximately 58% of the population.
fi brou s h istiocytoma were reported from Mayo Clin ic.
Th ese were collected from a review of 158 fi brosarco-
mas an d 962 osteosarcom as in th e fi les at th at time.
Seven teen of th e malign an t fi brous h istiocytom as h ad AGE
been previously quoted as “fi brosarcom a” an d 18 as
“osteosarcom a.” Sin ce th en , tumors h ave been coded Nearly any age may be affected; only one patient was
separately as m align an t fi brous h istiocytoma wh en younger than 10 years. This was a 6-year-old girl with a
appropriate. Th ere are 98 exam ples of th ese tum ors, tumor of the sacrum. The age distribution is more uni-
compared with 1,952 osteosarcomas an d 285 fi brosar- form than that of osteosarcoma and similar to that of
comas. fi brosarcoma.
Several electron microscopy studies have indicated
the similarity between these tumors and the malignant
fi brous histiocytoma primary in the soft tissues. The LOCALIZATION
tumors are apparently composed of cells with the capa-
bility of differentiating along fi broblastic and histiocytic Many different bones were affected, but the long bones
lines. were the site in 62 cases, with the region of the knee
Although most authors agree that malignant fi brous being the most common location. Only one patient pre-
histiocytoma is a clinicopathologic entity, its true his- sented with a multicentric process; this tumor has been
togenesis is still con troversial. Some studies have sug- reviewed several times and it does not appear to be an
gested that these tumors are of histiocytic derivation, example of lymphoma simulating malignant fi brous
whereas others have suggested that they are fi broblastic. histiocytoma.

184
 ■ Malignant Fibrous Histiocytoma 185

Figu re 15.1. Distribution of malignan t

fi brous histiocytomas accordin g to age and
sex of the patient and site of the lesion.

SYMPTOMS

As with other varieties of bone tumor, pain and swelling

were the most frequent symptoms. One patient had
symptoms for only 1 week, but most had symptoms for
6 months or more. Three of the tumors complicated
Paget disease of bone, and 12 developed in bones that
had been affected by previous radiation therapy. Two
malignant fi brous histiocytomas arose in association
with bone infarct. One arose at the site of a previous
total hip arthroplasty. Troop and coauthors and Haag
and Adler also h ave reported a case each of malignant
fi brous histiocytoma at the site of a previous total hip
replacement. Hence, 24.1% of all malignant fi brous his-
tiocytomas have to be considered secondary. Huvos and
coauthors reported that 28% of the malignant fi brous
histiocytomas of bone were considered secondary.

PH YSICAL FIN D IN GS

Pain or swelling or both were noted as a consequence

of the local lesion.

RAD IOGRAPH IC FEATU RES

The most common appearance is that of a purely lytic

destructive lesion. Cortical destruction is almost always
present and usually extensive. Cortical breakthrough
with an associated soft-tissue mass is common. The
features are those of an aggressive malignant tumor. The
F igu r e 15.2. Malign an t fi brous h istiocytoma associated
differential diagnosis includes osteosarcoma in younger with a path ologic fracture in th e distal femur in a youn g
patients and fi brosarcoma, lymphoma, metastasis, and woman . Th e lesion is purely lytic, alth ough th ere is some
myeloma in older patients ( Figs. 15.2–15.4) . sclerotic reaction in th e soft-tissue exten sion .
186 Chapter 15 ■

Figure 15.3. Anteroposterior radiograph of a malig-

nant fibrous histiocytoma forming a destructive mass
at the site of a previous arthroplasty in the femur in
a 72-year-old man. He had knee replacement surgery
9 years before this tumor was detected.

F igu re 15.4. Anteroposterior

( A) and lateral (B) radiographs
of malignant fi brous histiocytoma
associated with an infarct involv-
ing the distal femur in a 61-year-old
man. Pancreatitis had developed
approximately 40 years earlier.
Infarcts are seen in the femur
and the tibia. The gross specimen
( C) shows infarct in the distal por-
tion of the bone. The tumor is dark
red and has destroyed the cortex.

F igu r e 15.5. Malignant fi brous histiocytoma in a 22-year-
old man . Th is tumor forms a partially h emorrh agic mass th at
exten sively in volves the proximal an d mid h umerus an d is
associated with extension into soft tissue.
GROSS PATH OLOGIC FEATU RES
The tumors varied from fi brous to soft. A few lesions
were yellowish ( because of lipid content) or brown or
tan, and a few contained necrotic zones. Benign het-
erotopic ossifi cation occurred within one lesion. This
was the only periosteally located tumor; the rest were
predominantly intraosseous. Only one tumor had pro-
duced pathologic fracture. Three of the tumors arose in
association with Paget disease ( Figs. 15.5 & 15.6) .
H ISTOPATH OLOGIC FEATU RES
Microscopic quality determined inclusion of the tumor
in th is series. Th e features observed represen t wh at
domin ated th e fi elds studied; much variation existed
with in th e tumors. Multin ucleated tumor cells ( malig-
n an t gian t cells) with n uclei usually possessin g a h istio-
cytic appearan ce were foun d in every tumor, but th ese
varied from n umerous to few. A h istiocytic appearan ce
was provided by groovin g or in den tation of n uclei,
n ucleoli th at were often amph oph ilic an d large, an d,
frequen tly, a promin en t, well-defi n ed cytoplasmic mass.
A few tumors con tain ed promin en t foci of h istiocytic
mon on uclear cells, wh ich were suggestive of malign an t
lymph oma of bon e.
Fibrosis varied from sligh t to promin en t th rough -
out man y fi elds an d was recogn ized in most tumors.
Th e fi brogen ic areas frequen tly exh ibited a storiform
or “cartwh eel” pattern , with th e fascicles appearin g
to radiate irregularly from focal h ypocellular zon es.
Wh en th e fi brous tissue is h yalin ized, th e differen -
tiation from osteoid becomes arbitrary. In pleomor-
ph ic sarcoma, in wh ich even a small focus of wh at
was deemed to be osteoid was foun d, it was classifi ed
■ Malignant Fibrous Histiocytoma 187
F igu r e 15.6. Malign an t fi brous h istiocytoma formin g a
fl esh y mass in the proximal tibia in a 49-year-old woman . Th e
tumor extends through the articular cartilage. The tumor was
treated surgically, and th e patient was without eviden ce of dis-
ease 14 years later.
as an osteosarcoma. Th e differen tiation between a
h igh -grade osteosarcoma an d a h igh -grade malign an t
fi brous h istiocytoma is probably n ot sign ifi can t clin i-
cally ( Figs. 15.7–15.11) .
Chronic infl ammatory cells, usually lymphocytes,
were found in more than half of the tumors. These
cells occurred in small clusters, were scattered diffusely
throughout the tumor, or were most promin ent at the
periphery of the neoplasm. A few tumors had what
appeared to be immaturity of the cells; the differen-
tiation of malignant lymphoma of bone with fi brosis
from malignant fi brous histiocytoma can be very diffi -
cult. If the spindle cell nuclei are defi nitely malignant,
then the tumor is not a lymphoma. Any multicentric
tumor with a histiocytic quality should be suspected to
be a malignant lymphoma of bone. Although myofi brils
and cross striations were not identifi ed, the abundant
granular cytoplasm of the cells produced a myogenic
188 Chapter 15 ■
F igu r e 15.7. Malignant fi brous histiocytoma involving the
femur in a 27-year-old woman. A: Low-power view shows a sto-
riform arrangemen t of th e tumor cells. B: High -power view
sh ows marked cytologic pleomorph ism. C: Th is fi eld con tain s
several lymph ocytes an d plasma cells, a fi n din g n ot un com-
mon ly seen in malign an t fi brous h istiocytoma.
F igu r e 15.8. Example of grade 4 malign an t fi brous h istio-
cytoma with a predomin ately fascicular pattern . Th e resected
specimen sh owed n o eviden ce of osteoid production .
F igu r e 15.9. Because of hemorrhagic areas in this malig-
n an t fi brous histiocytoma of th e distal femur, telan giectatic
osteosarcoma needs to be in cluded in th e differen tial diag-
n osis. H owever, other sections contained broad areas of solid
tumor, a fi n din g n ot compatible with th e diagn osis of telan gi-
ectatic osteosarcoma.
quality in some instances. The foamy cytoplasm of the
tumor cells also raises the possibility of a diagnosis of
liposarcoma. Hemosiderin pigment, areas of necrosis,
and clusters of osteoclast-like giant cells were all seen
in about one-fourth of the tumors. The tumors usually
had a well-circumscribed pushing border when they
extended outside bone, but a few lesions invaded fat or
striated muscle.
Huvos has divided malignant fi brous histiocytoma
of bone into fi brous, histiocytic, and malignant giant
cell tumor variants. However, this subclassifi cation
did not have prognostic signifi cance. Because of the

F igu r e 15.10. Malign an t fi brous h istiocytoma with areas of
dense sclerosis. It occasionally can be diffi cult to determine
whether the eosinophilic hyalinized areas represent osteoid
or collagen , particularly in small biopsy specimen s.
F igu r e 15.11. Malignant fi brous histiocytoma arising in a
bon e in farct. A: Low-power view sh ows th e in farct ( right) adja-
cen t to malign ant fi brous h istiocytoma ( left) . B: High-power
view highlighting the cytologic atypia of the spindle cells in
the sarcoma.
■ Malignant Fibrous Histiocytoma 189
pleomorphism of the tumor cells inherent in the defi ni-
tion of the neoplasm, most malignant fi brous histiocy-
tomas have to be considered high grade. The possibility
of a metastatic sarcomatoid renal cell carcinoma must
always be kept in mind when a diagnosis of malignant
fi brous histocytoma of bone is considered.
TREATMEN T
Although the Mayo Clinic series does not provide defi n-
itive information, the tumors probably are relatively
radioresistant. Most of the tumors are managed with
surgical ablation. In the Mayo Clinic series, two patients
were apparently cured with radiation therapy.
It appears reason able to treat malignan t fi brous
h istiocytoma with th e same regimen applied for osteo-
sarcoma. Th ere is n ot enough in formation in th e Mayo
Clin ic fi les to kn ow wh eth er ch emoth erapy is effective.
H owever, studies from th e Neth erlan ds, Italy, an d Japan
h ave all suggested that preoperative ch emoth erapy
improves progn osis in malign an t fi brous h istiocytoma
of bon e.
PROGN OSIS
Most reports suggest that the prognosis in malignant
fi brous histiocytoma is similar to that of high-grade oste-
osarcoma and fi brosarcoma. In the series from Bologna,
the 5-year survival rate was 34% and the 10-year survival
was 28%. With adequate surgery, a 5-year survival rate
as high as 63% has been reported. It has also been sug-
gested that patients with secondary malignant fi brous
histiocytoma have a worse prognosis than those with
primary tumors. Taconis and van Rijssel have reported
that prognosis in fi brosarcoma of bone is similar to that
of malignant fi brous histiocytoma.
BIBLIOGRAPH Y
1972 Kempson, R. L. and Kyriakos, M.: Fibroxanthosarcoma of
the Soft Tissues: A Type of Malignant Fibrous Histiocytoma.
Cancer, 29:961–976.
1972 Soule, E. H. and Enriquez, P.: Atypical Fibrous Histiocy-
toma, Malignant Fibrous Histiocytoma, Malignant Histio-
cytoma, an d Epith elioid Sarcoma: A Comparative Study of
65 Tumors. Cancer, 30:128–143.
1974 Mirra, J. M., Bullough, P. G., Marcove, R. C., Jacobs, B., and
Huvos, A. G.: Malignant Fibrous H istiocytoma and Osteosar-
coma in Association With Bon e In farcts: Report of Four Cases,
Two in Caisson Workers. J Bone Joint Surg, 56A:932–940.
1975 Fu, Y.-S., Gabbian i, G., Kaye, G. L., an d Lattes, R.: Malig-
n an t Soft Tissue Tumors of Probable H istiocytic O rigin
( Malign an t Fibrous H istiocytomas) : Gen eral Con sideration s
an d Electron Microscopic an d Tissue Culture Studies. Can cer,
35:176–198.
190 Chapter 15 ■
1975 Newland, R. C., Harrison , M. A., and Wright, R. G.: Fibrox-
an thosarcoma of Bone. Path ology, 7:203–208.
1975 Spanier, S. S., Enneking, W. F., and Enriquez, P.: Primary
Malign an t Fibrous Histiocytoma of Bon e. Can cer, 36:2084–
2098.
1976 Alquacil-Garcia, A.: Personal Communication.
1976 Huvos, A. G.: Primary Malignant Fibrous H istiocytoma of
Bone: Clinicopathologic Study of 18 Patients. NY State J Med,
76:552–559.
1977 Dahlin, D. C., Unni, K. K., and Matsuno, T.: Malignant
fi brous Histiocytoma of Bon e: Fact or Fancy? Cancer, 39:1508–
1516.
1977 Feldman, F. and Lattes, R.: Primary Malignant Fibrous
Histiocytoma ( Fibrous Xanthoma) of Bone. Skeletal Radiol,
1:145–160.
1977 Mirra, J. M., Gold, R. H., and Marafi ote, R.: Malignant
fi brous Histiocytoma Arising in Association With a Bon e
In farct in Sickle-Cell Disease: Coin ciden ce or Cause-an d-
Effect? Cancer, 39:186–194.
1979 McCarthy, E. F., Matsuno, T., and Dor fman, H . D.: Malig-
n ant Fibrous H istiocytoma of Bone: A Study of 35 Cases. H um
Pathol, 10:57–70.
1981 Katenkamp, D. and Stiller, D.: Malignant Fibrous Histiocy-
toma of Bone: Light Microscopic and Electron Microscopic
Examin ation of Four Cases. Virchows Arch [ A] , 391:323–335.
1982 Ghandur-Mnaymneh, L., Zych, G., and Mnaymneh, W.:
Primary Malignant Fibrous H istiocytoma of Bon e: Report of
Six Cases With Ultrastructural Study and Analysis of the Litera-
ture. Cancer, 49:698–707.
1983 Weiner, M., Sedlis, M., Johnston, D., Dick, H. M., and Wolff,
J. A.: Adjuvant Chemotherapy of Malignant Fibrous Histiocy-
toma of Bon e. Cancer, 51:25–29.
1984 Capanna, R., Bertoni, F., Bacchini, P., Bacci, G., Guerra,
A., an d Campan acci, M.: Malign an t Fibrous Histiocytoma
of Bon e: Th e Experien ce at th e Rizzoli In stitute: Report of
90 Cases. Cancer, 54:177–187.
1984 Taconis, W. K. and Mulder, J. D.: Fibrosarcoma and Malig-
n an t Fibrous Histiocytoma of Long Bon es: Radiograph ic
Features and Grading. Skeletal Radiol, 11:237–245.
1985 den Heeten, G. J., Schraffordt Koops, H. S., Kamps, W. A.,
Oosterhuis, J. W., Sleijfer, D. T., and Oldhoff, J.: Treatment of
Malign an t Fibrous H istiocytoma of Bon e: A Plea for Primary
Ch emotherapy. Cancer, 56:37–40.
1985 Huvos, A. G., H eilweil, M., and Bretsky, S. S.: The Pathol-
ogy of Malign an t Fibrous H istiocytoma of Bon e: A Study of
130 Patients. Am J Surg Pathol, 9:853–871.
1985 Tacon is, W. K. and van Rijssel, T. G.: Fibrosarcoma of Lon g
Bon es: A Study of th e Sign ifi can ce of Areas of Malign an t
Fibrous Histiocytoma. J Bone Joint Surg, 67B:111–116.
1986 H uvos, A. G., Woodard, H. Q., and Heilweil, M.: Postradia-
tion Malignant Fibrous H istiocytoma of Bone: A Clinicopatho-
logic Study of 20 Patien ts. Am J Surg Path ol, 10:9–18.
1986 Strauchen, J. A. and Dimitriu-Bona, A.: Malignant Fibrous
Histiocytoma: Expression of Monocyte/ Macrophage Differen-
tiation Antigens Detected With Monoclonal Antibodies. Am
J Path ol, 124:303–309.
1986 Wood, G. S., Beckstead, J. H., Turner, R. R., Hendrickson,
M. R., Kempson , R. L., and Warn ke, R. A.: Malignan t Fibrous
Histiocytoma Tumor Cells Resemble Fibroblasts. Am J Surg
Pathol, 10:323–335.
1987 Fletcher, C. D.: Malignant Fibrous Histiocytoma? Histopa-
thology, 11:433–437.
1987 Frierson, H. F., Jr., Fechner, R. E., Stallings, R. G., and
Wan g, G. J.: Malign an t Fibrous Histiocytoma in Bon e In farct:
Association With Sickle Cell Trait an d Alcoh ol Abuse. Can cer,
59:496–500.
1988 Ushigome, S., Takakuwa, T., Shimoda, T., Nakajima, H.,
and Fukun aga, M.: Immun ocytochemical Aspects of th e Dif-
ferential Diagnosis of Osteosarcoma and Malignant Fibrous
Histiocytoma. Surg Path ol, 1:347–357.
1989 Haag, M. and Adler, C. P.: Malignant Fibrous Histiocytoma in
Association With Hip Replacement. J Bone Joint Surg, 71B:701.
1990 Lindeman, G., McKay, M. J., Taubman, K. L., and Bilous,
A. M.: Malign an t Fibrous Histiocytoma Developin g in Bon e 44
Years After Shrapn el Trauma. Can cer, 66:2229–2232.
1990 Troop, J. K., Mallory, T. H., Fisher, D. A., and Vaughn, B. K.:
Malign an t Fibrous Histiocytoma After Total Hip Arth roplasty:
A Case Report. Clin Orth op, 253:297–300.
1993 Yokoyama, R., Tsuneyoshi, M., Enjoji, M., Shinohara, N.,
and Masuda, S.: Prognostic Factors of Malign an t Fibrous H is-
tiocytoma of Bone: A Clinical and Histopathologic Analysis of
34 Cases. Can cer, 72:1902–1908.
1995 Naka, T., Fukuda, T., Shinohara, N., Iwamoto, Y., Sugioka Y.,
and Tsun eyoshi, M.: Osteosarcoma Versus Malign ant Fibrous
Histiocytoma of Bone in Patients Older Than 40 Years: A Clini-
copath ologic an d Immun oh istoch emical An alysis With Special
Referen ce to Malign an t Fibrous H istiocytoma-Like Osteosar-
coma. Cancer, 76:972–984.
1998 Bacci, G., Picci, P., Mercuri, M., Bertoni, F., an d Ferrari S.
Neoadjuvan t Ch emoth erapy for H igh Grade Malign an t Fibrous
H istiocytoma of Bon e. Clin O rth op Relat Res, 346:178–189.

Myeloma
Myeloma, a tumor of hematopoietic derivation, is the
most common primary neoplasm of bone. Among
malignancies involving the skeleton, only metastatic
carcinoma is more common. There are more than
5,000 patients with myeloma documented in the Mayo
Clinic fi les. However, this series includes only patients
whose diagnosis was made with needle biopsy or open
biopsy. The neoplasm is composed of plasma cells that
sh ow various degrees of differentiation. The process is
usually multicentric and often involves bone marrow
so diffusely that it is diagnosed most frequently on the
basis of bone marrow aspiration.
Most patients with myeloma present with pre-
dominant hematologic problems, and their therapy is
managed by hematologists or by oncologists and radio-
therapists. The discussion in this chapter is oriented
toward the problems encountered in surgical material.
The complex hematologic and protein disturbances will
not be considered, but some of the pertinent literature
is indicated in th e bibliography. Extraskeletal infi ltrates
of myeloma cells in a wide variety of tissues may occur in
patients with multiple myeloma. Nearly 80% of the infi l-
trates of solitary extramedullary plasmacytoma occur in
the upper air passages and oral cavity. In most cases,
these are cured with local therapy, which has included
electrocautery, excision, irradiation, or a combination
of these. In some patients with these extramedullary
plasma cell tumors, multiple myeloma develops.
Renal involvement with manifestations of renal insuf-
fi ciency is an important complication of myeloma that
may be the immediate cause of death. The usual histo-
logic fi nding is not myelomatous infi ltration but blockage
of the tubules by proteinaceous casts. Much less impor-
tant is the occasional development of renal amyloidosis,
“metastatic” calcifi cation of the kidneys in patients with
skeletal demineralization, or pyelonephritis.
Occasionally, a single osseous focus of myeloma is
associated with normal marrow and with few or none
of th e usual laboratory fi ndings so characteristic of mul-
tiple myeloma. In patients with such lesions, multiple
C H APT ER
16
myeloma usually develops, but this occurs sometimes
only after a latent period of 5 to 10 years or even longer.
Some patients experience long-term “cures.” “Solitary”
myeloma in bone must be differentiated from a focus
of chronic osteomyelitis with abundant plasma cells.
The distinction is aided by the fi nding of proliferation
of fi broblasts and capillaries as part of the response to
infl ammation and the sprinkling of polymorphonu-
clear leukocytes and histiocytes in the latter condition.
Rarely, immunohistochemical staining for monoclonal
antibodies may be needed to differentiate the mono-
clonal growth of cells in myeloma from the polyclonal
growth in osteomyelitis.
IN CID EN CE
The 1,057 myelomas of bone comprise 14.9% of
the malignant bone tumors in the Mayo Clinic series
( Fig. 16.1) . The major reasons for operation in the
surgical series included the presence of an indetermi-
nate osseous lesion, compression of the spin al cord, or
pathologic fracture.
SEX
Of the 1,069 patients who underwent surgery, 67.7%
were males.
AGE
The well-known rarity of myeloma in patients who are
younger than 40 years is shown in the Mayo Clinic series.
The youngest patient was a 16-year-old boy with a lesion
of the lumbar vertebra. Only 7.2% of the patients in
the surgical series were in the fi rst four decades of life.
The largest concentration was in the sixth and seventh
decades of life.
191
192 Chapter 16 ■
LOCALIZATION
The bones that contain hematopoietic marrow in adults
harbor most of the recognizable myeloma nodules.
Although these data are selective because they are based on
surgical cases only, the distribution shown is similar to that
observed at autopsy, except that the skull is usually involved
by the time that myeloma has caused the patient’s death.
In a review of the cases of 46 patients from the Mayo Clinic
files who had “solitary” plasmacytoma of bone, Frassica and
coauthors found that 54% of the lesions involved the ver-
tebral column. In a few tumors listed as maxillary, it was
difficult to be certain that the neoplasm began in bone.
SYMPTOMS
In creasin g pain is th e most frequen t complain t of
patien ts with myeloma, an d th e pain is most often cen -
tered in th e lumbar or th oracic spin al region . O n aver-
age, th e pain is of less th an 6 mon th s’ duration before
th e patien t seeks medical atten tion , but sometimes it
h as been presen t for several years. Nearly ever y patien t
with myeloma h as weakn ess an d loss of weigh t durin g
th e disease. Path ologic fracture, with abrupt on set of
symptoms, is common , an d most such fractures in volve
th e vertebral column . Neurologic symptoms, usually
from disease of th e spin al cord or n er ve roots sec-
on dar y to path ologic fracture or extraosseous exten -
sion of th e n eoplastic tissue, are frequen tly obser ved.
Periph eral n europath y associated especially with th e
F igu r e 1 6 .1 . Distribu tion of
myelomas according to age and
sex of the patient and site of the
lesion.
osteosclerotic form of myeloma is in creasin gly bein g
recogn ized. Th ere were 54 patien ts with osteosclerotic
myeloma, at least 36 of wh om h ad periph eral n europa-
th y. Not all patien ts with osteosclerotic myeloma pres-
en t with periph eral n europath y. Not all patien ts with
periph eral n europath y an d associated myeloma h ave
th e osteosclerotic form. Rarely, periph eral n europa-
th y may be associated with classic myeloma. Th e etiol-
ogy of th e periph eral n europath y in th ese two kin ds of
myeloma probably is differen t. Complain ts referable
to ren al in volvemen t may be en coun tered. Less com-
mon symptoms in clude palpable tumor, h emorrh agic
ten den cy, an emia, an d fever. Rarely, a patien t with
myeloma may presen t with a h ypercalcemic crisis.
In rare instances, other neoplasms coexist with
myeloma, and myeloma is occasionally secondary. One
patient in the Mayo Clinic series developed myeloma
of the proximal tibia after years of well-recognized sys-
temic mastocytosis. A biopsy specimen from the proxi-
mal tibia showed both mastocytosis and an anaplastic
myeloma. One patient had myeloma associated with an
enchondroma, producing the radiographic appearance
of dedifferentiated chondrosarcoma.
PH YSICAL AN D
LABORATORY FIN D IN GS
Physical fi ndings may refl ect secondary changes result-
ing from generalized malignant disease with replace-
ment of bone marrow. Local pain or tenderness, with
 ■ Myeloma 193

or without palpable tumor, and neurologic dysfunction

may be elicited.
Smears of peripheral blood often show excessive rou-
leau formation, and it has been reported that myeloma
cells are found in 70% of the patients. Rarely, plasma
cell leukemia develops. Generally, there is moderate
to severe anemia. The erythrocyte sedimentation rate
is usually rapid. Hypercalcemia occurs in 20% to 50%
of patients. Eventually, Bence Jones proteinuria can be
found in more than h alf of the patients. Evidence of
renal insuffi ciency or amyloidosis, which may be gen-
eralized, sometimes develops. Levels of serum alkaline
phosphatase are rarely elevated.
Elevation of various globulin fractions on electro-
phoretic studies of serum and urinary proteins pro-
vide critical diagnostic infl ammation. In a study of 869
patients, Kyle found skeletal radiographic abnormalities
in 79%. Serum protein electrophoresis showed a spike
in 76%, hypogammaglobulinemia in 9%, and minor
or no abnormalities in 15%; a globulin spike was seen F igu r e 16.2. Multiple myeloma. Radiograph of th e skull
in 75% of the urinary electrophoretic patterns. Serum sh ows multiple discrete osteolytic calcarial lesion s th at are th e
immunoelectrophoresis revealed only a monoclonal h allmark of multiple myeloma.
heavy chain in 83% and a monoclonal light chain in
8% ( Bence Jones proteinemia) . Amyloidosis was found
in 7% of the patients. There is an interrelationship
amon g amyloidosis, Waldenström macroglobulinemia,
an d myeloma. The complexities of these protein studies
were elaborated by Osserman and Takatsuki in 1963.

RAD IOGRAPH IC FEATU RES

The radiographic features result from replacement of

osseous structures by th e myelomatous masses. The fi rst
and most extensive changes usually occur in the ribs, ver-
tebrae, skull, and pelvis. Classically, there are “punched-
out” areas of bone destruction that vary up to 5 cm in
greatest dimension and have no surrounding zone of
sclerosis ( Figs. 16.2 & 16.3) . Expansion of the affected
bones may produce a “ballooned-out” appearance,
especially in the ribs. Variable osteoporosis is common,
and pathologic fracture, especially of vertebrae, is often
seen. From 12% to 25% of patients with myeloma have
no discernible foci of bone destruction. On close scru-
tiny, some of these patients are found to have diffuse
demineralization of portions of the skeleton. Computed
tomograms and magn etic resonance imagin g studies
may show small, discrete lesions when plain radiographs
are negative or show only diffuse osteoporosis. There is F igu re 16.3. Multiple myeloma involving the proximal femur.
The tumor is a purely lytic lesion that erodes the bone.
some variability in the appearance of multiple myeloma
on magnetic resonance images because the disease
does not involve the marrow in a homogeneous fash- can produce bone lesion s th at may simulate myeloma.
ion. In addition, the magnetic resonance appearance of Th e lesion s of metastatic carcin oma an d malignant lym-
the marrow depends on the extent of fatty replacement, ph oma are usually positive on bone scans, wh ereas th e
which is variable, particularly with age. Metastatic carci- lesion s of myeloma usually are n ot. “Solitary” myeloma
noma, malignant lymphoma, and h yperparath yroidism lesion s of bon e are classically lytic, an d th ey too may
194 Chapter 16 ■

expan d th e bon e ( Figs. 16.4 & 16.5) . Pugh h as stated
th at sclerosin g areas on radiograph s of patien ts with
myeloma are usually due to some process oth er th an
myeloma. H owever, osteosclerotic myelomas, espe-
cially th ose associated with periph eral n europath y, are
bein g diagn osed more frequen tly. Th e lesion s may be
solitary or multiple. Th e sclerosis may be in th e form
of a periph eral rin d aroun d a lytic focus or un iformly
sclerotic lesion s th at simulate th e appearan ce of blas-
tic metastases ( Fig. 16.6) .
GROSS PATH OLOGIC FEATU RES
Th e myelomatous masses are classically soft, pin k or
gray, an d friable; th e appearan ce h as been suggested to
be th at of curran t jelly. H owever, some myelomas h ave
a wh ite fi sh -fl esh appearan ce simulatin g th at of lym-
ph oma. As with oth er in vasive tumors, more marrow is
often seen to be in volved th an is in dicated by th e radio-
graphic changes. Expansion of th e affected bone and,
even more commonly, extraosseous extension of th e

F igu re 16.4. A: Plain radiograph of a purely lytic destructive lesion of the ischium in a 61-year-old
man. Biopsy was not per formed at this stage. B: Radiograph 5 years later shows a huge expansile mass
of the ischium. Staging studies showed that it was still a solitary lesion. However, multiple myeloma
developed later, and the patient died of disease 12 years after the initial tumor was discovered.

F igu re 16.5. Computed tomogram of the ilium in a

70-year-old man. The large soft-tissue mass was calcifi ed.
The calcifi cation was within the amyloid that was within
the myeloma. Because of this radiographic fi nding, chond-
rosarcoma was included in the differential diagnosis ( Case
provided by Dr. Markku Miettinen, Thomas Jefferson
University Hospital, Philadelphia, Pennsylvania.) .

F igu r e 16.6. O steosclerotic myeloma in a 53-year-old man .
A: Plain radiograph of th e cervical spin e sh ows multiple small
sclerotic areas. B: Computed tomogram sh ows in n umerable
sclerotic areas in volvin g th e sacrum an d th e ilium.
tumor damage th e adjacen t structures. Extraosseous
lesion s are sometimes grossly discern ible in oth er
portion s of th e h ematopoietic system, n otably in th e
lymph n odes an d spleen . In th is surgical series, n odes
con tain in g myeloma were removed from eigh t patien ts,
an d an in fi ltrated testis was removed from on e patien t.
As in dicated, path ologic fracture may be presen t an d
often results in damage to th e spin al cord. In very rare
in stan ces, en ough amyloid is formed by th e tumor to
be grossly obvious. In th ese circumstan ces, th e tumor
■ Myeloma 195
F igu r e 16.7. Typical gross appearance of myeloma involving
the femoral head.
F igu r e 16.8. Typical appearance of myeloma. The tumor
forms a fl esh y dark red-brown mass.
h as th e ligh t gray, waxy appearan ce of amyloid. An
un usual combin ation of sclerosis an d lysis in volved
almost an en tire femur in on e patien t; amputation
was per formed for plasma cell myeloma th at com-
plicated ch ron ic osteomyelitis of 40 years’ duration
( Figs. 16.7–16.10) .
196 Chapter 16 ■
F igu r e 16.9. Plasmacytoma in volvin g th e man ubrium of a
51-year-old woman who presented with chest pain. The tumor
was solitary at diagnosis; however, the multiple myeloma devel-
oped a couple of years after th e tumor was resected. Micro-
scopically, th e tan area of th e tumor con sisted predomin ately
of amyloid.
F igu r e 16.10. This resected rib was involved by multiple
myeloma. The fl eshy tan-gray appearance is similar to that
commonly seen with lymphoma.
H ISTOPATH OLOGIC FEATU RES
Typically, th e path ologist sees sh eets of closely packed
cells with little in tercellular substan ce. Th e cells h ave
abun dan t cytoplasm, wh ich ten ds to be gran ular an d
basoph ilic. In tissue section s, th e cytoplasm frequen tly
stain s pin k. Th e cell outlin es are distin ct, an d th e
n ucleus is ch aracteristically roun d or oval an d eccen -
tric. Two, or even th ree, n uclei are sometimes observed
in each cell. Wh en on e studies a series of cases of
myeloma, variation s are foun d, wh ich apparen tly
refl ect th e maturity or degree of differen tiation of
th e cells. At on e extreme are tumors with cells closely
resemblin g th e plasma cells in in fl ammatory con di-
tion s; th ese sh ow promin en t clumpin g of ch romatin ,
sometimes producin g a cartwh eel appearan ce. With
decreasin g differen tiation , n ucleoli become en larged
an d clumpin g of ch romatin is less pron oun ced. Cyto-
plasmic vacuoles in crease in promin en ce, an d th e cell
boun dary becomes in distin ct. Fin ally, th e n uclei may
h ave grooves an d lobules. An extremely un differen ti-
ated myeloma may be impossible to distin guish from
lymph oma ( Figs. 16.11–16.15) .
Mitotic fi gures are rare in the typical myeloma. The
similarity of the cells comprising the solid sheets in this
tumor contrast with the multiplicity of cell types in the
occasional chronic infl ammatory focus that superfi -
cially resembles myeloma. The infl ammatory pseudo-
neoplasm often contains a prominent capillary network
that aides in differentiation.
Myelomas frequently are extremely vascular. The ves-
sels may be thick-walled capillaries, which may contain
deposits of amyloid. Frequently, the capillaries have a
sinusoidal pattern resembling the appearance of an
endocrine neoplasm. Because of the similarity of the
nuclei of plasma cells to those of endocrine neoplasms
such as carcinoid tumor, it may be diffi cult to distin-
guish the two in a small biopsy specimen. Occasionally,
the vascular pattern consists of vessels with a staghorn
appearance, simulating the appearance of a hemangio-
pericytoma. The neoplastic cells may deform the capil-
laries as seen in hemangiopericytoma. If the cells tend
to become oval in addition to having a vascular pattern,
the appearance may strongly suggest the diagn osis of
hemangiopericytoma ( Figs. 16.16 & 16.17) .
Amyloidosis is related to the altered proteins, as
evidenced by its occurrence in approximately 10% of
patients with myeloma. The distribution of amyloid with
generalized deposition simulates that of primary systemic
amyloidosis, a diagnosis that depends on the exclusion
of myeloma as well as other more obvious causes of amy-
loidosis. Amyloid deposits are sometimes found within
the plasma cell proliferation and may be so abundant
as to mask the neoplasm or the amyloid deposits may
be subtle. When the deposits are massive, they are usu-
ally associated with a giant cell reaction. Amyloid tumors
of bone are extremely rare. The presence of amyloid in
bone usually means myeloma ( Figs. 16.18–16.20) . The
rare exception is the deposits of amyloid-like material
in bone in patients receiving long-term hemodialysis for
 ■ Myeloma 197

F igu r e 16.11. Th e n uclei of th is myeloma con tain promi- F igu r e 16.13. Pleomorph ic plasma cells were scattered
nen t nucleoli. throughout this tumor. Plenty of smaller cells in the back-
ground still have recognizable plasmacytic features.

F igu r e 16.12. Several small lymph ocytes are admixed with

th e malign an t plasma cells in th is myeloma. Lymph oma would F igu r e 16.14. Th is an aplastic myeloma h as a strikin g degree
be in th e differential diagn osis. of cytologic pleomorph ism.

F igu r e 16.15. O steosclerotic myeloma. A: Low-power view sh ows th at clusters of plasma cells in
osteosclerotic myeloma are usually surroun ded by den se sclerotic bon e. Th is can cause diffi culty
makin g a defi n itive diagn osis on th e basis of a small biopsy specimen . B: High -power view of th e
cells in on e of the clusters sh ows cytologic features typical of plasma cells.
198 Chapter 16 ■
F igu r e 16.16. Myeloma. A: Low-power view sh ows a prolifer-
ation of small roun d cells. Th e lesion con tain s dilated vascular
spaces, producing a h eman giopericytomatous appearan ce.
B: H igh -power view sh ows th e plasmacytic features of th e
tumor cells.
F igu r e 16.17. Th e clusterin g arran gemen t of th e tumor
cells in th is myeloma could lead to a mistaken diagn osis of
carcin oma, particularly n euroen docrin e carcin oma.
F igu r e 16.18. Abun dan t amyloid was foun d with in th is plas-
macytoma. The amyloid occurred in sheets, nodular deposits,
and around blood vessels.
F igu r e 16.19. A promin en t foreign body multin ucleated
giant cell reaction to amyloid in this plasmacytoma could lead
to an erroneous diagnosis of infection.
chronic renal failure. The deposits of amyloid may calcify
and may suggest the diagnosis of chondrosarcoma on
radiographs ( Fig. 16.5). Immunohistochemical staining
may be useful in establishing a diagnosis of myeloma.
A monoclonal staining pattern for kappa or lambda
light chain will establish a diagnosis of malignancy. This
is in contrast to reactive plasmacytosis, which has a poly-
clonal pattern. In most cases of myeloma, the light chain
type, as determined in tissues by immunohistochemical
methods, corresponds to the serum or urine protein
(or both) . Although no single antibody is useful in dif-
ferentiating myelomas from lymphomas that have plas-
macytic features, the combination of CD45 ( LCA) and

F igu r e 16.20. A: Vast sheets of amyloid were present in this resected femoral head. B: Only rarely
could plasma cells be foun d with in th e n odular masses of amyloid.
CD20, a B-cell marker, is strongly expressed in B-cell
lymphoma and is weak or negative in myeloma. Neo-
plastic and nonneoplastic plasma cells usually express
CD138. However, it is not entirely specifi c for plasma
cells since other tumors, in particular carcinomas, are
occasionally positive with CD138. Keratin stains can be
very helpful when carcinoma is included in the differ-
ential diagnosis. However, myeloma cells are frequently
positive with epithelial membrane antigen.
TREATMEN T
Patients with myeloma are most effectively treated with
ch emotherapy, oftentimes including high-dose therapy
with autologous stem cell transplantation. Radiation
therapy plays a role in solitary myeloma and certain
clinical settings where it is used to reduce pain and com-
pression of local structures. In patients with severe neu-
rologic symptoms, decompression of the spinal cord
may be necessary before radiation. General supportive
measures are necessary, such as adequate hydration and
management of hypercalcemia. Orthopedic oncologists
play a role in treatmen t through surgical management
of pathologic or incipient fractures. This may render the
patient pain free even if the life expectancy is short.
PROGN OSIS
In anition, anemia, involvement of the spinal cord, and
renal failure are the major factors contributin g to the
death of patients with disseminated myeloma, and many
patients die with in 2 years after diagnosis. In an earlier
■ Myeloma 199
series of surgical patients in whom the disease was not
in a solitary focus at diagnosis, slightly more than 10%
of them survived at least 5 years. Currently, the median
survival of all patients with multiple myeloma is approxi-
mately 3 years.
Solitary myeloma, as many authors have stressed,
is a forerunner of multiple myeloma. Approximately
50% of patients with solitary plasmacytoma of bone will
develop multiple myeloma after a median duration of
2 to 3 years. Frassica and coauthors reviewed 46 cases
of solitary plasmacytoma in the Mayo Clinic fi les. While
disease progressed in the majority of patients within the
fi rst 2 years, the overall survival was 74% at 5 years and
45% at 10 years.
BIBLIOGRAPH Y
1951 Pugh , D. G.: Roen tgen ologic Diagn osis of Dieases of Bon e.
New York, Th omas Nelson & Son s.
1960 En gels, E. P., Smith, R. C., an d Kran tz, S.: Bon e Sclerosis in
Multiple Myeloma. Radiology, 75:242–247.
1961 Kyle, R.A. and Bayrd, E. D.: “Primary” Systemic Amyloido-
sis an d Myeloma: Discussion of Relation sh ip an d Review of 81
Cases. Arch In tern Med, 107:344–353.
1963 Osserman, E. F. and Takatsuki, K.: Plasma Cell Myeloma:
Gamma Globulin Syn th esis an d Structure: A Review of Bio-
ch emical an d Clin ical Data, With th e Description of a Newly
Recogn ized an d Related Syn drome, “Hg–2-Chain ( Franklin ’s)
Disease.” Medicine ( Baltimore) , 42 :357–384.
1964 Cohen, D. M., Svien, H. J., and Dahlin, D. C.: Long-Term
Survival of Patients With Myeloma of the Vertebral Column.
JAMA, 187:914–917.
1972 Kotner, L. M. and Wang, C. C.: Plasmacytoma of the Upper
Air an d Food Passages. Can cer, 30 :414–418.
1972 Oberkircher, P. E., Miller, W. T., and Arger, P. H.:
Non osseous Presen tation of Plasma-Cell Myeloma. Radiology,
104:515–520.
200 Chapter 16 ■
1974 Getaz, P., Handler, L., Jacobs, P., and Tunley, I.: Osteo-
sclerotic Myeloma With Periph eral Neuropath y. S Afr Med J,
48 :1246–1250.
1974 Meyer, J. E. and Schultz, M. D.: “Solitary” Myeloma of Bone:
A Review of 12 Cases. Cancer, 34 :438–440.
1975 Berman, H . H.: Waldenström’s Macroglobulinemia With
Lytic Osseous Lesions and Plasma-Cell Morphology: Report of
a Case. Am J Clin Pathol, 63 :397–402.
1975 Kyle, R. A.: Multiple Myeloma: Review of 869 Cases. Mayo
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Malignant Lymphoma of Bone
Parker and Jackson, in 1939, fi rst described malignant
lymphoma of bone and separated it from Ewing tumor.
The discussion in this chapter is oriented to the problem
of lymphoma of the skeleton as encountered by the
surgical pathologist, the surgeon, and the therapist.
Detailed considerations of lymphoma and leukemia are
not appropriate here.
Th e term reticulum cell sarcoma is n o lon ger used
wh en referrin g to malign an t lymph omas. Man y lym-
ph omas of bon e sh ow a mixture of cells rath er th an
a pure growth of “reticulum” cells. Various types of
lymph omas an d H odgkin disease can also in volve th e
skeleton . H en ce, th e term malignant lymphoma is pre-
ferred for th e en tire group. Th ese tumors are morph o-
logically similar to th eir lymph n ode coun terparts, but
lymph oma of skeleton may h ave some un usual h isto-
logic features.
Wh en malign an t lymph oma is respon sible for an
osseous lesion , on e of th ree clin ical situation s may
obtain . Careful study of th e patien t may sh ow n o evi-
den ce of distan t disease, an d th e osseous lesion can
be presumed to be th e primary lesion . Curren tly, stag-
in g studies in clude a skeletal sur vey, a radioisotope
bon e scan , bon e marrow examin ation , an d a com-
puted tomograph ic scan of th e abdomen an d ch est to
rule out lymph n ode in volvemen t. Man y patien ts in
th e Mayo Clin ic series did n ot h ave complete stagin g.
H en ce, th e stagin g assign ed to man y of th e patien ts
was somewh at arbitrary. O f th e 905 patien ts in th is
series, 274 were con sidered to h ave primary lymph oma
of bon e. In th e series reported by O strowski an d coau-
th ors in 1986 in volvin g 422 patien ts with malign an t
lymph omas evaluated at Mayo Clin ic between 1907
an d 1982, th e tumors were con sidered to be primar y
in 179. Th e rest of th e patien ts h ad more disease th an
a solitary bon y focus. Furth ermore, 82 patien ts h ad
in volvemen t of multiple skeletal sites with n o appar-
en t in volvemen t of an y oth er soft tissue. In th e Mayo
C H APT ER
17
Clin ic series, 308 patien ts were con sidered to h ave
in volvemen t of oth er soft-tissue sites such as lymph
n odes, liver, or spleen , alth ough th ese patien ts pre-
sen ted with skeletal disease. Stagin g studies disclosed
disease in oth er sites. Lymph oma h ad been diagn osed
in 123 patien ts before th e skeletal biopsy was per-
formed. For 156 patien ts, n ot en ough in formation
was available to stage th e disease. Forty-four patien ts
presen ted with a skeletal lesion th at turn ed out to be
a man ifestation of leukemia. O f th ese, 22 were gran u-
locytic sarcomas an d 21 were lymph ocytic leukemia.
O n e patien t h ad megakar yoblastic leukemia.
IN CID EN CE
The 905 cases of malignant lymphoma comprised
as 12.7% of the malignant tumors in this series. The
274 “primary” lesions in bone comprised only 3.9%
( Fig. 17.1) .
SEX
Males predomin ated at a ratio of 4 to 3 in both th e pri-
mary an d the total groups. Th is is in gen eral agreemen t
with wh at has been reported in th e literature.
AGE
Malignant lymphoma can occur in a patient of any age
but is rare in the very young. Seven patients were in the
fi rst 5 years of life and 16 in the second 5 years. Approx-
imately 20% of the patients were in the sixth decade
of life. The age distribution for those with presumably
primary lesions in bone parallels that of the overall
group.
201
202 Chapter 17 ■
LOCALIZATION
When a malignant lymphoma arises in certain specifi c
sites, such as the maxillary antrum or along the spinal
column, it is often impossible to prove an osseous origin.
Many patients with involvement of the antrum and one
or more of its bony walls are excluded from the series
because an origin from bone could not be verifi ed. Simi-
larly, most surgical patients with lymphoma affecting the
spinal cord or its emerging nerves are excluded because
proof of osseous disease is not available. Most lympho-
mas involve the portion of the skeleton containing red
marrow. It is very unusual to fi nd lymphoma involv-
ing the small bones of the hands and feet. Five lesions
involved the tarsals and one a phalanx of a toe, but none
involved a metatarsal. A sin gle lesion involved one of the
carpal bones, and two patients presented with involve-
ment of the metacarpal bones. There were no cases of
the lesion involving the phalanges of the hand, although
involvement of these bones was seen as part of a systemic
process. The most common single site was the femur,
followed by the ilium. The distribution of the cases of
primary lesions was similar to that of the entire group.
SYMPTOMS
Pain, swelling, and subsequent disability are the cardinal
features of any malignant tumor of bone, including lym-
phoma. Pain of variable intensity is practically a constant
feature, and, occasionally, it has been present for several
years, although ordinarily its duration is measured in
months. Neurologic symptoms commonly occur when
F igu r e 17.1. Distribution of malig-
nant lymphomas according to age
and sex of the patient and site of the
lesion.
these tumors affect the spinal column. Many studies have
emphasized that patients with even extensive solitary malig-
nant lymphomas have an unexpected sense of well being,
and absence of the general complaints so commonly asso-
ciated with malignant disease. Pathologic fracture may
be the presenting symptom. In one patient in the Mayo
Clinic series, malignant lymphoma developed in a focus
of old chronic osteomyelitis of the tibia. Another patient,
a 94-year-old woman with lymphoma of the ilium, had
radiographic evidence of Paget disease in multiple bones.
Occasionally, patients present with lytic bone lesions and
hypercalcemia suggesting hyperparathyroidism.
PH YSICAL FIN D IN GS
A mass in a tender or warm region may be the main
fi nding and is often associated with disability of the
affected part. Enlarged regional lymph nodes may be
found. One should search for signs of disseminated
malignant lymphoma, such as involvement of mul-
tiple bones, distant lymph nodes, and other soft-tissue
structures. Because of the occasional similarity between
tumefactions due to malignant lymphomas an d those
due to leukemia, it is important to study the peripheral
blood of these patients.
RAD IOGRAPH IC FEATU RES
Radiographically, the lesion frequently is very exten-
sive, often involving 25% to 50% of the affected bone
and, in some cases, the entire bone. The lesion tends to
 ■ Malignant Lymphoma of Bone 203

F igu r e 17.2. Lymphoma involving multiple bones in a 47-year-old man. A: Anteroposterior radio-
graph of the knee region shows an extensive lesion with a mixture of lysis and sclerosis. B: Lateral
view shows a permeative destructive process. The bone appears to h ave multiple defects. There is a
large destructive area in the anterior cortex, with formation of a soft-tissue mass. Despite the exten-
sive in volvement of th e bon e, n o periosteal n ew bon e formation is seen .

involve the mid portion of the bone. Bone destruction

is the predominant feature of primary lymphoma. The
areas of destruction give the bone a mottled and patchy
appearance in many cases, and sometimes the outline
of the bone is completely lost. Because of the infi ltra-
tive nature of the disease, the inter face within adjacent
normal bone is poorly defi ned. Approximately half of
the patients in this series had evidence of some reac-
tive proliferation of new bone that is not laid down by
the tumor cells themselves. Hence, the typical appear-
ance of malignant lymphoma can be considered to be
that of an extensive lesion showing a mixture of lysis and
sclerosis. Nearly every malignant lymphoma destroys
cortical bone, and approximately 25% are associated
with some thickening of the cortex. Often, soft-tissue
extension of the tumors is obvious and large. In spite
of the extensive involvement of the bone, including
destruction of the cortex, periosteal new bone forma-
tion is uncommon. This is in contrast to the striking
periosteal new bone formation seen in Ewing sarcoma.
Approximately one-fourth of the patients have evidence
of pathologic fracture ( Figs. 17.2–17.4) .
Irregular sclerosis of the affected site is sometimes a F igu r e 17.3. Permeative destructive lesion involving the
noticeable feature, and this fi nding adds to the confu- proximal humerus in a 62-year-old woman. The histologic fea-
sion of malignant lymphoma with chronic osteomyelitis. tures were th ose of a myeloid sarcoma.
204 Chapter 17 ■
F igu r e 17.4. H odgkin disease in volvin g th e ilium in a 51-year-
old woman . There is in creased sclerosis in th e periacetabular
region .
F igu re 17.5. Bone scan of the hip in a 40-year-old woman
shows increased uptake in the proximal femur. The plain radio-
graph was negative. A positive bone scan with a negative plain
radiograph suggests malignan t lymphoma. ( Case provided by
Dr. James H. Coffey, Fargo Clinic, Fargo, North Dakota.)
Disseminated malignant lymphomatous involvement
of the skeleton may simulate osteoblastic metastatic
carcinomatosis. Malignant lymphoma may involve
multiple bones of the skeleton even in the absence of
visceral and lymph node involvement. Sclerosis may
precede the diagnosis of malignant lymphoma by sev-
eral years and may even resemble Paget disease of the
bone, especially in fl at bones.
When the disease is confi ned to the marrow cavity,
there may not be enough destruction of bone to be
identifi ed visibly on plain radiographs. Radioisotope
bone scans are considerably more sensitive in localizing
skeletal involvement with lymphoma. A positive bone
scan with a negative plain radiograph should suggest
malignant lymphoma as one of the possibilities. Malig-
nant lymphoma may also present as an abnormal marrow
signal on magnetic resonance imaging or increased
marrow density on computed tomograms, although the
plain radiographs may be negative ( Figs. 17.5 & 17.6) .
Wilson and Pugh, who studied the Mayo Clinic
series, concluded that the radiographic fi ndings varied
so much that they could not be regarded as charac-
teristic. Although the radiologist frequently suspects
the diagnosis of malignant lymphoma, other lesions,
including metastatic carcinoma, osteosarcoma, Ewing
tumor, eosinophilic granuloma, and chronic osteomy-
elitis, cannot always be excluded with certainty.
GROSS PATH OLOGIC FEATU RES
The gross features of primary malignant lymphoma of
bone are not pathognomonic, but some of them are
mentioned. Although any portion, and frequently a
large part, of the long bone may be involved, the main
mass of the tumor and its extraosseous extension, if
present, are most often in or near the metadiaphyseal
region. A variable amount of soft-tissue extension is
practically always present by the time the diagnosis is
made. The bone at the affected site is destroyed to a vari-
able extent, and occasionally white areas of necrosis or
zones of secondary sclerosis are seen. Residual osseous
trabeculae are frequently admixed with tumor, impart-
ing a fi rm and gritty consistency. When a malignant lym-
phoma extends into the soft tissues, it produces a soft
tissue mass that is fl eshy and simulates the appearance
of malignant lymphoma involving lymph nodes. The
margins of a malignant lymphoma in the bone, as well
as in the adjacent soft tissues, are ordinarily indistinct.
Regional lymph nodes may be involved, and, as indi-
cated above, there may be gross pathologic evidence of
disseminated malignant lymphoma ( Figs. 17.7–17.10) .
Malignant lymphoma of bone is frequently associated
with reactive medullary sclerosis. This may give rise to an
extremely hard gross specimen. It is important to resist
 ■ Malignant Lymphoma of Bone 205

F igu r e 17.8. Malignant lymphoma involving the sternum

and producing a large destructive tumor.

F igu re 17.6. Malignant lymphoma involving the femur in a

51-year-old man. A: Plain radiograph shows an ill-defi ned scle-
rotic area in the proximal left femur. B: Magnetic resonan ce F igu r e 17.9. Exten sive in volvemen t of an en tire arm with
image of the hip region shows extensive involvement of the malign an t lymph oma. Th e tumor affected n early all th e bon es
proximal left femur with malignant lymphoma. There is also of th e arm, in vaded soft tissue, an d exten ded in to skin . Th e
involvement of the proximal right femur. Malignant lymphoma en tire extremity appears to be tran sformed into a malignant
is one of the conditions to be considered when a plain radio- lymphoma.
graph is negative and the magnetic resonance image shows
abnormal signals ( Case provided by Dr. David G. Hicks, Uni-
versity of Rochester Medical Center, Rochester, New York.) .

F igu r e 17.10. Malignan t lymphoma involving the proximal

tibia produced a path ologic fracture. Th e dark red area in th e
F igu r e 17.7. Malignant lymphoma involving a rib. The tumor cen ter is th e biopsy site. Th e biopsy diagn osis was malign an t
has the fi sh-fl esh appearan ce typical of malignant lymphoma. fi brous histiocytoma, which led to the amputation.
206 Chapter 17 ■
the temptation to decalcify the entire biopsy specimen.
The decalcifi cation procedure may be long and cause
unnecessary delay in diagnosis and may even obscure
cytologic details. Also, such decalcifi cation may inter-
fere with immunophenotyping. It is important to exam-
ine the gross specimen carefully and to tease out any
fl eshy fragments of tissue. It may be necessary to use a
scalpel blade and extract small pieces of fl eshy material
that can be processed separately and may be used for
special studies.
H ISTOPATH OLOGIC FEATU RES
The majority of malignant lymphomas of bone are dif-
fuse large B-cell lymphomas rather than follicular or
small lymphocytic subtypes ( Fig. 17.11) . Most bon y lym-
phomas show a mixed cell infi ltrate—that is, there is
considerable difference in the sizes and shapes of the
tumor cells ( Fig. 17.12) . Indeed, this feature is the most
helpful in differentiating lymphoma from Ewing tumor,
the tumor cells of which show little variation in size and
shape.
Under low power, lymphomas show the same
infi ltrative pattern in bone that is so characteristic of
their growth pattern in other organs. The tumor grows
between medullary bony trabeculae and permeates
marrow fat, leaving behind intact normal structures.
Although lymphomas can form expansile masses, this
very characteristic infi ltrative pattern should suggest,
when seen under low power, the diagnosis of lymph oma.
The medullary bony trabeculae may show reactive scle-
rosis. Crush artifact is commonly found in lymphoma of
bone. For some reason, th is crush artifact is found more
Figure 17.11. Diffuse large B-cell lymphoma involving the
femur in a 41-year-old man. This is the most common type of lym-
phoma that forms a mass lesion in bone. This example contains a
uniform population of malignant cells with prominent nucleoli.
Figu re 17.12. Example of diffuse large B-cell lymphoma. This
tumor contains prominent nuclear irregularity and variability.
commonly in lymphoma than in other small cell malig-
nancies of bone, especially Ewing sarcoma. Occasionally,
the entire biopsy specimen may consist of replacement
of marrow spaces, with elongated crushed cells with no
distinguishing features ( Figs. 17.13 & 17.14) .
As mentioned above, most primary lymphomas of
bone are subclassifi ed as diffuse large B-cell lymphomas.
The tumor cells typically show centroblastic, and less fre-
quently immunoblastic, cytologic features. Occasionally
anaplastic large cell lymphoma presents as an osseous
mass. It is unusual for T-cell lymphomas to occur as pri-
mary lymphoma of bone. Immunohistochemical stains,
and occasionally molecular studies, are necessary for
typing lymphomas of bone. Oftentimes the diagnosis
can be made with a limited number of stains including
the B-cell marker CD20, the T-cell marker CD3, and
CD45. Additional stains such as CD30 ( anaplastic large
cell lymphoma) and CD79a, CD10, CD34, and TdT
( precursor B-cell lymphoblastic lymphoma) among
others may also be indicated. The tumor cells of lym-
phoma usually lie in a network of reticulum fi brils and
may show pronounced clustering. This clustering may
make differentiation from metastatic carcinoma dif-
fi cult. Keratin immunostains should usually help solve
the problem.
Hodgkin disease may present as a skeletal mass. In
the Mayo Clinic series of 694 cases, there were 23 exam-
ples of Hodgkin disease. The possibility of Hodgkin
disease should be considered when there is a mixed cell
infi ltrate with some very large bizarre cells. Eosinophils
may be a prominent feature of the infi ltrate. Classic
Reed-Sternberg cells may or may not be seen. It is
probably important to use immunoperoxidase stains,
especially CD15, CD30, and PAX5, to confi rm the
diagnosis of Hodgkin disease. Of the 23 examples of

F igu r e 17.13. A: Low-power appearan ce of malign an t
lymphoma invading preexisting medullary bone. There is
marked crush artifact, as in dicated by th e dark blue streaky
areas. Such crushing is seen typically in lymphoma involving
bon e. B: Oth er areas of biopsy tissue con tain ed in tact lymph o-
cytes th at permitted immun oh istoch emical subclassifi cation .
Figure 17.14. Diffuse large B-cell lymphoma. Part of this fi eld
shows cytologic distortion due to crush artifact. However, there
are some intact cells that stained positive with B-cell markers.
■ Malignant Lymphoma of Bone 207
Hodgkin disease in this series, 6 involved the spine, 8
the ilium, 3 the proximal femur, 2 the sacrum, 2 the
rib, and 1 each involved the scapula and sternum.
None of these cases could be considered primary in
bone. Fourteen presented as skeletal lesions, but stag-
ing studies showed evidence of involvement elsewhere,
usually in para-aortic lymph nodes. Nine patients with
known Hodgkin disease in other sites underwent skel-
etal biopsy for suspected involvement ( Fig. 17.15) .
Leukemic in fi ltrates may presen t as skeletal lesion s.
Forty-four patien ts h ad a bon e biopsy for leukemic
disease. Twen ty-two of th ese were myeloid sarcomas,
21 were small lymph ocytic leukemias, an d 1 was mega-
kar yoblastic leukemia. A skeletal lesion of myeloid
sarcoma may resemble a large B-cell lymph oma. Th e
presen ce of blastlike n uclei sh ould alert on e to th e
possibility of myeloid sarcoma. Imprin ts stain ed with
Wrigh t stain may be h elpful. O ccasion ally th e pos-
sibility of a myeloid sarcoma can be en tertain ed on
routin e section s. H owever, addition al immun ostain s
such as myeloperoxidase, lysozyme, an d CD33 sh ould
be added to th e T an d B cell marker pan el in order to
con fi rm th e diagn osis ( Figs. 17.16 & 17.17) .
Reactive fi brosis is not unusual in malignant lym-
phoma of bone. This fi brosis usually is very fi ne and in
between individual cells, rather than being denser bands
of fi brosis compartmentalizing the cells of the tumor. The
reactive fi brosis may give the neoplasm a spindle-shaped
appearance. Some of these may even have a storiform
pattern, hence, suggesting the diagnosis of malignant
fi brous histiocytoma. A useful distinguishing feature
is the characteristic permeative pattern of lymphoma
leaving behind normal structures in contrast with the
expansile nature of the growth in a malignant fi brous his-
tiocytoma ( Fig. 17.18) . It is also important to determine
if the nuclear features suggest a lymphoid neoplasm.
The presence of what appeared to be infl ammatory cells
in the background should also alert one to the possibil-
ity of lymphoma rather than sarcoma. The presence of
disease in multiple skeletal sites is a strong indicator of
malignant lymphoma. Hematopoietic immunoperoxi-
dase stains are useful in making that distinction.
The many lymphocytes in some of these tumors may
lead to a mistaken diagnosis of osteomyelitis. The clini-
cal and radiographic fi ndings can be similar in the two
conditions. The presence of plasma cells, polymorpho-
nuclear leukocytes, and capillary proliferation favors
the diagnosis of osteomyelitis.
One of the diagnostic features of lymphoma of bone,
that is, polymorphism of the infi ltrate, makes subclas-
sifi cation diffi cult, if not impossible. However, all mod-
ern staining techniques used in lymph node pathology
should also be used in studying bone lymphomas. Doso-
retz and coauthors have suggested that patients with
tumors composed predominantly of large cleaved cells
208 Chapter 17 ■
F igu re 17.15. Hodgkin lymphoma involving the spine in an
83-year-old woman. A: Low-power view shows a mixed popula-
tion of cells, including several eosinophils. With this appear-
ance, osteomyelitis is included in the differential diagnosis.
B: High-power view shows cytologic atypia. One of the cells
contains a bilobed nucleus within a lacunar space that is highly
suggestive of a Reed-Sternberg cell. C: Large atypical cells
within the tissue were immunoreactive with CD15, confi rming
the diagnosis of Hodgkin lymphoma.
F igu r e 17.16. Myeloid sarcoma presenting as a solitary mass
lesion in bone. There is a striking degree of cytologic atypia.
Sarcoma would also be in cluded in th e differen tial diagn osis.
Immun oh istoch emical studies are n ecessary to sort th rough
th e differen tial diagn osis.
F igu r e 17.17. An oth er example of myeloid sarcoma in volv-
ing a rib in a 54-year-old man. The tumor cells have more uni-
formity than the example shown in Figure 17.16. This tumor
more closely resembles lymphoma.
have a better prognosis than patients with tumors com-
posed of noncleaved cells. However, Pettit and coauthors
found that primary bone lymphoma has an unusually
high incidence of large cleaved and multilobated cells.
Care should be taken in order to avoid misdiagnos-
ing B-cell lymphoblastic lymphoma as Ewing sarcoma
since both tumors can be positive with CD99 an d nega-
tive with CD45. However, Ewing sarcoma should be neg-
ative with B-cell markers ( Fig. 17.19) . The histiocytes of
Langerhans cell histiocytosis may be diffi cult to differ-
entiate from those of malignant lymphoma, especially
if the cytologic features are distorted by decalcifi cation,
but generally the cells of Langerhans cell histiocytosis

F igu r e 17.18. Tumor cells in th is diffuse large B-cell lym-
phoma had a spindle cell appearance due to compression by
surroun din g fi brosis. Th is appearan ce can lead to a mistaken
diagnosis of sarcoma.
F igu r e 17.19. Precursor B-cell lymphoblastic lymphoma/
leukemia that formed a destructive mass in the tibia in a
5-year-old girl. The tumor cells were positive for PAX5, TdT,
and CD10. They were negative for CD20, CD2, and MPO. The
mon oton ous appearan ce of th e tumor cells resembles th at of
Ewin g sarcoma.
are obviously benign, lacking the pleomorphism and
hyperchromasia of malignant cells. However, there are
rare examples in which the cytologic features are those
of Langerhans cell histiocytosis but the clinical features
suggest that the tumor is a true histiocytic lymphoma.
TREATMEN T
Primary lymphoma of bone is usually treated with che-
motherapy and radiation. Surgery is only occasionally
indicated.
■ Malignant Lymphoma of Bone 209
PROGN OSIS
Many reports indicate that malignant lymphoma has
the best prognosis of any of the primary malignant
tumors of bone. Five-year survival rates of 50% to 90%
and even higher have been reported. Patients with
more advanced stage disease don’t do as well. In the
study of Ostrowski and coauthors, the 5-year survival for
patients with primary lymphoma of bone was 58% and
22% for patients with disseminated disease. However,
patients with involvement of multiple bones, but with-
out involvement of nonskeletal sites, had an unexpect-
edly good 5-year survival rate of 42%.
Most of the small group of patients with mandibular
tumors in the present series have become long-term
survivors. A gratifying percentage of patients with
locally invasive and basically inoperable lymphomas of
the maxillary region, not included in our series, can be
cured with appropriate radiation therapy.
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T. E., Wen ger, D. E., an d Un n i, K. K.: Osseous Hodgkin
Disease. Can cer, 85:1166–1178.
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Lai, R.: Anaplastic Large Cell Lymphomas Presented as Bone
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Ewing Tumor
Ewing tumor is a distinctive, small, round cell sarcoma
th at was, until recen tly, con sidered on e of the most
lethal of all bone tumors. It has been the subject of con-
troversy in the literature because of th e somewhat non -
specifi c histologic characteristics of the tumor, which is
composed of solidly packed small cells. Previously, the
controversy in volved wh eth er all Ewin g sarcomas rep-
resen ted metastatic neuroblastomas or not. Anoth er
controversy involved the question as to whether the
so-called primitive n euroectodermal tumor is distin ctly
different from Ewing sarcoma. Formerly, some of the
small cell osteosarcomas, most of th e malignan t lym-
ph omas, and even some benign con ditions, such as
eosin ophilic gran ulomas, were at times classifi ed with
Ewing tumor.
A practical working defi nition is to regard as Ewing
tumors all highly malignant, small, round-to-oval cell
sarcomas that have the clinical and radiographic char-
acteristics of a primary osseous lesion. Inherent in this
concept is the exclusion of cytologically incompatible
lesion s such as myeloma, malignant lymphoma, and
Langerhans cell histiocytosis. Production of a chon-
droid or osteoid matrix by the neoplastic cells likewise
excludes Ewing sarcoma. Similarly, true spindling of
the nuclei is incompatible with the diagnosis of Ewing
sarcoma. However, artifactual spindling, especially at
the periphery of the tumor, produced by crushing at
the time of biopsy, has to be distinguished from true
spindling of tumor cells. It is sometimes impossible to
differentiate a biopsy specimen of a metastatic malig-
nant tumor such as a neuroblastoma, small cell carci-
noma of the lun g, or even a leukemic infi ltrate from a
specimen of Ewing tumor, even after critical histologic
study, according to modern concepts. Immunoperoxi-
dase stains, however, can effectively rule out metastatic
carcinomas and lymph omas and leukemias.
There has been much speculation on the possible
origin of the cells that comprise Ewing tumor. Although
previously the tumor was considered to arise from undif-
ferentiated mesenchymal cells, it is now considered a
tumor of neuroectodermal origin.
C H APT ER
18
Although Ewing tumor and malignant lymphoma
can be distinguished histologically in most cases, an
occasional tumor has a histologic appearance that is
midway between the two. In the present series, some
tumors contain cells that were larger and somewhat
more irregular than those of classic Ewing tumor. Their
clinical characteristics and prognosis made it practical
to include them with Ewing tumors rather than attempt
to defi ne a new tumor type. These have been consid-
ered to be large cell or atypical Ewing tumors.
A soft tissue counterpart of Ewing sarcoma is occa-
sionally encountered.
IN CID EN CE
Ewing tumor comprises 8.64% of the total malignant
tumors in our series ( Fig. 18.1) .
SEX
Ewing tumor has a distinct predilection for males
(62%).
AGE
The patients affected by this tumor are, on average,
younger than those affected by any other primary
malignant tumor of bone. Just over 58% of all patients
were in the second decade of life, and approximately
75% were in the fi rst two decades of life. Twelve patients
were younger than 5 years. The youngest patient was
17 months. This small group included six females and six
males. The oldest patient was 59 years old. Four patients
were older than 50 years, and all were males. When con-
fronted with the problem of Ewing tumor in a patient
who is beyond the third decade of life, one must be espe-
cially careful to exclude metastatic carcinoma. Similarly,
211
212 Chapter 18 ■
in a very young patient, metastatic neuroblastoma and
even acute leukemia must be considered.
LOCALIZATION
Most Ewing tumors are in the extremities, but any bone
of the body may be involved. Any portion of a long tubu-
lar bone may be affected. Although the proximal and
distal metaphyses of long bone are more commonly
affected, the shaft is involved more often than in other
types of sarcomas. The lower extremities and pelvic gir-
dle accounted for 59.6% of the tumors in the Mayo Clinic
series. Although 29 lesions involved the small bones of the
feet, only 5 lesions involved the small bones of the hands,
3 involved the metacarpals, 1 each involved a carpal and
a phalanx. Sixty-one lesions involved the spinal column,
including the sacrum. The maxilla was not involved in
any case, but there were six examples of lesions in the
mandible and six in the skull bones. Three patients had
two skeletal sites of involvement at presentation as fol-
lows: one patient had tumors in the left ischium and right
ilium, one had lesions in a rib and the ilium, and one had
lesions of a metatarsal and the tibia. In addition, three
patients presented with disease involving multiple bones.
One tumor appeared to arise on the surface of bone.
SYMPTOMS
Pain and swelling are the most common symptoms of
Ewing tumor. Pain is the fi rst symptom in more than
half the patients. Pain may be intermittent at fi rst, and
F igu r e 18.1. Distribution of
Ewin g tumors accordin g to age
an d sex of th e patien t an d site
of th e lesion .
it tends to increase in severity with time. Although swell-
ing in the region of the tumor is common by the time
the patient seeks medical advice, it is rarely the fi rst
symptom. Pathologic fracture is unusual. The typical
patient has had symptoms for several months before
seeking medical care. In this series, the survival of
patients whose symptoms lasted for 6 months or longer
did not differ from that of patients who had symptoms
of a shorter duration.
PH YSICAL AN D
LABORATORY FIN D IN GS
Most patients have a palpable, tender mass, and some
have dilated veins over the tumor. Patients with Ewing
tumor sometimes have an elevated temperature and
increased erythrocyte sedimentation rate, often associ-
ated with secondary anemia and sometimes with leu-
kocytosis. These fi ndings may suggest that the osseous
lesion has an infl ammatory origin. When the lesion is
associated with systemic features, the prognosis is even
worse than average.
Neuroblastom a with m etastasis to bon e, sim ulat-
in g Ewin g sarcom a, can be diagn osed reliably in m ost
cases with qualitative an d quan titative determ in a-
tion of catech olam in e m etabolites in th e urin e. O n e
patien t in th is series h ad bilateral retin oblastom a,
an d an oth er patien t h ad a broth er wh o also h ad
Ewin g tum or. In on e patien t, carcin om a of breast
developed 13 years after treatm en t of Ewin g tum or
of th e sacrum .
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 ■ Ewing Tumor 213

RAD IOGRAPH IC FEATU RES

Ewing tumor tends to be extensive, sometimes involv-

ing the entire shaft of a long bone. Even so, generally
more bone will be found pathologically involved than
was obvious on the radiograph. Lytic destruction is the
most common fi nding, but there may be regions of
density due to stimulation of new bone formation. As
the tumor bursts through the cortex, which may show
only minimal radiographic changes, it often elevates
the periosteum gradually. This elevation produces the
ch aracteristic multiple layers of subperiosteal reactive
new bone, which produces the onionskin appearance
of Ewing tumor ( Fig. 18.2) . Radiating spicules from the
cortex of an affected bone are not uncommon, a fact
that complicates the differentiation from osteosarcoma.
This differentiation may be especially diffi cult when the
lesion involves a fl at bone such as the ilium. Occasion-
ally, Ewing tumor expands the affected bone and may
even superfi cially resemble a cyst ( Figs. 18.2–18.6) .
A rare example of Ewin g sarcoma may have little or
no medullary component. A few tumors are almost com-
pletely in a juxtaosseous position an d sh ow little cortical
destruction. Edeiken has stressed that saucerization
of th e exterior sur face of the cortex is an early an d
F igu r e 18.3. Ewin g sarcoma exten sively in volvin g th e radius
ch aracteristic sign of tumors presentin g subperiosteally in an 8-year-old boy. The lesion has a permeative pattern of
( Fig. 18.7) . bon e destruction .

F igu r e 18.2. Ewing sarcoma involving the proximal humerus

in a 15-year-old boy. Pron oun ced periosteal n ew bon e forma- F igu r e 18.4. Ewin g sarcoma in volvin g th e distal h umerus.
tion produces an “on ion skin ” appearan ce. Th ere is exten sive periosteal n ew bon e formation .

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214 Chapter 18 ■
F igu r e 18.5. Ewin g sarcoma in volvin g th e pelvis, a relatively common site for this tumor. A: Plain
radiograph sh ows a lytic mass in volvin g the left ilium. B: Magnetic resonance imagin g more clearly
sh ows th e massive size of th e tumor. It h as destroyed th e majority of th e ilium an d is associated with
a large soft-tissue mass.
F igu r e 18.6. Ewing sarcoma forming a sclerotic mass in the
calcan eus.
Experienced observers have concluded that although
Ewing tumor can sometimes be diagnosed with a high
degree of assurance on the basis of its radiographic
features and although the tumor very often produces
features that are virtually pathognomonic of malignant
bone tumor, several conditions can produce similar fea-
tures. When the tumor produces a permeative destructive
process, the differential diagnosis involves metastatic car-
cinoma, malignant lymphoma, and osteomyelitis. When
the lesion produces an area of geographic destruction,
other malignant tumors, including osteosarcoma, are
included in the differential diagnosis.
Modern imaging techniques such as computed tomog-
raphy and magnetic resonance imaging do not produce
images that are diagnostic of Ewing tumor. However, both
of these modalities are superior to plain radiographs in
defi ning the extent of the disease, both intermedullary
and in the soft tissues. The images are especially useful
in establishing the relationship of the neoplasm with the
neurovascular bundle. This information may be critical
in planning surgery (Figs. 18.5, 18.8, & 18.9).
GROSS PATH OLOGIC FEATU RES
Solid masses of viable tumor are characteristically gray-
white, moist, glistening, and sometimes translucent.
They may have an almost liquid consistency, which may
mimic pus. This appearance may result in the entire
specimen being sent to microbiology for culture, with
disastrous results. The tumor frequently invades bone
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 ■ Ewing Tumor 215

F igu r e 18.7. Occasionally, Ewing sarcoma is located on the sur face of the bone. A: This Ewing
sarcoma is producin g erosion an d saucerization of th e cortex. B: Axial T2-weigh ted magn etic reso-
nan ce image confi rms th at th e tumor is a sur face lesion .

F igu r e 18 .8. Ewing sarcoma involving the fourth metacarpal bone. A: Plain radiograph of the
hand sh ows only subtle changes suggesting a lytic lesion. B and C: Magnetic resonance imaging shows
a large soft-tissue mass surroun ding the bone that is not as apparent on the plain radiograph.

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216 Chapter 18 ■
beyond the limits indicated on the radiograph. Zones
of necrosis, hemorrhage, and even cyst formation are
common. The neoplastic tissue is often admixed with
proliferating bony and fi brous tissue in the periosseous
regions ( Figs. 18.10–18.14) .
The medullary cavity seems to be the site of origin of
nearly all these tumors. Although the tumor may affect
any portion of a long bone and commonly involves a
great len gth of it, most of the tumor is frequently in the
metadiaphyseal region.
Ch aracteristically, th e tumor metastasizes to th e
lun gs an d oth er bon es ( Fig. 18.15) . Metastasis to oth er
bon es is so promin en t th at it h as been suggested th at
Ewin g tumor may h ave a multicen tric origin . Metasta-
sis to lymph n odes h as been foun d in as man y as 20%
F igu r e 18.9. A: Ewing sarcoma forming a permeative lytic
lesion associated with periosteal reaction in the left femur
in an 11-year-old boy. B and C: Magnetic resonance imaging
sh ows th at th e tumor exten ds from th e metaph ysis to th e mid
sh aft an d cortical erosion is exten sive.
of patien ts, an d viscera oth er th an th e lun gs may be
in volved.
H ISTOPATH OLOGIC FEATU RES
Under low magnifi cation, Ewing tumor is seen to be
remarkably cellular, with little intercellular stroma
except for widely separated strands of fi brous tis-
sue ( Fig. 18.16) . These strands compartmentalize the
cellular aggregates into zones that are sometimes larger
than the area covered by high-power microscopic fi elds.
When studied under high magnifi cation, the cells that
lie in the compartments are noteworthy for their reg-
ularity and their round to oval nuclei. The cytoplasm
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 ■ Ewing Tumor 217

F igu r e 18.10. Ewin g sarcoma in volvin g th e mid h umerus

in a 20-year-old man. Periosteal new bone formation appears
to th icken th e cortex. Th e large soft-tissue mass is soft an d
almost liquefi ed.

F igu re 18.11. Ewing sarcoma involving the distal femur in a

15-year-old girl. The tumor was predominantly in soft tissue but
showed microscopic evidence of involvement of the marrow.

Figure 18.12. A: Large recurrence of Ewing sarcoma 6 years after radiation and chemotherapy in
a 19-year-old man. B: Magnetic resonance imaging appearance of recurrent Ewing sarcoma involving
the distal femur. The tumor fills the marrow cavity and has a large soft-tissue mass that surrounds the
involved bone.

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218 Chapter 18 ■
Figure 18.13. Large recurrent Ewing sarcoma involving the
scapula. There are large foci of necrosis.
F igu r e 18.14. Resected fi bula in a patien t with Ewin g sar-
coma. Th e patient h ad been treated with ch emoth erapy, an d
no residual tumor was identifi ed at th e time of surgery.
surrounding these nuclei is slightly granular, and the
outlines of th e cells are indistinct. The nuclei con-
tain a rather fi nely dispersed chromatin that imparts
a ground-glass appearance. Nucleoli may be present,
but they are inconspicuous. Mitotic fi gures are rarely
numerous ( Figs. 18.17–18.19) .
Special stains disclose that there is little stainable
reticulum within the compartments described above. In
some of these tumors, minor variation in nuclear size
often occurs from region to region because of zones of
necrosis and degeneration. A perithelial pattern, erro-
neously suggesting that this tumor arises from blood
vascular endothelial cells, is sometimes prominent. Col-
lars of viable cells often surround small blood vessels,
and beyond these viable collars the cells are necrotic—a
histologic pattern that is best explained on a nutritional
F igu r e 18.15. Nodule of metastatic Ewin g sarcoma in th e
lung. The tumor has the white fl evshy color of lymphoma or
small cell carcin oma.
F igu r e 18.16. Ch aracteristic lobulation of Ewin g sarcoma
tumor cells by widely separated septa of con n ective tissue.
basis and one that seems unlikely to explain the basis of
the derivation of the tumor.
Occasionally, the cells of the tumor contain nuclei
that have a somewhat larger and less regular shape than
those of a typical Ewing tumor. Otherwise, the general
histologic structure is like that of a typical Ewing sar-
coma. The lesion with these larger cells does not have
the specifi c cytologic features of a malignant lymphoma.
The prognosis is similar to that of classic Ewing tumor,
and it seems appropriate to regard this as an atypical or
large cell variant of Ewing tumor ( Figs. 18.20 & 18.21) .
In the past there was no specifi c immunoperoxidase
stain that was useful in the diagnosis of Ewing sarcoma.
More recently, CD99 or O-13, an immunostain that rec-
ognizes a product of the MIC-2 gene, has emerged as an
useful tool in the diagnosis of Ewing sarcoma. While it
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F igu r e 18.17. Ewin g sarcoma. Note th e regularity of n uclei
and poor delineation of cytoplasm. There is practically no
groun d substan ce. A mitotic fi gure is presen t.
F igu r e 18.18. Ewing sarcoma permeating fi brous tissue,
producing a fi ligree pattern.
F igu r e 18.19. Ewing sarcoma permeating cortical bone.
■ Ewing Tumor 219
F igu r e 18.20. Large cell, or atypical, Ewin g sarcoma. Low-
power ( A) and high-power ( B) views show cells that are larger
and not as uniformly shaped as those seen in typical Ewing
sarcoma.
is a very sensitive stain that shows immunoreactivity in
approximately 90% of Ewing tumors, it is n ot specifi c.
A number of tumors including some carcinomas, other
sarcomas, and a few hematopoietic malignancies such
as lymphoblastic lymphoma can also be positive with
this marker. Therefore, it should be interpreted in
combination with other fi ndings such as the histologic
features and additional immunochemical and at times,
molecular studies ( Figs. 18.18 & 18.22–18.26) .
The presence of reactive osseous and fi broblastic tis-
sue, resulting from periosteal elevation and invasion of
soft tissues, may complicate the histologic pattern. The
osseous trabeculae may be thin and make the differenti-
ation from small cell osteosarcoma diffi cult. In the reac-
tive bone, osteoblasts are seen rimming the trabeculae,
whereas in osteosarcoma, the malignant cells produce
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220 Chapter 18 ■

F igu r e 18.23. H igh -power view of Ewin g sarcoma sh ows

round-to-oval n uclei with a fi nely dispersed chromatin pat-
tern. The scant amount of eosinophilic cytoplasm is rather
indistinct.

F igu r e 18.21. Example of large cell, or atypical, Ewing

sarcoma. Low-power ( A) an d h igh power appearan ce ( B)
is similar to that of malignant lymphoma. Immunostains
and molecular genetic studies are helpful in differentiating F igu r e 18.24. Zones of necrosis are not un common in
atypical Ewing sarcoma from lymphoma. Ewin g sarcoma.

F igu r e 18.25. Occasionally, a population of dark blue cells

F igu r e 18.22. Mitotic fi gures are n ot un common ly seen in is admixed with cells that have the cytologic features typical of
Ewing sarcoma. However, they rarely are numerous. This fi eld Ewin g sarcoma. Th e dark blue cells may represen t degen era-
con tain s a mitotic fi gure. tive ch an ge.

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F igu r e 18.26. A: Typical h istologic features of Ewin g sar-
coma. B: Tumor cells sh ow diffuse membran ous immun ore-
activity with CD99.
the osteoid. Because the tumor may be largely necrotic,
frozen sections are useful in evaluating the adequacy of
the biopsy specimen.
In 1959, Schajowicz advocated the use of a glyco-
gen stain in the differentiation of Ewing sarcoma from
reticulum cell sarcoma, stating that the cells of the for-
mer contain glycogen whereas those of the latter do
not. However, some tumors that are necessarily called
Ewing sarcoma morphologically do not contain any
recognizable glycogen when special stains are used,
even when the specimen is fi xed in 80% ethanol.
In 1979, Askin and coauthors described a small cell
malignancy of the thoracopulmonary region that mor-
phologically resembled Ewing sarcoma. Furthermore,
they thought that this tumor was associated with a bad
prognosis and that the tumor may be neurally derived
■ Ewing Tumor 221
F igu r e 18.27. A: Low-power appearan ce of a primitive n eu-
roectodermal tumor arising from within the h umerus. Promi-
n ent rosette formation is evident. B: High -power appearance
of th e rosettes, wh ich are con sisten t with H omer Wrigh t
rosettes.
since it contained prominent rosette formation. Since
then, several studies have detailed the pathologic fea-
tures of this so-called primitive neuroectodermal tumor
(PNET). These may occur as primary tumors in bone or
in soft tissue. At low magnifi cation, the classic histologic
features are those of a lobulated growth pattern and the
presence of rosette formation ( Fig. 18.27). More recent
studies have shown that PNET and Ewing sarcoma share
similar immunohistochemical, cytogenetic, and molecu-
lar features. Hence, it is thought that they are at differing
stages of differentiation in a single Ewing sarcoma family
of tumors. Since they also have a similar prognosis, it is
probably not necessary to make a distinction.
The t( 11;22) (q24;q12) chromosomal translocation
or variants thereof can be found in more than 95% of
Ewing sarcomas. This results in the production of the
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222 Chapter 18 ■
F igu r e 18.28. Th is bon e was resected after ch emoth er-
apy for Ewing sarcoma. The tumor was 100% necrotic and
replaced by fi brous con nective tissue.
EWS-FLI-1 and EWS-ERG fusion genes which can be
detected by reverse transcriptase-polymerase chain reac-
tion and fl uorescence in situ hybridization techniques.
The more common EWS/ FLI-1 fusion gene is present
in up to 95% of Ewing sarcomas. Hence, molecular
studies can be a useful adjunctive test in the diagnosis
of Ewing sarcoma, but should always be interpreted in
the overall context of the clinical, histologic, and immu-
nohistochemical fi ndings.
TREATMEN T AN D PROGN OSIS
Multiagent chemotherapy has made a significant differ-
ence in the prognosis of Ewing sarcoma. It has improved
the 5-year survival rate from less than 10% to approxi-
mately 50% for patients with localized tumors. While
overall survival rates of up to 70% have been reported,
patients who present with metastatic disease have lower
survival rates that are closer to 20%. Experience from the
intergroup Ewing sarcoma study has indicated that the
anatomic location of the tumor has an important bearing
on the prognosis. Patients with tumors of the pelvic girdle
have the worst prognosis; patients with distal lesions have
a much better prognosis than those with proximal ones;
and patients with tumors of the ribs have an unexpect-
edly good prognosis (Fig. 18.28).
Several studies have confi rmed the improved progno-
sis for patients whose treatment regimen includes some
form of surgery. In a study from Mayo Clinic, Wilkins
and coauthors found that patients who underwent com-
plete surgical excision of the primary lesion had a 74%
survival at 5 years compared with 34% for those who
did n ot have complete excision. The authors concluded
that patients with surgically accessible lesions should
undergo treatment consisting of surgery, chemother-
apy, and, in selected cases, radiation.
Three patients in this series developed postradia-
tion sarcoma after treatment of Ewing tumor. Two oth-
ers with postradiation sarcoma in our series following
Ewing tumor did not have the original tumors treated at
Mayo Clinic, and they are not included in the statistics
for Ewing tumor. Another patient developed squamous
cell carcinoma of the chest wall after radiation therapy
for Ewing tumor of a rib.
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1981 Pilepich, M. V., Vietti, T. J., Nesbit, M. E., Tefft, M.,
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1981 Rosen, G., Caparros, B., Nirenberg, A., Marcove, R. C.,
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1982 Bacci, G., Picci, P., Gitelis, S., Borgh i, A., an d Campan acci,
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1982 Dickman, P. S., Liotta, L. A., and Triche, T. J.: Ewing’s
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1982 Miettinen, M., Lehto, V.-P., and Virtanen, I.: Histogenesis of
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1983 Kissane, J. M., Askin, F. B., Foulkes, M., Stratton, L. B., and
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1983 Li, W. K., Lane, J. M., Rosen, G., Marcove, R. C., Caparros,
B., Huvos, A., and Groshen, S.: Pelvic Ewing’s Sarcoma:
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1983 Mendenhall, C. M., Marcus, R. B., Jr., Enneking, W. F.,
Springfi eld, D. S., Thar, T. L., and Million, R. R.: The Prognos-
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1983 Thomas, P. R. M., Foulkes, M. A., Gilula, L. A., Burgert,
E. O., Evans, R. G., Kissane, J., Nesbit, M. E., Pritchard, D. J.,
Tefft, M., an d Vietti, T. J.: Primary Ewin g’s Sarcoma of th e
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1984 Jaffe, R., Santamaria, M., Yunis, E. J., Tannery, N. H.,
Agostin i, R. M., Jr., Medin a, J., an d Goodman , M.: Th e Neu-
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■ Ewing Tumor 223
1986 Llombart-Bosch, A., Contesso, G., Henry-Amar, M., Lacombe,
M. J., Oberlin, O., Dubousset, J., Rouëssé, J., and Sarrazin, D.:
Histopathological Predictive Factors in Ewing’s Sarcoma of
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Study of 261 Cases. Virchows Arch [A], 409:627–640.
1986 Wilkin s, R. M., Pritch ard, D. J., Burgert, E. O., Jr., an d
Un n i, K. K.: Ewin g’s Sarcoma of Bon e: Experien ce With 140
Patien ts. Can cer, 58:2551–2555.
1987 Edeiken , J., Raymon d, A. K., Ayala, A. G., Ben jamin , R. S.,
Murray, J. A., an d Carrasco, H. C.: Small-cell Osteosarcoma.
Skeletal Radiol, 16:621–628.
1987 Siegal, G. P., O liver, W. R., Rein us, W. R., Gilula, L. A.,
Foulkes, M. A., Kissane, J. M., an d Askin , F. B.: Primary Ewin g’s
Sarcoma Involving the Bones of the Head and Neck. Cancer,
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1988 Jürgen s, H., Bier, V., Harms, D., Beck, J., Bran deis, W.,
Etspüler, G., Gadner, H ., Schmidt, D., Treuner, J., Winkler, K.,
an d Göbel, U.: Malign an t Periph eral Neuroectodermal
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1989 Hayes, F. A., Th ompson , E. I., Meyer, W. H., Kun, L.,
Parham, D., Rao, B., Kumar, M., Han cock, M., Parvey, L.,
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1989 Lizard-Nacol, S., Lizard, G., Justrabo, E., an d Turc-Carel, C.:
Immun ologic Ch aracterization of Ewin g Sarcoma Usin g Mes-
enchymal and Neural Markers. Am J Pathol, 135:847–855.
1989 Tsuneyoshi, M., Yokoyama, R., Hashimoto, H ., an d Enjoji,
M.: Comparative Study of Neuroectodermal Tumor an d
Ewing’s Sarcoma of the Bone: Histopathologic, Immunohis-
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1991 Sch midt, D., Herrmann , C., Jürgen s, H., an d Harms, D.:
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sary Distin ction From Ewin g’s Sarcoma: A Report From th e
Kiel Pediatric Tumor Registry. Can cer, 68:2251–2259.
1992 Con tesso, G., Llombart-Bosch , A., Terrier, P., Peydro-Olaya,
A., Hen ry-Amar, M., O berlin , O., H abran d, J. L., Dubous-
set, J., Tursz, T., Spielman n , M., Gen in , J., an d Sarrazin , D.:
Does Malignant Small Round Cell Tumor of the Thoracopul-
mon ary Region ( Askin Tumor) Con stitute a Clin icopath ologic
Entity? An Analysis of 30 Cases With Immunohistochemical
an d Electron -Microscopic Support Treated at th e In stitute
Gustave Roussy. Can cer, 69:1012–1020.
1992 Fellinger, E. J., Garin -Ch esa, P., Glasser, D. B., Huvos, A. G.,
an d Rettig, W. J.: Comparison of Cell Sur face An tigen HBA71
( p30/ 32MIC2) , Neuron-Specifi c Enolase, and Vimentin in the
Immun oh istoch emical An alysis of Ewin g’s Sarcoma of Bon e.
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1992 Steph enson, C. F., Bridge, J. A., an d Sandberg, A. A.:
Cytogen etic and Path ologic Aspects of Ewing’s Sarcoma and
Neuroectodermal Tumors. Hum Path ol, 23:1270–1277.
1992 Ushigome, S., Sh imoda, T., Nikaido, T., Nakamori, K.,
Miyazawa, Y., Sh ish ikura, A., Takakuwa, T., Ubayama, Y., an d
Spjut, H. J.: Primitive Neuroectodermal Tumors of Bone and
Soft Tissue: With Reference to Histologic Differentiation in
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1993 Dierick, A. M., Lan glois, M., Van Oostveldt, P., and Roels,
H.: The Prognostic Signifi cance of the DNA Content in
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Cytometric Study. Histopath ology, 23:333–339.
1993 Frassica, F. J., Frassica, D. A., Pritchard, D. J., Sch omberg,
P. J., Wold, L. E., an d Sim, F. H.: Ewin g Sarcoma of th e Pelvis:
Clin icopath ologic Features an d Treatmen t. J Bon e Join t Surg,
75A:1457–1465.
224 Chapter 18 ■
1993 Maygarden , S. J., Askin, F. B., Siegal, G. P., Gilula, L. A.,
Schoppe, J., Foulkes, M., Kissan e, J. M., an d Nesbit, M.: Ewin g
Sarcoma of Bon e in Infan ts and Toddlers: A Clinicopatho-
logic Report From th e In tergroup Ewin g’s Study. Can cer, 71:
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1993 Ramani, P., Rampling, D., and Link, M.: Immunocytochemi-
cal Study of 12E7 in Small Roun d-Cell Tumours of Ch ildh ood:
An Assessmen t of Its Sen sitivity an d Specifi city. Histopath ol-
ogy, 23:557–561.
1994 Navarro, S., Cavazzana, A. O., Llombart-Bosch, A., and
Trich e, T. J.: Comparison of Ewin g’s Sarcoma of Bon e an d
Periph eral Neuroepith elioma: An Immunocytochemical an d
Ultrastructural Analysis of Two Primitive Neuroectodermal
Neoplasms. Arch Pathol Lab Med, 118:608–615.
1994 Perlman, E. J., Dickman, P. S., Askin, F. B., Grier, H. E.,
Miser, J. S., and Link, M. P.: Ewing’s Sarcoma—Routin e Diag-
nostic Utilization of MIC2 Analysis: A Pediatric Oncology
Group/ Ch ildren ’s Can cer Group In tergroup Study. Hum
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1994 Weidner, N. and Tjoe, J.: Immunohistochemical Profi le of
Monoclon al An tibody O13: Antibody That Recogn izes Gly-
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Poulik, J. M., an d Mott, M. P.: Ewin g Sarcoma vs Lymph oblas-
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C. J., Pritch ard, D. J., Gebhardt, M. C., Dickman, P. S., Perlman,
E. J., Meyers, P. A., Don aldson, S. S., Moore, S., Rausen , A. R.,
Vietti, T. J., an d Miser, J. S.: Addition of Ifosfamide an d Etopo-
side to Stan dard Ch emoth erapy for Ewin g’s Sarcoma an d
Primitive Neuroectodermal Tumor of Bon e. N En gl J Med,
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Liu, W., Dei Tos, A. P., and Weiss, S. W.: Morphologic an d
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Study of 66 Genetically Con fi rmed Cases. Am J Surg Path ol,
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an d Berton i, F.: Progn ostic Factors in Non -Metastatic Ewin g’s
Sarcoma Tumor of Bone: An Analysis of 579 Patients Treated
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th erapy Between 1972 and 1998. Acta O n col, 45:469–475.
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and Navid, F.: Analysis of Prognostic Factors in Ewing Sarcoma
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Llombart-Bosch, A. Peydro-Olaya, A.: Ewing’s Sarcoma of Bon e.
Un publish ed data.

Giant Cell Tumor (Osteoclastoma)
Gian t cell tumor of bon e is a distin ctive n eoplasm
of un differen tiated cells. Th e multin ucleated gian t
cells apparen tly result from fusion of th e proliferat-
in g mon on uclear cells, an d alth ough th ey are a con -
stan t an d promin en t part of th ese tumors, th e gian t
cells are probably of less sign ifi can ce th an th e mon o-
n uclear cells. In fact, th ese osteoclast-like gian t cells,
with or with out min or modifi cation , occur in man y
path ologic con dition s of bon e. Th e ubiquitous gian t
cell accoun ts for th e con fusion th at is foun d in th e
older literature an d in some of th e recen t literature on
gian t cell tumors. Auth ors h ave in cluded con dition s
such as metaph yseal fi brous defect, ben ign ch on dro-
blastoma, ch on dromyxoid fi broma, un icameral bon e
cyst with a cellular lin in g, gian t cell reparative gran u-
loma, an eur ysmal bon e cyst, h yperparath yroidism,
gian t cell-con tain in g osteosarcoma, an d oth er en tities
in th e gen eral categor y of gian t cell tumor. In clusion
of th ese “varian ts” with th eir widely divergen t biologic
beh avior h as delayed th e un derstan din g of th e clin i-
cal features an d respon se to treatmen t of true gian t
cell tumor. Th e exact cell of origin of th is n eoplasm
is still un kn own . Several immun oh istoch emical stud-
ies h ave suggested th at th e mon on uclear cells are of
h istiocytic origin an d th at th e gian t cells arise from
th eir fusion .
In addition to the recognized conditions that have
been confused with giant cell tumor, there are benign,
often fi brogenic, rarefying processes that do not fi t well
into any of the known categories. These rare benign
lesion s, which contain giant cells and variable amounts
of proliferative new bone, are likely to be found in the
small bones of th e hands and feet. They probably rep-
resent a peculiar reaction in bone. They fortunately are
associated with a good prognosis. They have been called
giant cell reaction or, more recently, giant cell reparative
granuloma.
Malignant giant cell tumor, discussed in the following
ch apter, cannot be diagnosed with assurance unless evi-
dence of ordinary ben ign giant cell tumor exists within
C H APT ER
19
the lesion or has been demonstrated previously at the
same site. If the stromal cells of a tumor that has many
benign giant cells are malignant throughout, with fea-
tures of osteosarcoma, malignant fi brous histiocytoma,
or fi brosarcoma, the tumor probably has no relation-
ship to giant cell tumor. The benign giant cells are but
an incidental and confusing component. The clinical
correlative studies reported by Troup and coworkers in
1960 have fortifi ed this concept.
To further confuse the issue, giant cell tumor can
metastasize even though the tumor is cytologically
benign. Metastasis is very rare, and only 20 examples
were found in the Mayo Clinic fi les of 671 cases of giant
cell tumor.
IN CID EN CE
The 671 cases of giant cell tumor represented 6.60%
of the total series and 21.87% of the benign tumors
( Fig. 19.1) .
SEX
In many series, females predominate. The Mayo Clinic
series included 376 females and 295 males. This 56.0%
of females contrasts with the 70.0% of females in the
subgroup of 89 patients in the fi rst two decades of life.
AGE
Approximately 85% of the neoplasms occurred in
patients older than 19 years, with a peak incidence
in the third decade of life. Only four patients were
younger than 10 years, and the youngest was 8 years.
Eleven patients were between the ages of 10 and 14.
Only 10.88% of the patients were older than 50 years,
and the oldest patient was 83 years.
225
226 Chapter 19 ■
LOCALIZATION
Most giant cell tumors are found at the ends ( epiphy-
ses) of long bones. Approximately 46.2% of the lesions
occurred around the knee joint, with the distal femur
being the most common single location. The distal end
of the radius and the sacrum were the third and fourth
most common locations, respectively. There were 42
lesions in the vertebrae above the level of the sacrum,
and most of these involved the body of the vertebra. This
fi ndin g emphasizes that in vertebrae above the sacrum
“variants” are more frequent than giant cell tumors.
These variants predominantly involve the posterior ele-
ments. The proximal femur is involved relatively infre-
quently. Four giant cell tumors involved the greater
trochanter. In contrast, 6 of the 147 chondroblastomas
involved the greater troch anter. The small bones of the
hands and feet are rarely involved; there were seven
giant cell tumors involving the tarsal bones and two
involving the metatarsals. There were fi ve tumors in the
carpal bones, six in the metacarpals, and fi ve in the pha-
langes of the hands. Two of the patients in this series
with tumors of the small bones of the hands and feet
had multicentric involvement. Information in th e lit-
erature suggests that the incidence of multicentricity is
higher in these sites. Multicentric involvement also may
be more aggressive clinically. Five patients had involve-
ment of the ribs and two of the sternum. Involvement
of these unusual locations should suggest the possibility
F igu r e 19.1. Distribution of
gian t cell tumors accordin g to
age an d sex of th e patien t an d
site of th e lesion.
of other diagnoses, such as hyperparathyroidism. The
pelvic bones were involved in 34 patients, and 22 of
these involved the ilium. Six patients had involvement
of the skull. Most involved the sphenoid. Chondroblas-
tomas are more likely to involve the skull than giant cell
tumor.
In the Mayo Clinic series, only one giant cell tumor
involved the patella. However, there are several giant
cell tumors of the patella in our consultation series.
There is also one giant cell tumor of the hyoid bone in
the consultation series. Three patients with giant cell
tumors, which apparently were primary in the parotid
gland, have been described. Most of the lesions with
osteoclast-like giant cells, such as those noted in the
pancreas, thyroid, and ovary, probably are examples of
metaplastic carcinomas.
Nine patients in this series had multicentric giant
cell tumor: there were 20 tumors in these 9 patients.
Two patients had involvement of three separate sites,
and one patient had two tumors in one bone, distal and
mid radius. The other six patients had two separate skel-
etal sites. Two of the patients also developed pulmonary
metastasis.
A few of the giant cell tumors did not extend com-
pletely to the articular cartilage, although most did.
Eight patients had giant cell tumors in the metaphy-
sis with complete sparing of the epiphysis. Six of the
patients were male: 8, 16, 18, 13, 13, and 50 years old.
Two were females ages 8 and 21.

SYMPTOMS
Pain of variable severity is almost always the predominant
symptom. More than three-fourths of the patients had
noted swelling of the affected region. Less common
symptoms included weakness, limitation of motion of
the joint, and signs of pathologic fracture.
PH YSICAL FIN D IN GS
A hard, sometimes crepitant and painful mass is found
in more than 80% of the patients. Atrophy of muscles
from disuse may be present as well as effusion in the
adjacent joint or local heat and wetness.
RAD IOGRAPH IC FEATU RES
Gee and Pugh summarized the radiographic features
as those of an expanding zone of radiolucency situated
eccentrically, usually in the end of a long bone of an
adult. The lesion usually extends to the articular car-
tilage, although there may be a thin zone of normal
bone between the lesion and the articular cartilage.
The lesion may be well marginated or poorly margin-
ated. It is unusual to see sclerosis around a ben ign giant
cell tumor. The tumor frequently destroys the cortex
and extends into the soft tissue. Periosteal new bone
formation is rarely seen. Some giant cell tumors pro-
duce large areas of destruction with poor margination,
suggesting the diagnosis of malignancy. The lesion may
destroy the articular cartilage and extend into the joint
( Figs. 19.2–19.6) .
F igu r e 19.2. Giant cell tumor in the most common loca-
tion, the distal femur, in a 40-year-old woman. The lesion is
purely lytic, although it has a partial sclerotic rim. Histologic
examin ation showed a few atypical cells, but because of the
typical radiographic appearance, an ordinary giant cell tumor
was diagnosed.
■ Giant Cell Tumor (Osteoclastoma) 227
F igu r e 19.3. Giant cell tumor involving the proximal meta-
carpal bon e of th e in dex fi n ger. Th e tumor is expan sile an d
extends to the articular cartilage.
The typical giant cell tumor produces an area of
lucency with no sclerosis in it. However, rarely, a giant
cell tumor may have ossifi cation within it which may
be apparent radiographically. This usually suggests the
diagnosis of osteosarcoma to the radiologist ( Fig. 19.7) .
Although giant cell tumors classically are considered
to be incapable of producing sclerosis, they typically
produce a peripheral shell of ossifi cation when they
recur in soft tissue or even when they metastasize to
lungs ( Figs. 19.8 & 19.9) . As indicated above, most giant
cell tumors involve the end of the bone; h owever, in
our series, eight were located in the metaphysis. When
a giant cell tumor–like lesion occurs in a metaphysis,
care should be taken to exclude an aneurysmal bone
cyst and an osteosarcoma rich in giant cells.
Cam pan acci an d coauth ors h ave developed a grad-
in g system for gian t cell tum ors based on th e radio-
graph ic appearan ce. A grade 1 tum or is associated
with a well-defi n ed m argin an d a th in rim of m ature
bon e. A grade 2 tum or appears well-defi n ed but lacks
a radiopaque rim . A grade 3 lesion h as fuzzy bor-
ders th at suggest an aggressive n eoplasm. H owever,
Campan acci an d coauth ors were n ot able to cor-
relate th ese differen t stages with clin ical outcom e
( Figs. 19.3–19.11) .
Giant cell tumor may occur in a lesion of Paget dis-
ease, a rare complication that seems to have a predi-
lection for the bones of the skull and face. Only one
neoplasm in the Mayo Clinic series, an iliac tumor,
developed in Paget disease.
Other lesions, most notably fi brosarcoma, may pro-
duce radiographic features similar to those of giant cell
tumor.
228 Chapter 19 ■

F igu r e 19.4. Giant cell tumor involving the sacrum in a 31-year-old man. A: Anteroposterior plain
radiograph sh ows a lytic lesion in the upper part of the sacrum. B: As often true of sacral tumors,
th e mass is visualized more easily with computed tomograph y. It is an expan sile, destructive mass
th at exten ds medially to in volve part of th e ilium.

F igu r e 19.5. A: An teroposterior plain radiograph sh ows

a gian t cell tumor formin g a purely lytic expan sile mass in
th e proximal fi bula. B: Magn etic reson an ce imagin g sh ows
expansion in to soft tissue.
 ■ Giant Cell Tumor (Osteoclastoma) 229

F igu r e 19.6. An teroposterior ( A) an d lateral ( B) radiograph s of th e kn ee sh ow a purely lytic

lesion in the proximal tibial epiphysis and metaphysis that extends to the articular sur face of the
lateral tibial plateau. The lesion has a well-defi ned margin without a sclerotic rim. It is associated
with some expansion of the cortex laterally, but no evidence of cortical destruction. The imaging
features are typical of benign giant cell tumor. Coronal T1- ( C) and T2- ( D) weighted magnetic
reson an ce images with fat saturation show that th e lesion has nonspecifi c signal characteristics, with
an expanded, but intact, lateral tibial cortex. The magnetic resonance images show that the lesion
is associated with surrounding bone marrow and tissue edema, also typical of giant cell tumor.
230 Chapter 19 ■
F igu r e 19.7. Benign giant cell tumor involving the proxi-
mal h umerus in a 58-year-old woman . Alth ough classic gian t
cell tumor is purely lytic, some gian t cell tumors may sh ow
focal mineralization. The lesion had been present for 10 years
( Case provided by Dr. F. Azizi, Kaiser Permanente, Fontana,
California.) .
F igu r e 19.8. Large, un resectable metastatic gian t cell tumor
in the lung in a patient who had a previous giant cell tumor
of th e distal femur resected 10 years earlier. Th ere are mul-
tiple smaller nodules. The patient underwent chemotherapy
but did n ot complete th e course. Th e patien t died of disease
3 years later.
GROSS PATH OLOGIC FEATU RES
The tumor tissue is characteristically soft, friable, and
dark brown . Firmer portions may be seen as a result
of previous fracture, treatment, or degeneration, all
of which may cause fi brosis and osteoid production.
Small cystic or necrotic portions, sometimes fi lled
with blood, may be presen t, but these ordinarily con-
stitute an insignifi cant feature of untreated lesion s not
modifi ed by previous fracture. This cystifi cation may
be suffi ciently prominent, especially in recurrent neo-
plasms, to cause them to be con fused with an eurysmal
bone cyst. The aggressive nature of giant cell tumors
accounts for the usually immense size when th ey h ave
been neglected. Intact gross specimens sh ow variable
degrees of expansion of the bone with corresponding
expansion or destruction of the cortex. The rest of the
osseous structure in the region of the tumor is com-
pletely replaced. Th e tumor practically always exten ds
to th e articular cartilage, an d its boundaries are only
moderately well demarcated from adjacent bone and
cartilage. Even with very large lesions, the periosteum is
rarely breached ( Figs. 19.10–19.21) .
Although the characteristic color of a giant cell tumor
is almost chocolate brown, some giant cell tumors are
white and fl eshy and may simulate the appearance of
a sarcoma. Some giant cell tumors have small foci of
brown neoplasm separated by large areas of white fi bro-
sis. Small foci or large areas of yellow discoloration cor-
responding to collections of foam cells may also be seen
( Figs. 19.22 & 19.23) .
H ISTOPATH OLOGIC FEATU RES
The basic proliferating cells have a round-to-oval or even
spindle-shaped nucleus in the fi elds that are diagnos-
tic of true giant cell tumor. This nucleus is surrounded
by an ill-defi ned cytoplasmic zone, and discernable
intercellular substance is absent. Mitotic fi gures can be
found in practically every lesion, and in some lesions,
they are numerous. Mitotic activity has no prognostic
signifi cance. The nuclei lack the hyperchromatism and
variation in size and shape that are characteristic of sar-
coma. Occasionally, however, an osteosarcoma is seen
with unusually small malignant cells and an abundance
of benign giant cells. Such a tumor may be diffi cult to
differentiate from a giant cell tumor histologically, but
these tumors nearly always are metaphyseal in location
and are seen in a younger age group. Histochemical
and ultrastructural methods for differentiating giant
cell tumor from its variants have not been of value, so
the pathologist must make the differentiation on the
basis of correlating the sometimes subtle cytologic and
histologic features with the radiographic fi ndings.
 ■ Giant Cell Tumor (Osteoclastoma) 231

F igu r e 19.9. Giant cell tumor involving an unusual

location, the proximal femur, in a 28-year-old woman.
A: Radiograph ic appearan ce. B: Magn etic reson an ce
image. The lesion is fairly well circumscribed and shows
n o soft-tissue extension . C: Eighteen mon ths later, a
soft-tissue recurrence developed. Th e recurrent soft-tis-
sue mass sh ows min eralization at th e periph ery, resem-
blin g an eggsh ell.

Giant cells, usually containing 40 to 60 nuclei, are
scattered uniformly th roughout the lesion. The evi-
dence that the giant cells are derived from fusion of
mononuclear cells includes some marked similarity of
their nuclei. In a given area, it may be diffi cult to dis-
cern where mon onuclear cells stop and giant cells start
( Figs. 19.24–19.27) .
The above description is that of a typical giant cell
tumor. However, quite a few variations may be encoun-
tered. Areas of infarct-like necrosis are commonly seen
in giant cell tumors. Some giant cell tumors may be
almost completely necrotic. The necrosis is not asso-
ciated with an infl ammatory response. Ghost outlines
of the nuclei, especially of the giant cells, are read-
232 Chapter 19 ■

F igu r e 19.10. Giant cell tumor involving the proximal

humerus in a 60-year-old man . A: Radiograph ically, th e tumor
forms a lytic mass associated with a pathologic fracture. B: The
correspon din g gross specimen h igh ligh ts th e soft-tissue exten -
sion an d ch aracteristic red-brown color.

ily discernible in the necrotic areas and may in deed

be diagn ostic of the neoplasm. Sometimes, a spindle
cell reaction occurs around a necrotic zone and care
must be taken not to overdiagnose this as a sarcoma
( Figs. 19.28–19.30) .
Small collections of foam cells are commonly found
in giant cell tumor. However, some giant cell tumors
F igu r e 19.11. Typical giant cell tumor involving the dis-
tal radius, the third most common location. A: The tumor
is purely lytic and has expanded into soft tissue. There is a
pathologic fracture. B: Gross specimen. The cortices have
been destroyed, an d th e lesion expan ds in to soft tissue. Th e
tumor also extends up to the articular cartilage.
 ■ Giant Cell Tumor (Osteoclastoma) 233

F igu r e 19.14. Large giant cell tumor with a typical dark

F igu r e 19.12. Gross specimen of a resected gian t cell tumor brown appearan ce fi llin g th e distal femur an d formin g a large
involving the sacrum. The chocolate color is typical of giant soft-tissue mass.
cell tumor. In th e Mayo Clin ic series, th e sacrum was th e
fourth most common site of in volvemen t.

F igu r e 19.13. Giant cell tumor forming a destructive red-

brown mass in volvin g th e en tire distal femur. Th e cystic areas
represent a secondary an eurysmal bone cyst compon ent.

contain extensive areas of foam cell change. This may

be associated with a spindle cell proliferation, and
the spindle cells may be arranged in a storiform pat-
tern. This frequently gives rise to a mistaken diagnosis
of fi brous histiocytoma. When a lesion in the end of a
bone with the appropriate radiographic appearance has
F igu r e 19.15. Very aggressive-appearing giant cell tumor
involving the proximal humerus in a 20-year-old woman. The
tumor has destroyed the medial cortex and extended into the
sh oulder join t. The radiograph ic appearan ce suggested malig-
n an t disease.
234 Chapter 19 ■

F igu r e 19.19. Giant cell tumor involving a metacarpal bone.

The tumor extends into th e epiphysis an d has a characteristic
ch ocolate color.
F igu r e 19.16. Giant cell tumor involving the greater tro-
ch an ter of th e femur. Both gian t cell tumors an d ch on dro-
blastomas may involve th e greater troch an ter.

F igu r e 19.17. Giant cell tumor from the ischium in a

37-year-old man is almost en tirely dark red-brown .

F igu r e 19.20. Recurrent giant cell tumor involving the thigh.

Wh en giant cell tumor recurs in th e soft tissue, it is usually well
F igu r e 19.18. Gian t cell tumor fi llin g th e proximal ph alan x circumscribed and is enclosed by a shell of ossifi cation. The
of a fi n ger in a 28-year-old man . lesion has the typical appearance of giant cell tumor.

F igu r e 19.21. Recurren t gian t cell tumor in volvin g th e dis-
tal tibia in a youn g girl. Th e lesion is locally aggressive an d
in vades th e fi bula. At th is time, th e patien t h ad bilateral pul-
mon ary metastatic lesion s. Th ey h ave remain ed stable over
several years.
a predominant fi brohistiocytic appearance, we believe a
diagnosis of giant cell tumor is appropriate. One may
see only very small foci of typical giant cell tumor in
such lesions ( Figs. 19.31–19.33) .
Even rarer and more diffi cult to diagnose are giant
cell tumors that have a predominance of spindle cells.
This may lead to a mistaken diagnosis of fi brosarcoma.
However, the nuclei do not show atypia, and the lesion
is much too cellular for a low-grade sarcoma. Every
attempt must be made to make a diagnosis of giant cell
tumor when the clinical features suggest it, even when
the h istologic features are somewhat atypical.
Giant cell tumors generally do not produce matrix.
However, foci of reactive new bone may be seen. Occa-
sionally, bone formation is abundant and, hence,
may lead to a mistaken diagnosis of osteosarcoma.
Although giant cell tumors classically do not produce
matrix, they invariably do so when extending into soft
tissue. The same is true when giant cell tumors metasta-
size to the lungs. Some nodules of metastatic giant cell
tumor may be transformed to mature-appearing bone
( Figs. 19.34 & 19.35) .
■ Giant Cell Tumor (Osteoclastoma) 235
F igu r e 19.22. Gian t cell tumor of th e proximal tibia. Th e
tumor h as th e ch aracteristic red-brown color of gian t cell
tumor with a central golden yellow area th at correspon ds with
degenerative necrosis.
Small foci of cystic ch an ges are common in gian t
cell tumors. In deed, gian t cell tumor is probably
th e most common bon e n eoplasm associated with
secon dary an eurysmal bon e cyst. Rarely, th e an eurys-
mal bon e cyst-like area is domin an t. In such cases, on e
h as to take in to accoun t th e location an d radiograph ic
appearan ce.
In travascular exten sion s of tumor may be foun d at
th e periph ery of a gian t cell tumor, but th is fi n din g does
n ot seem to correlate with in creased risk of metastasis
( Fig. 19.36) . It h as been suggested th at in volvemen t of
capillaries may n ot be sign ifi can t, but th ose of larger
vessels may be.
Gradin g of gian t cell tumors h as no progn ostic
sign ifi can ce. Mitotic fi gures do not h ave an y signifi -
can ce. Abnormal mitotic fi gures, h owever, are virtu-
ally n ever seen in a giant cell tumor. Foci of somewh at
enlarged n uclei of mon on uclear cells may be seen in
an otherwise typical gian t cell tumor. Tumors th at were
classifi ed previously as grade 3 gian t cell tumors almost
surely represen t osteosarcomas or malign an t fi brous
h istiocytoma.
236 Chapter 19 ■

F igu r e 19.25. Nuclei of th e mon on uclear cells are very simi-

lar to the nuclei of the giant cells, so that it may be hard to tell
where the giant cells stop and the mononuclear cells begin.

F igu r e 19.23. Large gian t cell tumor completely fi llin g th e

distal femur. The dark areas have the typical color of giant
cell tumor. Th e ligh ter areas sh ow th e yellow discoloration of
foam cell ch an ges.

F igu r e 19.26. Occasionally, hemorrhagic areas occur within

the tumor where the stromal cells and multinucleated giant
cells are separated by blood.

F igu r e 19.24. Typical appearan ce of gian t cell tumor.

Multinucleated giant cells with a varying number of nuclei
are arranged more or less uniformly within a background of
mon on uclear giant cells.

TREATMEN T

Removal of the tumor by curettage is the most widely

accepted therapy. Chemical or thermal cautery of the F igu r e 19.27. Mitotic fi gures are commonly found in the
walls of the cavity is advocated, and the defect is ordi- mon on uclear cells. Th is fi eld con tain s at least four mitotic
narily fi lled with bon e chips. Total excision of the tumor fi gures.
 ■ Giant Cell Tumor (Osteoclastoma) 237

F igu r e 19.28. H istologic features typical of gian t cell tumor

( left) merge into an area composed predominantly of spindle
cells ( right) .

F igu r e 19.31. A: Spin dle cell proliferation with a storiform

pattern. B: Spindle cell areas commonly contain foci of foam
cells.
F igu r e 19.29. Degenerative cytologic atypia in an area of
fi brosis in giant cell tumor.

F igu re 19.30. Infarct-like necrosis is found commonly in giant

cell tumor. Viable giant cell tumor is seen in the lower right
corner. Much of the rest of the tumor has undergone necrosis. F igu re 19.32. Plump spindle cells in this giant cell tumor are
Ghost outlines of the multinucleated giant cells are still visible. associated with foam cells and clusters of small lymphocytes.
238 Chapter 19 ■
F igu r e 19.33. A: Typical gian t cell tumor mergin g in to an area of den se fi brosis. B: Fibrosis begin s
to replace th e mon on uclear cells.
F igu r e 19.34. Alth ough gian t cell tumors classically do
not produce matrix, reactive bon e can be seen in giant cell
tumors. Such an appearance may suggest the diagnosis of
osteoblastoma or osteosarcoma.
F igu r e 19.35. Giant cell tumor permeating through corti-
cal bon e in to surroun din g soft tissue.
and its surrounding shell of bone and periosteum is
sometimes the treatment of choice, especially when a
small bone, such as the fi bula or radius, is involved. Total
resection may be indicated, even at the knee, although
it may result in loss of function of the joint. Amputation
may be necessary for extensive destructive lesions. Radi-
ation as primary or adjunctive therapy has its advocates,
but it is becoming less acceptable because of the poten-
tial danger of inducing malignant transformation and
the recognition that true giant cell tumors are relatively
radioresistant. Radiation should be reserved for giant
cell tumors not amenable to surgical excision.
When malignant change occurs, the treatment is the
same as indicated for radioresistant sarcoma.
PROGN OSIS
Long-term follow-up is essential in assessing the results
of therapy for giant cell tumor because malignant
change has been known to occur nearly 40 years after
primary treatment. Several older studies suggested that
the recurrence rate is approximately 50% after curet-
tage. However, with modern therapeutic modalities, the
fi gure is approximately 20%.
When a giant cell tumor recurs, it usually does so
within the fi rst 2 years after treatment. However, recur-
rences may be seen as late as 7 years.
Secondary malignant change is usually to pure fi b-
rosarcoma or osteosarcoma. This change was found in
33 of the 671 cases in the Mayo Clinic series. There are
six additional cases of malignancy in giant cell tumor in
our fi les. However, there was no histologic proof of the
giant cell tumor; hence, they are not included in the sta-
tistics of giant cell tumor. Twenty-six of these occurred
after treatment that included radiation. Eight occurred
at the site of a giant cell tumor that had been treated
 ■ Giant Cell Tumor (Osteoclastoma) 239

F igu r e 19.36. A: Multiple vascular ch an n els at th e periph -

ery of a gian t cell tumor contain tumor. B: H igh-power view
shows endothelial cells lining the vascular space and benign
giant cell tumor within the lumen.

only with surgery. In fi ve patients, a typical giant cell

tumor and malignancy coexisted.
It h as been kn own for some time th at a ben ign gian t
cell tumor can metastasize to th e lun gs. Th ere are 20
such examples in th e Mayo Clin ic fi les. Th e pulmon ary
metastases were presen t at diagn osis in two patien ts;
th e rest developed metastasis at in ter vals ran gin g from
6 mon th s to 10.5 years. O f th e 20 patien ts, 6 died, but
on ly 2 died of th e effects of tumor. O f th e oth er 14
patien ts, n o follow-up in formation was available for 2.
Th e oth er 12 patien ts are all alive from 1 year to 26 years
after diagn osis. Two patien ts h ave persisten t disease.
Th ere h ave been reports of spon tan eous regression of F igu r e 19.37. Giant cell tumor involving the pubis in a
metastatic gian t cell tumor ( Figs. 19.37–19.39) . 16-year-old girl. A: The tumor had marked secondary aneu-
On e patient with a gian t cell tumor of th e distal femur rysmal bone cyst-like changes. B: Computed tomogram of
the lung shows multiple nodules of metastatic benign giant
contracted osteomyelitis in a sinus tract. A squamous cell tumor. The patient had no previous surgical procedure.
cell carcinoma developed in th e sin us tract 19 years C: Gross specimen of a resected lung nodule that showed his-
later. tologic features typical of benign giant cell tumor.
240 Chapter 19 ■
Figu re 19.38. Metastatic benign giant cell tumor in the lung.
F igu r e 19.39. A shell of ossifi cation is seen at th e periphery
of a metastatic ben ign gian t cell tumor in th e lun g.
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1977 Inoue, H., Ishihara, T., Ikeda, T., and Mikata, A.: Benign
Gian t Cell Tumor of Femur With Bilateral Multiple Pulmon ary
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1977 Sim, F. H ., Dah lin, D. C., an d Beabout, J. W.: Multi-
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1978 Marcove, R. C., Weis, L. D., Vaghaiwalla, M. R., Pearson, R.,
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1978 Tuli, S. M., Varma, B. P., and Srivastava, T. P.: Giant-Cell Tumor
of Bone: A Study of Natural Course. Int Orthop, 2:207–214.
1979 Jacobs, T. P., Michelsen, J., Polay, J. S., D’Adamo, A. C., and
Can fi eld, R. E.: Gian t Cell Tumor in Paget’s Disease of Bon e:
Familial an d Geographic Clustering. Cancer, 44:742–747.
1979 Szyfelbein, W. M. and Schiller, A. L.: Cytologic Diagnosis of
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1980 Averill, R. M., Smith, R. J., and Campbell, C. J.: Giant-Cell
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1980 Lorenzo, J. C. and Dor fman, H. D.: Giant-Cell Reparative
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1980 Peimer, C. A., Schiller, A. L., Mankin, H. J., and Smith, R.J.:
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62A:652–656.
1980 Sanerkin, N. G.: Malignancy, Aggressiveness, and Recur-
ren ce in Gian t Cell Tumor of Bone. Can cer, 46:1641–1649.
1981 Mirra, J. M., Bauer, F. C., and Grant, T. T.: Giant Cell Tumor
With Viral-Like Intranuclear In clusions Associated With
Paget’s Disease. Clin Orthop, 158:243–251.
1981 Schwimer, S. R., Bassett, L. W., Mancuso, A. A., Mirra, J. M.,
an d Dawson , E. G.: Gian t Cell Tumor of th e Cervicoth oracic
Spine. Am J Roentgenol, 136:63–67.
1982 Mirra, J. M., Ulich, T., Magidson, J., Kaiser, L, Eckardt, J.,
an d Gold, R.: A Case of Probable Ben ign Pulmon ary “Metas-
tases” or Implants Arising From a Giant Cell Tumor of Bone.
Clin Orthop, 162:245–254.
1983 Picci, P., Manfrini, M., Zucchi, V., Gherlinzoni, F., Rock, M.,
Berton i, F., an d Neff, J. R.: Gian t-Cell Tumor of Bon e in Skel-
etally Immature Patients. J Bone Join t Surg, 65A:486–490.
1983 Upchurch, K. S., Simon, L. S., Schiller, A. L., Rosenthal, D. I.,
Campion , E. W., an d Kran e, S. M.: Gian t Cell Reparative Gran -
uloma of Paget’s Disease of Bon e: A Un ique Clin ical En tity.
Ann Intern Med, 98:35–40.
1983 Wolfe, J. T., III, Scheithauer, B. W., and Dahlin, D. C.:
Gian t-Cell Tumor of th e Sph en oid Bon e: Review of 10 Cases.
J Neurosurg, 59:322–327.
1984 Cooper, K. L., Beabout, J. W., and Dahlin, D. C.: Giant
Cell Tumor: Ossifi cation in Soft-Tissue Implan ts. Radiology,
153:597–602.
1984 Eusebi, V., Martin, S. A., Govoni, E., and Rosai, J.: Giant
Cell Tumor of Major Salivary Glan ds: Report of Th ree Cases,
One Occurring in Association With a Malignant Mixed Tumor.
Am J Clin Path ol, 81:666–675.
1984 Rock, M. G., Pritchard, D. J., and Unni, K. K.: Metastases
From Histologically Ben ign Giant-Cell Tumor of Bon e. J Bone
Joint Surg, 66A:269–274.
1984 Wold, L. E. and Swee, R. G.: Giant Cell Tumor of the
Small Bones of the Hands and Feet. Semin Diagn Pathol,
1:173–184.
1985 Bertoni, F., Present, D., and Enneking, W. F.: Giant-Cell
Tumor of Bone With Pulmonary Metastases. J Bone Joint Surg,
67A:890–900.
1985 Dahlin, D. C.: Caldwell Lecture: Giant Cell Tumor of Bone:
Highligh ts of 407 Cases. Am J Roentgenol, 144:955–960.
■ Giant Cell Tumor (Osteoclastoma) 241
1986 Brecher, M. E., Franklin , W. A., an d Simon, M. A.: Immu-
noh istoch emical Study of Mononuclear Ph agocyte An tigen s in
Gian t Cell Tumor of Bon e. Am J Path ol, 125:252–257.
1986 Emura, I., In oue, Y., Oh n ish i, Y., Morita, T., Saito, H ., an d
Tajima, T.: Histochemical, Immunohistochemical and Ultra-
structural In vestigation s of Gian t Cell Tumors of Bon e. Acta
Path ol Jpn, 36:691–702.
1986 McDonald, D. J., Sim, F. H ., McLeod, R. A., an d Dah lin ,
D. C.: Giant-Cell Tumor of Bone. J Bone Joint Surg, 68A:
235–242.
1986 Presen t, D., Bertoni, F., Hudson, T., and Enn ekin g, W. F.:
Th e Correlation Between th e Radiologic Stagin g Studies an d
Histopathologic Findings in Aggressive Stage 3 Giant Cell
Tumor of Bone. Cancer, 57:237–244.
1986 Presen t, D. A., Bertoni, F., Sprin gfi eld, D., Braylan, R., an d
Enneking, W. F.: Giant Cell Tumor of Bone With Pulmonary
an d Lymph Node Metastases: A Case Report. Clin Orth op,
209:286–291.
1987 Campan acci, M., Baldin i, N., Borian i, S., an d Sudanese, A.:
Gian t-Cell Tumor of Bone. J Bone Joint Surg, 69A:106–114.
1988 Bertoni, F., Presen t, D., Sudan ese, A., Baldini, N., Bacch ini,
P., an d Campan acci, M.: Gian t-Cell Tumor of Bon e With Pul-
mon ary Metastases: Six Case Reports an d a Review of th e Lit-
erature. Clin Orthop, 237:275–285.
1989 Exarchou, E., Maris, J., and Assimakopoulos, A.: Soft Tissue
Recurrence of Osteoclastoma. J Bone Joint Surg, 71B:432–433.
1989 Ladan yi, M., Traganos, F., an d Huvos, A. G.: Benign Metas-
tasizing Giant Cell Tumors of Bone: A DNA Flow Cytometric
Study. Cancer, 64:1521–1526.
1990 Bridge, J. A., Neff, J. R., Bhatia, P. S., Sanger, W. G., and
Murph ey, M. D.: Cytogen etic Fin din gs an d Biologic Beh avior
of Giant Cell Tumors of Bone. Can cer, 65:2697–2703.
1990 Matsuno, T.: Benign Fibrous H istiocytoma In volvin g th e
Ends of Lon g Bon es. Skeletal Radiol, 19:561–566.
1991 Potter, H. G., Schn eider, R., Ghelman , B., Healey, J. H.,
an d Lan e, J. M.: Multiple Gian t Cell Tumors an d Paget Disease
of Bon e: Radiograph ic an d Clin ical Correlation s. Radiology,
180:261–264.
1992 Berton i, F., Un n i, K. K., Beabout, J. W., and Ebersold, M. J.:
Gian t Cell Tumor of the Skull. Cancer, 70:1124–1132.
1992 Fukunaga, M., Nikaido, T., Shimoda, T., Ush igome, S., an d
Nakamori, K: A Flow Cytometric DNA An alysis of Gian t Cell
Tumors of Bone Including Two Cases With Malignant Trans-
formation . Cancer, 70:1886–1894.
1992 López-Barea, F., Rodríguez-Peralto, J. L., García-Giron, J.,
and Guemes-Gordo, F.: Benign Metastasizing Giant-Cell Tumor
of the Hand: Report of a Case and Review of th e Literature.
Clin Orth op, 274:270–274.
1993 Huan g, T.-S., Green, A. D., Beattie, C. W., an d Das Gupta,
T. K.: Mon ocyte-Macroph age Lin eage of Gian t Cell Tumor of
Bone: Establishment of a Multinucleated Cell Line. Cancer,
71:1751–1760.
1993 Medeiros, L. J., Beckstead, J. H ., Rosenberg, A. E., Warn ke,
R. A., an d Wood, G. S.: Gian t Cells an d Mon on uclear Cells of
Giant Cell Tumor of Bone Resemble H istiocytes. Appl Immu-
noh istoch em, 1:115–122.
1993 San jay, B. K., Sim, F. H., Unn i, K. K., McLeod, R. A., an d
Klassen , R. A.: Gian t-Cell Tumours of th e Spin e. J Bon e Join t
Surg, 75B:148–154.
1993 Sch ütte, H. E. and Tacon is, W. K.: Gian t Cell Tumor in
Children an d Adolescents. Skeletal Radiol, 22:173–176.
1994 Kay, R. M., Eckardt, J. J., Seegar, L. L., Mirra, J. M.,
an d H ak, D. J.: Pulm on ar y Metastasis of Ben ign Gian t
Cell Tum or of Bon e: Six H istologically Con fi rm ed Cases,
In clu d in g O n e of Sp on tan eou s Regression . Clin O rth op ,
302:219–230.
242 Chapter 19 ■

1994 Reed, L., Willison, C. D., Schochet, S. S., Jr., and Voelker, J. L.: 2000 Biscaglia, R., Bacch in i, P., and Berton i, F.: Gian t Cell Tumor
Gian t Cell Tumor of th e Calvaria in a Ch ild: Case Report. of th e Bon es of th e Han d and Foot. Cancer, 88:2022–2032.
J Neurosurg, 80:148–151. 2006 Hoch, B., Inwards, C., Sundaram, M., and Rosenberg, A. E.:
1994 Singhal, R. M., Mukhopadhyay, S., Tanwar, R. K., Pant, G. Multicen tric Gian t Cell Tumor of Bon e: Clin icopath ologic
S., an d Julka, P. K.: Case Report: Gian t Cell Tumour of Meta- Analysis of Th irty Cases. J Bon e Join t Surg Am, 88:1998–2008.
carpals: Report of Three Cases. Br J Radiol, 67:408–410.
1998 Siebenrock, K. A., Unni, K. K., and Rock, M. G.: Giant-Cell
Tumour of Bon e Metastasisin g to th e Lun gs: A Lon g-Term
Follow-Up. J Bon e Joint Surg, 80B:43–47.

Malignancy in
Giant Cell Tumor of Bone
To be certain of the diagnosis of malignant giant cell
tumor, the pathologist must demonstrate zones of typi-
cal benign giant cell tumor in the malignant neoplasm
under appraisal or in previous tissue obtained from the
same neoplasm. When confronted with an obviously
malignant growth that contains a few or many benign
osteoclast-like giant cells, the pathologist can prove
a relationship to benign giant cell tumor in no other
way because other neoplasms of bone, including many
of the osteosarcomas, contain a scattering or many of
these benign giant cells. Even classic low-grade parosteal
osteosarcoma can recur as a highly malignant sarcoma
with such an abundance of benign giant cells that, with-
out reference to the original neoplasm, the recurrent
lesion may be mistaken for a malignancy in giant cell
tumor. Some of the osteosarcomas of soft-tissue origin
also contain numerous benign giant cells but obviously
bear no relation to giant cell tumor of bone. For any
given neoplasm, the stromal cells, not the benign multi-
nucleated cells, must determine its classifi cation. In
1960, Troup and coworkers provided clinicopathologic
correlations to support this view.
With this strict defi nition of malignant giant cell
tumor, 39 examples were found in the Mayo Clinic fi les.
Of these, 34 were judged to occur after treatment of typi-
cal benign giant cell tumors—tumors that contained no
features differentiating them from the rest of the giant
cell tumors. These are referred to as secondary malig-
nant giant cell tumors. Of the 34 cases, 26 occurred
after treatment of a benign giant cell tumor which had
included radiation. The other eight tumors occurred
after surgical treatment of a giant cell tumor. In 6 of the
34 cases, the clinical features suggested that the origi-
nal diagnosis was giant cell tumor, although this mate-
rial h as not been reviewed at Mayo Clinic. The interval
from the diagnosis of giant cell tumor to the diagnosis
of sarcoma varied from 1 to 42 years. In only one case
C H APT ER
20
was residual giant cell tumor present at the time the
sarcoma was diagnosed. The other fi ve primary tumors
contained foci of sarcoma along with a giant cell tumor
at the time of diagnosis.
Evidence is increasing that radiation may trigger the
malignant transformation of various osseous lesions,
especially giant cell tumor. As indicated above, however,
radiation was not implicated in 13 of the 39 tumors.
Analysis of the literature on malignant giant cell tumor
is virtually impossible because of lack of strict defi ni-
tion. The subject is further clouded by the fi nding of an
extremely rare benign metastasizing giant cell tumor. As
indicated in the preceding chapter, 20 of the 671 benign
giant cell tumors produced pulmonary metastasis.
IN CID EN CE
The malignant giant cell tumors comprised less than
0.55% of the total group of malignant tumors and 5.8%
of all giant cell tumors ( Fig. 20.1) .
SEX
In this small group, there was a slight female predomi-
nance, slightly less than that seen in the overall giant
cell tumor group.
AGE
Patients with malignant giant cell tumor were some-
what older, on average, than those with benign giant
cell tumor. This difference is explained at least partly by
the fact that most of the tumors developed several years
after treatment of the benign precursor.
243
244 Chapter 20 ■
LOCALIZATION
Th e distribution of th ese tumors is n ot sign ifi can tly
differen t from th at of th e ben ign gian t cell tumors
th at do n ot un dergo malign an t tran sformation . Th e
region of th e kn ee join t, in volvin g th e distal femur
an d proximal tibia, accoun ted for more th an h alf of
th e tumors.
SYMPTOMS
At on set, most of the patients had symptoms of ordinary
benign giant cell tumor. Thirty-four of the 39 tumors
occurred an average of 12.85 years after the histologic
diagnosis of giant cell tumor and 26 had been irradi-
ated. Th e longest interval between the diagnosis of
giant cell tumor and the development of sarcoma in the
same area was 42 years. The fi ve patients whose giant
cell tumors contained malignant foci at the original
operation had had preoperative pain the the region for
3 months and for 1, 1, 2, and 8 years. The fi fth patient
had a fracture in the area.
When the originally benign giant cell tumors became
sarcomas, the clinical features changed abruptly from
those of slowly progressing or quiescent giant cell
tumors to those of the rapidly growing sarcomas they
had become.
F igu r e 20.1. Distribution of
malign an t giant cell tumors
according to age and sex of the
patient and site of the lesion.
PH YSICAL FIN D IN GS
The physical examination fi ndings are likely to be the
same as those seen with any malignant tumor of bone.
Cutaneous changes from previous radiation are com-
mon and may prompt the physician to elicit the history
of such therapy.
RAD IOGRAPH IC FEATU RES
Radiograph ic chan ges do not differ from those
described for fi brosarcoma or osteosarcoma, except
th at in lon g bones the lesion always involved the very
en d of th e bon e. Th e classic features of malignant
destruction are present, and the process usually is com-
pletely lytic. Earlier radiograph s of the lesion ordinar-
ily afford evidence of the preexisting benign giant cell
tumor. Sometimes, the malign an t change is refl ected in
th e radiograph considerably later than its occurrence
as suggested by the clinical h istory ( Figs. 20.2–20.4) .
GROSS PATH OLOGIC FEATU RES
Th e rare malign an t gian t cell tumor th at h as both
ben ign an d sarcomatous zon es at th e time of th e fi rst
treatmen t usually is grossly in distin guish able from its

F igu r e 20.2. Primary malignant giant cell tumor in a 32-year-
old man . Radiograph s suggested a gian t cell tumor. H istologic
examin ation showed osteosarcoma in addition to the giant cell
tumor ( Case provided by Dr. James H . Graham, St. Elizabeth
Hospital, Cambridge, Massachusetts.) .
F igu r e 20.3. Primary malignant giant cell tumor involving
the proximal tibia in a 55-year-old woman. The proximal lytic
compon en t h as th e appearan ce of a gian t cell tumor, wh ereas
the distal mineralizing portion showed an osteosarcoma ( Case
provided by Dr. K. S. Ratnakar, Nizam’s Institute of Medical
Sciences, Hyderabad, India.) .
■ Malignancy in Giant Cell Tumor of Bone 245
F igu r e 20.4. Secon dary malign an t gian t cell tumor in th e
distal femur in a 35-year-old woman. Giant cell tumor was
removed from this location by curettage 12 years earlier. Th ere
was no history of radiotherapy. Biopsy at this time showed a
grade 4 fi brosarcoma. Th e patient also h ad pulmonary metas-
tasis ( Case provided by Dr. Douglas Ackerman n , North ern
H ospital, Louisville, Ken tucky.) .
ben ign coun terpart. H owever, th e tumor may con tain
zon es of abn ormal con sisten cy. Th e tumor exten ds to
th e en d of a bon e an d ordin arily is con tain ed by th e
expan ded periosteum. Th e more common secon d-
ary malign an t gian t cell tumor exh ibits ch aracteristic
eviden ce of sarcoma, such as in vasion of surroun din g
osseous an d soft tissues, h emorrh age, an d n ecrosis,
alth ough th e last two are by n o mean s un common
in ben ign gian t cell tumor. Th e gross appearan ce of
th ese secon dary sarcomas often h as been modifi ed by
previous treatmen t, wh ich common ly in cludes in cor-
poration of bon e grafts in to th e defect of curettage.
Such grafts usually are partially or completely dissolved
( Fig. 20.5) .
In general, the gross features of a malignant giant
cell tumor are not specifi c, and frequently, multiple
microscopic sections must be taken to establish the
presence of foci of sarcoma in a lesion that still contains
benign areas. Any grossly unusual appearing areas must
be included in the microscopic assessment.
246 Chapter 20 ■

F igu r e 20.5. Fibroblastic osteosarcoma of the distal femur

in a 35-year-old woman. The patient had treatment for giant
cell tumor 16 and 12 years earlier. Th e treatmen t h ad in cluded
radiotherapy.

H ISTOPATH OLOGIC FEATU RES

In most cases when sarcomatous changes occur, the

preexisting benign giant cell tumor is no longer recogniz-
able as such. The sarcomatous component is ordinarily
overtly malignant and presents no problem in diagnosis.
In fact, in this series, for the 34 sarcomas that originally
were completely benign giant cell tumors, the relation-
ship to benign giant cell tumor could not have been sus-
pected from study of the subsequent sarcoma. Twenty-two
of the secondary sarcomas were considered to be fibro-
sarcomas, 13 were diagnosed as osteosarcoma and 3 as
malignant fibrous histiocytoma. Three of the malignan-
cies arising primarily in giant cell tumor were considered
to be osteosarcoma, and the other two were considered to
be fibrosarcoma. The sarcomatous foci contrasted sharply
with the zones of residual benign giant cell tumor. The
sarcomas apparently arose from the stromal cells.
In this series, careful review of the numerous tissue
sections of the benign tumors that subsequently under-
went malignant change offered no histologic clue by F igu r e 20.6. Malign an cy in gian t cell tumor th at was diag-
which one might differen tiate them from those that n osed at in itial surgery for a path ologic fracture of the dis-
remained benign. Furthermore, the giant cell tumors tal femur in a 58-year-old woman. A: Most of the tumor in
that recurred after conventional therapy were not dis- this fi eld has features of a benign giant cell tumor. H owever,
a few pleomorphic cells are seen in the right side of the fi eld.
tinguishable from those that did not. Grading of giant B: Low-power appearance of an area containing high-grade
cell tumors on a histologic basis has not been of value sarcoma. C: High-power view with pleomorphic tumor cells in
( Figs. 20.6 & 20.7) . a sarcomatous area.

F igu r e 20.7. A: Ben ign gian t cell tumor in a patien t wh o
received radiotherapy. B: Recurren t tumor sh owed features of
a h igh -grade spin dle cell sarcoma.
The differential diagnosis of a malignant giant cell
tumor involves other sarcomas in which giant cells may
be found, especially osteosarcoma and malignant fi brous
histiocytoma. In giant cell-rich osteosarcoma, the cyto-
logic evidence of malignancy in the mononuclear cells
can be very subtle. Hence, the diagnosis of a primary
malignant giant cell tumor has to be made with caution.
When the interval between the treatment of ordinary
giant cell tumor and the development of sarcoma is short,
it is not always possible to be sure that the original tumor
was not initially malignant. Fortunately, this differentia-
tion is only of academic interest because the prognosis
for malignant giant cell tumor is the same as for high-
grade osteosarcoma or malignant fi brous histiocytoma.
TREATMEN T
When in disputable evidence of a malignant change is
foun d in a giant cell tumor or in the zone previously
■ Malignancy in Giant Cell Tumor of Bone 247
occupied by one, ablative surgical treatmen t is the pro-
cedure of choice. The sarcoma that develops is ch ar-
acteristically radioresistant, ordinarily being either a
fi brosarcoma or osteosarcoma. The same principles
outlined for the treatment of th ese sarcomas when they
occur primarily should be followed. Radiation , at least
as a palliative measure, may be administered for tumors
not amenable to ablation .
PROGN OSIS
Wh en a fran kly malign an t tran sformation h as occurred
in a ben ign gian t cell tumor, th e progn osis is th at of
th e sarcoma. Some studies h ave suggested th at patien ts
with a primary malign an t gian t cell tumor h ave a bet-
ter progn osis th an patien ts with a secon dary malig-
n an t gian t cell tumor. Rock an d coauth ors reported
on 19 cases of secon dary malign an t gian t cell tumor
of bon e an d foun d a survival rate of 32% at a mean of
9.6 years.
BIBLIOGRAPH Y
1956 Murphy, W. R. and Ackerman, L. V.: Benign and Malignant
Gian t-Cell Tumors of Bon e: A Clin icopath ological Evaluation
of Th irty-O n e Cases. Can cer, 9:317–339.
1962 Hutter, R. V. P., Worcester, J. N., Jr., Francis, K. C., Foote,
F. W., Jr., and Stewart, F. W.: Benign an d Malign an t Gian t Cell
Tumors of Bone: A Clinicopathological Analysis of the Natural
History of the Disease. Cancer, 15:653–690.
1979 Nascimento, A. G., Huvos, A. G., and Marcove, R. C.: Pri-
mary Malign an t Gian t Cell Tumor of Bon e: A Study of Eigh t
Cases and Review of th e Literature. Can cer, 44:1393–1402.
1980 Sanerkin, N. G.: Malignancy, Aggressiveness, and Recur-
ren ce in Gian t Cell Tumor of Bone. Cancer, 46:1641–1649.
1986 Rock, M. G., Sim, F. H., Unn i, K. K., Witrak, G. A., Frassica,
F. J., Sch ray, M. F., Beabout, J. W., an d Dah lin , D. C.: Secon d-
ary Malign an t Gian t-Cell Tumor of Bon e. J Bon e Join t Surg,
68A:1073–1079.
1989 Gitelis, S., Wang, J.-W., Quast, M., Schajowicz, F., and Tem-
pleton , A.: Recurren ce of a Gian t-Cell Tumor With Malign an t
Transformation to a Fibrosarcoma Twenty-Five Years After
Primary Treatmen t: A Case Report. J Bon e Join t Surg, 71A:
757–761.
1992 Hefti, F. L. Gächter, A., Remagen, W., and Nidecker, A.:
Recurren t Gian t-Cell Tumor With Metaplasia an d Malign an t
Ch an ge, Not Associated With Radioth erapy: A Case Report.
J Bone Join t Surg, 74A:930–934.
2001 Marui, T., Yamamoto, T., Yoshihara, H., Kurosaka, M.,
Mizuno, K., and Akamatsu, T.: De Novo Malignant Transforma-
tion of Giant Cell Tumor of Bone. Skeletal Radiol, 30:104–108.
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 C H APT ER
21
Chordoma
Chordoma is a neoplasm that develops from remnants
of the primitive notochord. It apparently can arise from
the normal products of the notochord ( the nuclei pul-
posi) or from abnormal rests of notochordal tissue.
Ordinarily, it grows slowly and is malignant because of
local invasion, but metastasis is relatively uncommon.
Chordoma has a distinct predilection for the ends of
the spinal column. Thus, most of the lesions are found
in the sacrococcygeal region and at the base of the skull
near the site of the spheno-occipital synchondrosis.
Small, n onneoplastic masses of vestigial notochordal
tissue are occasionally found near the spheno-occipital
junction in the midline and have been termed ecchon-
drosis physaliphora.
This tumor is relatively uncommon in the spinal col-
umn, especially in the dorsal portion, which is curious
because the largest masses of notochordal products, in
the form of nuclei pulposi, occur in this region.
One might question whether a chordoma is correctly
classed among the neoplasms of bone. However, the
intimate relationship of the notochord with the skel-
eton and the clinical and radiographic features of these
tumors make the inclusion logical.
IN CID EN CE
Chordoma is a relatively rare neoplasm and accounted
for 6.15% of the malignant tumors in the Mayo Clinic
fi les ( Fig. 21.1) .
SEX
Chordoma affects males much more commonly than
females. In the overall group of 437 patients, approxi-
mately 64% were males. However of the 170 patients
with involvement of the spheno-occipital region, only
just over 55% were males. The male predominance was
most pronounced in the 197 patients with tumors of the
sacrum; approximately 71% were males.
248
AGE
Chordoma is distinctly uncommon in patients younger
than 30 years. Only eight patients were in the fi rst
decade of life, and all the tumors involved the spheno-
occipital region. Eighteen patients were in the second
decade, and twelve had tumors involving the clivus.
Four patients had involvement of the spine and two,
the sacrum. The youngest patient with a lesion of
the sacrum was a 13-year-old girl. Chordomas in the
spheno-occipital region are recognized clinically about
a decade earlier in life than those in the sacrococcygeal
region. In the Mayo Clinic series, there are no examples
of high-grade chordomas of childhood, as described by
Coffi n and coauthors.
LOCALIZATION
Chordoma is so strictly localized to the midline regions
of the body that this affords important diagnostic evi-
dence. Just over 45% of the lesions occurred in the
sacrococcygeal region, and just over 38% involved the
spheno-occipital region. Of the 70 lesions involving
the rest of the spine, 32 involved the cervical spine, 24
the lumbar spine, and only 14 the thoracic spine. The
tumor frequently involved more than one contiguous
vertebral body.
SYMPTOMS
The duration of symptoms before the patient seeks
medical care varies from months to several years. Pain is
a nearly constant feature of sacrococcygeal chordoma,
and it characteristically occurs at the tip of the spinal
column. Constipation due to the presence of the tumor
and complaints resulting from pressure on or destruc-
tion of nerves emerging from the distal portion of the
spinal cord may develop. Nearly all these tumors extend

F igu r e 21.1. Distribution of
ch ordomas accordin g to age
and sex of the patient and site
of th e lesion .
an terior to the sacrum, but in rare instances, a sacrococ-
cygeal chordoma produces a postsacral mass.
Spheno-occipital chordoma may cause symptoms
referable to any of the cranial nerves, but symptoms
resulting from involvement of the nerves to the eye are
by far the most common. This tumor may destroy the
pituitary gland and produce evidence of its dysfunc-
tion, it may protrude laterally and give signs suggestive
of a tumor in the cerebellopontine angle, or it may
erode inferiorly and obstruct the nasal passages. A large
in tracranial extension may evoke the general features
of intracranial neoplasms.
Chordomas arising along the rest of the spinal col-
umn frequently produce either symptoms, by compres-
sion of the spinal nerve roots or the spinal cord, or a
mass.
PH YSICAL FIN D IN GS
Almost every sacrococcygeal chordoma has a presacral
extension that may be detected on careful rectal exami-
nation. The mass is fi rm and fi xed to the sacrum. Digi-
tal and proctoscopic examinations disclose that the
lesion is extrarectal. Evidence of nerve dysfunction,
such as “cord” bladder, anesthesias, and paresthesias, is
relatively unusual and late to appear.
Ch ord om as th at arise at th e base of th e brain
m ay, as in dicated, produ ce sign s referable to an y of
■ Chordoma 249
th e cran ial n er ves or to in volvem en t of th e pituitar y
glan d . Exam in ation of th e visual field s m ay d isclose
defects th at are su ggestive of th e correct d iagn osis.
Som e m ay presen t as a cerebellopon tin e an gle
tu m or. O n ly rarely does th e p atien t com plain of n asal
obstruction .
Becau se ch ord om a of th e cer vical, th oracic, an d
lu m bar p ortion s of th e vertebral colu m n m ay p re sen t
p osteriorly, laterally, or an teriorly, a great variety of
sym p tom s are p rod u ced . For exam p le, a ch ord om a
in th e cer vical region of th e sp in al colu m n m ay p ro-
d u ce clin ical featu res su ggestive of ch ron ic retrop h a-
r yn geal abscess. Ph ysical exam in ation often p rovid es
evid en ce of en croach m en t on th e n er ves or sp in al
cord .
RAD IOGRAPH IC FEATU RES
Radiograph ic features depen d on th e site of in volve-
men t. In a study of 20 cases of ch ordoma in volvin g
th e sacrococcygeal region , Utn e an d Pugh foun d evi-
den ce of th e path ologic process in 85% of cases. Plain
radiograph s sh owed in volvemen t of th e bon e in 75%
of cases an d a soft tissue mass in 85% ( Fig. 21.2) . Typi-
cally, th e area of destruction begin s in th e midlin e
an d sh ows irregular areas of destruction . A soft-tissue
mass is usually presen t an teriorly. In direct eviden ce of
displacemen t of th e rectum may be seen . In creased
250 Chapter 21 ■

F igu r e 21.2. An teroposterior ( A) an d lateral ( B) views of a ch ordoma in volvin g th e sacrum in a

70-year-old woman . Th e lesion is diffi cult to identify in th e anteroposterior view, but destruction of
bon e an d a soft-tissue mass are clearly sh own in th e lateral view.

F igu r e 21.3. A: An teroposterior radiograph of a sacral ch ordoma in a 52-year-old woman . O ver-

lying shadows of bowel gas make it diffi cult to visualize the mass. B: The tumor is easily seen in a
magn etic resonan ce image.

Figu re 21.4. Sacral chordoma in a 61-year-old man who pre-
sented with what was initially thought to be a mass in the colon.
Axial computed tomographic scan (A), sagittal T1-weighted (B),
and sagittal T2-weighted (C) magnetic resonance images show a
massive tumor in the sacrum that was compressing the colon.
■ Chordoma 251
F igu r e 21.5. Ch ordoma formin g a massive sacral tumor.
Magnetic resonance imaging is helpful in delineating the
extent of th e tumor.
den sities are seen in h alf of th e cases. Th ese den si-
ties may represen t calcifi cation with in th e n eoplasm
or residual bon y trabeculae. Because of th e overlyin g
bowel gas sh adows, ch ordomas of th e sacrum are fre-
quen tly overlooked on an teroposterior radiograph s,
delayin g diagn osis. A lateral view is more likely to sh ow
th e lesion . Computed tomograph y an d magn etic reso-
n an ce imagin g h ave been h elpful in recogn izin g th e
lesion an d defi n in g its exten t for plan n in g surgery
( Figs. 21.3–21.5) .
Cranial chordoma nearly always produces
changes visible on plain radiographs. Destruction of
bone in the spheno-occipital and hypophyseal regions
is usually evident. Some portion of the sella tursica is
affected in the majority of cases. Destruction of the cli-
vus is commonly seen. Computed tomograms show the
presence of calcifi c densities in almost three-fourths of
the cases of cranial chordomas. Magnetic resonance
imaging is now considered the best single test, especially
because of its ability to defi ne the extent of the tumor
(Figs. 21.6 & 21.7).
Chordomas that involve the cervical, thoracic, and
lumbar segments of the spinal column usually produce
marked radiographic changes ( Fig. 21.8) . Zones of
bone destruction, sometimes containing sclerotic foci,
are seen to involve one or more vertebrae ( Fig. 21.9) . In
a study of 14 cases of chordomas of the spine, de Bruine
and Kroon found that 64% were sclerotic and the rest
were purely lytic. Some of the tumors, especially if they
displace the pharynx or trachea, produce a pronounced
soft-tissue mass.
252 Chapter 21 ■
Figure 21.6. Computed tomogram of a large chordoma of
the clivus. The lesion arises in the midline and extends to the
left.
F igu r e 21.7. Magnetic reson ance image of chordoma.
Alth ough much of th e tumor is situated to on e side, th ere
is defi nite involvement of the midline. ( Case provided by
Dr. Lin da Spollen , Un iversity of Missouri H ospital, Columbia,
Missouri.)
F igu r e 21.8. Chordoma involving the mobile spine. A: Plain
radiograph sh ows a permeative, lytic, and destructive lesion
involving the vertebral body with cortical destruction. B: Mag-
n etic resonance imaging shows soft-tissue extension posteri-
orly. Th ere is mild an terior wedgin g of th e vertebral body. Th e
h istologic features of this tumor were th ose of a con ventional
ch ordoma.
 ■ Chordoma 253

F igu r e 21.9. Giant notochordal rest. A: Lateral radiograph shows a subtle ill-defi ned region of
sclerosis in th e secon d lumbar vertebral body. Usually, th e radiograph ic fi n din g is n egative, but
occasion ally th ere is min imal sclerosis. B: Sagittal T2-weigh ted magn etic reson an ce image of th e
lumbar spine with fat suppression shows abnormal increased T2 signal throughout the second
lumbar vertebral body.

GROSS PATH OLOGIC FEATU RES
A ch ordoma is a soft, lobulated, grayish tumor th at is
semitran slucen t an d resembles a ch on drosarcoma or
even a mucin ous aden ocarcin oma. It is usually well
en capsulated, except in th e region of bon e in vasion ,
wh ere a distin ct edge of th e tumor may n ot be delin -
eated. Sacral ch ordomas n early always h ave a presacral
exten sion th at is usually covered by th e elevated perios-
teum. Th e lesion may exten d in to th e spin al can al.
Sph en o-occipital ch ordomas almost always bulge in to
th e cran ial cavity an d distort th e structures at th e base
of th e brain . Sometimes, a ch ordoma at th e base of
th e brain pen etrates an d fi lls th e sph en oid sin us or
even th e n asal or n asoph aryn geal cavities. In th ree
tumors, all in volvin g th e spin e, radiograph ic an d surgi-
cal features suggested n o in volvemen t of bon e. Th ese
appear to be soft-tissue lesion s. In all oth er respects,
h owever, th ey appear to be typical ch ordomas ( Figs.
21.10–21.15) .
An occasional chordoma contains focal calcifi cation
or ossifi cation, but such foci are rarely prominent. Like
chondrosarcomas, some chordomas are relatively fi rm
and other are extremely myxoid and semiliquid.
Recurren ces often produce multiple n odules in
th e region of th e previous surgical excision . Metasta-
sis is usually th rough th e h ematogen ous route. Th e
process may develop in an un usual location , in clud-
in g th e skin . Su an d coauth ors reported in volvemen t
of th e skin in 19 of 207 ch ordomas studied. Seven of
th ese were recogn ized at th e time of clin ical presen ta-
tion . Most of th is in volvemen t was at th e site of th e
n eoplasm. Th ey foun d on ly on e metastatic focus in a
distan t site.
254 Chapter 21 ■

F igu r e 21.12. Ch ordoma formin g a destructive lesion in

th e posterior aspect of th e th ird lumbar vertebral body in an
81-year-old man . Th e tumor broke th rough th e posterior cor-
tex. Radiograph ically, th e tumor was th ough t most likely to
represent metastatic disease.

F igu r e 21.10. Sacral chordoma that has lobulation with

fi brous septa an d a gelatin ous appearan ce. Much of th e tumor
has a deep red-brown color.

F igu r e 21.13. Chordoma forming a mass involving the infe-

rior sacrum and coccyx. A gian t notochordal h amartoma that
F igu r e 21.11. Large sacral ch ordoma with a heterogen eous formed a yellow-tan in traosseous n odular mass ( arrow) in th e
appearance. Some of the tumor is tan whereas in other areas vertebral body superior to the ch ordoma was identifi ed in the
it is red-brown. The cut sur face has a glistening appearance. resected specimen.

F igu r e 21.14. Soft-tissue recurrence of a sacral
ch ordoma th at was resected 1 year earlier. Th e
recurrent tumor was palpable per rectum.
F igu r e 21.15. Ch ordoma arisin g as a soft-tissue
mass an terior to th e secon d cervical vertebra, with
no apparen t involvemen t of bon e. Th e clin ical
diagnosis was a neural tumor.
H ISTOPATH OLOGIC FEATU RES
When suffi cient tissue is examined, chordomas are
always lobulated. The tumor cells form lobules separated
by fi brous septa. Such a pattern may not be seen in a
spheno-occipital chordoma because of the small amount
of tissue that may be obtained. The tumor cells lie in a
blue myxoid background. Very typically, the tumor cells
form strands that produce cords of tumor cells in a myx-
oid background. The nuclei are usually round and regu-
lar, with little cytologic atypia. The tumor cells tend to
have cytoplasmic vacuolization, which may range from
single, small vacuoles reminiscent of a signet ring cell
to multiple vacuoles creating a bubbly appearance. The
cells, with such abundant cytoplasm, have been termed
physaliferous cells ( Figs. 21.16–21.23) .
Some ch ordomas h ave spin dle cells with sligh t
cytologic atypia th at n everth eless are arran ged in th e
■ Chordoma 255
ch aracteristic lobulated pattern . Th ese spin dle cells
do n ot represen t areas of dedifferen tiation . Some
ch ordomas h ave abun dan t pin k cytoplasm, givin g rise
to an epith elial appearan ce. Focal pleomorph ism of
th e tumor cells may be seen . H owever, th ese n uclei
h ave th e “degen erate” appearan ce of th ose associ-
ated with pseudomalign an t con dition s with smudgy
n uclear features. Mitotic activity may be seen but is
rarely abun dan t. In on e oth er wise typical ch ordoma,
sh eets of gian t cells focally simulated gian t cell tumor
( Figs. 21.24 & 21.25)
Chondroid chordoma is a term coin ed by H effelfi n -
ger an d coauth ors for n eoplasms at th e base of th e
brain , a location con sisten t with th at of ch ordomas,
th at h ave features of both ch ordoma an d ch on drosar-
coma ( Fig. 21.26). This concept has led to much contro-
versy in the literature. Some authors have suggested, on
the basis of special studies, that these tumors are actually
256 Chapter 21 ■

F igu r e 21.16. Ch ordomas are always lobulated, with th e F igu r e 21.17. Chordoma with cellular nodules and frag-
lobules separated by fi brous septa, as shown here. men t of en trapped residual bon e. Such fragmen ts may give
rise to mineralization visible on radiographs.

F igu r e 21.18. Chords and stran ds of tumor cells fl oatin g in F igu r e 21.19. Example of chordoma with anastomosing
a mucinous background. ch ords of tumor cells.

F igu r e 21.21. Some ch ordomas h ave areas wh ere tumor

F igu r e 21.20. H igh -power view sh ows cells with abun dan t cells are stretch ed out in th e mucin ous backgroun d, h en ce
vacuolated cytoplasm. h aving a spindled appearan ce.
 ■ Chordoma 257

Figure 21.22. Lobules of cells with abundant eosinophilic F igu r e 21.23. Th is lobule con tain s few cells an d abun dan t
cytoplasm occurred in some areas of this chordoma, producing gray-blue mucinous material.
an epithelioid appearance. Particularly with a limited amount of
biopsy tissue, this could be mistaken for metastatic carcinoma.

F igu r e 21.24. Chordoma with typical cytologic features

( left) that merge with an area containing cells with large
hyperchromatic nuclei ( right) .

ch ondrosarcomas and not chordomas. However, other

studies have confi rmed their relationship with chordo-
mas. To diagnose chondroid chordoma, one must iden-
tify cells in the lacunae. The myxoid background may
be similar in both chordomas and chondrosarcomas. As
indicated above, surgical pathologists may receive only
small fragments of a biopsy specimen from the base of
the skull. If the histologic features are those of a low-
grade chondrosarcoma and the radiographic features
suggest that the lesion involves the midline, a diagno-
sis of chondroid chordoma is justifi ed. Most ch ondroid
ch ordomas occur at the base of the brain, and 51 of
the 170 cases in the Mayo Clinic fi les were classifi ed as
ch ondroid chordomas. It is extremely unusual to fi nd F igu r e 21.25. A an d B: O ccasion al pleomorph ic an d multi-
this h istologic type in any other location; however, one n ucleated cells are found in areas of an oth erwise typical chor-
tumor in the spine had chondroid features, and three doma, as shown in these two examples. This characteristic
sacral tumors had questionable chondroid features. apparently does not correlate with the prognosis.
258 Chapter 21 ■
F igu r e 21.26. Chondroid chordoma. A: Some areas of the
tumor display features typical of ch ordoma. B: O th er areas of
th e tumor are chon droid an d lack keratin immun oreactivity.
Occasionally, a proliferation of spindle cells may
be seen at the periphery of the lobules of chordoma.
If these cells do not have pronounced cytologic atypia,
they probably represent a reactive change. However,
if sheets of malignant spindle cells are seen, a diagno-
sis of dedifferentiated chordomas is justifi ed. Four of
the chordomas in the Mayo Clinic fi les, three of the
sacrum and one of the sphenoid, showed such areas
of dedifferentiation; three of these had been radiated
previously. There are several reports in the literature of
dedifferentiated chordoma; most of the patients had
previously had radiation ( Fig. 21.27) .
The pathologic diagnosis of chordoma is usually
straightforward. However, metastatic carcinoma may be
in the differential diagnosis, especially if the biopsy sam-
ples are limited, such as those obtained with fi ne-needle
aspiration. Most metastatic carcinomas, however, show
more cytologic atypia than seen in classic chordoma
and do not usually h ave a lobulated growth pattern and
the typical chording pattern of chordoma. A myxopap-
F igu r e 21.27. Recurrent dedifferentiated chordoma within
the sacrum in a 72-year-old man. Five years earlier, the patient
had a chordoma that was treated surgically and with radiation.
A: Low-power view shows histologic features typical of chor-
doma ( right) that merge with a high-grade malignancy ( left). B:
The high-grade portion of the tumor is a spindle cell sarcoma.
illary ependymoma may be included in the differential
diagnosis of lesions of the sacrum. With immunoperoxi-
dase stains, ependymomas are positive for glial fi brillary
acid protein, whereas chordomas are not.
Recently, evidence has been presented to support
the concept of a notochordal hamartoma or giant
notochordal rest involving the vertebrae or sacrum. In
these rare lesions, radiographs do not show destruc-
tion of the cortex or a soft-tissue extension ( Fig. 21.9) .
Under low power, the marrow spaces are replaced by
cells that have round nuclei and cytoplasmic features
of fat cells ( Fig. 21.28) . Because the trabeculae of mar-
row bone are not destroyed, the tumor appears perme-
ative. This entity is differentiated from chordoma by the
lack of myxoid matrix, lobulation, and obvious cytologic
atypia. Several studies with immunoperoxidase staining
have confi rmed that chordomas are positive for keratin

F igu r e 21.28. Gian t n otoch ordal rest. A: In th is low-power
view, the tumor replaces the bone marrow but does not destroy
the medullary bone. The tumor has a bland histologic appear-
ance that resembles fat. B: High-power view shows tumor
cells with min imal n uclear atypia an d vacuolated cytoplasm.
C: Tumor cells show positive immunoreactivity with keratin.
■ Chordoma 259
and occasionally with S-100 protein. More recent stud-
ies have shown brachyury to be a sensitive and more spe-
cifi c immunostain. Results of immunoperoxidase stains
have been contradictory in chondroid chordomas.
Immunostains can be helpful in separating chondrosar-
coma from chordoma since chondrosarcoma should be
negative with keratin and brachyury and positive with
S-100 protein.
A rare type of meningioma, called chordoid menin-
gioma, that has a myxoid background and cells forming
chords has been described. These tumors tend to have
an associated lymphoplasmacellular infi ltrate. The dif-
ferential diagnosis is helped by the location, the gross
characteristics of a well-circumscribed mass, the pres-
ence of typical meningothelial cells, and the absence of
keratin positivity in meningiomas.
TREATMEN T
Until recently, the treatment of chordoma was unsatis-
factory. The tumor was removed only partially, and the
patient was afforded palliative benefi t at best. The only
hopeful aspects were that because of the slow growth of
the tumor, a few patients obtained several years of free-
dom from symptoms after subtotal removal and some
chordomas proved to be radiosensitive.
It has now been established that radical, complete
removal of many sacrococcygeal tumors is feasible
and should be attempted. To avoid recurrence due to
implantation, the plane of excision must be well beyond
the edge of the tumor. Radiation should be adminis-
tered for tumors not amenable to complete removal
and for inoperable recurrent lesions after surgical
therapy. Fuchs and coauthors reported on 52 patients
with sacral chordomas treated surgically at Mayo Clinic
between 1980 and 2001. A wide surgical margin was
achieved in 21 patients. Twenty-three patients ( 44%)
had local recurrence. The most important predictor of
local recurrence and survival was a wide surgical mar-
gin. More recently, even vertebral chordomas are being
aggressively treated surgically.
The location of spheno-occipital chordomas pre-
cludes complete surgical removal. However, several
studies have shown that gross total removal of the tumor
may be possible and may be associated with longer sur-
vival. Proton beam radiation therapy certain ly has been
helpful in treating chordomas and chondrosarcomas of
the basisphenoid.
PROGN OSIS
Before more radical surgical techniques were adopted,
even patients with sacrococcygeal chordomas were
doomed to eventual, though perhaps delayed, death
260 Chapter 21 ■
from local extension of the tumor. The sacrococcygeal
neoplasm often extended to block the genitourin ary or
gastrointestinal tract, and the spheno-occipital tumor
produced lethal intracranial complications.
Distant metastases are uncommon in chordomas and
death usually results from local effects of the tumor. Metas-
tases are rare at the time of diagnosis. In a study of 40
patients with chordomas of the vertebral column, Björns-
son and coauthors found only two patients with distal
metastases. Although the 5-year survival rate was 58% for
this group of patients, 63% eventually died of the tumor.
Chambers and Schwinn, however, found distant metas-
tasis in 30% of patients with chordoma. The metastases
were predominantly to the skin and other bones. Fuchs
and coauthors reported a recurrence-free survival rate of
59% at five years and 46% at ten years for sacral chordo-
mas. The overall survival rates were 74%, 52%, and 47%
at five years, ten years, and fi fteen years, respectively.
The study of Heffelfi nger and coauthors suggesting
that chondroid chordomas had a much better prog-
nosis than conventional chordomas has led to much
controversy. In a study of 51 intracranial chordomas,
Forsyth and coauthors found that 19 were chondroid.
They reported that the prognosis was not affected by
the histologic type of the chordoma. They did, however,
fi nd that younger patients had a better prognosis than
older ones. In a study of chordomas at the base of the
brain, Mitchell and coauthors also found that age was
the most important factor in prognosis. Patients who
were younger than 40 years, whether the chordoma was
chondroid or not, had a much better prognosis than
those who were older than 40. These authors classifi ed
as chondroid chordomas only those tumors in which
keratin positivity was foun d. However, they did not fi nd
that keratin positivity had any correlation with the clini-
cal course. Moreover, many of these studies have had
other selection factors. While still debatable, it appears
that chondroid chordomas may have a more indolent
clinical course than ch ordomas. Chondrosarcomas
are very rare at the base of the skull, and may have a
better clinical course than chordoma. Rosenberg and
coauthors reported an excellent prognosis for skull
base chondrosarcomas treated with surgery and pro-
ton beam irradiation. Therefore, an attempt should be
made to separate them from chordomas at this site.
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1984 Kaiser, T. E., Pritchard, D. J., and Unni, K. K.: Clinicopatho-
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1984 Miettinen, M., Lehto, V. P., and Virtanen, I.: Malignant
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1986 Belza, M. G. and Urich, H .: Chordoma and Malignant
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1987 Mierau, G. W. and Weeks, D. A.: Chondroid Chordoma.
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1988 de Bruine, F. T., and Kroon, H. M.: Spinal Chordoma: Radio-
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1988 Kepes, J. J., Chen, W. Y., Connors, M. H., and Vogal, F. S.:
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1989 Matsumoto, J., Towbin, R. B., and Ball, W. S., Jr.: Cranial
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1989 Sen, C. N., Sekhar, L. N., Schramm, V. L., and Janecka, I. P.:
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1990 Hruban, R. H., May, M., Marcove, R. C., and Huvos, A. G.:
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1990 Hruban, R. H., Traganos, F., Reuter, V. E., and Huvos, A. G.:
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1992 Fukuda, T., Aihara, T., Ban, S., Nakajima, T., and Machinami, R.:
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1992 Tomlinson, F. H., Scheithauer, B. W., Forsyth, P. A., Unni,
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1993 Björnsson, J., Wold, L. E., Ebersold, M. J., and Laws, E. R.:
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of 40 Patien ts. Can cer, 71:735–740.
■ Chordoma 261
1993 Coffi n, C. M., Swanson , P. E., Wick, M. R., and Deh ner,
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1993 Flemin g, G. F., H eimann , P. S., Steph ens, J. K., Simon , M.
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1993 Forsyth, P. A., Cascin o, T. L., Sh aw, E. G., Scheith auer,
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1993 Lanzino, G., Sekhar, L. N., Hirsch, W. L., Sen, C. N., Pomonis, S.,
and Synderman, C. H.: Chordomas and Chondrosarcomas
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1993 Mitchell, A., Scheithauer, B. W., Unni, K. K., Forsyth, P. J., Wold,
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1993 Romero, J., Cardenes, H., la Torre, A., Valcarcel, F., Magallon,
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1993 Samson, I. R., Springfi eld, D. S., Suit, H. D., and Mankin, H. J.:
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1993 Su, W. P., Louback, J. B., Gagne, E. J., and Scheithauer,
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1994 Rosenberg, A. E., Brown, G. A., Bhan, A. K., and Lee, J. M.:
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 C H APT ER
22
Benign Vascular Tumors
H eman giomas of bon e are of min or importan ce
wh en con siderin g lesion s th at require surgical proce-
dures for diagn osis or th erapy. Th e alteration s com-
mon ly in terpreted as h eman giomas of vertebrae by
th e radiologist are n early always asymptomatic an d
are probably zon es of telan giectasis rath er th an true
h eman giomas. Most bon a fi de h eman giomas in bon e
are solitary lesion s. H owever, h eman giomas may affect
two or more bon es of a sin gle extremity, sometimes
also in volvin g th e overlyin g soft tissues an d occasion -
ally producin g serious malformation an d dysfun ction .
Diffuse skeletal h eman giomatosis is a rare disorder
in wh ich th e lesion s most common ly are in th e spin e,
ribs, pelvis, skull, an d sh oulder. Wh en such h eman -
giomatosis affects visceral organ s as well as bon es, th e
progn osis is poor; oth er wise, th e osseous process ten ds
to become stabilized, with variable degrees of lytic an d
sclerotic ch an ge.
Disappearing or phantom bone disease, also called
massive osteolysis or Gorham disease, m ay be a form of
h em an giom a of bon e. Th is relatively rare con d ition ,
wh ich usually occurs in ch ildren or youn g adults, is
ch aracterized by th e dissolution , wh olly or partly, of
on e or several adjacen t bon es. Th e affected bon es
m ay h ave a cavern ous an giom a-like perm eation as
a prom in en t path ologic feature. Th e process is self-
lim ited, but th e exten t of th e progression is un pre-
dictable.
Hemangioendothelioma, or hemangiosarcoma of bone,
en compasses a somewh at con troversial group of
tumors th at var y from debatably malign an t capil-
lar y an d cavern ous proliferation s to h igh ly leth al
en doth elial sarcomas th at sometimes are of multi-
cen tric origin . H eman giopericytoma, an oth er poorly
un derstood n eoplasm with poorly defi n ed h istologic
delin eation , is a ver y rare primar y lesion of bon e.
Malign an t vascular n eoplasms of bon e are discussed
in an oth er ch apter.
262
Lymph atic vascular proliferation s also produce soli-
tary or multiple zon es of rarefaction of th e skeleton .
When blood escapes from th e spaces of a h eman gioma,
th e spaces resemble th ose of lymph an gioma; con -
versely, if blood is in troduced in to lymph atic spaces,
th e features resemble th ose of h eman gioma. Perh aps
both types of vascular malformation s coexist in some
cases.
Glomus tumor may erode bone or even arise within it.
The foregoing suggests the wide range of the clini-
cal and pathologic spectrum of vascular proliferations
in bone. A well-defi ned and lucid classifi cation of these
disorders is not available. Accordingly, portions of the
following brief description are general.
The bibliography indicates a wide spectrum of vascu-
lar disorders affecting bone.
IN CID EN CE
The 149 hemangiomas comprised less than 1.5% of the
total series ( Fig. 22.1) . In addition, there were 21 exam-
ples of massive osteolysis. The 109 angiosarcomas and
15 hemangiopericytomas are discussed in Chapter 23.
SEX
Females predominated in a ratio of 3:2.
AGE
Accordin g to most reports, h eman giomas are usually
foun d in adults. In th e Mayo Clin ic series, about 24%
of th e patien ts were in th e fi fth decade of life. Th e
youn gest patien t was 2 years old an d th e oldest was
85 years.

F igu r e 22.1. Distribution of
heman giomas accordin g to age
and sex of the patient and site
of th e lesion .
LOCALIZATION
Approximately h alf of th e h eman giomas were in th e
cran ium or vertebrae. Fifteen affected th e jawbon es.
Sixteen patien ts ( eigh t males an d eigh t females ran g-
in g in age from 6 to 66 years) h ad multiple h eman -
giomas. In fi ve of th ese patien ts, multiple skeletal sites
were in volved. Th e rest h ad multiple h eman giomas
in volvin g on e bon e or multiple bon es in on e topo-
graph ic site, such as th e spin e or th e ribs. O n e patien t
h ad features suggestive of on cogen ic osteomalacia. Th e
distin ction between multiple skeletal h eman giomas
an d massive osteolysis can be diffi cult an d sometimes
arbitrary.
SYMPTOMS
Many of the hemangiomas of the skeleton in the Mayo
Clinic series were asymptomatic and discovered dur-
ing a radiographic study for other reasons. Heman-
giomas that expand the bone and produce new bone
may cause notable swelling. Local pain is sometimes a
feature. There may be fractures, including compression
fractures of vertebrae. Rarely, spinal cord compression
may result. Severe hemorrhage may be encountered
durin g surgical procedures, especially those involving
the jawbones. Patients with massive osteolysis h ave pain
■ Benign Vascular Tumors 263
and disability commensurate with the degree of osseous
involvement.
PH YSICAL FIN D IN GS
Physical examination usually does not contribute any
specifi c information. Occasionally, soft tissue or cuta-
neous hemangiomas provide evidence indicating the
nature of the osseous disease. However, such nonosseous
hemangiomas are also part of Maffucci syndrome, which
includes skeletal chondromatosis.
RAD IOGRAPH IC FEATU RES
H eman giomas in vertebrae ch aracteristically cause
rarefaction , with exaggerated vertical striation or a
coarse h on eycombed appearan ce. Th ese ch an ges
produce a ch aracteristic polka-dot appearan ce on
computed tomograms. Ross an d coauth ors described
th e magn etic reson an ce imagin g features of verte-
bral h eman giomas. Un like most n eoplasms of bon e,
h eman giomas of th e vertebrae sh owed in creased sign al
in both T1- an d T2-weigh ted images. Th e extraosseous
compon en t was n ot en h an ced on T1-weigh ted images.
Th e auth ors attributed th ese sign al ch aracteristics to
th e presen ce of fat in th e in traosseous compon en t of
vertebral h eman giomas. In th e skull, h eman giomas
produce a well-circumscribed zon e of rarefaction th at
264 Chapter 22 ■
F igu r e 22.2. H eman gioma of th e vertebral body. Th e
ch aracteristic vertical striation s produce a corduroy appear-
ance. ( From Wold, L. E., Swee, R. G., and Sim, F. H.: Vascular
Lesions of Bone. In Sommers, S. C., Rosen, P. P., and Fechner,
R. E. [ eds] . Pathology An n ual, Part 2, Vol. 20. Norwalk, CT,
Appleton -Cen tury-Crofts, 1985, pp. 101–137. By permission of
the publisher.)
F igu r e 22.3. Computed tomogram of a vertebral heman-
gioma. In cross section , bon y trabeculae produce a polka-dot
appearance.
F igu r e 22.4. Hemangioma of the vertebral body has
destroyed the vertebra and extended into soft tissue.
F igu r e 22.5. Lateral ( left) an d an teroposterior ( right) views
of a collapsed vertebral body associated with h eman gioma.
Eith er th e collapsed body or exten sion of th e lesion in to th e
spin al can al produces symptoms.
may h ave a h on eycombed appearan ce an d is often
associated with outward expan sion of th e bon y pro-
fi le. Th is expan ded zon e may sh ow striation s of bon e
radiatin g outward from th e cen ter of th e lesion , givin g
rise to a sun burst appearan ce. In oth er bon es, h eman -
giomas produce rarefaction s th at may h ave features
like th ose described above. In most lon g bon es, h ow-
ever, th e appearan ce is n on specifi c. Wh en a h eman -
gioma occurs in soft tissue, th e lesion may con tain
ph lebolith s ( Figs. 22.2–22.8) .
 ■ Benign Vascular Tumors 265

F igu r e 22.6. An teroposterior ( A) an d lateral

( B) views of th e skull in a 49-year-old woman with
multiple h emangiomas. Th e lesion s are purely
lytic and well circumscribed. Multiple heman-
giomas are unusual.

F igu r e 22.8. Path ologic fracture of th e sh aft of th e fi bula

F igu r e 22.7. H eman giomatosis in volvin g bon e an d soft in a 67-year-old woman. The appearance of a hemangioma
tissues. Note the extensive permeative destruction of the bone involving a long bone is frequently nonspecifi c. ( Case pro-
and pathologic fracture. Massive involvement of the soft tissue vided by Dr. George R. Lindholm, Holy Family Hospital,
is associated with phleboliths. Spokane, Washington.)
266 Chapter 22 ■

Karlin and Brower suggested that multiple benign

vascular lesions of bone should be divided into two
groups: diffuse cystic angiomatosis and multiple pri-
mary hemangiomas. The former condition is char-
acterized by multiple cystic areas of bone destruction
without periosteal reaction. Multiple primary heman-
giomas, in comparison, consist of a collection of solitary
hemangiomas, and this radiographic appearance would
depend on the site of involvement.
Radiographically, massive osteolysis is characterized
by progressive dissolution of part or all of one or several
adjacent bones, with tapering of the edge of the lesion.
The process does not respect boundaries and may cross
joints. Shives and coauthors suggested that the early
changes in massive osteolysis may start either in bone
or soft tissue. The early changes in an intraosseous
location may mimic a neoplasm or dysplasia. When
the process starts in the soft tissue, it may be associated
with a soft-tissue mass or alteration of normal muscle
and fat planes. When the initial abnormality is limited
to the soft tissue, the bon e changes occur fi rst on the
sur face of bone, with thinning and tapering of the cir-
cumference producing the appearance of sucked candy
( Figs. 22.9 & 22.10) .

F igu r e 22.10. Plain radiograph ic ( A) an d magn etic reso-

F igu r e 22.9. Path ologic fracture in volvin g th e proximal
femoral sh aft in a 35-year-old woman with massive osteolysis.
( From Shives, T. C., Beabout, J. W., and Unni, K. K.: Massive
O steolysis. Clin O rth op, 294:267–276, 1993. By permission of
J. B. Lippincott Company.)
n an ce imaging (B) appearance of the skull in an 11-year-
old boy with massive osteolysis. Multiple large, purely lytic
defects involve multiple bones of the skull. Multicentric-
ity is uncommon in massive osteolysis. ( Case provided by
Dr. Pat Creagan, University of California San Francisco, San
Francisco, California.)

Localized hemangiomas of soft tissues in a periosteal
location are associated, in rare instances, with consider-
able sclerosis and deformity of nearby, but uninvolved,
bone. This may suggest a diagnosis of osteoid osteoma
or even osteoma ( Fig. 22.11) .
F igu r e 22.11. Marked thickening of the cortex of the fi bula
in a 24-year-old woman, produced by a hemangioma of skel-
etal muscle. ( Case provided by Dr. Gerson Paull, Crawford
Long Hospital of Emory University, Atlanta, Georgia.)
F igu r e 22.12. Un usual h eman gioma in volvin g th e n asal
bon e. Th e lesion, partly cystic an d partly solid, expan ds th e
bon e.
■ Benign Vascular Tumors 267
GROSS PATH OLOGIC FEATU RES
On exposure, a hemangioma is likely to be blue, and
a honeycombed feature may be obvious. A fi rm, fl eshy
appearance without obvious vessels suggests that the
lesion may be cellular and possibly malignant. Bony
trabeculae may be evident and even create a sunburst
effect ( Figs. 22.12–22.15) .
H ISTOPATH OLOGIC FEATU RES
The interpretation of vascular lesions of bone is com-
plicated by the diffi culty in knowing when a conglom-
eration of vascular channels is a hemangioma and not
a hamartomatous malformation. If blood has escaped,
the hemangioma can simulate lymphangioma, further
complicating the problem. In fact, hemangioma and
lymph angioma may coexist, as has been observed in
examples of massive osteolysis. Most hemangiomas of
bone are basically cavernous, although occasionally a
capillary component is present and may even be domi-
nant ( Figs. 22.16–22.19) . Some hemangiomas may be
associated with an abundance of reactive new bone for-
mation. The new bone trabeculae are usually rimmed
with prominent osteoblasts, which may simulate the
appearance of an osteoblastoma.
The pathologic features of massive osteolysis are
somewhat nebulous. Most articles stress the vascular
nature of the lesion. Indeed, most examples of massive
osteolysis show increased vascularity in bone, which usu-
ally extends into the soft tissues ( Fig. 22.20). Some cases
may have a vascular proliferation that suggests a diagno-
sis of lymphangioma. Some examples of massive osteoly-
sis are associated with lymphangiomas in other locations,
especially in the mediastinum. However, the histologic
changes may be quite nonspecifi c in what otherwise
appear to be classic examples of massive osteolysis.
Some angiosarcomas of bone with their component
of spindle-shaped vasoformative cells are readily rec-
ognizable as such, but the borderline between benign
and malignant capillary proliferation is not always easily
drawn.
Primary glomus tumors of bone are extremely
rare and usually involve the distal phalanx of a fi nger
( Fig. 22.21) . Histologically, there is a proliferation of
small round cells that tend to congregate around capil-
lary channels ( Fig. 22.22) . There are only two examples
of glomus tumors of bone in our fi les.
TREATMEN T
H eman giomas usually respond well to con servative
surgical procedures. Radiation may be required for
268 Chapter 22 ■

F igu r e 22.13. Recurren t h eman gioma in volv-

ing the skull in a 67-year-old man. The fi rst
tumor was removed 7 years earlier. Th e bon e is
expan ded an d, radiographically, h as a sunburst
appearance.

F igu r e 22.14. Cross section of th e femoral sh aft

in a 35-year-old woman with massive osteolysis.
Th e radiograph ic appearan ce is sh own in Figure
22.9. Th e cortex seems diffusely in volved with a
vascular proliferation .

F igu r e 22.15. Loss of substance of the bone

in the proximal portion of a femur with massive
osteolysis.
 ■ Benign Vascular Tumors 269

F igu r e 22.18. Capillary hemangioma of the sixth thoracic

vertebra consists of small-caliber vascular spaces.

F igu r e 22.16. Cavernous hemangioma of the mandible.

A: Low-power view sh ows several large, gapin g vascular spaces
occupyin g th e marrow space between preexistin g trabeculae F igu r e 22.19. Epithelioid hemangioma consisting of numer-
of bon e. B: High -power view sh ows small en doth elial cells lin - ous well-formed vascular spaces lin ed by plump en doth elial
ing the vascular spaces. cells.

F igu r e 22.20. “Phan tom” bon e disease. A mixed cavernous

and capillary hemangioma pattern was found in a biopsy spe-
F igu r e 22.17. This hemangioma of a vertebra contains cimen from th e h umerus. Th e h istologic appearan ce is ch ar-
thick-walled vascular spaces. acteristic of that of massive osteolysis.
270 Chapter 22 ■
F igu r e 22.21. Glomus tumor in the distal phalanx of
th e in dex fi n ger, a common location . ( Case provided by
Dr. P. Mao of Phoenix, Arizona.)
F igu r e 22.22. Glomus tumor composed of small round glo-
bus cells an d vascular spaces.
lesion s th at are in inaccessible sites. Th e unpredict-
able course of massive osteolysis has made th e results
of treatmen t diffi cult to assess, but recon structive sur-
gical procedures an d radiation h ave been used. Mas-
sive h eman giomas, especially with in volvemen t of soft
tissues, may require amputation . Th ese h eman giomas
may result in massive deformities or even con sumptive
coagulopathy. Patien ts with multiple h eman giomas or
even cystic an giomatosis do well unless visceral organ s
are in volved.
BIBLIOGRAPH Y
1942 Thomas, A.: Vascular Tumors of Bone: A Pathological and
Clin ical Study of Twen ty-Seven Cases. Surg Gyn ecol Obstet,
74:777–795.
1951 Pugh, D. G.: Roentgen ologic Diagnosis of Diseases of
Bones. New York, Thomas Nelson & Sons, 316 pp.
1955 Coh en , J. an d Craig, J. M.: Multiple Lymphangiectases of
Bon e. J Bone Joint Surg, 37A:585–596.
1955 Gorh am, L. W. and Stout, A. P.: Massive Osteolysis ( Acute
Spontaneous Absorption of Bone, Phantom Bone, Disappear-
in g Bon e) : Its Relation to Heman giomatosis. J Bon e Join t
Surg, 37A:985–1004.
1957 Klein sasser, O. an d Albrech t, H.: Die Hämangiome und
Osteohämangiome der Schädelknochen. Langenbecks Arch
Chir, 285:115–133.
1958 Jaffe, H. L.: Tumors and Tumorous Condition s of th e
Bones and Joints. Philadelphia, Lea & Febiger, pp. 224, 341.
1961 Hayes, J. T. and Brody, G. L.: Cystic Lymph angiectasis of
Bon e: A Case Report. J Bone Joint Surg, 43A:107–117.
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1964 Lun d, B. A. and Dah lin, D. C.: Heman giomas of th e Man-
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1964 Wallis, L. A., Asch, T., an d Maisel, B. W.: Diffuse Skel-
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 C H APT ER
23
Angiosarcoma and
H emangiopericytoma
Malign an t vasoformative tum ors com prise on e-h alf
of 1% of malign an t n eoplasms in th is series. Th ese
lesion s h ave varied from such h igh ly an aplastic on es
th at recogn izin g th em as spin dle cell sarcom a with
vasoformative capability is diffi cult, an d sometimes is
man ifested on ly in part of th e tumor, to well-differ-
en tiated n eoplasms th at are question ably m align an t.
Th e term in ology used in th e discussion of malign an t
en doth elial tumors h as been quite con fusin g. Th e
terms hemangiosarcoma, angiosarcoma, hemangioendothe-
lioma, an d hemangioendothelial sarcoma h ave all been
used eith er as syn on yms or to den ote separate path o-
logic en tities. Some auth ors use th e term angiosarcoma
to den ote th e ver y malign an t vascular tumors an d th e
term hemangioendothelioma to den ote low-grade malig-
n an t n eoplasm s. H eman gioen doth elial sarcoma,
alth ough descriptive, is cum bersome. In th e latest
edition of th e World H ealth O rgan ization Classifi -
cation of bon e an d soft tissues, th e accepted term is
angiosarcoma.
Vascular spindle cell sarcomas that are not of prov-
able endothelial origin and metastatic carcinoma are
differential diagnostic problems. Metastatic carcinoma,
especially renal cell carcin oma to bone, may be very vas-
cular, and its aggregates of plump cells mimic those of
some angiosarcomas.
Multifocality, especially in a limited portion of the
skeleton ( e.g., in one extremity) , may occur in as many
as one-th ird of patients. Hemangiopericytoma of bone
is extremely rare. There were only 15 examples in the
Mayo Clinic fi les. When a diagnosis of hemangiopericy-
toma of bone is considered, it is imperative to rule out a
primary lesion elsewhere, such as in the meninges.
272
AN GIOSARCOMA
IN CID EN CE
The 109 cases in the Mayo Clinic fi les comprised just
over 1.5% of malignant tumors of bone ( Fig. 23.1) .
SEX
There is a slight male predominance, with approxi-
mately 59% of the patients being male.
AGE
Angiosarcoma tends to affect young and older adults.
Only three patients were younger than 10 years. The dis-
tribution is more or less even from the second through
the seventh decades of life.
LOCALIZATION
Angiosarcoma may affect any portion of the skeleton.
There is a tendency toward the axial skeleton, with
approximately one-third of the lesions involving the
spine and pelvic bones. Fifteen lesions involved the
small bones of the hands and feet. Thirty-fi ve of the 109
patients had multifocal disease. In two of these cases,
there were multiple lesions in one bone. By far, the most
common manifestation of multifocality was in the same
topographic area, such as involvement of multiple bones
of one extremity. This pattern occurred in 20 patients.
However, in 13 patients, the tumor involved different
areas of the skeleton.
 ■ Angiosarcoma and Hemangiopericytoma 273

F igu r e 23.1. Distribution of

angiosarcomas according to age
and sex of the patient and site of
th e lesion .

SYMPTOMS

There were no specifi c symptoms, although pain was

usual.

PH YSICAL FIN D IN GS

There were no specifi c physical fi ndings, but tender-

ness was sometimes elicited locally.

RAD IOGRAPH IC FEATU RES

The majority of angiosarcomas produced a purely

osteolytic lesion. Occasionally, a tumor has a mixture
of lysis and sclerosis. Some low-grade tumors showed
well-marginated areas of lysis, with or without a sclerotic
rim. However, most tended to be poorly marginated,
with the lesion gradually fading into the surrounding
bone. Periosteal reaction is unusual and usually associ-
ated with the production of a soft-tissue mass. A soft-
tissue mass is more commonly associated with a higher
grade of malignancy. The occurrence of multiple lytic
lesions, especially in contiguous bones, strongly sug-
gests a diagnosis of angiosarcoma ( Figs. 23.2–23.8) .

GROSS PATH OLOGIC FEATU RES
The lesional tissue is typically bloody, suggesting its
primary vascular nature. The tumors are usually soft.
Although the presence of a soft, bright red lesion,
F igu r e 23.2. Plain radiograph of the distal femur in a
14-year-old boy with multicen tric grade 1 h eman gioen doth e-
lioma. There are multiple well-defi ned lytic defects in the
bon e. Some of these defects h ave destroyed th e cortex. Other
bon es in th e legs were also in volved.
274 Chapter 23 ■

F igu re 23.3. Anteroposterior radiograph ( A) and coronal T1-weighted magnetic resonance image
( B) of the distal forearm and wrist show multiple osteolytic lesions involving the distal radius, ulna,
and lunate bones. The lesion in the radius shows cortical destruction with an associated soft-tissue
mass. The imaging features of the lesions are nonspecifi c, but the multiplicity of lesions clustered in a
geographic region such as the distal extremity suggest that the diagnosis is low-grade angiosarcoma.

F igu r e 23.4. A: Multicen tric grade 1 an giosarcoma in volv-

ing multiple bones in the region of the knee in a 47-year-old
man . B: Computed tomogram sh ows multiple lesion s.
 ■ Angiosarcoma and Hemangiopericytoma 275

F igu r e 23.5. Anteroposterior radiograph ( A) and coronal T1-weighted magnetic resonance

image ( B) of the right foot show severe osteoporosis associated with multicentric angiosarcoma
forming destructive osteolytic lesions involving the third through fi fth metatarsals. All the lesions
have malign an t aggressive features, with cortical destruction an d associated malignant periosteal
new bon e formation . Pan el B sh ows that th e lesion of the forth metatarsal is associated with a
pathologic fracture.

F igu r e 23.6. Epithelioid hemangioendothe-

lioma in a 42-year-old man. A: Radiograph shows
a partly sclerotic lesion of a vertebral body.
B: Computed tomography shows multiple foci of
involvement of the liver in addition to the scle-
rosin g lesion of th e vertebral body. C: Computed
tomography of the lung shows diffuse involve-
men t of th e pulmon ary paren ch yma with epith e-
lioid hemangioendothelioma. The patient died
of disease with in 1 year.
276 Chapter 23 ■

F igu r e 23.7. A: Grade 1 hemangioendothelioma involving multiple small bones of the foot. Some
of th e lesion s have destroyed th e cortex an d exten ded in to soft tissue. B: Gross specimen in a case
similar to th at in A. Multiple dark red areas correspon d to th e vascular n eoplasm. Th ere is n o fl esh y
tumor-like material.

F igu r e 23.8. Epithelioid hemangioendothelioma involving the

ilium in a young man. A: The lesion is lucent but has areas of sclero-
sis. Th e margin s are well defi n ed an d lobulated. B: Correspon din g
gross specimen with a lobulated, dark red neoplasm.

especially when multifocal, may suggest the diagnosis
of angiosarcoma, there are no gross pathognomonic
features ( Figs. 23.7 & 23.9–23.11) .
H ISTOPATH OLOGIC FEATU RES
To qualify as an giosarcoma, th e lesion h ad to h ave
tumor cells th at formed vascular spaces. H owever,
th ere was much variation in th e quality an d quan tity
of th e vascular spaces formed. In low-grade lesion s,
th e tumors ten ded to h ave well-formed vascular spaces
lin ed by tumor cells sh owin g sligh t atypia. In grade
2 lesion s, th e vasoformation was still quite obvious.
Th e cells lin in g th e vascular spaces ten ded to h ave
a more cuboidal appearan ce an d cytologic atypia.
Mitotic fi gures were also more common . Grade 3
lesion s ten ded to sh ow eith er sh arply circumscribed
F igu r e 2 3.9. Soft h emorrh agic tumor in volvin g th e distal
tibia. Th e tum or h as destroyed th e cortex to in volve soft
tissues.
F igu r e 23.11. Grade 3 angiosarcoma arising in
the setting of a sinus tract within chronic osteo-
myelitis. Th ickened bon e refl ects th e un derlyin g
osteomyelitis th at h ad been presen t for 30 years.
Th e tumor is dark red-brown .
■ Angiosarcoma and Hemangiopericytoma 277
spaces lin ed with obviously atypical cells or spin dlin g
malign an t tumors in wh ich th e vascular spaces were
less obvious. Th e cells ten ded to be loosely arran ged
an d some sh owed cleftin g con tain in g red blood cells.
Th e vascular spaces ten ded to an astomose with on e
an oth er, especially in th e lower- an d medium-grade
tumors. Th e spaces in h igh -grade tumors may be
separated, alth ough desmoplastic reaction is un usual
( Figs. 23.12–23.20) .
Formation of reactive bone can be a prominent fea-
ture in angiosarcoma, especially in low-grade tumors.
New bone formation may be seen at the periphery or
throughout the lesion ( Fig. 23.21) . The bony trabeculae
tend to be well formed and rimmed with osteoblasts. This
may, indeed, suggest the diagnosis of osteoblastoma. How-
ever, the presence of sheets of cells without bone forma-
tion should rule out that possibility. Infl ammatory cells,
F igu r e 23.10. Grade 1 angiosarcoma forms a destructive,
solitary mass in the mid clavicle in a 26-year-old woman .
278 Chapter 23 ■

F igu r e 23.12. Low-power appearan ce of a grade 1 angiosar- F igu r e 23.14. Grade 1 angiosarcoma. The tumor cells lin-
coma sh ows a vasoformative tumor composed of an astomos- ing the vascular spaces are spindle shaped and do not show
ing vascular channels and blood. prominent cytologic atypia.

F igu r e 23.15. Grade 2 angiosarcoma. A: A vasoformative

F igu r e 23.13. Grade 1 angiosarcoma. A and B: Cellular pattern is easily identifi ed. B: The endothelial cells show more
areas blend with vasoformative areas in two examples of cytologic atypia th an th ose in grade 1 h eman gioen doth e-
angiosarcoma. lioma.
 ■ Angiosarcoma and Hemangiopericytoma 279

F igu re 23.16. Grade 2 angiosarcoma. A: Compact sheets of spindle cells (left) blend into a looser
hemorrhagic region (upper right) of the tumor. B: Endothelial cells show moderate cytologic atypia.

F igu r e 23.17. Grade 3 an giosarcoma. A and B: The tumor is vasoformative an d contain s marked
cytologic atypia. C: Th e tumor can be con fused with carcin oma because th e malign an t cells
are immun oreactive with keratin . D: Positive CD31 immun oreactivity con fi rms th e diagn osis of
an giosarcoma.
280 Chapter 23 ■

F igu r e 23.18. Grade 3 angiosarcoma. A: In solid areas without a vasoformative pattern, it is diffi -
cult to differen tiate th is tumor from oth er types of h igh -grade spin dle cell sarcomas. B: High -power
view sh ows an aplastic en doth elial cells an d promin en t n ucleoli.

F igu r e 23.19. Grade 3 angiosarcoma. Intracytoplasmic

lumina are seen within highly atypical endothelial cells. Figure 23.21. Reactive new bone within a grade 1 angiosarcoma.

especially eosinophils, may be seen in vascular tumors,

F igu r e 23.20. Grade 3 angiosarcoma. Plump atypical
endoth elial cells lin e vascular spaces, creatin g a pattern th at
mimics metastatic aden ocarcin oma.
especially in low-grade ones. Clusters of multinucleated
giant cells may also be present.
Epithelioid hemangioendotheliomas may also occur
in bone. Under low power, the lesion appears lobu-
lated, with a central myxoid area usually surrounded
by clusters of giant cells. This may suggest the diagno-
sis of chondromyxoid fi broma. The tumor cells tend
to be arranged in nests and chords within a myxoid
matrix. Very typically, the tumor cells h ave abun dant
pin k cytoplasm th at may con tain cytoplasmic vacuoles.
The presen ce of a myxoid stroma con tain in g cells with
a sign et ring appearan ce is quite typical of epith elioid
hemangioendothelioma ( Figs. 23.22 & 23.23) . In the
Mayo Clinic series, only 11 of the 109 patients were con-
sidered to have epithelioid hemangioendoth elioma.

F igu r e 23.22. Epithelioid hemangioendothelioma showing
a lobulated appearance and central myxoid area continuing
ch ords of spin dled cells. Th ere is in creased cellularity, with
osteoclast-like gian t cells at th e periph ery of th e lobule. Th ese
features resemble th ose seen in ch on dromyxoid fi broma.
One of these patients presented with a lesion involving
the vertebra, and within 6 months, tumors developed
in the liver and lungs with the features characteristic
of epithelioid hemangioendothelioma when it involves
those organs. The patient died very quickly. In another
patient, epithelioid hemangioendothelioma developed
in the ilium. Within the next 10 years, lesions developed
in volving the clavicle and humerus. However, the patient
does not yet have evidence of systemic involvement. In
the series reported by Tsuneyoshi and coauthors, almost
half of the vascular tumors were considered to be epi-
thelioid. Almost two-th irds of these were considered to
be multicentric.
Th e presen ce of epith elioid cells in vascular tumors
h as been n oted for a lon g time. Some h igh -grade vas-
cular tumors can also h ave epith elioid cells in clusters.
Th ere are on ly four classic epith elioid an giosarco-
mas in th is series. Metastatic carcin oma is usually
in th e differen tial diagn osis with vascular tumors,
especially wh en th ey occur in older person s an d th e
lesion s are multicen tric. Metastatic h ypern eph roma
can be extremely vascular. Vascular tumors usually
h ave an astomosin g spaces, wh ereas carcin omas h ave
discrete spaces. Desmoplastic reaction is un common
in an giosarcoma, but it is th e rule in metastatic carci-
n oma. Several immun operoxidase markers h ave been
suggested to be specifi c for vascular tumors. Keratin ,
h owever, may be positive in epith elioid-appearin g vas-
cular tumors. Markers such as factor VIII, CD31, an d
CD34 sh ould be n egative in metastatic carcin oma an d
positive in an giosarcoma.
■ Angiosarcoma and Hemangiopericytoma 281
F igu r e 23.23. Epithelioid hemangioendothelioma. A: Low-
power view shows several epithelioid endothelial cells with
cytoplasmic lumin a producin g a sign et rin g-like appearan ce.
B: The cells are embedded in a pale blue background that
resembles ch ondroid matrix.
The differentiation of low-grade angiosarcoma from
hemangioma may be very diffi cult. Both hemangiomas
and angiosarcomas can be multicentric, although
multicentricity is more common in malignant vascular
tumors. Some authors have suggested that at least some
low-grade angiosarcomas actually represent epithelioid
hemangiomas, which are recognized by the presence of
endothelial cells that are cuboidal and have abundant
eosinophilic cytoplasm.
As referred to above, angiosarcomas are graded
depending predominantly on the cytologic atypia of
the endothelial cells. Although this is subjective, it is no
more so than any other system of grading. Forty tumors
were grade 1. Of the other tumors, 27 were grade 2 and
31 were grade 3. Eleven were called epithelioid heman-
gioendothelioma and not graded. The suggestion in
the literature, that low-grade tumors tend more often
282 Chapter 23 ■
to be multicentric, is not supported in this series. One
of the tumors included in this series was Kaposi sarcoma
involving bone. The patient had well-established Kaposi
sarcoma of the skin. Two of the lesions were postradia-
tion, and one involved th e sinus tract of long-standing
osteomyelitis. There were 35 patients with multicentric
tumors. Of these, 11 were grade 1, 8 were grade 2, and
10 were grade 3. The other six patients had epithelioid
hemangioendothelioma.
Bacillary angiomatosis is another condition that
should be differentiated from a malignant vascular
tumor. In this condition, associated with immunosup-
pression, there is proliferation of capillaries that may
have prominent endothelial cells. There is, however, an
associated infl ammatory reaction that includes a large
number of polymorphonuclear leukocytes and smudgy
deposits representing bacterial colonies.
TREATMEN T
Evidence of multicentricity must be sought before
deciding on therapy. Surgical resection and radiation
therapy seem appropriate, although radiation therapy
alone has been effective in some patients with low-grade
multicen tric tumors. One patient with a low-grade
angiosarcoma treated with radiation developed a post-
radiation sarcoma 7 years later and died of leukemia
approximately 6 months after that. A second patient
with a low-grade angiosarcoma died 17 years later. This
patient probably had a postradiation sarcoma, but there
was no histologic proof of it.
PROGN OSIS
In a series of 29 patients with angiosarcoma of bone
reported from the Rizzoli Institute, none of the patients
with a grade 1 tumor died. Only one patient with a grade
2 tumor died. However, at least 10 of the 15 patients
with a grade 3 angiosarcoma died. In the series of 112
cases reported by Wold an d coauthors, the disease-free
survival was 95% for patients with grade 1 tumors, 62%
for patients with grade 2 tumors, and 20% for those with
grade 3 tumors. In th is study, no difference in prognosis
was foun d between patients with solitary lesion s and
those with multicentric disease.
An giosarcoma has been treated with various meth-
ods, including surgery and radiation therapy. Of the
40 patients with grade 1 angiosarcoma, 7 have died
at intervals ranging from 0 to 17 years. One of these
patients committed suicide. One patient died with post-
radiation sarcoma and leukemia, and another patient
probably died of postradiation sarcoma. The other
four patients, however, apparently died of tumor. Of
the 27 patients with grade 2 angiosarcoma, 6 died:
1 of carcinoma of the lung and the other 5 of angiosar-
coma. Of the 31 patients with grade 2 angiosarcoma,
3 patients were alive at 12.8, 13, and 19 years after
treatment. The other patients died from 0 to 3.6 years
after diagnosis. One patient may have died of an unre-
lated cause. These results show that grading of the neo-
plasm has signifi cant prognostic implication. It also
shows that more patients with grade 1 angiosarcoma die
of tumor than is generally recognized in the literature.
H EMAN GIOPERICYTOMA
Only 15 examples of primary hemangiopericytoma of
bone were found in the Mayo Clinic fi les. The series
included six males and nine females. The patients were
either young or older adults ( Fig. 23.24) . The peak
incidence was in the fourth and fi fth decades of life.
The ilium was most commonly involved, accounting for
three of the 15 tumors. No other skeletal site accounted
for more than a single case. The most usual symptoms
were pain and swelling or both. The radiographic
appearance is nonspecifi c, showing evidence of purely
lytic, expansile lesions.
The gross appearance of hemangiopericytoma is not
pathognomonic. The lesion usually is fi rm and may be
rubbery. It may appear reasonably well circumscribed.
Catastrophic bleeding may be encountered during
surgery ( Figs. 23.25 & 23.26) .
The histologic features of hemangiopericytoma of
bone are identical to the better known counterpart in
soft tissue. Currently, the World Health Organization
considers hemangiopericytoma to be closely related, if
not identical, to solitary fi brous tumor of soft tissue. The
tumor cells are oval to round. Focal areas of spindling
may be seen. Cytoplasmic outlines are indistinct. The
tumor cells do not show marked pleomorphism. Very
characteristically, the tumor cells are arranged around
vascular spaces. The clusters of tumor cells deform the
vascular spaces, producing the characteristic appear-
ance of deer antlers. Reticulum stains may highlight
occult blood vessels ( Fig. 23.27) .
This pattern of an intimate relationship between the
tumor cells and the vascular spaces should be present
throughout the lesion. Focal hemangiopericytoma-
tous areas may be seen in several sarcomas, includ-
ing fi brosarcoma, malignant fi brous histiocytoma,
and osteosarcoma. Mesenchymal chondrosarcomas
contain chondroid islands, and the tumor cells look
much more anaplastic than those of hemangiopericy-
toma. Metastatic hemangiopericytoma, especially from
the meninges, cannot be distinguished from primary
hemangiopericytoma of bone on morphologic grounds
alone. Most hemangiopericytomas are at least low-grade
malignant. Tang and coauthors have suggested a grad-
ing system for hemangiopericytoma of bone. From a
 ■ Angiosarcoma and Hemangiopericytoma 283

F igu r e 23.24. Distribution of

heman giopericytomas accord-
in g to age and sex of the patient
and site of the lesion.

F igu r e 23.25. Destructive lesion involving the acetabulum

in a 48-year-old woman. Biopsy showed a hemangiopericy-
toma. A: The radiographic features are nonspecifi c. B: Com-
puted tomography shows destruction of bone with extension
of tumor in to soft tissue. C: Resected gross specimen con -
tains a well-demarcated, fi rm, rubbery tumor.
284 Chapter 23 ■

F igu r e 23.26. Hemangiopericytoma involving

th e stern um in a 75-year-old woman wh o h ad been
treated 8 years previously for breast carcin oma.
( Case provided by Dr. Charles Platz, Un iversity of
Iowa H ospitals and Clin ics, Iowa City, Iowa.)

F igu r e 23.27. H eman giopericytoma. A: Low-power view shows th at tumor cells are roun d to oval
sh aped an d th e tumor h as man y bran ch in g vascular ch an n els. B: Th e oval-sh aped cells arran ged
around the vascular channels show minimal cytologic atypia.

review of the literature, Tang and coauthors reported
that the 5-year survival rate was 75% and the 10-year was
44%. Of the 15 patients reported by Wold and coau-
thors, only 3 were alive an d free of disease.
BIBLIOGRAPH Y
1962 Hartmann, W. H. and Stewart, F. W.: H emangioendothe-
lioma of Bon e: Un usual Tumor Ch aracterized by In dolen t
Course. Cancer, 15:846–854.
1968 Otis, J., Hutter, R. V. P., Foote, F. W., Jr., Marcove, R. C., and
Stewart, F. W.: H emangioendothelioma of Bone. Surg Gynecol
Obstet, 127:295–305.
1971 Dor fman, H. D., Steiner, G. C., and Jaffe, H. L.: Vascular
Tumors of Bon e. Hum Pathol, 2:349–376.
1971 Un n i, K. K., Ivins, J. C., Beabout, J. W., and Dah lin , D. C.:
Hemangioma, Hemangiopericytoma, and Hemangioendothe-
lioma ( Angiosarcoma) of Bon e. Can cer, 27:1403–1414.
1972 Dube, V. E. an d Fisher, D. E.: Hemangioen doth elioma
of th e Leg Followin g Metallic Fixation of th e Tibia. Can cer,
30:1260–1266.
1972 Garcia-Moral, C. A.: Malign an t H eman gioendoth elioma of
Bone: Review of World Literature and Report of Two Cases.
Clin Orth op, 82:70–79.
1973 Dunlop, J.: Primary Haemangiopericytoma of Bone: Report
of Two Cases. J Bone Join t Surg, 55B:854–857.
1975 Larsson , S.-E., Lorentzon , R., an d Boquist, L.: Malig-
nant Heman gioen doth elioma of Bon e. J Bon e Join t Surg,
57A:84–89.
1979 Rosai, J., Gold, J., an d Landy, R.: Th e Histiocytoid Heman -
giomas: A Unifying Concept Embracing Several Previously
Described Entities of Skin, Soft Tissue, Large Vessels, Bone,
and H eart. Hum Path ol, 10:707–730.

1980 Campanacci, M., Boriani, S., and Giunti, A.: Heman-
gioendothelioma of Bone: A Study of 29 Cases. Cancer, 46:
804–814.
1981 Volpe, R. and Mazabraud, A.: Hemangioendothelioma
( Angiosarcoma) of Bone: A Distinct Pathologic Entity With an
Unpredictable Course. Cancer, 49:727–736.
1982 Weiss, S. W. and Enzinger, F. M.: Epithelioid Hemangio-
endothelioma: A Vascular Tumor O ften Mistaken for a Carci-
noma. Can cer, 50:970–981.
1982 Wold, L. E., Unni, K. K., Beabout, J. W., Ivins, J. C.,
Bruckman, J. E., and Dahlin, D. C.: H emangioendothelial Sar-
coma of Bone. Am J Surg Pathol, 6:59–70.
1982 Wold, L. E., Unni, K. K., Cooper, K. L., Sim, F. H., and Dahlin,
D. C.: Hemangiopericytoma of Bone. Am J Surg Pathol, 6:53–58.
1985 Maruyama, N., Kumagai, Y., Ishida, Y., Sato, H., Sugano,
I., Nagao, K., an d Kon do, Y.: Epith elioid Haeman gioen doth e-
lioma of th e Bone Tissue. Virch ows Arch [ A] , 407:159–165.
1986 Mirra, J. M. and Kameda, N.: Case Report 366: Myxoid
An gioblastomatosis of Bon e ( Dissemin ated) . Skeletal Radiol,
15:323–326.
1986 Tsuneyoshi, M., Dor fman, H. D., and Bauer, T. W.: Epithe-
lioid H eman gioen doth elioma of Bon e: A Clin icopath ologic,
Ultrastructural, an d Immun oh istoch emical Study. Am J Surg
Path ol, 10:754–764.
1988 Jennings, T. A., Peterson, L., Axiotis, C. A., Friedlaender,
G. E., Cooke, R. A., an d Rosai, J.: An giosarcoma Associated
With Foreign Body Material: A Report of Three Cases. Can cer,
62:2436–2444.
1988 Tang, J. S., Gold, R. H., Mirra, J. M., and Eckardt, J.: Heman-
giopericytoma of Bone. Cancer, 62:848–859.
1988 van der List, J. J., van Horn, J. R., Slooff, T. J., and ten Cate,
L. N.: Malignant Epithelioid Hemangioendothelioma at the
Site of a H ip Prosthesis. Acta Orth op Scand, 59:328–330.
1989 Case Records of the Massachusetts General Hospital.
N Engl J Med, 320:854–860.
1989 LeBoit, P. E., Berger, T. G., Egbert, B. M., Beckstead,
J. H., Yen, T. S., and Stoler, M. H.: Bacillary Angiomatosis: The
■ Angiosarcoma and Hemangiopericytoma 285
Histopath ology an d Differential Diagn osis of a Pseudon eo-
plastic In fection in Patien ts With Human Immun odefi cien cy
Virus Disease. Am J Surg Path ol, 13:909–920.
1990 Baron, A. L., Stein bach , L. S., LeBoit, P. E., Mills, C. M.,
Gee, J. H., and Berger, T. G.: Osteolytic Lesions and Bacillary
An giomatosis in HIV In fection : Radiologic Differen tiation
From AIDS-Related Kaposi Sarcoma. Radiology, 177:77–81.
1993 De Youn g, B. R., Wick, M. R., Fitzgibbon , J. F., Sirgi, K. E.,
an d Swan son , P. E.: CD31: An Immun ospecifi c Marker for
Endothelial Differentiation in Human Neoplasms. Appl
Immunohistochem, 1:97–100.
1993 O’Conn ell, J. X., Kattapuram, S. V., Man kin , H. J.,
Bhan, A. K., and Rosenberg, A. E: Epithelioid H emangioma of
Bone: A Tumor Often Mistaken for Low-Grade Angiosarcoma
or Malign an t Heman gioen doth elioma. Am J Surg Path ol,
17:610–617.
1993 Tsang, W. Y. and Ch an , J. K.: Th e Family of Epithelioid Vas-
cular Tumors. Histol Histopathol, 8:187–212.
1996 Kleer, C. G., Un ni, K. K., McLeod, R. A.: Epith elioid
H emangioendoth elioma of Bon e. Am J Surg Path ol, 20:
1301–1311.
2000 Miettinen , M. and Fetsch , J. F.: Distribution of Kera-
tins in Normal En doth elial Cells an d a Spectrum of Vascu-
lar Tumors: Implication s in Tumor Diagn osis. Hum Path ol,
31:1062–1067.
2000 Wen ger, D. E. and Wold, L. E.: Malign an t Vascular Lesion s
of Bon e: Radiologic an d Path ologic Features. Skeletal Radiol,
29:619–631.
2003 Desh pan de, V., Rosen berg, A. E., O’Conn ell, J. X., an d
Nielsen , G. P.: Epith elioid An giosarcoma of Bon e: A Series of
10 Cases. Am J Surg Pathol, 27:709–716.
2003 Evan s, H. L., Raymon d, A. K., an d Ayala, A. G.: Vascular
Tumors of Bone: A Study of 17 Cases Other Than Ordinary
Hemangioma, With an Evaluation of the Relationship of
Hemangioendothelioma of Bone to Epithelioid Heman-
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An giosarcoma. Hum Pathol, 34:680–689.
 C H APT ER
24
Adamantinoma of Long Bones
Adamantinoma of long bones is a peculiar neoplasm
that, on the basis of radiographic and pathologic fea-
tures, arises within th e osseous substance. The origin of
the epithelial islands in this tumor is unknown. Immu-
nohistochemical and electron microscopy studies have
confi rmed the epithelial nature of these islands. It has
been postulated that traumatic implantation of epithe-
lium is the cause of these tumors because almost all
reported adamantinomas have occurred in bone near
the cutaneous sur face. Others have considered congen-
ital rests of epithelium as the source of the tumors, and
still others have stated that the so-called adamantinoma
of long bones is not epithelial at all but represents
an unusual manifestation of sarcoma, either synovial
sarcoma or angiosarcoma.
In 1957, Changus and coauthors proposed that the
tumor had an angioblastic origin. Many of the histo-
logic features would favor this concept. Many tumors
have a vascular appearance, with the cells that line
spaces apparently continuous with obvious epithelial
cells. However, endothelial markers have not been posi-
tive in the neoplastic cells and, as mentioned elsewhere,
epithelial markers have.
Despite this controversy, the fact remains that ada-
mantinomas of long bones comprise a small group of
distinctive tumors that present as primary lesions of
bone. It is possible that several histogenetically differ-
ent tumors can produce the features of adamantinoma.
None of the proposed theories of origin explains its
peculiar predilection for the tibia.
The name adamantinoma was given to this tumor
because of its histologic resemblance to the more com-
mon adamantinoma ( ameloblastoma) of the jawbones.
These odontogenic tumors of the jaws and the histo-
logically related tumors that arise from Rathke pouch
are obviously not related and are excluded from the dis-
cussion that follows.
286
IN CID EN CE
There are 44 examples of adamantinoma of long bones
in the Mayo Clinic fi les ( Fig. 24.1) . This represents 0.56%
of the malignant primary tumors of bone. In 1986,
Moon and Mori collected 180 cases from the literature
and added 15 of their own.
SEX
In this series, there was a slight male predominance,
similar to other reports in the literature.
AGE
The majority of patients with adamantinoma are adoles-
cents and young adults. Approximately 72% of all patients
in this series were in the second and third decades of life.
Only two patients were in the fi rst decade of life; both
were 7 years old: one girl and one boy with lesions of the
mid tibia. The oldest patient was a 79-year-old man, who
also had a lesion of the mid tibia.
LOCALIZATION
Of all reported adamantinomas of long bones, 90%
have involved the tibia, although examples have been
found in all the long tubular bones. Some cases of ada-
mantinoma have also been reported in short tubular
bones, but the diagnoses in these cases have to be con-
sidered suspect. Of the 43 lesions ( in 40 patients) in
the Mayo Clinic series, 34 involved the tibia: 29 involved
the mid tibia, and 5 involved the distal metaphysis.
Four patients had involvement of the fi bula: two in the

F igu r e 24.1. Distribution of
adamantinomas according to
age and sex of the patient and
site of th e lesion.
mid portion and two in the lower portion. One of the
patients with involvement of the fi bula was treated in
1951 and returned 17 years later with a lesion of the
tibia. One patient had synchronous involvement of the
tibia and fi bula. The other two had involvement only of
the fi bula. In the series reported by Keeney and coau-
thors, 70 of the 85 patients had a tumor in the tibia.
Eleven of these patients also had involvement of the
ipsilateral fi bula. The other cases were distributed as
follows: two in th e distal ulna, one in the mid radius,
and two in the femur ( one in the mid portion and one
in the lower portion) .
SYMPTOMS
The prolonged clinical course of many of the patients
with this tumor indicates its generally slow growth. Pain
is the most common initial symptom, although local
tumefaction is the fi rst complaint of a few patients.
The duration of symptoms before diagnosis has varied
from a few months to 50 years. In the series reported by
Keeney and coauthors, approximately one-third of the
patients had symptoms for more than 5 years. Patho-
logic fracture is uncommon.
PH YSICAL FIN D IN GS
A mass, which may be painful, is the only physical fi nd-
ing of consequen ce.
■ Adamantinoma of Long Bones 287
RAD IOGRAPH IC FEATU RES
The most common, or typical, appearance is that of
multiple, sharply circumscribed, lucent defects of dif-
ferent sizes with sclerotic bone interspersed between
the zones and extending above and below the lucen-
cies. Some of the lucent zones are small, entirely corti-
cal, and similar to those seen in osteofi brous dysplasia.
Rarely, the rarefi ed area is elongated and located pre-
dominantly within the medullary cavity, with a zone of
irregular sclerosis at its margins. Typically, one of the
lytic areas, usually in the mid shaft of the bone, is larger
and more destructive appearing. When both the tibia
and the fi bula are involved, the appearance is consis-
tently as described. The multiple lucent zones may rep-
resent multifocal involvement initially, but because the
intervening bone is abnormally sclerotic, these zones
probably represent one lesion ( Figs. 24.2–24.5) .
Rare lesions of various bones have presented as
large, multilobulated lucent areas with expansion and
thinning of the cortex. The most frequent differential
problem is osteofi brous dysplasia.
GROSS PATH OLOGIC FEATU RES
Ordinarily, adamantinomas are clearly delimited periph-
erally, as indicated on radiographs. The contours of
these tumors are often lobulated. Most of the tumors
are gray or white, and they vary in consistency from
288 Chapter 24 ■

F igu r e 24.2. Adaman tin oma in volvin g th e tibia an d fi bula in a 19-year-old woman .
A: Exten sive in volvemen t of th e cortex of th e tibia in cludes a large destructive area in th e mid
portion. This appearance is quite typical. The lower fi bular shaft is also involved. B: Corre-
spon din g gross specimen . Th e cortical in volvemen t is much more exten sive th an th e obvious
large destructive areas in the mid portion of the tibia.

fi rm and fi brous to soft and brainlike ( Fig. 24.6) . They

may contain spicules of bone and calcareous material.
Cystic cavities, which may contain blood or clear fl uid,
are sometimes encountered. Some of the tumors erode
through the overlying cortex, but this is unusual in
patients who have not undergone a prior surgical proce-
dure. As mentioned above, a few adamantinomas have
been distinctly eccentric, not involving the medulla
but confi ned to the cortex. An occasional adamanti-
noma has been described in the soft tissues adjacent to
the tibia.

H ISTOPATH OLOGIC FEATU RES

Various histologic patterns have been described, but

Figure 24.3. The radiographic appearance is sometimes atyp-
ical, as in this distal tibial lesion in a 14-year-old boy. The appear-
ance is nonspecific.
all of them have an epithelial quality. The typical histo-
logic appearance is that of small epithelial islands in a
fi brous stroma ( Figs. 24.7–24.10). The relative amounts
of epithelium and fi brous tissue vary. Some tumors are
predominantly fi brous, with inconspicuous small islands
of cells to prominent epithelial islands with little inter-
vening stroma. The epithelial islands also vary in struc-
ture and shape (Fig. 24.11). Typically, there are islands
with peripheral palisading of basaloid-appearing cells
with a microcystic center containing stellate-shaped
 ■ Adamantinoma of Long Bones 289

F igu r e 24.4. Adaman tin oma. A: Typical appearan ce is of multiple lucen cies in volvin g th e
cortex of th e middle an d distal portion s of th e tibia. B: In th e correspon din g gross specimen ,
fl esh y tumor involves th e cortex an d exten ds in to th e medullary cavity. ( From Raymon d, A.
K. an d Un n i, K. K.: Bon es an d Join ts. In Karcioglu, Z. A. an d Someren , A. [ eds] . Practical
Surgical Path ology. Lexin gton , MA, Collamore Press, 1985, pp. 769–821. By permission of
D. C. H eath an d Compan y.)

F igu r e 24.5. Adaman tin oma in a 79-year-old man wh o h ad pain for 10 years. A: Multiple
cortical lucen cies are surroun ded by sclerosis. B: Magn etic reson an ce image sh ows destruc-
tion of th e cortex an d in volvemen t of soft tissue.
290 Chapter 24 ■

F igu re 24.8. Epithelial cells within an adamantinoma do not

show pronounced atypia.

F igu r e 24.6. Adamantinoma of the tibia in a 31-year-old

woman. In addition to the fl eshy tumor, fi brous dysplasia-like
areas involve the cortex and medullary cavity.

F igu re 24.9. Adamantinoma containing reactive new bone.

F igu re 24.7. Typical low-power appearance of adamanti-

noma of the tibia. Irregularly shaped islands of epithelial cells
are surrounded by fi brous tissue.

cells reminiscent of the stellate reticulum seen in

ameloblastomas (Fig. 24.12). Anastomosing spaces, with
the appearance of vascular channels, are conspicuously
present in some cases (Fig. 24.13). The cells lining these
spaces, however, have the same qualities as the obviously
epithelial cells and often a transition between the two can
be seen. Clear-cut squamous differentiation is uncom-
mon, present in only approximately 10% of the cases. F igu r e 24.10. Foamy histiocytes within an adamantinoma.
 ■ Adamantinoma of Long Bones 291

F igu r e 24.11. Adaman tin oma with cuboidal-sh aped epith e-

lial cells. Hemosiderin is present within some of the epithelial
islands.

F igu r e 24.12. Basaloid pattern of adamantinoma. There is a

periph eral layer of cuboidal cells within the epith elial islands.

In some cases, islands of squamous cells with central

keratin formation can also be seen ( Fig. 24.14). Rarely,
an adamantinoma has a pure spindle cell pattern, with
even a herringbone arrangement suggesting the diagno-
sis of fi brosarcoma (Fig. 24.15). However, the cells are
small and compactly arranged, with no intervening colla-
gen production. Although the cells are small, the nuclei
do not show marked atypia. Occasionally, the spindle
cells may give rise to islands surrounded by hypocellular
stroma, imparting an epithelial appearance. The pres-
ence of a spindle cell neoplasm in the cortex of the tibia
is practically diagnostic of adamantinoma. Sixteen of the
85 cases reported by Keeney and coauthors showed this F igu r e 24.13. An oth er fi eld from th e same lesion as in Fig-
ure 24.9. A: The tubular pattern suggests a vascular neoplasm
pattern (Figs. 24.9–24.11 & 24.15). Whatever the micro- with sinusoidal spaces that anastomose. B: The spaces are
scopic pattern of the tumor, one important feature is the lined by fl attened epithelial cells. C: The epithelial cells are
lack of pronounced cytologic atypia in adamantinoma. immunoreactive for keratin.
292 Chapter 24 ■
F igu r e 24.14. Squamous differentiation with keratin produc-
tion in an adamantinoma located in the tibia in a 17-year-old
boy.
F igu r e 24.15. Spin dle cell pattern of adaman tin oma. Th e
spin dle cells h ave in terlacin g fascicles, an d th ere is n o matrix
production.
This is an important consideration in differentiating
adamantinoma from metastatic carcinoma, on the one
hand, and a fi brosarcoma, on the other hand. Moreover,
it is unusual to fi nd metastatic carcinoma in the tibia, and
adamantinomas usually occur in an age group in which
metastatic carcinoma is distinctly uncommon.
It has long been recognized that adamantinoma of
the tibia can have fi brous dysplasia-like areas. More
recen tly, these have been suggested to be osteofi brous
dysplasia-like areas. These areas may be a prominent
component of some adamantinomas. The epithelial
islands may be incon spicuous and, indeed, overlooked.
Osteofi brous dysplasia has radiographic features very
similar to those of adamantinoma. Adamantin omas
usually, but not necessarily, have the prominent destruc-
tive component, which should not be present in osteo-
fi brous dysplasia. However, some adamantinomas may
have radiographic features indistinguishable from
those of osteofi brous dysplasia. Several studies have
demonstrated the presence of keratin-staining cells in
osteofi brous dysplasia. Thus, it is not unexpected that
the relationship between osteofi brous dysplasia and
adamantinoma has been suggested. One suggestion
has been that osteofi brous dysplasia may be a precursor
lesion to adamantinoma. However, two large studies of
osteofi brous dysplasia, one from Mayo Clinic and the
other from the Armed Forces Institute of Pathology, did
not identify a single case of progression of osteofi brous
dysplasia to adamantinoma.
Czerniak and coauthors have suggested a different
relationship between osteofi brous dysplasia and ada-
mantinoma. They suggest that adamantinomas can be
divided into two distinct groups. The fi rst group is the
classic adamantinoma, which involves the cortex and
medulla of the tibia and usually affects young adults.
The second group, termed differentiated adamantinoma,
tends to affect children, and the lesion is well circum-
scribed and cortical. These differentiated adamanti-
nomas have a prominent osteofi brous dysplasia-like
pattern. The authors suggested that at least some exam-
ples of osteofi brous dysplasia may be a reparative pro-
cess in adamantinoma. However, these authors did not
provide any clinical follow-up to support the idea that
the cortical lesions are somehow different from classic
adamantinoma.
Several larger studies of osteofi brous dysplasia have
suggested that they are self-limited lesions and, indeed,
may not require treatment. The presence of cells with
epithelial characteristics seen on immunoperoxidase
stains is not suffi cient to qualify these as adamantinoma.
Currently, the term differentiated or osteofi brous dysplasia–
like adamantinoma refers to lesions that resemble osteofi -
brous dysplasia but contain nests or strands of epithelial
cells that can be seen in hematoxylin-eosin–stained sec-
tions. There is no question that osteofi brous dysplasia
and adamantinoma can have identical radiographic
features, and there is no question that some cases of
adamantinoma have the histologic features of osteofi -
brous dysplasia. However, the relation between the two
is still unclear.
TREATMEN T
After carefully reviewing all the recorded cases and
amplifying the available information by sending ques-
tionnaires to the authors who reported the cases, Baker
and associates concluded that amputation is the treat-
ment of choice. This conclusion was based on the fi nd-
ing that two-thirds of the patients had recurrence after
local excision and that eight had died after recurrence.

F igu r e 24.16. Adaman tinoma metastatic to an in guin al
lymph node in a 30-year-old man. The primary tumor was
located in the tibia and was resected 4 years before the lymph
node metastasis was discovered.
However, with the advances made in limb-salvage sur-
gery, many patients with adamantinoma can be treated
with local resection.
PROGN OSIS
Early radical therapy should result in a high proportion
of cures. However, temporizing with inadequate attempts
at local excision has resulted in death from metastasis.
Although the average adamantinoma has an indolent
course, some otherwise typical examples metastasize
early. Metastasis may be by the hematogenous or the lym-
phatic route ( Fig. 24.16) . Keeney and coauthors reported
a recurrence rate of 31% at an interval ranging from
3 months to 19.4 years. Lymph node metastasis occurred
in 6 patients and lung metastasis in 13. The metastases
occurred as late as 17.9 years after initial treatment. The
majority of differentiated adamantinomas behave in a
benign fash ion with only rare case reports of progres-
sive disease.
BIBLIOGRAPH Y
1942 Dockerty, M. B. and Meyerding, H. W.: Adamantinoma of
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1954 Lederer, H. and Sinclair, A. J.: Malignant Synovioma
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1957 Changus, G. W., Speed, J. S., and Stewart, F. W.: Malignant
An gioblastoma of Bon e: A Reappraisal of Adaman tin oma of
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1962 Cohen, D. M., Dahlin, D. C., and Pugh, D. G.: Fibrous Dys-
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■ Adamantinoma of Long Bones 293
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1965 Moon , N. F.: Adamantinoma of the Appen dicular Skeleton :
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1974 Un n i, K. K., Dahlin, D. C., Beabout, J. W., an d Ivin s, J. C.:
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1977 Weiss, S. W. an d Dor fman , H . D.: Adamantinoma of Long
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Metastasizin g Lesion s an d Fibrous Dysplasia-Like Ch an ges.
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1977 Yoneyama, T., Winter, W. G., and Milsow, L.: Tibial Ada-
man tin oma: Its H istogen esis From Ultrastructural Studies.
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1981 Campan acci, M., Giun ti, A., Berton i, F., Laus, M., an d
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1982 Kn app, R. H ., Wick, M. R., Sch eith auer, B. W., an d Un n i,
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of Adaman tin oma Sixteen Years After Kn ee Disarticulation :
A Report of a Case. J Bon e Join t Surg, 68A:772–776.
1986 Moon , N. F. and Mori, H .: Adaman tin oma of th e Appen -
dicular Skeleton : Updated. Clin Orthop, 204:215–237.
1986 Sowa, D. T. an d Dor fman , H. D.: Unusual Localization of
Adaman tin oma of Lon g Bon es: Report of a Case of Isolated
Fibular In volvement. J Bon e Join t Surg, 68A:293–296.
1987 Gebh ardt, M. C., Lord, F. C., Rosen berg, A. E., an d Mankin ,
H. J.: The Treatment of Adamantinoma of the Tibia by Wide
Resection an d Allograft Bon e Tran splan tation . J Bon e Join t
Surg, 69A:1177–1188.
1989 Czerniak, B., Rojas-Corona, R. R., and Dor fman, H. D.: Mor-
phologic Diversity of Lon g Bone Adaman tinoma: Th e Con cept
of Differentiated ( Regressing) Adaman tinoma and Its Rela-
tionsh ip to Osteofi brous Dysplasia. Cancer, 64:2319–2334.
1989 Keen ey, G. L., Un n i, K. K., Beabout, J. W., an d Pritch ard, D.
J.: Adamantinoma of Long Bones: A Clinicopathologic Study
of 85 Cases. Can cer, 64:730–737.
1989 Sch ajowicz, F. an d San tin i-Araujo, E.: Adaman tinoma of
the Tibia Masked by Fibrous Dysplasia: Report of Three Cases.
Clin Orth op, 238:294–301.
1991 Bloem, J. L., van der Heul, R. O., Sch uttevaer, H. M., an d
Kuipers, D.: Fibrous Dysplasia vs Adaman tin oma of th e Tibia:
294 Chapter 24 ■
Differen tiation Based on Discrimin an t An alysis of Clin ical an d
Plain Film Findings. Am J Roentgenol, 156:1017–1023.
1992 Ishida, T., Iijima, T., Kikuchi, F., Kitagawa, T., Tanida,
T., Imamura, T., and Machin ami, R.: A Clinicopathological
an d Immunohistochemical Study of Osteofi brous Dysplasia,
Differen tiated Adaman tin oma, an d Adaman tin oma of Lon g
Bon es. Skeletal Radiol, 21:493–502.
1992 Sweet, D. E., Vinh, T. N., and Devaney, K.: Cortical Osteo-
fi brous Dysplasia of Lon g Bone and Its Relationsh ip to
Adaman tinoma: A Clinicopathologic Study of 30 Cases. Am
J Surg Path ol, 16:282–290.
1993 Hazelbag, H. M., Fleuren, G. J., Van Den Broek, L. J., Tamin-
iau, A. H., and Hogendoorn, P. C.: Adamantinoma of the Long
Bones: Keratin Subclass Immunoreactivity Pattern With Refer-
ence to Its Histogenesis. Am J Surg Pathol, 17: 1225–1233.
1993 Kuruvilla, G. and Steiner, G. C.: Adamantinoma of the
Tibia in Children an d Adolescents Simulating Osteofi brous
Dysplasia of Bon e ( Abstract) . Mod Path ol, 6:7A.
1993 Park, Y. K., Unni, K. K., McLeod, R. A., and Pritchard, D. J.:
Osteofi brous Dysplasia: Clin icopath ologic Study of 80 Cases.
Hum Path ol, 24:1339–1347.
1997 Hazelbag, H. M., Van den Broek, L. J., Fleuren, G. J.,
Taminiau, A. H., Hogendoorn, P. C.: Distribution of
Extracellular Matrix Componen ts in Adaman tin oma of Lon g
Bones Suggests Fibrous-to-Epithelial Transformation. Hum
Pathol, 28:183–188.
2000 Qureshi, A. A., Sh ott, S., Mallin , B. A., and Gitelis, S.:
Curren t Tren ds in th e Man agemen t of Adaman tin oma of
Lon g Bon es: An In tern ation al Study. J Bone Join t Surg Am,
82-A:1122–1131.
2003 Kah n, L. B.: Adaman tin oma, Osteofi brous Dysplasia and
Differen tiated Adamantin oma. Skeletal Radiol, 32:245–258.
2008 Gleason , B. C., Liegl-Atzwan ger, B., Kozakewich , H. P., Con -
n olly, S., Gebhardt, M. C., Fletcher, J. A., and Perez-Atayde,
A. R.: O steofi brous Dysplasia an d Adaman tin oma in Ch ildren
an d Adolescen ts: A Clin icopath ologic Reappraisal. Am J Surg
Pathol, 32:363–376.
2008 Jain , D., Jain, V. K., Vash ista, R. K., Ran jan , P., an d Kumar,
Y.: Adaman tin oma: A Clin icopath ological Review an d Update.
Diagn Pathol, 3:8.

Miscellaneous U nusual
Tumors of Bone
Th is chapter is concerned with some uncommonly rare
tumors of bone. Some of these are included in the clas-
sifi cation of bone tumors ( see Chapter 1) and some are
not. This includes neural and fatty tumors discussed in
Chapters 25 and 26, respectively, of the previous edition
of this book.
SCH WAN N OMA
Neurogenic tumors of bone are rare. In a review of the
English-language literature in 1992, Turk and coau-
thors found 79 examples of intraosseous schwannoma
( neurilemmoma) . Neurofi bromas should be distin-
guished from schwannomas because the latter have
practically no potential for malignant transformation.
The differentiation is usually straightforward: schwan-
nomas are well-circumscribed masses arising from a
nerve, whereas neurofi bromas are usually fusiform and
course along the nerve.
In approximately half of the large group of cases stud-
ied at Mayo Clinic by Hunt and Pugh in 1961, neurofi -
bromatosis was associated with various skeletal changes.
These changes included erosive effects in bone caused
by contiguous neurogenic tumors, dysplasia of vertebral
bodies with scoliosis, defects of the posterior orbital wall,
congenital bowing, and pseudarthrosis. Intraoasseous
neurofi bromas are distinctly rare. Some of the osseous
defects noted in patien ts with von Recklinghausen dis-
ease have been coincidental, unrelated processes.
Malign an t peripheral n erve sheath tumors h ave
rarely been described arisin g in bon e, an d eviden ce in
reported cases is n ot altogeth er con vincin g. Th e in her-
ent ch aracteristics of a malignan t growth make it dif-
fi cult to verify the exact tissue of origin in a question -
able case. Growth in relation to a n erve is importan t
in establishin g the n eurogenic origin of a sarcoma. In
C H APT ER
25
any even t, th e problem is academic because the treat-
men t for such a sarcoma would be th e same as for
fi brosarcoma of bone. In th e Mayo Clin ic fi les, four
patien ts with von Recklin gh ausen disease h ad spin dle
cell sarcoma of th e bone. Alth ough th e lesions in th ese
cases may represent malign an t periph eral n erve sh eath
tumors, th ere is no proof of th eir n eurogen ic n ature,
and th ey h ave been in cluded with fi brosarcomas.
IN CID EN CE
Schwannoma is a rare primary bone tumor. In the Mayo
Clinic series, the 23 cases accounted for less than 1% of
the primary benign tumors of bone ( Fig. 25.1) .
SEX
Thirteen of the twenty-three patients were females.
AGE
A wide age range was represented, but 11 of the
23 patients were in the second and third decades of life.
LOCALIZATION
The mandible and the sacrum were the most commonly
involved bones, accounting for six and nine tumors,
respectively. Schwannomas are not uncommon in the
region of the sacrum. Quite often, it is impossible to
know whether the lesion arose from the sacrum or from
one of the nerves and eroded the bone secondarily. A
case was included only if the radiographic features sug-
gested that the tumor was a primary neoplasm of bone.
Three lesions were in the skull, two in the mid femur,
and one each in the rib, distal tibia, and scapula. The lit-
erature suggests a pronounced predilection for involve-
ment of the mandible.
295
296 Chapter 25 ■

F igu r e 25.1. Distribution of

sch wan n omas accordin g to age
an d sex of th e patien t an d site
of th e lesion .

SYMPTOMS

Many schwannomas of bone are asymptomatic, a few

produce prominent pain, and some result in local
tumefaction.

PH YSICAL FIN D IN GS

There are no specifi c physical fi ndings unless a patient

has neurofi bromatosis.

RAD IOGRAPH IC FEATU RES

Well-defi ned cystlike rarefactions, sometimes with a

slightly sclerotic border, are produced by schwanno-
mas. When in a long tubular bone, these rarefactions
are typically in the shaft and often near its end. The
defect sometimes has a bubbly appearance because of
the irregular corrugations in the wall of the cavity that
houses the lesion ( Figs. 25.2–25.5) .

GROSS PATH OLOGIC FEATU RES

Material removed from a schwannoma of bone, like that

of its soft-tissue counterpart, is a relatively fi rm mass of
fi broblastic tissue. It may be somewhat gelatinous or F igu r e 25.2. Schwannoma involving the mandible produces
myxoid, and a yellow or brownish discoloration is occa- a well-defi ned expansile lucency. The lesion is surrounded by
sionally present. The relationship to a nerve or its canal, a sclerotic rim, suggesting a benign process.
 ■ Miscellaneous Unusual Tumors of Bone 297

F igu r e 25.3. Schwannoma. Lesion of

the sacrum in a 40-year-old man who
had experien ced back pain for 2 years.
A: Plain radiograph shows a large lytic
mass. Sharp margination, sclerotic rim,
and foraminal expansion favor a benign
neurogenic process. B: Computed tomo-
gram shows clearly that the lesion arose
from within the bone.

F igu r e 25.4. Computed tomograms at two levels show a

large schwannoma involving the temporal bone in a 12-year- F igu r e 25.5. Schwannoma forming an expansile benign-
old girl. appearing lesion in the distal fi bula in a 50-year-old man.

if such can be established, is an important diagnostic
clue. The lesion may be partially cystic ( Fig. 25.5) .
H ISTOPATH OLOGIC FEATU RES
degeneration. Although these nuclei are suggestive of a
malignant tumor, the virtual absence of mitotic fi gures
and the benign radiographic appearance indicate the
benign quality of the neoplasm.

Schwannomas are well-circumscribed lesions, and the

edges are sharply demarcated from surrounding bone.
There is no invasion of surrounding medullary bone.
The lesion is essentially a spindle cell process, which
may be quite vascular. Typically, the vessels have a thick
hyaline wall. The spindle cells have a very characteristic
wavy nucleus, and nuclear palisading may be prominent
( Figs. 25.6–25.7) . Areas of foam cells and hemosiderin
pigment are commonly seen. As with schwannomas of
soft-tissue localization, the nuclei may be irregular in
size, dark staining, and bizarre, probably because of
TREATMEN T
Conservative local removal is indicated. Lesions of the
sacrum may be gigantic and, if the patient is asymptom-
atic, an attempt at complete removal may be hazardous.
PROGN OSIS
A good result is to be expected. The consequence of
neurofi bromatosis, if that disease is present, may infl u-
ence the long-term results.
298 Chapter 25 ■
F igu r e 25.6. A: Sch wan n oma con tain in g an An ton i A area with sh ort fascicles an d focal palisad-
ing of bland spindle cells. B: Tumor cells express S-100 protein.
F igu r e 25.7. Same tumor as in Figure 25.6. Antoni B area
with a haph azard loose arran gemen t of spin dle cells in a myx-
oid backgroun d.
LIPOMA AN D LIPOSARCOMA
Despite the abundance of adipose connective tissue
in bone marrow, lipomas of bone are extremely rare.
In 1976, Morefi eld and coworkers reported on 26
cases that they collected from the literature. In 1988,
Milgram reported on 61 histologically confi rmed soli-
tary intraosseous lipomas. He thought that lipomas
probably undergo involution and divided the histologic
features into three distinct stages. In stage 1, the tumors
contained viable lipocytes. Stage 2 is characterized by
partial fat necrosis and calcifi cation. In stage 3, which
Milgram considered to be a late stage, the fat cells have
been replaced with calcifi cation, with features of bone
infarct.
IN CID EN CE
There were only 11 examples of lipoma in the surgical
fi les of Mayo Clinic ( Fig. 25.8) . This probably does not
represent the true incidence of the lesion because they
are frequently asymptomatic.
SEX
This small series of lipomas consisted of fi ve female and
six male patients.
AGE
All 11 patients with lipoma were adults ranging in age
from 23 to 71 years.
LOCALIZATION
Lipoma may involve any portion of the skeleton. Two
lesions involved the skull, three the femur, and one each
involved the ulna, fi bula, tibia, rib, humerus, an d calca-
neous. In a large series of cases, Milgram found that the
proximal femur was the most common location. In the

F igu r e 25.8. Distribution of
lipomas according to age and
sex of th e patien t an d site of
the lesion.
consultation cases seen at Mayo Clinic, the calcaneous
appears to be a favorite site. It was the second most com-
mon site in Milgram’s series.
SYMPTOMS
Five of the lipomas were incidental radiographic fi nd-
ings. One lesion of the ulna produced swelling. The
patient with the lesion of the distal femur complained
of pain. However, this pain was probably unrelated to
the lipoma. In the series reported by Milgram, there was
a remarkable lack of symptoms.
PH YSICAL FIN D IN GS
Physical examination is usually unremarkable. Swelling
was noted in one patient with a lesion of the ulna.
RAD IOGRAPH IC FEATU RES
Radiographically, lipomas present as well-circumscribed
areas of lucency. There may or may not be a thin scle-
rotic rim around the lesion. With imaging modalities
such as computed tomography and magnetic resonance
imaging, the fatty nature of the lesion becomes obvious.
Typically, the cen ter of the lesion shows an area of min-
eralization. This combination of a well-circumscribed
lucency with central areas of sclerosis is quite typical of
intraosseous lipoma ( Figs. 25.9–25.10) .
■ Miscellaneous Unusual Tumors of Bone 299
GROSS PATH OLOGIC FEATU RES
Grossly, lipomas are yellow areas with or without
admixed trabecular bone.
H ISTOPATH OLOGIC FEATU RES
A lipoma of bone may be overlooked because it
resembles fatty marrow ( Fig. 25.11) . The distinction is
made because of the tumefactive nature of the fat and
the virtual absence of medullary bone. However, small
fragments of medullary bone may be present with a
lipoma. The central area of calcifi cation seen radio-
graphically has amorphous calcifi cation similar to that
present in bone infarcts ( Figs. 25.12–25.14) .
Primary liposarcomas of bon e are extremely rare.
Th ere are only two incidences of liposarcomas occur-
rin g in bone in th e Mayo Clinic fi les. O ne patien t who
presented with exten sive in volvement of th e humerus
also h ad a liposarcoma of the retroperitoneum, wh ich
was probably the primary site. Th e on ly patient with a
probable primary liposarcoma of bon e was a 54-year-
old woman with an exten sive lesion of th e proximal
humerus. Sh e underwen t a forequarter amputation.
Two years later, sh e died, with clin ical evidence of
metastases to the vertebrae and liver. No oth er soft-tis-
sue primary site was foun d. Milgram h as described four
examples of primary liposarcomas of bone. He th ough t
th at th ey arose from preexisting lipomas.
300 Chapter 25 ■

F igu r e 25.9. An teroposterior ( A) an d lateral ( B) radiograph s of th e righ t kn ee sh ow a mixed

lytic an d sclerotic lesion that is in determin ate in th e medial femoral con dyle. Coronal T1-weighted
image ( C) and coronal T2-weighted image with fat suppression ( D) show that the lesion is com-
posed predominantly of fat, with a central area of nonlipomatous signal. The magnetic resonance
imaging features are characteristic of a benign intraosseous lipoma with central necrosis, degenera-
tive ch an ge, an d dystroph ic calcifi cation . Magn etic reson an ce imagin g was in strumen tal in exclud-
ing a diagn osis of malign an cy.
 ■ Miscellaneous Unusual Tumors of Bone 301

F igu r e 25.10. A: Lateral radiograph sh ows a well-defi n ed lytic lesion in th e body of th e calcan eus.
Th e differen tial diagn osis would in clude simple cyst an d in traosseous lipoma. Sagittal ( B) an d axial
( C) T1-weighted and sagittal T2-weighted with fat suppression ( D) magnetic resonance images
sh ow th at th e lesion con sists predomin an tly of fat with an area of cen tral n ecrosis, diagn ostic of an
intraosseous lipoma.
302 Chapter 25 ■

F igu r e 25.11. Viewed at low-power, the diagnosis of F igu r e 25.14. Fin e, powdery calcifi cation with fi brosis in an
intraosseous lipoma can be missed because the adipose tissue intraosseous lipoma. There are no viable cells. These features
that is part of the lesion is assumed to be marrow fat. H owever, resemble th ose seen in in farcts of bone.
there is no evidence of bone marrow elements.

F igu r e 25.12. Areas of fi brosis are commonly seen in

intraosseous lipomas.

F igu r e 25.15. Ph osph aturic mesen ch ymal tumor. A: Th e

lesion is composed of fusiform or spindled cells without atypia
F igu r e 25.13. Focal calcifi cation is found in an area of associated with a capillary vascular pattern. B: Smudgy blue to
degenerative fi brosis within this intraosseous lipoma. pale purple calcifi cation is a common fi nding.

PH OSPH OTU RIC
MESEN CH YMAL TU MOR
It has been recognized for some time that hypophos-
phatemic osteomalacia can be associated with neo-
plasms ( oncogenic osteomalacia) usually of somatic soft
tissue but also of bone. Although in the past the tumors
were considered to have a wide variety of pathologic
features, these neoplasms have been unifi ed under
the term phosphoturic mesenchymal tumor. These tumors
almost always have vascular proliferation ( which fre-
quently led to a diagnosis of sclerosing hemangioma or
hemangiopericytoma) , proliferation of giant cells, and
an unusual latticelike calcifi cation ( Fig. 25.15) .
Th ree bon e tumors in th e Mayo Clin ic series h ave
h istologic an d clin ical features th at qualify th em for
th e diagn osis of ph osph oturic mesen ch ymal tumors.
Th ese lesion s ten ded to be small an d diffi cult to
detect. Th ere were two males, ages 35 an d 52 years,
an d on e female, age 52 years. Th e tumors in volved th e
proximal femur, distal femur, an d th e fi rst cer vical ver-
tebra. H istologically, each on e sh owed vascular prolif-
eration , gian t cells, an d matrix calcifi cation .
ALVEOLAR SOFT PART SARCOMA
Alveolar soft part sarcoma is an extremely rare soft-tissue
sarcoma involving the buttocks and thigh of young
adults. However, it can occur in unusual locations, such
as the tongue.
Two examples of alveolar soft part sarcoma arisin g
in bon e are con tain ed in th e Mayo Clin ic fi les. O n e
F igu r e 25.16. Alveolar soft part sarcoma th at was located
in the distal femur in a 27-year-old woman. The tumor has
an organoid arrangement of polygonal tumor cells that con-
tain vesicular n uclei an d abun dan t gran ular, eosin oph ilic
cytoplasm.
■ Miscellaneous Unusual Tumors of Bone 303
in volved th e proximal tibia of a 25-year-old woman ,
an d th e oth er in volved th e distal femur of a 17-year-
old girl. Th e h istologic features were classic, n amely,
aggregates of tumor cells in an alveolar pattern with
promin en t sin usoidal vessels. Th e cytoplasm was gran -
ular, an d th e n uclei h ad a sin gle promin en t n ucleolus
( Fig. 25.16) . Th e h istologic features are similar to th ose
of metastatic ren al cell carcin oma.
CLEAR CELL SARCOMA
Clear cell sarcoma, considered to be a form of mela-
noma, is a rare soft-tissue sarcoma usually associated
with tendons and aponeuroses. The tumor cells are
spindle shaped and arranged in clusters. The nucleoli
are prominent, and clusters of giant cells are commonly
seen. We have two examples of clear cell sarcoma appar-
ently primary in bone. The fi rst involved a rib of an
18-year-old man, and the other involved the coccyx of a
43-year-old woman. The histologic features were identi-
cal to those primary in soft tissue ( Fig. 25.17) .
PARAGAN GLIOMA
Paragangliomas, or chemodectomas, arise from
chemoreceptor cells and are usually associated with the
carotid or aortic bifurcation. They can also occur in the
jugular body or organ of Zuckerkandl. The tumors have
an “endocrine” appearance, with tumor cells arranged
in clusters ( Zellballen) around sinusoidal vessels. The
nuclei are centrally placed and round, and the cyto-
plasm is granular ( Fig. 25.18) .
F igu r e 25.17. Clear cell sarcoma. This tumor arose from
a rib. Fibrous septa separate the tumor cells into nests and
groups. Th e oval n uclei are surroun ded by clear to sligh tly
eosinoph ilic cytoplasm.
304 Chapter 25 ■
F igu r e 25.18. Paragan glioma metastatic to th e sacrum. Th e
nests of tumor cells with n euroen docrin e features are situated
in a h emorrh agic backgroun d. Th e tumor is wrapped around
a fragment of medullary bone.
Paragangliomas can metastasize without the overt
histologic features of malignancy. Several examples of
paraganglioma with bone metastasis are contained in
our fi les. There are three examples of what appear to
be primary paragangliomas of the skeleton in our fi les.
Two involved the sacrum. One patient was a 41-year-old
woman, and the other was a 52-year-old man. The third
patient was a 32-year-old man who had a tumor of the
ilium. A diagnosis of primary paraganglioma of bone
is valid only if an occult primary site elsewhere can be
ruled out.
EPEN D YMOMA
Ependymomas are considered to arise from the walls
of the brain ventricles or from the spinal canal. Myxo-
papillary ependymomas occur almost exclusively in
the cauda equina region. The tumors are composed
of round to oval nuclei arranged around stromal cores
and associated with a myxoid matrix. Two tumors in the
Mayo Clinic fi les presented as tumors of the sacrum sim-
ulating chordoma. One patient was a 46-year-old man,
and the other was a 51-year-old woman.
MIXED TU MOR
Mixed tumor ( pleomorphic adenoma, myoepithe-
lioma) is a benign tumor of salivary gland origin, but
it may occur in other sites, such as the skin and soft tis-
sues. Rarely, one of these metastasizes to bone without
the histologic features of malignancy. Even more
uncommonly, a mixed tumor arises in bone. There is
only one example of such a tumor in our fi les, that of a
44-year-old woman with a tumor of the cuboid. The his-
tologic appearance was typical, with chondroid lobules
admixed with clusters of myoepithelial cells.
BIBLIOGRAPH Y
1961 Hunt, J. C., and Pugh, D. G.: Skeletal Lesions in Neurofi -
bromatosis. Radiology, 76:1–20.
1970 Salassa, R. M., Jowsey, J., and Arnaud, C. D.: H ypophos-
ph atemic Osteomalacia Associated With “Non en drocrin e”
Tumors. N En gl J Med, 283:65–70.
1972 Evans, D. J. and Azzopardi, J. G.: Distinctive Tumours of
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Osteomalacia. Lancet, 1:353–354.
1976 Moorefi eld, W. G., Jr., Urbaniak, J. R., and Gonzalvo,
A. A. A.: In tramedullary Lipoma of th e Distal Femur. South
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1981 Gadgil, R. K and Ranadive, N. U.: Chondroid Syringoma
( Mixed Tumour) of Radius. In dian J Can cer, 18;81–83.
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Neoplastic Path ology of O n cogen ic O steomalacia/ Rickets.
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1988 Marzola, C., Borguetti, M. J., and Consolaro, A.: Neurilem-
moma of th e Mandible. J Oral Maxillofac Surg, 46:330–334.
1988 Milgram, J. W.: Intraosseus Lipomas: A Clinicopathologic
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Diagn osis an d Man agemen t of Gian t In trasacral Sch wan n oma.
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1994 Park, Y. K., Unni, K. K., Beabout, J. W., and Hodgson, S.
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1996 Yokoyama, R., Mukai, K., Hirota, T., Beppu, Y., and Fukuma,
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1999 Park, Y. K., Unni, K. K., Kim, Y. W., Han, C. S., Yang, M. H.,
Wen ger, D. E., Sim, F. H., Lucas, D. R., Ryan , J. R., Nadium,
Y. A., Nojima, T., an d Fletch er, C. D.: Primary Alveolar Soft
Part Sarcoma of Bon e. Histopath ology, 35:411–417.
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Weh rli, B. M., Wh ite, K. E., Zain o, R. J., an d Weiss, S. W.: Most
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hen sive Review of th e Literature. Am J Surg Pathol, 28:1–30.
2008 Aisner, S. C., Beebe, K., Blacksin, M., Mirani, N., and
Hameed, M.: Primary Alveolar Soft Part Sarcoma of Fibula
Demonstratin g ASPL-TFE3 Fusion : A Case Report an d Review
of th e Literature. Skeletal Radiol, 37:1047–1051.
2009 Bahrami, A., Weiss, S. W., Montgomery, E., H orvai, A. E.,
Jin , L., In wards, C. Y., an d Folpe, A. L.: RT-PCR An alysis for
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In duced Osteomalacia. Am J Surg Path ol, In Press.

Conditions That Commonly
Simulate Primary
N eoplasms of Bone
Adequate consideration of all the reactive, traumatic,
infectious, metabolic, congenital, and other condi-
tions of bone that may simulate benign or malignant
neoplasms is not within the scope of this book. Many
of these conditions are recognized clinically and radio-
graph ically, and the surgical pathologist is not involved
in making the diagnosis. The purpose in this chapter is
to indicate the types of problems that are encountered
and to document briefl y some of those most often seen
in material sent for consultation from other patholo-
gists. Among the conditions that are not discussed are
pseudotumors of bone in hemophiliac patients and
hydatid disease of bone that produces a severe problem
rarely seen in the United States.
METASTATIC CARCIN OMAS
Metastatic deposits from carcinomas are by far the most
common malignant tumors affecting the skeleton.
Although the correct diagnosis is usually obvious when
the clinical history is considered, it is often unsafe to
assume that any given skeletal lesion or lesions are nec-
essarily related to the proved carcinoma. For example,
the punched-out areas of destruction characteristic of
myeloma may be mistaken for areas of lytic metastatic
deposits. Metastatic carcinoma is especially likely to be
a diagnostic problem when only one skeletal lesion is
found and no primary tumor is known. A destructive
process secondary to hypernephroma is particularly
likely to simulate a primary lesion of bone because this
cancer tends to produce a clinically solitary metastatic
lesion , the cells often show pronounced spindling, and
the primary tumor is in an obscure location. Carcino-
mas may invade bone by direct extension.
C H APT ER
26
PH YSICAL FIN D IN GS
The osseous lesions of metastatic carcinoma may closely
simulate a primary malignant tumor. The most promi-
nent symptoms are pain, with or without swelling, and
those resulting from pressure on neighboring struc-
tures or from pathologic fracture. Systemic symptoms
of a malignancy may or may not be present.
RAD IOGRAPH IC FEATU RES
Metastatic tumors usually produce irregular destruction
of bone indicative of their malignant quality. Although
most such lesions are osteolytic, many metastatic depos-
its from carcinoma of the prostate and occasionally
those from other tumors are osteoblastic. Th e presence
of a large, purely lytic destructive lesion, which may
have an aneurysmal dilatation, strongly suggests the
possibility of metastatic renal cell carcinoma. Radioac-
tive bone scans may show involvement of other skel-
etal sites. Magnetic resonance imaging, especially with
involvement of the vertebrae, may show more extensive
disease than is obvious clinically. Computed tomograms
may similarly show the occult primary tumor, such as a
hypernephroma ( Figs. 26.1–26.4) .
GROSS PATH OLOGIC FEATU RES
Carcin omas metastatic to bon e do n ot h ave gross diag-
n ostic ch aracteristics. Th e lesion s vary from th ose th at
are fi brotic because of a desmoplastic reaction pro-
duced by th e tumor to th ose th at are extremely soft
an d mush y. Th e osteoblastic metastatic lesion s seen
so often in prostatic carcin oma are ver y den se an d
relatively ch aracteristic. Rarely, bon e th at may result
305
306 Chapter 26 ■
from reaction to a deposit of metastatic carcin oma is
con fusin gly similar to th at produced by osteosarcoma
( Figs. 26.5–26.7) .
H ISTOPATH OLOGIC FEATU RES
Most often, the patient presenting with metastatic car-
cinoma to the skeleton has a known primary neoplasm.
A biopsy may be per formed just to confi rm the pres-
ence of skeletal metastasis. Fine-needle aspiration is an
F igu r e 26.1. Metastatic ren al cell carcin oma. Computed
tomograph ic scout ( A) an d 2D coron al computed tomo-
graph ic recon struction ( B) sh ow an aggressive osteolytic
destructive lesion in th e left pubic bon e an d acetabulum.
C: Coron al T2-weigh ted magn etic reson an ce images sh ow
th at th e lesion is associated with a large circumferen tial soft
tissue mass an d exten ds from th e pubic symph ysis to th e h ip
join t. Th e lytic lesion in th e pubic bon e is typical of ren al
cell carcin oma metastasis.
excellent method for documenting metastatic disease.
It is important to compare the biopsy specimen with the
previous primary neoplasm if available.
Most metastatic carcin omas are h istologically obvi-
ous. Most metastatic aden ocarcin omas an d squamous
cell carcin omas do n ot presen t diagn ostic diffi culties.
H owever, wh en th e skeletal lesion is th e on ly sign of
carcin oma, th e path ologist may be in a position to
guide th e clin ician for a search of th e primary n eo-
plasm. Th is exercise may be of more th an academic
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 307

F igu r e 26.2. Metastatic breast carcinoma to the femur. A: Anteroposterior radiograph of the
left femur shows a predominantly sclerotic lesion in the subtrochanteric region of the left femur
with associated destruction of the lesser trochanter. B: Bone scan shows that this represents a soli-
tary lesion . C: Coronal T1-weigh ted magnetic resonance image delineates th e anatomical extent of
destruction. Although not specifi c, the radiographic fi ndings are consistent with metastasis.

F igu re 26.3. A: Anteroposterior radiograph of the left humerus in a 50-year-old woman shows a
lytic destructive lesion in the mid-humeral diaphysis with cortical thinning and periosteal reaction. It
was suspicious for metastasis, but lymphoma and myeloma were also included in the differential diag-
nosis. Histologically, it was an undifferentiated carcinoma. B: Further work-up, including chest radi-
ography, showed a large mass in the right hilum consistent with primary bronchogenic carcinoma.
308 Chapter 26 ■

F igu r e 26.4. Extensive lytic carcinomatous deposits sec-

on dary to a primary lesion in th e breast. ( From Pugh , D. G.:
Roen tgen ologic Diagn osis of Diseases of Bon es. New York,
Th omas Nelson & Son s, 1951, p. 277. By permission of th e
Williams & Wilkins Compan y.)

F igu r e 26.6. Metastatic grade 4 ren al cell carcin oma with

sarcomatoid features. Th e fl esh y tan -gray part of th e tumor
correspon ds to th e sarcomatoid differen tiation , an d th e red
portion shows clear cell features.

F igu r e 26.5. Metastatic renal cell carcinoma, clear cell

type, in volvin g th e proximal h umerus in a 69-year-old man .
Th e red-brown color of th e tumor is typical of ren al cell car-
cin oma. Ten years earlier, h e h ad pulmon ary metastases an d
nephrectomy for ren al cell carcin oma.

in terest. Some metastatic carcin omas, such as carci-

n oma of th e breast, may respon d to treatmen t, an d
th e patien t may h ave prolon ged sur vival. It is obviously
importan t to correctly iden tify a prostatic carcin oma
so th at appropriate h ormon al th erapy can be admin -
F igu r e 26.7. Metastatic aden ocarcin oma from th e lun g
istered. H owever, a patien t with a metastasis from forms a destructive mass in the proximal humerus. The
th e lun g or a kidn ey usually h as a poorer progn osis mass also was in volved by ch ron ic lymph ocytic leukemia/
( Figs. 26.8–26.12) . lymphoma.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone
F igu r e 26.8. This metastatic renal cell carcinoma illustrates
how th ese tumors are often times quite vascular.
F igu r e 26.9. Typical appearance of metastatic renal cell car-
cin oma with clear cells in an organ oid pattern .
F igu r e 26.10. Metastatic aden ocarcin oma from a breast pri-
mary tumor. Th e tumor is associated with den se fi brous tissue.
Glandular differentiation is easily recognizable.
309
F igu r e 26.11. Metastatic sarcomatoid carcin oma from th e
lung. A: Pleomorphic tumor cells resemble those seen in pri-
mary h igh -grade spin dle cell sarcoma. B: Tumor cells sh ow
stron g immun oreactivity with keratin . Th is con fi rms th e diag-
n osis of metastatic carcin oma.
With some malign an cies, th e path ologist can accu-
rately pin poin t th e primar y site. Metastatic carcin oma
from th e th yroid, metastatic h epatocellular carci-
n oma, metastatic clear cell carcin oma, an d oth ers are
so ch aracteristic th at a defi n ite diagn osis can be made
( Figs. 28.8–28.10) . H owever, with un differen tiated
aden ocarcin omas or squamous cell carcin omas, th e
path ologist can on ly suggest possible primary sites.
Immun operoxidase stain s h ave become in creasin gly
importan t as an adjun ct in poin tin g toward a primar y
site. An example is th e use of immun operoxidase
stain s for prostate-specifi c an tigen an d prostatic acid
ph osph atase in con fi rmin g a diagn osis of prostatic
carcin oma.
Rarely, a metastatic carcin oma is spindled an d may
simulate the appearan ce of a sarcoma. Most spin dlin g
310 Chapter 26 ■
F igu r e 26.12. Metastatic sarcomatoid carcin oma from a pri-
mary breast tumor. A: An aplastic tumor cells are associated
with reactive bone formation that can lead to a mistaken diag-
nosis of osteosarcoma. B: Tumor cells are diffusely immuno-
reactive with keratin .
carcin omas have plump cells, an d, in th e appropriate
age group, th is possibility sh ould be considered wh en -
ever a diagn osis of a primary sarcoma of bon e is enter-
tain ed. Samplin g of th e specimen may sh ow obvious
epith elial differentiation . Th is problem is especially
common with metastatic hypern eph romas th at may
be sarcomatoid. Immun operoxidase stain s may show
the epith elial ch aracteristics of the tumor in question
( Figs. 26.11 & 26.12) . H owever, n ot all sarcomatoid
carcin omas show epith elial differen tiation, an d some
sarcomas may be positive for keratin. It is importan t to
clin ically rule out the possibility of a sarcomatoid car-
cin oma, especially of th e kidney, before defi n itive sur-
gery is per formed for a presumed sarcoma in an adult.
In spite of exten sive search , h owever, the kidney tumor
may n ot become apparent.
Metastatic carcinoma can also cause confusion
because of other histologic features. Some metastatic
carcinomas produce a large amount of reactive new
bone formation. Occasionally, it may be diffi cult to
know whether the bone is produced by the tumor or
is reacting to it. As indicated previously, some osteosar-
comas may appear epithelial. Hence, this problem can
be very diffi cult. Some metastatic carcinomas produce
reactive osteoclastic proliferation, and the appearance
may simulate that of a giant cell tumor.
TREATMEN T
The treatment of patients with skeletal metastases is
becoming increasingly important. For patients with cer-
tain carcinomas, especially those from the prostate and
breast, both medical and surgical hormonal therapy
are benefi cial. Carcinoma metastatic from the thyroid
may be controlled for prolonged periods with the use of
radioactive iodine. Orthopedic surgical procedures in
combination with radiation or other therapy are often
of much value in the management of carcinoma meta-
static to the skeleton. Because patients with metastatic
carcinoma are living longer, they will more likely receive
aggressive treatment for incipient or actual pathologic
fractures.
PROGN OSIS
As indicated above, the prognosis for metastatic carci-
noma depends on the primary site. A patient with meta-
static renal cell carcinoma whose primary tumor had
been removed previously may live for a long time. How-
ever, patients with renal cell carcinoma presenting with
metastatic skeletal disease have a poorer prognosis.
FIBROU S LESION S
Various benign fi brous proliferations can simulate pri-
mary neoplasms of bone.
METAPH YSEAL FIBROU S D EFECT
Metaphyseal fi brous defect, fi broma, nonossifying
fi broma, and fi brous cortical defect all refer to the
same histopathologic process in bone. The spontane-
ous resolution of most metaphyseal fi brous defects and
their relationship to the growing portions of bones sup-
port the concept that they represent faulty ossifi cation
rather than neoplasm. Although the term metaphyseal
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 311

fi brous defect is preferred, the term fi broma is used inter- I n ci den ce

changeably. Radiographic evidence of small cortical
defects may be found in approximately one-third of
growing children, most commonly in the distal femur.
Few of these lesions pose a signifi cant diagnostic prob-
lem or produce enough symptoms to require surgery.
A few fi broblastic masses, which histologically are
in distinguishable from the innocuous ones, continue
to grow and may produce pathologic fracture of even a
major tubular bone. Patients may have multiple fi brous
defects in one or more extremities.
When there are several metaphyseal fi brous defects,
the patient may have other problems and may have
Jaffe-Campanacci syndrome, as described by Mirra and
colleagues.
Despite the innocuous clinical behavior of metaphy-
seal fi brous defect, its component of benign multinucle-
ated cells still frequently results in its being erroneously
considered a giant cell tumor of bone.
The so-called periosteal desmoid appears to be a
hypocellular variant of the group of fi brous defects. The
term periosteal desmoid is an unfortunate one, suggesting,
as it does, an aggressive process. The lesion is situated
on th e posteromedial aspect of the lower end of the
femur and probably results from an avulsive injury to
the insertion of the aponeurotic sheath from the exten-
sor tendon of the adductor magnus muscle; hence, the
term avulsive cortical irregularity is preferred.
Although metaphyseal fi brous defects are uncommon
in a surgical practice, their true incidence is much
greater because most patients with these defects never
undergo surgery. There were a total of 147 cases in the
Mayo Clinic fi les ( Fig. 26.13) .
Sex
There was a slight male predominance.
Age
In its classic form, metaphyseal fi brous defect is almost
exclusively a disease of childhood and adolescence. The
oldest patient in this series was 37 years old. Sixteen
patients were older than 20 years, and approximately
73% were in the second decade of life.
Loca li za ti on
Every lesion in this series was in a long bone except for
three involving the clavicle and one involving the rib. In
the long bones, almost all lesions were in the metaph-
ysis. Seven lesions involved the diaphysis: three in the
femur, two in the humerus, and one each in the tibia
and fi bula. This probably is related to the growth of the
bone, which pulls away from the stationary lesion.

F igu r e 26.13. Distribution

of metaph yseal fi brous defect
according to age and sex of the
patient and site of the lesion.
312 Chapter 26 ■

Four patients had two lesions each. Two patients each R a di ogr a phi c Fea tu r es
had lesions of the tibia and fi bula, and two patients had
Most metaphyseal fi brous defects have a characteristic
lesions of the tibia and femur. Four patients had poly-
radiographic appearance that is virtually diagnostic.
ostotic involvement with metaphyseal fi brous defects.
When a large tubular bone is affected, the lesion is prac-
One of these patients had skin pigmentation similar
tically always located eccentrically and often produces
to that described in the Jaffe-Campanacci syndrome.
some bulging of the cortical outline, which is usually
Another patient had hemangiomas of soft tissue in
thin over the defect ( Figs. 26.14–26.17) .
addition to the skin pigmentation.
The lucency begins in the metaphysis, near or at the
epiphyseal line, and appears to migrate toward the center
Symptoms of the bone as the epiphyseal region grows away from it.
The inner boundary of the lesion is demarcated by a thin
Metaph yseal fi brous defect of bon e is common ly silen t
or prominent scalloped line of sclerosis (Fig. 26.18). Tra-
clin ically, an d it is discovered in ciden tally wh en a
beculae frequently appear to traverse a defect and give it
region is studied radiograph ically for un related rea-
a multilocular appearance; however, these trabeculae are
son s. Local pain , usually of sh ort duration , is some-
nearly always incomplete and the appearance is actually
times produced an d may be related to small path ologic
produced by the shadows of corrugations on the inner
fractures. O ccasion ally, a patien t presen ts with a path o-
surface of the cavity that houses the defect. Occasionally,
logic fracture.
the entire width of the bone may be affected. The radio-
graphic features are so characteristic that usually only
Physi ca l Fi n di n gs chondromyxoid fi broma is in the differential diagnosis.
Physical examination is of little value in diagnosing
metaphyseal fi brous defect of bone. In rare instances,
Gr oss Pa thologi c Fea tu r es
slight swelling may be observed if the affected bone is
near the sur face of the body. Occasionally, the fracture It is unusual to see intact specimens of metaphyseal
may be a compound one. As mentioned previously, two fi brous defect. Curetted fragments show a granular
patients showed skin pigmentation. lesion that is predominantly brown but has foci of yellow

F igu r e 26.14. Radiograph ( A) and computed tomogram ( B) of a meta-

physeal fi brous defect involving the distal tibia in a 19-year-old woman.
Th e lesion h as a multiloculated appearan ce with some bulgin g of th e
cortex. H owever, th e lesion is con fi n ed to th e bon e.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 313

F igu r e 26.15. Multiple metaph yseal fi brous defects in volv- F igu r e 26.16. Typical radiograph ic appearan ce of metaph y-
ing the distal femur and proximal tibia. The lesions have a seal fi brous defect. Th e metaph yseal lesion is located eccen tri-
ben ign radiograph ic appearan ce. cally, is well demarcated, an d h as a multilocular appearan ce.

F igu r e 26.17. A: Metaph yseal fi brous defect in volvin g th e proximal fi bula in a 10-year-old girl.
Th e surgeon decided n ot to operate. B: Radiograph taken 8 years later sh ows th at th e lesion h as
grown , but still has a ben ign appearan ce.
314 Chapter 26 ■
F igu r e 26.18. Metaphyseal fi brous defect involving the
distal radius. There is some expan sion of th e bone, with a scle-
rotic rim.
discoloration. If the gross specimen is intact, it will have
the characteristic lobulated appearance expected from
the radiographic features. The lesion attenuates the
cortex but does not breach it ( Fig. 26.19) .
H i stopa thologi c Fea tu r es
Metaphyseal fi brous defects ch aracteristically show
a spindle cell proliferation, with a loose storiform
arran gemen t of the cells ( Fig. 26.20) . The arrange-
ment of the spin dled cells is much less compact th an
in true fi brohistiocytic n eoplasms. Th e cells are plump
but sh ow n o hyperch romasia of th e nuclei. Mitotic fi g-
ures may be foun d ( Fig. 26.21) . Very ch aracteristically,
a yellow to brown pigment, which special stains sh ow to
be iron, is presen t with in the spindle cells ( Fig. 26.22) .
Benign gian t cells are always found. Th ese are usually in
clusters but focally may be very prominent an d, out of
context, may suggest th e diagnosis of a gian t cell tumor.
Foam cells containin g lipid are almost always found
in metaphyseal fi brous defect an d produce the yellow
appearance grossly ( Fig. 26.23) .
Typically, metaphyseal fi brous defects do not con-
tain bone. However, small foci of reactive new bone
F igu r e 26.19. Metaph yseal fi brous defect in a 15-year-old
boy was an in ciden tal fi n din g; amputation h ad been n ecessi-
tated by trauma. Th e lesion h ad produced sligh t “expan sion ”
of th e tibia, but its boun daries are discrete.
formation may be seen, especially in association with a
pathologic fracture ( Fig. 26.24) . Spontaneous necrosis
is very unusual unless pathologic fracture has occurred.
With pathologic fracture, the lesion may undergo com-
plete infarctlike necrosis ( Fig. 26.25) .
Because of the presence of giant cells, the lesion
may be mistaken for a giant cell tumor. However, the
giant cells usually are arranged in clusters, unlike that
seen in a true giant cell tumor. The occurrence in the
second decade of life and the characteristic location
in the metaphysis practically rule out the diagnosis of
giant cell tumor. The presence of foam cells, giant cells,
and spindle cells in a storiform arrangement may sug-
gest a diagnosis of fi brohistiocytic neoplasm. Indeed, at
least some of the so-called fi brous histiocytomas of bone
reported in the literature probably represent metaphys-
eal fi brous defects in unusual locations.
Tr ea tmen t
If one is confi dent of the radiographic diagnosis and
the structural integrity of the bone is not in question,
no treatment is needed and the progress of the lesion
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 315

F igu r e 26.21. Metaph yseal fi brous defect. H igh -power view

sh ows th e plump spin dle cells an d mitotic activity, wh ich can
be worrisome for sarcoma.

F igu r e 26.20. A: Low-power view of metaph yseal fi brous

defect shows a cellular fi brogenic lesion with scattered multi-
nucleated gian t cells. Alth ough it resembles gian t cell tumor,
the multinucleated giant cells are sparser than in an average
gian t cell tumor. B: H igh-power view sh ows th at th e tumor F igu r e 26.22. H emosiderin deposition with in a metaph yseal
cells are arran ged in wh orled bun dles with a vague storiform fi brous defect.
pattern, giving them a fi brohistiocytic appearance.

can be followed by repeat radiographs. If the diagnosis

is uncertain, diagnosis and therapy can be accom-
plished with one surgical procedure. The lesion is read-
ily eradicated by conservative surgical means, ordinarily
curettage.

Pr ogn osi s
Most metaphyseal fi brous defects are thought to
undergo spontaneous regression. Patients with multiple
lesion s are at risk for developing multiple pathologic
fractures. However, these tend to regress as the skeleton F igu r e 26.23. Prominent nests of foam cells in fi broblastic
matures. stroma with in a metaph yseal fi brous defect.
316 Chapter 26 ■

F igu r e 26.24. Reactive n ew bon e formation with in meta-

physeal fi brous defect can be seen with or without previous
pathologic fracture.

F igu r e 26.25. Necrosis in th is metaph yseal fi brous defect

was associated with a pathologic fracture.

PERIOSTEAL D ESMOID (D ISTAL IRREGU LARITIES

OF TH E FEMU R SIMU LATIN G MALIGN AN CY,
AVU LSIVE CORTICAL IRREGU LARITY)

Periosteal desmoid refers to a fi brous cortical defect that

typically occurs on the posteromedial aspect of the dis-
tal femur. They are usually incidental fi ndings on radio-
graphs made for another reason. The cortex shows
some irregular destruction, and this may suggest a diag-
nosis of malignancy. However, the typical location and
the small size should lead to the correct diagnosis. If
the lesion is removed, the histologic features are those
of fi brous replacement of a portion of the cortex. A few Figu re 26.26. A: So-called cortical desmoid of the medial
side of the distal femur in a 12-year-old boy. The area was associ-
benign giant cells may be seen. It is important to be ated with vague pain for 2 months. Resection was performed
aware of this condition to avoid an unnecessary biopsy because of the suggestion that the lesion was malignant. B: Simi-
( Figs. 26.26 & 26.27) . lar lesion, essentially an incidental fi nding, in a 14-year-old girl.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 317

F igu r e 26.27. Non n eoplastic tissue from a cortical desmoid,
sometimes called a “n on tumor.” Rath er h ypocellular fi brous
tissue is next to somewhat irregular cortical bone. The lesion
involved the distal part of the femoral shaft.
F igu r e 26.28. “Xanth oma” of bon e was removed by curet-
tage in pieces, aggregatin g 7 cm in diameter, from th e ilium
of a 31-year-old man . Ch olesterol clefts an d ben ign gian t cells
were prominent th rough out. At 15-year follow-up, the patient
was well.

XAN TH OMA OF BON E

The term xanthoma of bone is used when the biopsy

specimen shows either a collection of foam cells inter-
mingled with innocuous-appearing spindle cells or cho-
lesterol crystals with foreign body reaction ( Fig. 26.28) .
A lesion may have both features. Forty-three lesions in
the Mayo Clinic fi les were classifi ed as xanthomas.
These lesions tend to involve the fl at bones such as
the skull or innominate bone. They may be painful or
discovered as an incidental radiographic fi nding. Radio-
graph s usually show a well-circumscribed lytic defect
with a sclerotic rim ( Fig. 26.29) . Occasionally, the lesion
is completely surrounded by a sclerotic rim. Grossly, the
lesion is bright yellow. As mentioned above, microscopi-
cally, the lesion shows cholesterol crystals, foam cells,
and giant cells.
The differential diagnosis includes many conditions F igu r e 26.29. “Xanth oma” producin g rarefaction in the ala
in which foam cells may be found, and the diagnosis of of th e ilium. Th is was an in ciden tal, asymptomatic fi n din g in
a 60-year-old man. Xanthic, fi brotic central rarefi ed zone was
xanthoma is valid only if no other histologic features surroun ded by bon e sh owin g n on specifi c sclerosis.
are found. Fibrous dysplasias, metaphyseal fi brous
defects, and giant cell tumors all can contain promi-
nent foam cells. The location and the radiographic fea- quite small, and the cytoplasm is abundant. The nuclei
tures of some of these lesions suggest that they are the of the cells of hypernephroma are usually larger and
end product of an underlying lesion, especially fi brous have nucleoli.
dysplasia and metaphyseal fi brous defect. It is possible
that an occasional giant cell tumor may also undergo
FIBROU S D YSPLASIA
regression to become a xanthoma. The most important
differential diagnosis involves metastatic clear cell car- Fibrous dysplasia is probably the result of an aberration
cinoma, especially hypernephroma. On limited biopsy in the development of bone. It is characterized by the
material, especially with fi ne-needle aspiration, the occurrence of one, a few, or numerous discrete skele-
foam cells may be mistaken for the cells of a clear cell tal defects. Yellow or brown patches of cutaneous pig-
carcinoma. However, the nuclei of foam cells are usually mentation may accompany the bone lesions, especially
318 Chapter 26 ■
in patien ts with severe disseminated disease. When, in
addition to cutaneous pigmentation, such polyostotic
disease is accompanied by signs of endocrine abnormal-
ity, especially precocious puberty in girls, the condition
is commonly called Albright syndrome.
Fibro-osseous dysplasia is a term that is gaining accep-
tance for many of the defects involving the base of the
skull and the jawbones. Dysplastic lesions at these sites
often contain such an abundance of osseous trabeculae
intermingled with the fi brous tissue that they are dis-
tinctly hard and may cause a dense shadow in the radio-
graph. Many, if not all, the so-called osteofi bromas and
fi bro-osteomas in these locations are in fact examples of
fi bro-osseous dysplasia.
I n ci den ce
There were a total of 671 fi brous dysplasias in the Mayo
Clinic fi les ( Fig. 26.30) . This probably does not rep-
resen t the true incidence because many patients with
fi brous dysplasia are asymptomatic.
Sex
In th e overall group of patien ts with fi brous dysplasia,
fem ales predomin ated sligh tly. H owever, th ere were
distin ct differen ces in sex distribution wh en differ-
en t sites of in volvemen t with fi brous dysplasia were
con sidered. Th ere was a distin ct fem ale predomi-
n an ce in th e group of patien ts with in volvem en t of
th e jaws an d lon g an d fl at bon es, wh ereas th ere was
male predomin an ce in th e group with rib an d skull
disease.
Age
The age distribution of patients with fi brous dysplasia
involving different sites is given in Figure 26.31. The
majority of patients with fi brous dysplasia were in the
second and third decades of life. However, patients with
fi brous dysplasia of the ribs tend to be older. Th e expla-
nation of this discrepancy probably is that older patients
are more likely to have chest radiography, which shows
these incidental fi ndings.
Loca li za ti on
Patients with fi brous dysplasia were divided into four dis-
tinct groups: those with involvement of the jaws, those
with involvement of the skull bones, those with involve-
ment of the ribs, and those with involvement of all other
bones. The largest single group was the last, and of this
group, the proximal femur was by far the most com-
mon site. The jawbones accounted for the second larg-
est group, and of these, the maxilla was involved much
more commonly than the mandible.
Sixty-four patients had polyostotic fi brous dysplasia.
Several patients with involvement of the jawbones had
lesions of both the mandible and maxilla; these were not
counted as examples of polyostotic fi brous dysplasia.
F igu r e 26.30. Distribution
of fi brous dysplasia accordin g
to age an d sex of th e patien t
and site of the lesion.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone
F igu r e 26.31. Distribution of
fi brous dysplasia according to
age of the the patien t and site
of the lesion.
Symptoms
Many lesions of fi brous dysplasia are asymptomatic and
are incidental fi ndings on radiographs. This is espe-
cially true of the lesions of the ribs. Fibrous dysplasia
may present with a pathologic fracture, especially in
the femoral neck region. Some examples of fi brous dys-
plasia may produce swelling, especially in the region of
the jaw and the skull. Occasionally, fi brous dysplasia in
other locations can also become massive.
Physi ca l Fi n di n gs
In volvement of the skull and the jawbones with fi brous
dysplasia may show deformities. Patients with polyostot ic
fi brous dysplasia may have characteristic café-au-lait
pigmentation of the skin.
Some patients with fi brous dysplasia have associated
intramuscular myxomas, as described by Mazabraud.
There are four cases of such patients in the Mayo Clinic
fi les. However, fi brous dysplasia was confi rmed histo-
logically in only two of these patients; in the other two,
radiographs supported the diagnosis of fi brous dyspla-
sia and there was histologic confi rmation of soft-tissue
myxomas.
R a di ogr a phi c Fea tu r es
The defects of fi brous dysplasia are usually well-defi ned
zones of rarefaction. The rarefi ed zone is often sur-
rounded by a narrow rim of relatively sclerotic bone
319
( Figs. 26.32–26.37) . Expansion with thinning of the
cortex is especially likely to occur in narrow bones such
as the ribs. Occasionally, the lesion produces a large
expansile mass that bulges into soft tissues. Lesions with
a large osseous component, such as are commonly seen
around the base of the skull and maxilla, are likely to be
relatively radiopaque. This characteristic is accentuated
if the lesion bulges into an air-containing sinus. Some
examples of fi brous dysplasia contain large amounts of
cartilage, which may be evident on radiographs as ring-
like or dotlike calcifi cation. This is especially common in
the femoral neck region. Rarely, an example of fi brous
dysplasia has a superimposed aneurysmal bone cyst.
This may give rise to an aggressive-looking radiographic
appearance that suggests the diagnosis of sarcoma.
Gr oss Pa thologi c Fea tu r es
Examin ation sh ows considerable variation in the
lesion s of fi brous dysplasia, but th e average lesion is
well defi n ed and composed of den se fi brous tissue
( Figs. 26.38 & 26.39) . Usually embedded in th is fi brous
tissue are en ough small trabeculae of bone to impart a
distinctly gritty quality. H owever, rarely is the ossifi ca-
tion suffi cien t to require decalcifi cation before a sec-
tion is made. Slight to exten sive cyst formation may be
present, wh ereas lesion s with pronoun ced ossifi cation
may resemble osteoma. Lesions contain in g cartilage
may have small n odules of well-defi n ed islands of carti-
lage or the cartilaginous component may dominate th e
appearan ce.
320 Chapter 26 ■
F igu r e 26.32. Typical radiograph ic ch an ges of in tramedul-
lary fi brous dysplasia exhibiting convex lateral outward bow-
ing of the mid-femoral shaft. The lesion extends from the left
femoral neck to the distal femoral diaphysis.
H i stopa thologi c Fea tu r es
Th e major feature is a proliferation of fi broblasts
th at produce a den se collagen ous matrix. The fi bro-
blasts tend to be plump; they show n o cytologic atypia.
Mitotic fi gures are extremely un common. In an other-
wise typical fi brous dysplasia, on e may fi nd large areas
without bon e production . In th ese areas, th e spindle
cells may form a storiform pattern. Ch aracteristic
metaplastic bon e formation is seen in fi brous dyspla-
sia. Typically, the bon y trabeculae sh ow no osteoblas-
tic rimming. H owever, the presence of osteoblastic
rimming does not rule out the possibility of fi brous
dysplasia. The bon y trabeculae form a woven bone pat-
tern un like the arch itecture in mature bone. The bon y
trabeculae are arranged in a meaningless fash ion and
may have peculiar shapes characterized as “Chinese
ch aracters” ( Figs. 26.40–26.46) . Occasion ally, fi brous
F igu re 26.33. Typical appearance of a femur in a patient with
polyostotic fi brous dysplasia. The deformity in the proximal
femur has been referred to as “shepherd’s crook deformity.”
dysplasia shows trabecular bone formation , especially in
th e jawbones. The bony trabeculae may form roun ded
ossicle-like structures resembling psammoma bodies
( Fig. 26.47) . Th is pattern is especially promin en t in th e
base of the skull and may lead to a mistaken diagn osis
of men in gioma. However, this pattern may also be seen
in other location s.
Collection s of foam cells almost always occur in
fi brous dysplasia an d may be mistaken for metastatic
clear cell carcin oma, especially in limited biopsy sam-
ples. Clusters of gian t cells are also common ly seen
in fi brous dysplasia ( Fig. 26.48) . O ccasion ally, on e
may fi n d large collection s of gian t cells simulatin g th e
appearan ce of a true gian t cell tumor.
Some examples of fi brous dysplasia show marked
myxoid change of the matrix. The lesion is extremely
hypocellular, and characteristic areas are seen only
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 321

F igu r e 26.34. A: An teroposterior radiograph of th e

right hip sh ows a lytic lesion in th e femoral n eck with a
narrow zon e of tran sition an d suggestion of h azy groun d-
glass density typical of fi brous dysplasia. Coronal T1- ( B)
and T2- ( C) weighted magnetic resonance images show
that the lesion has fl uidlike signal characteristics, with
homogen eous hyperin ten se sign al on T2 image. The mag-
netic reson an ce imagin g features are n on specifi c; h owever,
when interpreted in conjunction with the radiographs, the
fi n din gs are typical of fi brous dysplasia, with suggestion of
cystic ch an ge in th e lesion . Th e h istologic features con -
fi rmed degen erative cystic ch an ge.

at the periphery ( Figs. 26.49 & 26.50) . Many of the
fi bromyxomas reported in the literature are undoubt-
edly examples of myxoid fi brous dysplasia.
Large islands of cartilage may dominate the histologic
appearance of fi brous dysplasia. The cartilage forms
rounded nodules or, occasionally, plate-like structures
that resemble epiphyseal plates ( Fig. 26.51) . Second-
ary aneurysmal bone cyst areas may be seen engrafted
upon fi brous dysplasia.
Tr ea tmen t
Treatmen t sh ould be con ser vative. Th e lesion s com-
mon ly stop growin g wh en th e patien t reach es puberty.
Th erapy sh ould be directed at restorin g th e n ormal
322 Chapter 26 ■

F igu r e 26.35. A: Lateral radiograph of fi brous dysplasia forming a mildly lucent lesion in the
distal diametaphysis of the left femur, with a thin rim of surrounding sclerosis and associated corti-
cal th in n in g an d un displaced path ologic fracture. B: Magn etic reson an ce imagin g sh ows th at th e
lesion scallops the inner sur face of the cortex, resulting in thinning but no cortical breakthrough.

F igu r e 26.36. A: Fibrous dysplasia of th e orbital bon e area on th e righ t side in a 14-year-old girl.
Sh e h ad n oted increasin g proptosis for 9 years. Th e skull, in cludin g its base, is a common site of
fi brous dysplasia. B: Computed tomography aided in delimitin g the zon e of in volvement.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 323

F igu r e 26.37. Computed tomograms of a 68-year-old man. A: Pelvis. The appearance is that of
fi brous dysplasia. B: Th igh . A mass lesion in the muscle had been growin g slowly for 20 years. Biopsy
sh owed a myxoma. Rarely, a myxoma of skeletal muscle is associated with fi brous dysplasia of th e
skeleton .

F igu r e 26.38. Fibrous dysplasia involving the prox-

imal femur in a 66-year-old man. There is fi brous
replacemen t of the marrow. Th e lesion is extremely
well circumscribed, and the proximal margin is
sh arply demarcated from bon e. Th e cen tral golden
yellow area corresponds to degenerative change.

F igu r e 26.39. Fibrous dysplasia in another com-

mon location , a rib. Note th e marked expan sion
of th e bon e with a red, gran ular-appearin g lesion .
Alth ough th e bon e is expan ded, th e cortex is still
intact.

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324 Chapter 26 ■
F igu r e 26.40. A: Typical low-power appearan ce of fi brous
dysplasia. The lesion contains branching and anastomosing
irregularly shaped trabeculae of osteoid. B: A hypocellular to
moderately cellular fi brous stroma surroun ds th e trabeculae
of bon e. C: Blan d oval to spin dle-sh aped stromal cells without
cytologic atypia.
F igu r e 26.41. Another example of fi brous dysplasia shows
th e ch aracteristic pattern of woven bon e formation an d sh ort
spin dle cells within th e stroma.
F igu r e 26.42. Variable stromal cellularity with in fi brous dys-
plasia. Hypocellular spindle cell stroma on the right merges
with hypercellular area on the left.
F igu r e 26.43. Fibrous dysplasia frequen tly in volves th e rib,
as in this example. The tumor forms an expansile mass that
pushes into surrounding soft tissue.
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 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 325

F igu r e 26.47. In th is example of fi bro-osseous dysplasia, th e

F igu r e 26.44. Bone in this fi brous dysplasia has a pagetoid tumor produces sph erical masses of osteoid. Th is pattern is
appearance. often seen in lesions at the base of th e skull and h as been mis-
taken for men in gioma.

F igu r e 26.48. Clusters of foam cells are common in fi brous

F igu r e 26.45. In this example of fi brous dysplasia, woven dysplasia.
bon e appears to be emergin g from th e fi brous stroma.

F igu r e 26.49. Diffuse myxoid change in the stroma may be

seen in fi brous dysplasia. Th is fi eld con tain s on ly a solitary
n odular mass of woven bon e. It may be very diffi cult to make a
F igu r e 26.46. Abun dan t collagen separates stromal cells in diagnosis when the biopsy specimen contains only the myxoid
th is example of fi brous dysplasia in volvin g a rib. area and no bone.

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326 Chapter 26 ■
F igu r e 26.50. H igh -power view of myxoid ch an ge with in th e
fi brous stroma of fi brous dysplasia.
F igu r e 26.51. Islan ds of cartilage may also be seen in fi brous
dysplasia. Typical areas of fi brous dysplasia are on the left.
con fi guration wh en th e skull or jawbon es are affected.
In large bon es, deformity caused by th e disease may
require correction . Radiation th erapy is probably
of n o value an d in troduces a h azard of sarcomatous
ch an ge.
Pr ogn osi s
The prognosis in fi brous dysplasia is good. Deforming
lesions of the jawbones or skull may sometimes recur,
but these lesions ordinarily respond favorably to addi-
tional conservative surgical therapy. Some of the large
lesions in weight-bearing bones require curettage and
F igu r e 26.52. Computed tomogram of the skull in a 66-year-
old woman with sarcoma arisin g in fi brous dysplasia. Th e
patient had received radiation to this site 54 years previously.
bone grafting for maintenance of function. Patients
with extensive disease of the ribs may experience
respiratory problems. In our fi les, one patient with
polyostotic fi brous dysplasia of the ribs died of respira-
tory complications.
SARCOMAS IN FIBROU S D YSPLASIA
Rarely, malign an cies can arise in fi brous dysplasia
( Figs. 26.52–26.54) . In 1972, H uvos an d coauth ors
documen ted, from th e fi les of th e Memorial H ospi-
tal in New York, 12 examples of sarcomas arisin g in
fi brous dysplasia. O f th ese patien ts, on ly on e h ad previ-
ously h ad radiation treatmen t. Ruggieri an d coauth ors
reported on 28 cases from th e Mayo Clin ic fi les. Th ere
were 1,122 examples of fi brous dysplasia in th is series,
wh ich in cluded cases seen in con sultation . Th irteen
of th e patien ts h ad previous radiation th erapy; h en ce,
th ese sarcomas can be con sidered postradiation .
Th ere are n ow 19 examples of sarcomas associated
with fi brous dysplasia in th e Mayo Clin ic fi les. Twelve
patien ts h ad mon ostotic fi brous dysplasia, an d seven
h ad polyostotic fi brous dysplasia. O f th ese 19 patien ts,
12 previously h ad radiation as part of th e treatmen t
of fi brous dysplasia. Seven of th e lesion s in volved th e
jawbon es an d two th e skull. Twelve of th e secon dary
sarcomas were con sidered osteosarcoma, four were
con sidered fi brosarcoma, an d th ree were ch on dro-
sarcomas. O n e of th e ch on drosarcomas was of th e
clear cell type. Th e progn osis for th ese patien ts was
poor. O n e patien t with a lesion of th e maxilla was alive
with out eviden ce of disease 11.5 years later. Fourteen
patien ts h ave died of disease at in ter vals ran gin g from
4 mon th s to 28 years. No follow-up is available for four
patien ts. It used to be th ough t th at sarcomas arisin g
in fi brous dysplasia are extremely un usual with out
previous radiation , but it n ow appears th at sarcomas
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 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone
F igu re 26.53. High-grade osteosarcoma arising in the proxi-
mal tibia in a 41-year-old man with polyostotic fi brous dysplasia
associated with Albright syndrome. A: Radiograph shows an
aggressive-appearing lytic area within the underlying fi brous
dysplasia. B: Magnetic resonance imaging highlights the
destructive growth pattern with extension into soft tissue.
327
F igu r e 26.54. Histologic features corresponding to the
tumor in Figure 26.53. A: Proximal part of th e tibial tumor
sh ows features typical of fi brous dysplasia. B: High-grade oste-
osarcoma correspon din g to th e lytic area of th e tumor. Th e
patient had not been treated with radiation. He was alive with-
out eviden ce of disease 14 years after treatmen t th at in cluded
surgery an d ch emoth erapy.
do arise spon tan eously in fi brous dysplasia. H owever,
th e in ciden ce is still low ( Fig. 26.54) .
OSTEOFIBROU S D YSPLASIA
Osteofi brous dysplasia, originally described as ossi-
fying fi broma by Kempson in 1966, h as generated
much con troversy recently. Kempson believed that it
was an aggressive lesion, although it was h istologically
similar to fi brous dysplasia. Campan acci th ought th at
th e lesion was benign and un derwent spon taneous
regression . He preferred th e term osteofi brous dysplasia
( Figs. 26.55–26.57) .
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328 Chapter 26 ■

F igu r e 26.55. A: Lateral radiograph sh ows a mixed lytic an d

sclerotic, mildly expan sile lesion in volvin g th e cortex of th e prox-
imal tibial diaphysis an teriorly in a skeletally immature patien t.
B: Axial T2-weighted magnetic resonance image confi rms that
th e lesion is in tracortical. C: Sagittal T1-weigh ted magn etic reso-
n an ce image illustrates the an atomical extent of the lesion. Th ese
imagin g features are ch aracteristic of osteofi brous dysplasia.

O steofi brous dysplasia h as several peculiarities, th e
most pron oun ced bein g its ten den cy to in volve th e
tibia an d, less often , th e fi bula. It also ten ds to in volve
th e cortex of th e bon e. Alth ough it is predomin an tly
a disease of patien ts in th e fi rst two decades of life,
even adults with th e disease h ave been described.
Radiograph s sh ow multiple lucen cies in volvin g th e
an terior cortex of th e tibia, with in ter ven in g sclero-
sis ( Figs. 26.55 & 26.56) . Th is radiograph ic appear-
an ce is very similar to th at of adaman tin oma of th e

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 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 329

F igu r e 26.56. Osteofi brous dysplasia in

an infant. A: Radiograph of a tibia shows
the classic features. The bone is exten-
sively in volved, with an terior bowin g an d a
pathologic fracture. B: Thirteen years later,
radiograph of th e tibia sh ows “h ealing” of
the lesion.

F igu r e 26.57. Low-power ( A) an d h igh -power ( B) views of osteofi brous dysplasia. Irregular,
immature bon e trabeculae are surroun ded by promin en t osteoblastic rimmin g. Th e bon e is sur-
roun ded by a fi brous stroma with no cytologic atypia.

tibia. Several studies h ave sh own th e presen ce of ker-
atin -positive cells in osteofi brous dysplasia. Th is h as
led to th e suggestion th at osteofi brous dysplasia an d
adaman tin oma may be related con dition s. O n e study
postulated th at osteofi brous dysplasia is a regressed
form of adaman tin oma. Th e oth er possibility sug-
gested is th at osteofi brous dysplasia may progress to
adaman tin oma. In studies in volvin g osteofi brous dys-
plasia of th e lon g bon es, n o progression of th is con di-
tion in to adaman tin oma was n oted.

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330 Chapter 26 ■

As noted above, osteofi brous dysplasia involves the
cortex, whereas classic fi brous dysplasia is a disease
of the medullary bone. The lesion is composed of a
spindle cell proliferation that may have a storiform pat-
tern. The bony trabeculae show prominent osteoblastic
rimming, in contrast to that seen in fi brous dysplasia
( Fig. 26.57) . The lesion also tends to mature toward the
periphery and seems to merge with cortical bone, giv-
ing rise to a zonation phenomenon.
The relationship between osteofi brous dysplasia
and adamantinoma, if any, is still unclear. Osteofi brous
dysplasia probably is a form of fi brous dysplasia that is
confi ned to the tibia and fi bula and has a tendency to
involve the cortex.
FIBROCARTILAGIN OU S MESEN CH YMOMA
Fibrocartilaginous mesenchymoma was fi rst described by
Dahlin and coauthors in 1984. These authors described
fi ve cases of an entity that had previously been classifi ed
with fi brous dysplasia. Because of a tendency for local
recurrence, the term fi brocartilaginous mesenchymoma with
low-grade malignancy was used. Bulychova and coauthors
published 12 cases, including those of 1984. Longer term
follow-up suggested that although the lesion may recur,
there has been no instance of malignant behavior. Hence,
the more noncommittal term fi brocartilaginous mesenchy-
moma of bone was thought to be more appropriate.
Fibrocartilaginous mesenchymoma is one of the
rarest lesions of bone. The Mayo Clinic fi les contain only
one example, a case involving the pubis in a 19-year-old
man. The lesion does affect young people. The proxi-
mal fi bula is one of the sites of predilection.
O n radiograph s, th e lesion s ten d to in volve th e meta-
ph yseal portion of th e bon e abuttin g on th e growth
plate. Th e lesion s are predomin an tly lucen t but h ave
some min eralization , suggestin g a cartilagin ous com-
pon en t ( Fig. 26.58) .

F igu r e 26.58. A: Fibrocartilaginous mesenchymoma involving the proximal fi bula. The lesion
exten ds up to th e articular cartilage an d expands th e bon e. Large areas of min eralization are seen.
B: Gross specimen of a fi brocartilaginous mesenchymoma involving the proximal fi bula. The lesion
is large and extends close to, but does not encroach on, the open epiphyseal plate. Large carti-
laginous islands are obvious. ( Case provided by Dr. Vivienne Tobias, Prince of Wales Children’s
Hospital, Ran dwick, New South Wales, Australia.)

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 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone
Microscopically, the lesion shows a combination of
cartilage, bone formation, and spindle cell proliferation.
The cartilage has a very characteristic arrangement in
plates with enchondral bone formation, simulating the
appearance of epiphyseal plates ( Fig. 26.59) . A densely
cellular spindle cell proliferation is found between well-
formed bony trabeculae. The spindle cells are elon-
gated and show little collagen production, unlike the
appearance in fi brous dysplasia ( Fig. 26.60) .
Man y of th e lesion s h ave n ot been adequately treated
surgically. Alth ough local recurren ces were n ot un com-
mon , th ese were usually man aged with repeat excision .
F igu r e 26.59. Low-power view of fi brocartilaginous mes-
ench ymoma. The fi eld is domin ated by a plate of cartilage.
O ccasion ally, the cartilage h as features similar to th ose of epi-
physeal cartilage.
F igu r e 26.60. An oth er area in fi brocartilagin ous mesen ch y-
moma. Un like fi brous dysplasia, th e spin dle cells are arran ged
in fascicles and are less plump.
331
No patien t in th e series described by Bulych ova an d
coauth ors h as died of disease.
MYOFIBROMA (IN FAN TILE MYOFIBROMATOSIS,
CON GEN ITAL FIBROMATOSIS)
Infantile myofi bromatosis or congenital fi bromatosis
is a condition that usually affects infants and can be
present as a solitary subcutaneous lesion or as multiple
lesions involving the subcutaneous tissue and other
organs. In the multiple form, it has been known that
the skeleton is frequently involved. In the skeleton, the
lesion tends to form lucent defects in the metaphyseal
region of long bones ( Fig. 26.61) . Both the solitary and
multiple forms of myofi bromatosis are associated with a
good prognosis, and the lesions tend to regress sponta-
neously ( Fig. 26.62) . In the rare form in wh ich visceral
organs such as the lung, liver, or gastrointestinal tract
are involved, the prognosis is poor.
It has been recognized recently that the solitary form,
myofi broma, can involve the skeleton. Inwards and
coauthors have described 14 cases, 13 of which involved
the craniofacial bones. The lesions tend to form lucent
defects with a sclerotic border.
F igu r e 26.61. Myofi broma formin g a large solitary diameta-
physeal lesion in a 3-year-old boy. It is well circumscribed and
h as a scalloped edge.
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332 Chapter 26 ■

F igu r e 26.62. Skeletal survey of a newborn with multicentric myofi bromatosis ( congenital fi bro-
matosis) . A: Skeletal survey sh owed typical in volvemen t of th e skeleton , with bilateral, symmetrical
lytic defects involving the metaphyseal regions of the long bones. B: Radiographic appearance of the
limbs approximately 2.5 years later. Note resolution of th e lesion s. ( Case provided by Dr. Roger E.
Riepe, Marsh fi eld Medical Cen ter, Marsh fi eld, Wiscon sin .)

F igu r e 26.63. A: Myofi broma con tain in g wh orls an d n odular bun dles of myoid cells. B: O ccasion -
ally, the myoid cells are set in a pale blue background, imparting a chondroid appearance.

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 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone
F igu r e 26.64. Branching dilated blood vessels in myofi bro-
mas can produce a h eman giopericytomatous appearan ce.
Microscopically, myofi bromas are composed of
whorls an d n odules of plump spindle cells with a
myxoid backgroun d ( Fig. 26.63) . A prominen t vascular
proliferation is seen between th e n odules. Th e vascular
spaces are large, gapin g, an d do n ot h ave a muscular
wall. In some areas, the n odules of spin dle cells are
associated with smaller spindling cells th at have a
very ch aracteristic h eman giopericytomatous vascular
pattern ( Fig. 26.64) . Th e spin dle cells h ave pink cyto-
plasm th at imparts a myogenic quality.
It is important to recognize myofi bromas because
they are frequently mistaken for low-grade sarcoma.
Follow-up information in the cases of myofi bromatosis
of skeleton is limited, but the lesions do not seem to
recur after excision. Because lesions of multiple myo-
fi bromatosis regress spontaneously, solitary ones may
also do so.
CYSTIC LESION S OF BON E
Various lesions that grossly appear cystic occur in bone
and may simulate primary neoplasms.
AN EU RYSMAL BON E CYST
Features th at make it logical to exclude an eur ysmal
bon e cyst from th e n eoplastic categor y in clude th e
obser vation th at th e lesion h as been kn own to regress
after in complete removal. Recen t cytogen etic an d
molecular gen etic studies, h owever, h ave sh own th at
man y of th ese lesion s con tain USP6 fusion gen es, most
common ly CDH11-USP6. Th ese fi n din gs len d support
333
to th e n otion th at an eur ysmal bon e cysts are n eo-
plastic rath er th an reactive lesion s. Th e cause of th is
stran ge process in bon e is un kn own , alth ough th ere
are several examples of an eur ysmal bon e cyst th at
apparen tly arose followin g a fracture. It is similar to
an d probably related to oth er reactive n on n eoplastic
processes, in cludin g gian t cell reparative gran uloma
of th e jaws, traumatic reaction s obser ved in perios-
teum an d bon e, an d even fl orid h eterotopic ossifi ca-
tion . An eur ysmal bon e cyst may arise de n ovo in bon e;
th at is, a defi n ite preexistin g lesion can n ot be dem-
on strated in th e tissue. Th e data sh own h ere relate
to such cases. Areas similar to an an eur ysmal bon e
cyst are foun d in various ben ign con dition s, in cludin g
gian t cell tumor, ch on droblastoma, ch on dromyxoid
fi broma, an d fi brous dysplasia. Rarely, even malign an t
tumors of bon e may con tain such ben ign areas. O bvi-
ously, recogn ition of an un derlyin g process is impor-
tan t because th e clin ical capability will be dictated by
th at process.
I n ci den ce
In the Mayo Clinic series, aneurysmal bone cyst was just
about half as frequent as giant cell tumor ( Fig. 26.65) .
Other lesions, such as giant cell tumor, that contain
areas of aneurysmal bone cyst have been categorized as
a preexisting condition. Hence, there is no record of the
relative incidence of primary versus secondary aneurys-
mal bone cyst in this series. In a series of 123 cases of
aneurysmal bone cyst reported by Martinez and Sissons,
approximately 28% were considered secondary.
Sex
Approximately 53% of the 377 patients in the Mayo
Clinic series with aneurysmal bone cyst were females.
Age
Just over 75% of patients with aneurysmal bone cyst were
in the fi rst two decades of life. In contrast, only 15% of
patients with giant cell tumor of bone were in the fi rst
two decades of life. The oldest patient with aneurysmal
bone cyst was older than 65 years.
Loca li za ti on
Th e region aroun d th e kn ee, in cludin g th e distal femur
an d proximal tibia, is th e most common site for an eu-
rysmal bon e cyst. H owever, practically all portion s of
th e skeleton may be in volved. Th e spin e was frequen tly
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334 Chapter 26 ■
F igu r e 26.65. Distribution of aneurysmal bone cyst according to age and sex of the patient
and site of the lesion.
in volved, with lesion s in th e cervical an d th oracic
portion bein g equally common . In th e lon g bon es,
an eurysmal bon e cysts ten d to in volve th e metaph ysis,
wh ereas in th e vertebrae th ey ten d to in volve th e pos-
terior elemen ts.
Symptoms
Pain and swelling are the most common complaints.
Rarely, pathologic fracture may produce the presenting
symptom. Patients with involvement of the vertebrae
may present with paresthesias and numbness of the
extremities.
Physi ca l Fi n di n gs
A mass lesion may be palpated. Neurologic signs may be
elicited in patients with spinal cord compression.
R a di ogr a phi c Fea tu r es
Th e typical radiograph ic appearan ce is an area of
lucen cy situated eccen trically in th e medullary cavity
in th e metaph ysis of a lon g bon e. Less common ly,
th e lesion may be situated cen trally in th e medullary
cavity. Much less common ly, th e lesion may appear
to arise in th e cortex or even in th e periosteum. Th e
lesion ten ds to in volve th e cortex an d may destroy it
completely. Th e lesion may th en bulge in to th e soft
tissue, wh ere it usually forms a th in rim of calcifi cation
( Figs. 26.66–26.68) .
Most an eurysmal bon e cysts are completely lytic,
but a few con tain fain t traces of min eral. Th e margin s
may be well defi n ed or poorly defi n ed. In approxi-
mately on e-h alf of th e cases, th e radiograph ic features
suggest a ben ign process. In a small proportion , th e
features suggest a malign an t lesion an d in th e rest, th e
features are in determin ate. Computed tomograph y
an d magn etic reson an ce imagin g may sh ow in tern al
septation . More often , multiple fl uid–fl uid levels are
seen because of th e separation of serum an d blood
products with in th e lesion ( Figs. 26.69–26.71) . Com-
puted tomograph y also h igh ligh ts th e calcifi ed rim at
th e periph er y.
Gr oss Pa thologi c Fea tu r es
Frequen tly, th e lesion is curetted, an d fragmen ts of
red, brown gran ular material are received in th e labo-
rator y. A strikin g feature is th e disparity between th e
size of th e lesion seen on radiograph s an d th e amoun t
of tissue received in th e laboratory. If th e lesion is
received in tact, blood-fi lled spaces separated by septa
of various th ickn esses are seen . Rarely, th e en tire
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 335

lesion appears solid, with out eviden ce of cavities an d

septation ( Figs. 26.72 & 26.73) .

H i stopa thologi c Fea tu r es

F igu r e 26.66. An eurysmal bon e cyst of th e distal radius. Th e
tumor forms an eccentrically placed mass in the metaphysis.
Th e essen tial feature is th e presen ce of cavern oma-
tous spaces, th e walls of wh ich lack th e n ormal fea-
tures of blood vessels. Th in stran ds of bon e are often
presen t in th e fi brous tissue of th ese walls. Som etimes,
th e min eralizin g formed elemen ts h ave a ch on droid
aura, wh ich is un usual in an y oth er lesion of bon e. It
is also un usual for th e spaces to h ave an en doth elial
lin in g. Th e septa almost in variably con tain gian t cells.
Nearly all an eur ysmal bon e cysts h ave more solid
areas th at con tain spin dle cell proliferation , wh ich
is loosely arran ged. Th e spin dle cells may sh ow brisk
mitotic activity, but atypical mitotic fi gures are n ot
seen . Th e cells also lack cytologic atypia. Clusters of
gian t cells, or even sh eets of gian t cells, may be seen .
Capillar y proliferation is also foun d. Som e of th e
larger septa h ave spin dle cell proliferation with abun -
dan t bon e formation . Th e bon y trabeculae are an as-
tomosin g an d sh ow promin en t osteoblastic activity
( Figs. 26.74–26.78) .
In some an eurysmal bon e cysts, th e relatively solid
portion is more promin en t th an in an oth er wise typical

F igu r e 26.67. A: A periph eral rim of bon e is often seen in association with an eurysmal bon e cysts.
B: Computed tomography can be helpful in detecting the osseous shell of bone.
336 Chapter 26 ■

F igu r e 26.68. Recurrent aneurysmal bone cyst in the

proximal humerus in a 14-year-old boy. One year before
th is radiograph was taken , th e tumor h ad been treated with
curettage an d bone graftin g.

F igu r e 26.69. A: An teroposterior radiograph of left h an d

sh ows a markedly expan sile lesion in volvin g n early th e en tire
fi fth metacarpal, with an in tact periph eral shell of cortical
bon e an d coarse trabeculation s. Axial T1-weigh ted ( B) an d
axial T2-weighted with fat suppression ( C) magnetic resonance
images show that the lesion consists of multiple round fl uid-fi lled
spaces with in terven in g septation s an d fl uid-fl uid levels in dica-
tive of in tralesional h emorrh age. Magn etic reson an ce imagin g
also confi rms the intact cortical sh ell, with no eviden ce of associ-
ated soft-tissue mass. These imaging fi ndings are diagnostic of
aneurysmal bone cyst.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 337

F igu r e 26.70. A: An teroposterior radiograph of th e lumbar

spin e sh ows a lytic lesion in volvin g th e posterior elemen ts of
th e fourth lumbar vertebra, but it is n ot possible to distin guish
between ben ign an d malign an t lesions on th e radiograph .
B: Axial computed tomogram con fi rms th at th e lesion is purely
lytic, in volves th e posterior elemen ts, an d is markedly expan -
sile, with a thin in tact periph eral sh ell of cortex. C: Sagittal
T2-weigh ted magn etic resonan ce images, as well as th e axial
image, sh ow th at th e lesion con sists of ch aracteristic multiple
roun d spaces with fl uid-fl uid levels.

aneurysmal bone cyst. Cystic spaces and septa may not be
identifi ed. The term solid aneurysmal bone cyst has been
applied to this entity. Grossly, the lesion may be com-
pletely solid. Microscopically, a spindle cell proliferation
with loose arrangement of the cells is found. Very charac-
teristically, the lesion shows abundant reactive new bone
formation, with prominent osteoblastic activity similar to
that of heterotopic ossifi cation (Fig. 26.79).
The differen tial diagnosis of aneurysmal bon e cyst
includes giant cell tumor, low-grade osteosarcoma,
and telangiectatic osteosarcoma. Occasionally, a large
number of giant cells may be seen in an aneurysmal
bone cyst, suggesting the diagnosis of giant cell tumor.
However, the age of the patient and the location of the
lesion in th e metaphysis should suggest the correct diag-
nosis. Low-grade osteosarcomas are much less cellular
338 Chapter 26 ■

F igu r e 26.71. Large an eurysmal bon e cyst in volvin g th e rib

in a young man. The patient presented with dyspnea because
of compression of th e pulmon ary paren ch yma.

F igu r e 26.72. Gross specimen removed from th e rib sh own

in Figure 26.71. Multiple cysts are separated by septa of
different width s.

F igu r e 26.74. A: Typical low-power appearance of aneurys-

F igu r e 26.73. Gross specimen of an aneurysmal bone cyst
in the proximal radius. The tumor is hemorrhagic, and mul-
tiple thin septa separate the cystic spaces.
mal bon e cyst. It con tain s several twisted septa of varyin g sizes.
B: Deposits of fi ne fi brillary osteoid beneath the lining of the
septum are typical in aneurysmal bone cyst. C: A loose slender
spindle cell proliferation within the cyst wall is accompanied
by multinucleated giant cells.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 339

F igu r e 26.75. A an d B: Irregular deposits of calcifi cation are common ly foun d in th e septa of
aneurysmal bone cysts. C: In this fi eld, the calcifi cation is parallel to the septa. D: A more delicate
lacelike pattern of calcifi cation within the septa is similar to that seen in chondroblastoma.

F igu r e 26.76. Numerous multin ucleated gian t cells fi ll th e F igu r e 26.77. Mitotic fi gures are easy to fi nd in aneurysmal
cyst wall in th is aneurysmal bon e cyst. bon e cysts. Th is fi eld con tain s four mitotic fi gures.
340 Chapter 26 ■
F igu r e 26.78. Th ere is n o eviden ce of cytologic atypia in
aneurysmal bone cysts. This is in contrast to the marked pleo-
morph ism typically seen in telan giectatic osteosarcoma.
F igu r e 26.79. Low-power ( A) an d h igh -power ( B) views of
a solid area in an aneurysmal bone cyst. It is quite cellular
and contains numerous multinucleated giant cells mixed with
abundant reactive new bone formation.
and less mitotically active th an typical aneurysmal bon e
cysts. The most diffi cult differen tial diagnosis is telan gi-
ectatic osteosarcoma. The low-power appearance of
telangiectatic osteosarcoma may be exactly that of
aneurysmal bone cyst. H owever, in telan giectatic osteo-
sarcoma, th e septa are composed of very pleomorph ic-
appearing cells. Hence, only cytologic features can
help separate aneurysmal bone cyst from telangiectatic
osteosarcoma.
Tr ea tmen t
The most successful treatment has been surgical
removal of the entire lesion or as much of it as possible.
Occasionally, bone grafting of the resulting defect may
be necessary. Recurrence sometimes develops, but even
these can be managed relatively conservatively.
Pr ogn osi s
The prognosis for aneurysmal bone cyst is excellent.
Recurrences are rare, and even incomplete removal
may be followed by regression of the lesion. Sponta-
neous malignant transformation was not documented
in the Mayo Clinic fi les. However, Kyriakos and Hardy
have reported an example of malignant tran sforma-
tion of aneurysmal bone cyst. In the Mayo Clinic fi les,
there are three examples of postradiation sarcoma fol-
lowing treatment of aneurysmal bone cyst that included
radiation therapy.
SIMPLE CYST
The simple, or “unicameral,” cyst of bone is of unknown
cause, but it apparently results from a disturbance of
growth at the epiphyseal line. The lesion is relatively
common and usually becomes manifest during the fi rst
two decades of life. Generally, the lesion occurs in the
upper part of the diaphysis of the humerus, the diaphy-
sis of the proximal femur, or the proximal part of the
diaphysis of the tibia, in that order of frequency.
Physi ca l Fi n di n gs
Patients with a simple cyst of bone may have local pain,
but for most of them, the cyst comes to attention only
after pathologic fracture has occurred. Occasionally,
there is swelling in the region.
R a di ogr a phi c Fea tu r es
Unicameral bone cyst is seen as a lucency in the medul-
lary portion of the shaft of the bone and abutting the
epiphyseal plate. Typically, th e involved bone is no wider
than the adjacent epiphyseal plate. Th e cortex ordinarily
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 341

is eroded an d thin but intact unless pathologic fracture

has occurred. Fine trabeculation is sometimes seen
with in the lesion, an d a healed fracture may be evident
as a partition th rough it. A simple cyst usually reaches
maximal size before skeletal maturation. Frequently,
serial radiographs show that the epiph ysis grows away
from the region of the cyst so that it lies near th e cen ter
of the shaft. A cyst not abutting the epiphysis is some-
times referred to as a latent cyst ( Figs. 26.80–26.82) .

Gr oss Pa thologi c Fea tu r es

The cystic cavity may be empty, although it is usually
fi lled with a clear or yellowish green fl uid of low viscos-
ity. The inner sur face of the cyst wall frequently has
ridges separating depressed zones, and sometimes the
wall is covered by a layer of fl eshy tissue 1 cm or more
thick. Occasionally, partial or complete septa are seen,
the latter type making the cyst multicameral. Recent
pathologic fractures modify this pattern.

H i stopa thologi c Fea tu r es

Th e lin in g of th e cyst may be on ly a very th in layer of F igu r e 26.81. Simple cyst involving the femur in a 4-year-old
fi brous tissue th at may h ave scattered ben ign gian t boy. Th e lesion does n ot exceed th e width of th e ph ysis. ( Case
con tributed by Dr. Susan H . Bowers, Meth odist Hospital,
St. Louis Park, Minnesota.)

F igu r e 26.80. Typical appearan ce of a simple cyst. Th e

lesion forms an expansile mass in the metaphysis of the proxi- F igu r e 26.82. Recurren t simple cyst in volvin g almost th e
mal h umerus. It is associated with a path ologic fracture. en tire humerus in an 8-year-old girl.
342 Chapter 26 ■

cells. Th icker areas, wh en presen t, are composed

of fi brogen ic con n ective tissue th at often con tain s
n umerous ben ign gian t cells, h emosiderin pigmen t, a
few ch ron ic in fl ammatory cells, an d lipoph ages. Because
of th e gian t cell compon en t, some of th ese lesion s h ave
been erron eously classed with gian t cell tumor. An in di-
vidual septum, wh en presen t, closely resembles septa
seen in a typical an eurysmal bon e cyst. Th e h istologic
as well as th e gross features may h ave been modifi ed by
fracture. Proliferatin g fi broblastic tissue an d callus may
be promin en t outside an d with in th e cyst. Fibrin ous
deposits often occur, an d th ese may become min eral-
ized in focal masses an d resemble cemen tum foun d in
some odon togen ic tumors. Th e lesion h as been mis-
taken for cemen toma ( Figs. 26.83–26.85) .

Tr ea tmen t a n d Pr ogn osi s

Un til several years ago, th e treatm en t of sim ple cyst
con sisted of curettage an d bon e graftin g. H owever,
Scaglietti an d coauth ors h ave sh own th at favorable
results can be obtain ed in 90% of patien ts with topi-
cal in jection of m eth ylpredn isolon e acetate. Even
more recen tly, it h as been suggested th at drillin g
multiple h oles in th e lesion is th erapeutic. In 1954,
Garceau, Gregor y, an d oth ers n oted a h igh recur-
ren ce rate if patien ts were youn ger th an 10 years an d
th e cyst h ad a juxtaepiph yseal location . Th e ch an ce
for perm an en t cure was good for patien ts wh o were
older th an 10 years wh en th e cyst was left beh in d by
th e growin g epiph yseal lin e. In 1962, Joh n son an d
coworkers described four examples of extrem ely rare
sarcomatous ch an ge in sim ple cyst. O n e fi brosarcom a
of th e fem ur in th e Mayo Clin ic series possibly began
in a cyst.

F igu r e 26.84. Low-power ( A) an d, h igh -power ( B) views

F igu r e 26.83. Th e cyst wall in th is simple cyst is blan d an d
composed of partially h yalin ized fi brous tissue.
of a sim ple cyst th at con tain s th ick aggregates of degen erat-
in g fi brin in th e cyst wall, probably from a previous h emor-
rh age. C: An oth er fi eld in th e same tumor sh ows a more
cellular cyst wall with h emosiderin deposits an d multin ucle-
ated gian t cells.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone
F igu r e 26.85. A an d B: Some of th e fi brin ous deposits in th e
wall of this simple cyst have become partially mineralized.
F igu r e 26.86. Ganglion cyst involving the distal fi bula. The
lesion is purely lytic, is well circumscribed, and extends to the
end of th e bon e.
343
GAN GLION CYST
Cysts in bone are seen occasionally at or near the end
of the bone and are fi lled with a glary mucoid fl uid.
Typically, the cysts have a thick fi brous wall similar to
that of a “ganglion” of a tendon sheath, are associated
with no signifi cant degenerative changes in the nearby
joint, and, appropriately, seem considered to be collec-
tions in synovial spaces in unusual locations. In a study
of 88 examples of intraosseous ganglia, Schajowicz and
coauthors found that the hip region was the site most
commonly involved. The knee and ankle were almost
equally affected. The carpal bones were also involved
frequently. Radiographs show a well-defi ned lucency
extending to the articular cartilage ( Figs. 26.86 & 26.87) .
The lesion usually has a sclerotic rim at the periphery.
Grossly, one fi nds a fi brous lining and mucinous mate-
rial ( Fig. 26.88) . Occasionally, there are thin fi brous
strands within the cyst. The mucinous material stains
light blue on sections, similar to material in the ganglia
seen frequently in the wrist area ( Figs. 26.89 & 26.90) .
The differential diagnosis includes cyst associated
with degenerative joint disease. These cysts also may
contain blue-staining mucinous material. The lack of
evidence of associated degenerative joint disease of the
nearby joint on radiographs is the most useful fi nding,
confi rming the diagnosis of a ganglion cyst.
CYST OF D EGEN ERATIVE JOIN T D ISEASE
One must be aware that an osseous defect near a joint
may be related to primary synovial disease.
Severe degenerative joint disease is often accompa-
nied by “cysts” in the juxta-articular bone. The patho-
genesis of these somewhat spherical zones of rarefaction
is not clear. They are fi lled by a degenerative fi bromyx-
oid material. The cyst may be so extensive that it inter-
feres with orthopedic surgical procedures designed to
palliate the malfunction of the affected joint. When
extensive, the cyst may radiographically suggest that a
neoplasm of bone is present ( Fig. 26.91) .
The infl ammatory tissue of rheumatoid synovitis
often produces a rarefactive lesion of bone at the joint
in the hands. Less commonly, signifi cant defects adja-
cent to major joints or in the vertebrae are caused by
invading granulomatous masses in rheumatoid disease.
EPID ERMOID CYST
Islan ds of squamous epith elium sometim es becom e
em bedded in bon e, an d with con tin ued slow growth ,
a m arkedly expan sile lesion m ay be produ ced. Most
such cysts occur in th e bon es of th e skull. In addi-
tion to expan din g th e affected bon e, th e cyst may
protrude an d displace adjacen t soft tissue, in cludin g
344 Chapter 26 ■

F igu r e 26.87. An teroposterior ( A) an d oblique ( B) radio-

graph s of th e right an kle sh ow a well-circumscribed, lytic lesion
in the distal tibial epiphysis with a sclerotic rim. The lesion abuts
th e articular sur face an d appears to con tain a few coarse trabe-
culation s. Th e distal tibia is th e most common an atomical site
for th is lesion , and th e lack of degen erative arth ritis of th e an kle
join t excludes th e diagn osis of a degen erative cyst. C: Coron al
T2-weigh ted magn etic reson an ce image sh ows th at th e lesion
likely communicates with the ankle joint via a focal tiny breach
of th e cortex of the tibial articular sur face medially.

parts of th e brain . Accordin gly, som e of th ese cysts,
especially if th ey are in radiograph ically obscure loca-
tion s, m ay m im ic tum ors arisin g in th e brain . An epi-
dermoid cyst may be dum bbell sh aped an d protrude
beyon d both th e in n er an d outer tables of th e skull
( Fig. 26.92) .
Roth reviewed th e literature an d foun d reports
of more th an 55 cysts of th e ph alan ges. Nearly all
th e cysts were in th e h an ds ( Fig. 26.93) . Except for
squamous epith elium-lin ed cysts in th e jaws, wh ere
th ey are common , an d in th e temporal bon e, wh ere
th ey result from middle ear in fection , epidermoid
cysts are foun d in practically n o bon es oth er th an th e
skull an d distal ph alan ges. Eviden ce suggests th at th e
cysts in th e skull h ave a developmen tal basis, wh ereas
th ose in th e ph alan ges are probably due to traumatic
implan tation of epidermis.
R a di ogr a phi c Fea tu r es
The rarefi ed defect in bone produced by an epidermoid
cyst is typically very sharply defi ned and surrounded by a
thin layer of sclerotic bone. The cortex is often thinned
and expanded.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone
F igu r e 26.88. Gross appearance of an intraosseous gan-
glion. The lesion is composed of fi brous septa. Mucinous
material with in the cavity is very similar to th at in th e more
common gan glia of soft tissue.
F igu r e 26.89. A: In traosseous gan glion con tain s a fi brous
walled cyst. B: A small amount of mucinous material is present
in the cavity.
345
F igu r e 26.90. Th e wall of th is in traosseous gan glion is com-
posed of loose myxoid fi brous tissue.
F igu r e 26.91. Cyst of degen erative join t disease forms a
large defect in the distal femur. Narrowing of the space in the
knee joint is consistent with degenerative joint disease.
Pa thologi c Fea tu r es
Epidermoid cysts are usually fi lled with a pearly white
mass of heavily keratinized squamous epithelium. The
microscopic diagnosis depends on the demonstration
of a squamous epithelial lining in at least some portion
of the cyst wall.
346 Chapter 26 ■

F igu r e 26.92. Large epidermoid cyst of the skull

produced a mass that bulged into the cranial cavity
and outwardly as well.

F igu r e 26.93. An teroposterior ( A) an d lateral ( B) views of
epidermoid cyst of a fi nger. ( Case provided by Dr. J. W. Reagan
of Clevelan d, O hio.)
SU BU N GU AL KERATOACAN TH OMA
Subungual keratoacanthoma is an uncommon prolif-
erating lesion of the nailbed with a pronounced pro-
pensity for eroding the underlying bone. Patients usu-
ally complain of a rapidly progressive painful swelling
of the nailbed. Physical examination usually shows that
the nailbed and paronychial areas are swollen, indu-
rated, and erythematous. Radiographs show a sharply
circumscribed lytic defect involving the end of the dis-
tal phalanx. Grossly, large amounts of keratinous debris
are found. Microscopically, the lesion has the typical
appearance of a keratoacanthoma of the skin. Large
squamous cells with glassy cytoplasm proliferate, with
a cup-shaped depression containing large amounts of
keratin ( Figs. 26.94 & 26.95) .
Subungual keratoacanthoma is a benign self-limited
condition that may regress spontaneously. Hence, it is
important not to overtreat these lesions.
Squamous cell carcinomas can arise under the nail-
bed and may invade bone. Patients with squamous cell
carcinoma have complaints for years, rather than for
weeks, and the clinical appearance may suggest an infec-
tion. When it involves the underlying bone, squamous
cell carcinoma has a permeative appearance on radio-
graphs rather than the sharply circumscribed defect
seen in subungual keratoacanthoma. Squamous cell
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone
F igu r e 26.94. Subungual keratoacanthoma involving the
distal ph alanx in a 35-year-old man . Th e distal portion of
th e ph alan x is almost completely destroyed. ( Case provided
by Dr. J. R. H en n eford, Columbus H ospital, Great Falls,
Montan a.)
F igu r e 26.95. In th e typical h istologic appearan ce of sub-
ungual keratoacanthoma, islands of squamous cells invade
bon e. Th e cells have large amoun ts of cytoplasm an d produce
keratin.
carcinomas invading bone in this location are extremely
well differentiated and are differentiated from subun-
gual keratoacanthoma by the tendency of the tumor to
permeate between preexisting bony trabecula. These
lesions need to be treated aggressively, which will prob-
ably involve amputation of the involved segment of the
bone.
347
H ETEROTOPIC OSSIFICATION
Heterotopic ossifi cation (myositis ossifi cans) may occur
in muscle or other soft tissues. In its early, or fl orid, phase,
the lesion may have such pronounced cellular activity
that it is mistaken for sarcoma. The lesions of this trou-
blesome disease are rarely explored surgically in their
fl orid stage, so they are not commonly encountered.
PH YSICAL FIN D IN GS
The patient may or may not have recently experienced
signifi cant trauma. Patients sometimes have a history of
unusual muscular exertion. A mass is present in most
patients treated surgically. The mass commonly devel-
ops in as short a time as 1 or 2 weeks, and, rarely, it
recurs just as rapidly after surgical removal. This rate of
development affords a diagnostic clue, because sarco-
mas rarely grow as fast.
RAD IOGRAPH IC FEATU RES
In the early stages, plain radiographs are usually nega-
tive or they may show an ill-defi ned mass lesion. In later
stages, they show a well-circumscribed lesion with min-
eralization at the periphery. The central area is less min-
eralized, giving rise to the appearance of zonation. The
mass is not attached to the underlying cortex of bone,
and there is usually a lucent zone between the cortex
and the mass. However, periosteal reaction may be seen.
As the lesion matures and if surgical intervention is not
per formed, the lesion becomes more and more calci-
fi ed, smaller, and may attach itself to the underlying
bone. Computed tomograms show that the lesion is well-
circumscribed, with a shell of ossifi cation at the periph-
ery and a less mineralized area in the center. Magnetic
resonance images, however, may be misleading in that
the lesion may appear poorly defi ned and permeating,
suggesting malignancy because of surrounding edema
( Figs. 26.96–26.97) .
GROSS PATH OLOGIC FEATU RES
The lesion is well circumscribed, except in very early
phases. It may be completely contained in the belly
of a muscle, although an entirely similar process that
has n o apparent relationship to the muscle sometimes
develops. It is usually obvious that the lesion did n ot
arise in bon e, but a similar reactive ch ange may be
related to periosteum and even deeper osseous struc-
tures. Characteristically, ossifi cation is most pronoun ced
at the periphery of the mass and may have the appear-
ance of an eggsh ell. The central portion usually sh ows
edematous-appearing skeletal muscle and may show
cystic ch ange.
348 Chapter 26 ■

F igu r e 26.96. H eterotopic ossifi cation in volvin g th e th igh in an 11-year-old

boy. A: Th e lesion is un iformly min eralized an d well demarcated. Th is appear-
ance is most consistent with the diagnosis of heterotopic ossifi cation. B: With
magn etic reson ance imagin g, th e lesion appears to be poorly demarcated an d
sign als are n ot uniform, suggesting a diagnosis of sarcoma. C: Gross appearan ce
of th e lesion . A cen tral area of th e process is loosely arran ged. Th ere is a rim of
calcifi cation at the periph ery. Th is correspon ds to th e zon ation seen microscopi-
cally.

H ISTOPATH OLOGIC FEATU RES
Active fi broblastic proliferation is the dominant fea-
ture, and mitotic fi gures may be numerous. Alth ough
the spindle cells may be plump and mitotically active,
they lack cytologic atypia. Moreover, the cells tend to
be arranged loosely without any organization. Toward
the periphery of the lesion, the fi broblasts tend to orga-
nize into strands, an d osteoblasts appear with the for-
mation of reactive new bone. The osteoid undergoes
mineralization, so that toward the periphery of the
lesion are well-formed parallel arrays of almost n ormal-
appearing bone. This functional arrangement and mat-
uration are the two most signifi cant clues for diagnosis
of heterotopic ossifi cation. Large amounts of cartilage
may be seen in heterotopic ossifi cation and may sug-
gest the diagnosis of chondrosarcoma. However, these
chondroid islands have a tendency to mature into tra-
becular-appearing bone. Some examples of heterotopic
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 349

F igu r e 26.97. Subperiosteal ossifi cation as it appeared

1 month after injury.

ossifi cation have cystic spaces in the center and may

indeed have the appearance of an aneurysmal bone cyst
( Figs. 26.98 & 26.99) .
Several conditions such as subungual exostosis,
bizarre parosteal osteoch ondromatous proliferation,
fl orid reactive periostitis, and fi bro-osseous pseudo-
tumor of the digits all represent various forms of
heterotopic ossifi cation. They h ave peculiarities in
clinical presentation, radiographic appearance, and
even microscopic appearance, depending on th e site of
involvemen t.

TREATMEN T

Treatment is usually unnecessary if the correct diagno-

sis has been made. If the lesion is removed surgically, it
may recur rapidly.
PROGN OSIS
Th e progn osis is good wh eth er th e lesion is excised
or n ot. Rarely, a patien t will h ave myositis ossifi can s
progressiva or fi brodysplasia ossifi can s progressiva.
F igu re 26.98. A: Fibroblastic proliferation undergoing
metaplasia to osteoblasts to produce parallel strands of bone.
This is a zonation phenomenon. B: Actively proliferating fi bro-
blasts with mitotic fi gure in an early lesion of heterotopic ossifi -
cation. The nuclei do not appear anaplastic. C: Loose arrange-
ment of spindle cells, vascular proliferation, and production of
osteoid rimmed by osteoblasts are seen. The lack of compact
arrangement of the spindle cells suggests a benign process.
350 Chapter 26 ■
F igu re 26.99. Florid heterotopic ossifi cation. A: Hypercel-
lular chondroid foci with nuclear enlargement may simulate
chondrosarcoma or chondroblastic osteosarcoma. B: Immature
woven bone in a lacelike pattern that simulates osteosarcoma.
The spindle cell stroma merging with the osteoid is loose, myx-
oid, and devoid of atypia. C: More mature trabeculae of woven
bone lined by osteoblasts in a similar spindle cell stroma.
Th ese patien ts, usually youn g ch ildren , develop h et-
erotopic ossifi cation an d calcifi cation in several sites.
Th is may be a life-th reaten in g situation . Th ere are n o
specifi c path ologic features to substan tiate th is diag-
n osis. H owever, th ere is a h ereditar y ten den cy, an d th e
lesion s are always associated with radiograph ic abn or-
malities of th e digits an d occasion ally th e h an ds.
A few instances of malignant transformation of myo-
sitis ossifi cans have been recorded, but it is diffi cult to
assess the authenticity of these cases. There is one exam-
ple in the Mayo Clinic fi les of an extra-osseous osteo-
sarcoma arising in association with massive heterotopic
ossifi cation of dermatomyositis. This case, however, is
not included in the list of osteosarcomas.
EXU BERAN T CALLU S
A healing fracture, in its early phases, exhibits pro-
nounced cellular activity with abundant mitotic fi gures.
At this stage, osteoid and chondroid material may not
have the obvious functional arrangement of a reactive
process, and the histologic appearance is ominous when
studied out of context ( Fig. 26.100) . Later, maturation
of these substances resolves the problem. Patients with
some clinical conditions, such as osteogenesis imper-
fecta, and neurologic problems, such as paraplegia, are
susceptible to formation of exuberant, hypertrophic
callus. The orderly maturation of cartilage an d spin-
dle cells into bone suggests the correct diagnosis. It is
important to correlate the histologic features with the
radiographic appearance to ascertain that an underly-
ing neoplasm was not missed at the time of biopsy.
Stress fractures are usually associated with repeti-
tive activities such as marching and jogging. Some skel-
etal sites, such as the tibial shaft or the metatarsals, are
especially vulnerable to these fractures ( Fig. 26.101) .
Patients complain of persistent pain, but radiographs
may not show an obvious fracture. There may be exuber-
ant periosteal new bone formation, sometimes covering
an entire bone. This appearance may simulate that of
a permeative neoplasm such as Ewing sarcoma. Bone
scans are usually positive. Magnetic resonance images
may show disturbing abnormalities in the marrow and
adjacent soft tissues. When plain radiographs are nega-
tive and the bone scans and magnetic resonance images
show abnormalities in the marrow, stress fracture and
malignant lymphoma should be considered as diagnos-
tic possibilities.
Biopsy of a stress fracture usually shows reactive new
bone formation within the marrow cavity. This new bone
may appear permeative, entrapping preexisting bony
trabeculae ( Fig. 26.102) . This appearance can suggest
the diagnosis of sclerotic osteosarcoma. However, the
newly formed bony trabeculae are not packed together
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 351

F igu r e 26.101. “Stress” fracture in a common location . The

fracture lin e may be obscure; atten tion was focused on reac-
tive proliferative cartilage an d bon e removed for biopsy from
callus.

F igu r e 26.100. Fracture callus. A: Cellular cartilage with

enlarged nuclei and irregular masses of osteoid could be mis-
taken for osteosarcoma. H owever, th e spin dle cell stroma asso-
ciated with th e matrix sh ows n o eviden ce of atypia. B: An oth er
fi eld sh ows maturation in to more mature trabeculae of bon e.

F igu r e 26.102. H istologic features of stress fracture. A: Th e pattern of reactive woven bon e differs
from th at of th e portion of preexistin g bon e in th e bottom left h an d part of th e fi eld. B: An astomos-
ing trabeculae of reactive new bone with a pseudopagetoid appearance. The bone is surrounded
by loose fi brovascular stroma.
352 Chapter 26 ■
F igu r e 26.103. Radionuclide bone scan in a postmeno-
pausal woman with insuffi ciency fractures. Increased uptake
on both sides of the sacrum an d in th e middle gives rise to an
“H ” con fi guration . Th is appearan ce is quite typical of stress
fractures.
but rather are separated by marrow. The usual lack of
a mass lesion on radiographs also should rule out the
possibility of osteosarcoma.
Insuffi ciency fractures are a peculiar type of fracture
that usually in volves the pelvic girdle in postmen opausal
women. Patients may have a h istory of malignancy and
may have had radiation therapy to the pelvis for this
tumor. Patients complain of pain in the pelvis, and a
bone scan may be per formed to rule out the possibil-
ity of metastatic carcin oma. Bone scan s show increased
uptake in the sacrum an d pubic bones ( Fig. 26.103) .
Plain radiograph s usually show fractures in the pubis.
The sacral fractures are visualized best on computed
tomograms because in pain radiographs the sacrum is
often obscured by the overlying bowel content. Biopsy
usually shows reactive n ew bone formation. Knowledge
of the condition by clin ician s and radiologists should
obviate biopsy.
Avulsive injuries, such as those that can occur in the
tibial tubercle and ischial tuberosity, can cause exu-
berant new bone formation, suggesting a neoplasm.
Patients usually are active young people who have avul-
sive in juries, especially in the ischium ( ischial apophyse-
olysis) . Patients usually complain of sudden and severe
pain. Radiographs usually show an irregular crescentic
mass lyin g close to the ischial tuberosity ( Fig. 26.104) .
Serial radiographs may show the ischial apophysis in the
soft tissue and, later, reactive new bone formation.
F igu r e 26.104. Isch ial apoph yseolysis ( avulsion fracture) in
a 12-year-old boy whose trouble began with stress. Radiographic
fi ndin gs in dicate th at the mass was produced by trauma and
was not a neoplasm. ( Case provided by Dr. J. L. Broady of
Kn oxville, Ten n essee.)
GIAN T CELL REPARATIVE
GRAN U LOMAS
Th ese “gran ulomas” are peculiar to jawbon es. Th e
lesion h as common ly been con fused with true ben ign
gian t cell tumor of bon e. Th e gen erally accepted
con cept is th at it is n ot a n eoplasm but rath er some
peculiar reactive lesion . Th e lesion con sists of
proliferatin g fi broblasts an d often zon es in wh ich
metaplasia results in th e formation of orderly osseous
trabeculae. A variable amoun t of vascularity an d micro-
cyst formation may be seen ( Figs. 26.105–26.107) .
Th e basic fi brogen ic quality of th e lesion al tissue is
th e main feature th at differen tiates gian t cell repara-
tive gran uloma from true gian t cell tumor. Also, gian t
cell tumors do n ot occur in th e jawbon es except in
association with Paget disease. Th ere are n o examples
of true gian t cell tumor of th e jawbon es in th e Mayo
Clin ic fi les.
It is important to differentiate giant cell reparative
granuloma from giant cell tumor. Complete removal of
a giant cell reparative granuloma almost always effects
a cure, whereas true giant cell tumors may recur in
25% to 50% of patients, and about 7% of the lesions
undergo malignant change. Giant cell reparative granu-
loma commonly occurs in patients who are in the fi rst
or second decade of life, but they may be found in older
people.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 353

Th ere is probably little differen ce between th e

lesion s with in bon e th at h ave th e h istologic ch aracter-
istics of gian t cell reparative gran uloma an d th ose th at
are basically soft-tissue tumors of th e gums with little or
n o osseous in volvemen t. A lesion th at is h istologically
in distin guish able from gian t cell reparative gran uloma
sometimes affects th e jaw of a patien t with h yperpara-
th yroidism an d is un doubtedly evoked by th e en docrin e
disease. Th e possibility of h yperparath yroidism sh ould
always be con sidered if th e lesion recurs.
As suggested above and implied, giant cell reparative
granulomas probably result from a reactive process, a
likelihood suggested by the histologic similarity with
aneurysmal bone cyst.

F igu r e 26.106. Reactive bon e is a common fi n din g in gian t

cell reparative gran uloma.

F igu r e 26.105. Giant cell reparative granuloma of the

man dible. A: Gross specimen sh ows a large red-brown lesion
exten sively in volving the bon e. Low- ( B) an d h igh - ( C) power F igu r e 26.107. Giant cell reparative granulomas occasion-
appearance of a lesion that contains several multinucleated ally contain hemorrhagic areas in which the lesional cells
gian t cells in a fi brogen ic stroma. separate in th e blood.
354 Chapter 26 ■
GIAN T CELL REACTION ,
OR “LESION S”
Th is lesion was illustrated in the Armed Forces In sti-
tute of Path ology fascicle on Tumors of Bone and Cartilage
by Ackerman and Spjut. Although lesions con taining
benign giant cells in the small bones of th e hands an d
feet are un usual, a few have the characteristics of gen u-
in e giant cell tumor, chon droblastoma, or aneurysmal
bone cyst. There also is a group, apparently non neo-
plastic, in which the stroma has a rather prominen t
fi brogen esis and new bon e formation. These are basi-
cally solid but small tumefactions. The nuclei appear
benign. Th e major importan ce is th at th ese lesion s may
be mistaken for a more ominous process. The lesion s
are benign, and recurren ce is unusual. Lorenzo and
Dor fman have used the term giant cell reparative granu-
loma for the same process ( Figs. 26.108–26.110) .
OSTEOMYELITIS
The alteration of bone that results from acute or chronic
infection may produce radiographic changes that sim-
ulate those of bone tumors. Antimicrobial therapy
F igu r e 26.108. A: Giant cell “reaction” producing lytic
defect at the base of the proximal phalanx of the fourth fi n-
ger in a 16-year-old boy. ( Case provided by Dr. M. M. Alvarado,
Dayton, Ohio.) B: Similar lesion, which in this instance is exo-
phytic, on the middle phalanx of the fi fth fi nger in a 51-year-
old woman . ( Case provided by Dr. A. C. H oh eb an d Alban y
Plastic Surgeons Associated of Albany, New York.)
sometimes attenuates the infection to such a degree
that normal radiographic progression is distorted, thus
increasing the likelihood of mistaking an infection of
bone for a neoplasm.
PH YSICAL FIN D IN GS
The febrile and septic course of acute osteomyelitis is
sometimes obscured by therapy. Furthermore, certain
neoplasms, notably Ewing sarcoma, produce fever and
leukocytosis.
RAD IOGRAPH IC FEATU RES
The earliest sign of osteomyelitis is irregular rarefaction,
usually near the end of the shaft of a long bone. Periosteal
elevation commonly occurs, and one or more layers of
subperiosteal new bone may be produced. Islands of
dead bone ( sequestrum) , which develop later, are rela-
tively radiopaque because of the osteoporosis that occurs
in the surrounding living bone. Occasionally, the radio-
graphic features may simulate exactly those produced
by a malignant bone tumor ( Figs. 26.111 & 26.112) . In
the acute phase, the radiographic features usually sug-
gest a permeative malignancy such as Ewing sarcoma.
F igu r e 26.109. Giant cell “reaction” forming a benign-
appearing, well-circumscribed, and expansile lesion in the
metacarpal in a 37-year-old woman .
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 355

F igu r e 26.111. O steomyelitic lesion th at radiograph ically

simulates sarcoma. Th is, like th e on e sh own in Figure 26.112,
was caused by Micrococcus pyogenes and had destroyed bone
and caused periosteal formation of new bone.

F igu r e 26.110. A an d B: Gian t cell reaction with a prolifera-

tion of slen der spin dle cells, scattered multin ucleated gian t
cells, an d reactive n ew bon e formation .

In chronic osteomyelitis, geographic areas of destruc-

tion may be produced, and it may suggest a neoplasm
such as osteosarcoma or giant cell tumor. Specifi c
ch ronic infection s such as tuberculosis, coccidioidomy-
cosis, or blastomycosis sometimes produce a discretely
demarcated zone of bone destruction resembling that
produced by a slowly growing benign tumor of bone
( Figs. 26.113 & 26.114) . At other times, a large zone of
sclerosis results from an indolent focus of infection in
bone, and such a lesion can mimic an osteoid osteoma
( Brodie abscess) ( Fig. 26.115) .

GROSS PATH OLOGIC FEATU RES

The granulation tissue that is present at the site of osteo-

myelitis may not be identifi able as nonneoplastic.

H ISTOPATH OLOGIC FEATU RES

F igu re 26.112. O steomyelitis of th e h umerus simulatin g
Usually, th e differentiation of osteomyelitis from neo- sarcoma in a 9-year-old boy wh o h ad noted local pain for
plasm is readily apparen t. Th e gran ulation tissue 1 month. Cultures from the lesion revealed Micrococcus pyogenes.
356 Chapter 26 ■
F igu r e 26.113. Brucellar osteomyelitis simulating ch ondro-
blastoma of th e h umerus.
characteristically contains n umerous, n ewly formed
capillaries and an admixture of polymorph on uclear
leukocytes, plasma cells, an d lymphocytes in varied pro-
portions ( Figs. 26.116 & 26.117) . It is un usual to fi nd
polymorph on uclear leukocytes in a n eoplasm unless a
previous biopsy in troduced an in fection . O n occasion ,
when th ere is an almost pure plasma cell reaction , th e
h istologic pattern resembles th at of multiple myeloma
and h as resulted in an erron eous diagn osis of n eo-
plasm. O rdinarily, h owever, th e n etwork of proliferat-
ing capillaries produces th e un mistakable pattern th at
is associated with a reaction to in fection. Moreover, in
chron ic osteomyelitis, there is always an admixture of
oth er in fl ammatory cells.
TREATMEN T
Th e treatmen t of osteomyelitis varies with th e organ -
isms respon sible for th e in fection . Man agemen t of th e
con dition can be facilitated greatly by examin ation of
fresh frozen section s at th e time of operation . In cer-
tain specifi c fun gal in fection s, th e diagn osis can be
made or stron gly suspected on th e basis of th e h isto-
logic appearan ce. Wh en ever th e h istologic pattern is
th at of a gran ulomatous in fl ammation , bacteriologic
F igu r e 26.114. Tuberculosis producin g n eoplasm-like rare-
faction of th e femoral n eck.
in vestigation can be directed appropriately. A wide
variety of bacterial an d fun gal in fection s can produce
lesion s in bon e. It is importan t n ot to make th e diag-
n osis of osteomyelitis in a bon e biopsy specimen as
a diagn osis of exclusion . Th e diagn osis of osteomy-
elitis is a serious on e th at en tails expen sive th erapy
( Figs. 26.113 & 26.114) .
In most examples, osteomyelitis forms a single focus
of infection in bone. However, rarely, patients acquire
chronic, recurrent, multifocal osteomyelitis. Children
and adolescents are usually affected. They have recur-
rent attacks of pain and swelling that may persist for
several years. Cultures are invariably negative.
Garré described a sclerosing form of osteomyelitis that
causes distention and thickening of the bone without
suppuration. Radiographs show marked sclerosis of the
involved bone, and the process may involve a long bone,
the clavicle, or the jawbones. Because of the sclerotic
appearance on radiographs, the lesion may be mistaken
for a neoplasm. The term condensing osteitis applied to
lesions involving the clavicle probably refers to the same
condition.
Th e possibility of malign an t ch an ge in lon g-stan d-
in g ch ron ic osteomyelitis must be con sidered. Th e
usual malign an t tumor is squamous cell carcin oma,
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 357

F igu r e 26.115. Ch ron ic osteomyelitis simulatin g osteoid

osteoma ( arrows) . Lytic lesion is surrounded by sclerotic
bon e.

F igu r e 26.116. Acute osteomyelitis. A: Preexistin g fragmen t

wh ich develops from th e regen eratin g skin at th e edge of lamellar bon e is en gulfed by th e in fl ammatory process. B:
of th e cutan eous ulceration an d in vades th e un derly- In fl ammation consists of plasma cells, n eutroph ils, an d lym-
in g, already diseased bon e ( Fig. 26.118) . Th e usual phocytes admixed with capillary proliferation.
story is of a patien t wh o h as lon g-stan din g ch ron ic
osteomyelitis with a ch ron ic drain in g sin us. Th e devel-
opmen t of malign an cy is h eralded by an in crease in
pain an d disch arge from th e sin us th at becomes more
foul smellin g th an usual. Radiograph s usually sh ow a
destructive area at th e site of ch ron ic osteomyelitis.
Th e carcin oma th at develops in a sin us tract is usu-
ally extremely well differen tiated an d may be mistaken
for pseudoepith eliomatous h yperplasia. H owever, th e
presen ce of squamous epith elial cells with in bon e
supports th e diagn osis of squamous cell carcin oma
( Fig. 26.119) . Successful man agemen t depen ds on
complete removal of th e diseased bon e, usually by
amputation . Th ere are 49 examples in th e Mayo Clin ic
fi les of squamous cell carcin oma arisin g in a sin us tract
of osteomyelitis. Th e majority of th ese are extremely
well-differen tiated squamous cell carcin omas. A few
F igu r e 26.117. Granulomatous osteomyelitis involving the
are h igh er grade squamous cell carcin omas. In addi- proximal tibia in an adult man. Note epithelioid granulo-
tion , th ere h ave been two osteosarcomas, two fi brosar- mas with polymorph on uclear leukocytes in th e cen ter. Th is
comas, on e malign an t lymph oma, an d on e myeloma appearance suggests a diagnosis of blastomycosis. Blastomyces
th at arose in association with osteomyelitis. grew on cultures.
358 Chapter 26 ■
F igu r e 26.118. Ligh ter con glomerate masses of grade 1
squamous cell carcin oma on th e sur face an d in volvin g much
of th e medulla of th e tibia in a 77-year-old man wh o h ad h ad
intermittent symptoms of chronic osteomyelitis since fracture
through the zone 69 years previously.
LAN GERH AN S CELL H ISTIOCYTOSIS
(H ISTIOCYTOSIS X, EOSIN OPH ILIC
GRAN U LOMA)
This category includes conditions that range from the
usually solitary and curable Langerhans cell histiocytosis
( LCH) through the disseminated process that produces
Schüller-Christian disease to the disseminated, rapidly
fatal variety known as Letterer-Siwe disease. Lichten stein
fi rst proposed that these three seemingly dissimilar con-
ditions were united by a common pathology. However,
this view has been questioned by other authors. It seems
reasonably certain that LCH and Schüller-Christian dis-
ease represent the same disease process. It is possible
that Letterer-Siwe disease is caused by various condi-
tions, including LCH.
Letterer-Siwe disease usually affects very young chil-
dren. However, the disseminated form can occur in
adults. Schüller-Christian disease and LCH are found
most often in children and young adults. Practically any
bone of the body may be affected, but there is a predi-
lection for the skull.
PH YSICAL FIN D IN GS
The variety of symptoms is great. Patients with LCH ordi-
narily have a solitary, painful focus and often a palpable
F igu r e 26.119. Squamous cell carcin oma arisin g in th e set-
tin g of ch ron ic osteomyelitis. A: Th e tumor permeates th rough
preexisting medullary bone. B: Squamous cell carcinomas in
th is settin g are typically well-differen tiated tumors.
or visible mass. Some patients may present with a limp.
The classic triad of Schüller-Christian disease includes
exophthalmos ( often unilateral) , diabetes insipidus,
and rarefi ed defects of bones of the skull. A partial triad,
however, has the same signifi cance if there is other evi-
dence of dissemination, such as anemia, splenomeg-
aly, fatigability, loss of weight, and lymphaden opathy.
Patients with LCH may complain of discharge from the
ears ( from involvement of the temporal bones) , loos-
ening or falling out of teeth ( from lesions of the jaw) ,
and any of the other symptoms that may be produced
by focal destruction of bone. Any bone may be the site
of a painful and sometimes expansile lesion. Vertebral
involvement may result in collapse of the vertebral body,
with resultant neurologic symptoms. Cutaneous mani-
festations, lymphadenopathy, and splenomegaly are
most common in the progressive, diffuse form of the
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 359

disease. Pulmonary infi ltration may become clinically

important, and, on rare occasions, it is the most signifi -
cant evidence of the disease. Diffuse pulmonary lesions
of LCH, however, may occur in the absence of osseous
lesion s; such patients are usually adults who are not seri-
ously ill, may have episodes of spontaneous pneumotho-
rax, and have an unpredictable clinical course.

RAD IOGRAPH IC FEATU RES

Th e defects in bon e are usually discretely defi n ed

an d lytic. In th e skull, th ere m ay be a “h ole in a h ole”
appearan ce because of th e differen tial destru ction of
th e two tables of th e bon e. Periosteal n ew bon e forma-
tion may be presen t; it is usually th ick an d solid. Th e
lesion m ay be poorly defi n ed an d appear to destroy
th e cortex, especially in fl at bon es such as th e clavicle.
Th is m ay suggest a diagn osis of malign an cy. Multiple
adjacen t defects often becom e con fl uen t. Lesion s
in th e m an dible are usually con cen trated alon g
th e alveolar process. Con sequen tly, th e teeth may
appear to h ave n o bon y support, wh ich is in deed true
( Figs. 26.120–26.124) .
F igu r e 26.121. Disseminated Langerhans cell histiocytosis
with severe involvement of the skull. The patient was a 3-year-
GROSS PATH OLOGIC FEATU RES old boy wh o died a year after diagn osis.

The lesional tissue is soft and may be gray, pink, yellow,

or even green.

H ISTOPATH OLOGIC FEATU RES

The microscopic appearance is what links together

these three general conditions of Schüller-Christian dis-
ease, Letterer-Siwe disease, and LCH. The salient and

F igu r e 26.122. H uge solitary lesion of Lan gerh an s cell h is-

tiocytosis. Note the pronounced sclerosis of adjacent bone.

pathognomonic feature consists of foci of proliferating

F igu r e 26.120. Skull defect produced by Lan gerh an s cell
histiocytosis. Th e skull is on e of the most common sites for
lesions in this disease.
histiocytes. The histiocytes frequently have ill-defi ned
cytoplasmic boundaries and characteristically contain
an oval or indented nucleus. Multinucleated giant
cells may be present. Occasionally, the giant cell prolif-
eration is suffi cient to suggest a diagnosis of giant cell
tumor. In addition to histiocytes, eosinophils are com-
mon. Other infl ammatory cells, such as lymphocytes,
plasma cells, and neutrophils, are also commonly seen.
Large areas of necrosis are frequently found in LCH of
bone. Occasionally, the histiocytic cells have a rounded
360 Chapter 26 ■
F igu r e 26.123. Severe man dibular Lan gerh an s cell h istio-
cytosis with teeth about to exfoliate, a complication th at is
common .
F igu r e 26.124. Lytic lesion of Lan gerh an s cell histiocytosis.
Th e features are worrisome for malign an cy.
F igu r e 26.125. Lan gerh an s cell h istiocytosis. A: In addi-
tion to sh eets of Lan gerh an s cells, n umerous lymph ocytes
are presen t in th is lesion in volvin g th e skull. B: H igh -power
view sh ows th e ch aracteristic oval n uclei surroun ded by pale
eosinoph ilic cytoplasm. Eosin ophils are scattered through out
th e fi eld.
nucleus and pink cytoplasm, imparting an epithelioid
appearance ( Figs. 26.125–26.127) .
Un der low power, th e cells of LCH h ave a clustered
quality; h owever, th ey do n ot form tigh t sh eets. If com-
pact sh eets of cells are seen , th e possibility of malig-
n an t lymph oma sh ould be con sidered. Alth ough th e
cells of LCH h ave ch aracteristic cytologic features,
an occasion al in fectious process, especially a specifi c
in fection such as blastomycosis, can h ave similar cyto-
logic features.
Lan gerh an s cells are usually immun oreactive with
S-100 protein . H owever, CD1a an d Lan gerin ( CD207)
are more specifi c markers. Cytoplasmic in clusion s
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone
F igu r e 26.126. Zones of n ecrosis lead to a mistaken diagn o-
sis of osteomyelitis in th is example of Lan gerh an s cell h istio-
cytosis. A: Th e Langerh an s cells are in th e upper righ t corn er.
Langerhans cell histiocytosis should always be considered
before diagn osin g acute osteomyelitis. B: H igh -power view
sh ows a diagn ostic fi eld with typical Lan gerh an s cells.
Figu re 26.127. This Langerhans cell histiocytosis contains
numerous multinucleated giant cells that blend with and partially
obscure the Langerhans cells in the central part of the field.
361
called Birbeck granules are also ch aracteristic of Lan ger-
h an s cells.
TREATMEN T
It is possible that a single lesion of LCH requires no
treatment. It may regress spontaneously. Some patients
have received small doses of radiation and have had a
good response. Corticosteroids and other chemothera-
peutic agents have been used successfully in severe, dis-
seminated LCH.
PROGN OSIS
Complete evaluation of patients who present with a
defect characteristic of LCH is important in estimating
prognosis. Patients who have only one or a few lesions
are usually cured with local radiation or observation.
Patients with Schüller-Christian disease have a poor
long-term outlook, but prolonged palliation can be
expected if therapy is administered judiciously. In 1967,
Enriquez and coworkers, in a study of 116 patients with
LCH at Mayo Clinic, found that patients younger than
3 years, those with more than three bones involved,
those with hemorrhagic manifestations, and those with
splenomegaly all had an ominous prognosis. Patients
who survived more than 3 years after the onset of symp-
toms had a good prognosis.
From th e Mayo Clin ic fi les, Kilpatrick an d coauth ors
reported on 263 patien ts with LCH . Th ey foun d th at
youn g age at diagn osis, h epatosplen omegaly, th rom-
bocytopen ia, an d in volvemen t of more th an th ree
bon es predicted a poor progn osis.
ERD H EIM-CH ESTER D ISEASE
Erdheim-Chester disease is a disorder of unknown
cause. Most of the patients are males, and they are either
asymptomatic or may have systemic symptoms such as
weight loss. They may also complain of bone pain. The
characteristic fi nding of Erdheim-Chester disease is the
presence of bilateral, symmetrical sclerosis of the meta-
physeal and diaphyseal regions of the long bones. Flat
bones are rarely affected ( Fig. 26.128) .
In som e patien ts, th e disease rem ain s station ar y. In
oth ers, it m ay progress an d in volve sites such as th e
lun g an d pituitar y, producin g diabetes in sipidus. H is-
tologic exam in ation sh ows in fi ltration of th e in volved
tissue by foam y m acroph ages, scattered lym ph ocytes,
an d variable am oun ts of fi brosis. Th e trabeculae of
bon e are th icken ed an d sclerotic with , at tim es, a pag-
etoid appearen ce. Multin ucleated gian t cells are also
som etim es presen t ( Fig. 26.129) .
362 Chapter 26 ■

F igu r e 26.128. Radiograph s of both legs sh ow bilateral,

symmetrical sclerotic lesion s in volvin g both en ds of th e tibia.
Th is appearan ce is typical of Erdh eim-Ch ester disease.

MASTOCYTOSIS

Involvement of the skin in the form of urticaria pig-

mentosa is the most common manifestation of mast cell
disease. Urticaria pigmentosa may start in infan cy or
adulthood. Children with urticaria pigmentosa usually
have spontaneous remission. Adults usually have persis-
tent disease.
Systemic mastocytosis is the term used when mast cell
infi ltration is seen in other organs. Systemic mastocyto-
sis may or may not be associated with skin involvement.
It has been suggested that the lack of skin involvement
is an unfavorable prognostic sign.
Patients with systemic mastocytosis may presen t with
various symptoms, includin g systemic symptoms such
as fatigue, fl ushin g, an d syncopal attacks. Frequen tly, F igu r e 26.129. Erdheim-Chester disease. A: Low-power
view shows thickened trabeculae of bone with a pagetoid
th e liver, spleen , and gastrointestin al tract are in volved. appearance. B and C: The stroma contains variable amounts
Some patients presen t with diarrhea. Because of th e pro- of foamy h istiocytes, fi brosis, an d lymph ocytes. O ccasion ally,
tean manifestations, a clinical diagnosis of systemic mast multin ucleated giant cells are also foun d.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 363

F igu r e 26.130. A: Mastocytosis producin g multifocal scle-

rosin g lesion s, especially in pelvic bon es. Th ese lesion s are
common ly mistaken for metastatic osteoblastic carcin oma. B:
Similar sclerosing lesions of the humerus in mastocytosis.

cell disease is rarely suspected. In a study of 58 cases

of systemic mastocytosis, Travis an d coauth ors found
th at 28% of the patien ts presented with symptoms of
bone involvement, such as bon e pain or path ologic
fracture. H owever, radiograph s sh owed involvement of
th e skeleton in 59% of the patients. Radiographs show
F igu r e 26.131. A: Mastocytosis characterized by a nodu-
multiple areas of sclerosis sometimes admixed with lysis lar spindle cell proliferation adjacent to a trabecula of bone.
( Fig. 26.130) . Th is usually leads to the diagnostic con- B: The spindle cells resemble fi broblasts. Mast cells are also pres-
sideration of metastatic carcinoma. ent. C: Th e spindle cells are immun oreactive with tryptase.
364 Chapter 26 ■
Mastocytosis in bone is usually associated with scle-
rosis. The bony trabeculae appear thickened, and the
paratrabecular areas appear hypercellular and fi brotic.
Mast cells are present as small, oval cells that may aggre-
gate, producing a microgranulomatous appearance
( Fig. 26.131) . Eosin ophils are usually present in these
nodules. Mast cells stain positive with special stains such
as Giemsa, chloroacetate esterase, and aminocaproate
esterase.
The prognosis in systemic mastocytosis is unpredict-
able. Most patients do not die of mast cell disease but
of associated malignant diseases, many of which are
hematologic.
SIN U S H ISTIOCYTOSIS WITH
MASSIVE LYMPH AD EN OPATH Y
(ROSAI-D ORFMAN D ISEASE)
Sinus histiocytosis with massive lymphadenopathy is an
unusual disease of unknown cause fi rst described in
patients with lymph node involvement in the neck. It
soon became apparent th at the disease can affect sev-
eral organ systems. In a review of the subject, Foucar
and coauthors found 33 examples of Rosai-Dor fman
disease with skeletal involvement. The involvement
may or may not be associated with lymph node disease.
Some patients present with skeletal disease and lymph
nodes may become involved.
Patien ts usually presen t with bon e pain . Radio-
graph s sh ow defects th at are eith er purely lucen t or
mixed with sclerosis. H istologically, th e lesion is domi-
n ated by proliferation of h istiocytes th at h ave small,
roun d n uclei an d abun dan t clear cytoplasm. Very
ch aracteristically, th e cytoplasm of th e h istiocytes con -
tain ph agocytosed lymph ocytes an d plasma cells. In
addition , th ere is plasma cell proliferation outside th e
h istiocytes. Areas of fi brosis are also frequen tly seen
( Fig. 26.132) .
The differential diagnosis includes various condi-
tions that may show histiocytes. It is necessary to identify
phagocytosis by the histiocytes to establish the diagnosis
of Rosai-Dor fman disease. These cells are also positive
with the S-100 protein stain.
The prognosis in Rosai-Dor fman disease is unpre-
dictable. Some patients have progressive disease and
die. In others, the disease seems to regress.
PAGET D ISEASE
Paget disease is of un kn own cause, alth ough it h as been
suggested to have a viral cause. In some parts of th e
world, such as Asia, Paget disease is extremely rare,
whereas in other parts, such as England, it is relatively
common . Th is disease occurs in patien ts of middle or
old age. Th e pelvis, femur, skull, tibia, an d vertebrae
are common ly in volved sites, alth ough an y bon e may be
affected. Th e radiograph ic appearan ce of Paget disease
is usually quite characteristic. Th e lesion n early always
exten ds to th e en d of th e bon e. Th e bone is ch aracteris-
tically widen ed, an d th e cortex an d medullary bon e are
markedly th icken ed ( Fig. 26.133) . Th e demarcation
from unin volved bon e is sh arp and h as been likened
to a blade of grass in lon g bon es ( Fig. 26.134) . Lesion s
of Paget disease sh ow in creased uptake on bon e scan s,
and th is is con sidered to be ch aracteristic. Occasion -
ally in Paget disease involvin g vertebrae, the body of
a vertebra is completely sclerosed, producin g an ivory
vertebra. The differen tial diagn osis in cludes metastatic
carcin oma, malign ant lymph oma, an d Paget disease.
The ch aracteristic en largemen t of th e bon e seen in
Paget disease affords a clue to th e correct diagn osis. In
some in stan ces, Paget disease may presen t as a purely
lytic area in bone an d, th us, may be mistaken for a neo-
plasm ( Fig. 26.135) .
The gross specimen shows thickening of the cortex
and coarse medullary bone. Microscopically, the bony
trabeculae appear thickened and irregular. Irregular
blue cement lines are very characteristic. The bone mar-
row is replaced by a fi ne fi brovascular connective tissue,
and osteoblastic and osteoclastic activity is increased
( Fig. 26.136) . Although these features are quite typical,
they are not diagnostic of Paget disease. Pagetoid bone
may be seen in various conditions, including osteosar-
coma and reactions to metastatic carcinoma. Hence,
good radiographic correlation is important before
Paget disease is diagnosed.
Patien ts with Paget disease h ave a defi n ite but small
risk of developin g sarcoma. Lytic areas may be foun d in
typical Paget disease, an d it may be virtually impossible
to separate th at from sarcoma. Moreover, fl orid Paget
disease can exten d in to soft tissue an d simulate malig-
n an cy. In th e Mayo Clin ic series, 73 tumors arose in
Paget disease. Th ere were 61 osteosarcomas, 7 fi brosar-
comas, 3 malign an t fi brous h istiocytomas, 1 malign an t
lymph oma, an d 1 gian t cell tumor.
H YPERPARATH YROID ISM
H yperparath yroidism results from n eoplasms or dif-
fuse h yperplasia of th e parath yroid glan ds. It may be
primary or secon dary to ren al disease. In volvemen t
of th e skeleton occurs with both types. O rdin arily,
diffuse demin eralization of th e skeleton occurs, but
pron oun ced focal absorption sometimes produces a
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 365

F igu r e 26.132. A: Well-demarcated, purely lytic lesion involv-

ing the proximal tibia in a 22-year-old woman. The radiographic
features suggest a diagnosis of giant cell tumor. The biopsy exami-
nation sh owed sin us histiocytosis with massive lymphadenopath y.
B: Corresponding magnetic resonance image. The radiographic
features are nonspecifi c. ( Case provided by Dr. David M. Resk,
St. Francis Pathologists, Milwaukee, Wisconsin.) C: Biopsy speci-
men from th e lesion . A large n umber of plasma cells an d h istio-
cytes surroun d th e trabecula of bon e. D: Th e h istiocytes h ave a
large amount of clear to pink cytoplasm. They are characterized
by emperipolesis, wh ich is en gulfmen t of in tact lymph ocytes.
E: The histiocytes are immunoreactive with S-100 protein.
366 Chapter 26 ■
F igu r e 26.133. Paget disease involving the proximal femur
associated with a transverse fracture. There is marked thicken-
ing of th e cortex and the medullary bon e. Th e lesion exten ds
up to the end of the bone.
F igu r e 26.134. Paget disease involving the proximal femur.
A sharp demarcation separates involved and uninvolved bone.
This has been referred to as a “blade of grass” or “fl ame” sign.
F igu r e 26.135. Lytic phase of Paget disease involving a ver-
tebral body. The entire body seems to have disappeared. The
features clearly do not suggest a diagnosis of Paget disease.
cystlike appearan ce on radiograph y th at can simulate
a primary n eoplasm of bon e. In some in stan ces, th e
fi broblastic tissue fi llin g th e defect is so exuberan t th at
th e con tour of th e bon e bulges, suggestin g even more
stron gly th at a n eoplasm is presen t. Radiograph s gen er-
ally sh ow oth er features of h yperparath yroidism, espe-
cially resorption of subperiosteal bon e, particularly in
th e h an d ( Figs. 26.137 & 26.138) .
Because hyperparathyroidism is so well known, the
osseous lesions it produces are rarely subject to biopsy.
The diagnosis is best established by determination of
the serum levels of calcium and phosphorous or para-
thyroid hormone or by fi nding an increased amount of
urinary calcium. Suspicion is aroused when a lesion sug-
gests the diagnosis of giant cell tumor, but the histologic
appearance or skeletal location is incorrect for giant
cell tumor. Parathyroid osteopathy sometimes produces
a lesion similar to aneurysmal bone cyst.
The lesion does not present pathognomonic histo-
logic features. Where the osseous trabeculae are being
resorbed, proliferating fi broblastic connective tissue is
usually so richly sprinkled with benign osteoclast-like
giant cells that the diagnosis of giant cell tumor may be
considered. However, the basic fi brogenic quality of the
lesion should preclude the diagnosis of giant cell tumor
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 367

F igu r e 26.136. A: Paget disease with ch aracteristic mosaic

pattern in irregular osseous trabeculae. Osteoclasts are numer-
ous, an d th e marrow space is replaced by loose fi brovascular
conn ective tissue. B: An oth er fi eld in th e same bon e shows an
earlier stage, with little mosaic ch an ge in th e bon e an d more
osteoblastic activity. Th is zon e could be mistaken as reactive
new bone or a fi bro-osseous lesion .

F igu r e 26.138. A: Parath yroid osteopath y in a 55-year-old

woman. A left mandibular lesion simulated malignancy. The
lesion resolved after removal of parathyroid tumor. On biopsy,
the lesion had been called “fi brous dysplasia.” B: Parathy-
roid osteopath y producin g a markedly “expansile” lesion of
the orbital plate of the frontal bone in a 27-year-old woman.
A parath yroid adenoma of 2100 g was later removed from the
mediastin um.

because the latter is not fi brogenic in its proliferating,

diagnostic fi elds. The lesion also may have pronounced
Figure 26.137. Typical changes of hyperparathyroidism in the new bone formation, and, in fact, the appearance is
second and third digits of the hand. Tumor of parathyroid oste- very similar to that of giant cell reparative granuloma
opathy involves most of the first phalanx of the second finger. ( Figs. 26.139 & 26.140) .
368 Chapter 26 ■

TRAN SIEN T OSTEOPOROSIS

Transient osteoporosis affects middle-aged adults.

Patients usually complain of pain in a joint, especially
the hip. Radiograph s show osteopenia of the femoral
head. This usually is not associated with a previous
history of trauma. Bone scans show increased uptake.
These features may suggest a diagnosis of malignancy.
Computed tomograms are helpful in that they are
negative. On biopsy, no diagnostic features are identi-
fi ed. The disease is self-limited, and treatment consists
of management of pain and prevention of fracture. It
is important for clinicians and radiologists to be aware
of the condition so that an unnecessary biopsy is not
per formed. F igu r e 26.139. Gross specimen of a brown tumor of h yper-
parathyroidism removed from the jaw. It is red-brown and
resembles gian t cell tumor.
TRAU MATIC OSTEOLYSIS

Traumatic osteolysis is a condition involving the lateral

portion of the clavicle. Patients usually complain of pain
and may give a history of injury to the area. The injury

F igu r e 26.140. O sseous lesion of h yperparath yroidism.

A: A fi brogenic giant cell-containing area ( left) merges with
an osteoid-producing area ( right) . B: High-power view of the
area containing multinucleated giant cells. The stroma is
more fi brogen ic than th at typically seen in gian t cell tumor.
C: The osteoid-producing area resembles fi brous dysplasia.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 369

F igu r e 26.141. Traumatic osteolysis in volvin g th e

right clavicle in a 28-year-old man . Th e distal end
of th e clavicle h as disappeared. ( Case provided by
Dr. Daniel D. Benninghoff, Greenwich Hospital
Association , Greenwich , Con n ecticut.)

may have involved hyperextension in the shoulder

joint. Radiographs show apparent loss of the distal por-
tion of the clavicle ( Fig. 26.141) . No soft-tissue mass is
identifi ed. Biopsy does not show any diagnostic change.
Biopsy is not necessary if the lesion is recognized clini-
cally and radiographically.

BON E IN FARCT

In farction of bone is common after decompression sick-

ness as in caisson workers and patients with sickle cell
anemia. In a surgical practice, infarction is seen most
commonly in the femoral head. Femoral head necrosis
may be associated with a specifi c cause, such as corti-
costeroid therapy, or it may be idiopathic. Patients usu-
ally complain of pain in the hip. Radiographs show an
area of lucency, with a zone of hazy sclerosis around
it. Later, the articular cortex may collapse. The gross
specimen has a crescentic zone of yellow discoloration
in the area of the femoral head immediately adja-
cent to the articular cartilage. Because of loss of sub-
stance in this area, th e articular cartilage may appear F igu r e 26.142. Anteroposterior standing radiograph of th e
depressed and may lift off from the bone. The area of kn ees in a 60-year-old patien t sh ows th e classic radiograph ic
necrosis is frequently surrounded by an area of sclerosis features of medullary in farcts in both distal femoral diaph y-
ses an d metaph yses. Th e in farcts presen t as patch y mixed lytic
( Figs. 26.142 & 26.143) .
and sclerotic lesions in the medullary canal with well-demar-
Infarcts of bon e can be idiopathic, usually involving cated periph eral margin s of sclerosis th at h ave a serpigin ous
the metaphysis of long bones. In the early stages, the morph ologic appearan ce.
radiographs may be n egative. As the lesion evolves, it
becomes mineralized. Typically, the mineral is situated
along the edges of the lesion. Because of the presence Microscopically, infarcts of bone have nonviable
of calcifi cation, the lesion is frequently mistaken for a bony trabeculae. These are manifest as bony trabeculae
cartilage tumor. In a chondroid neoplasm, th e lesion in which the osteocytic lacunae appear empty. However,
usually is mineralized throughout, whereas in an infarct, the lack of nuclei in lacunae cannot be taken as an abso-
the mineralization is at the periphery. lute sign of an infarct because this appearance may be
370 Chapter 26 ■

F igu r e 26.143. Bone infarct. A: Anteroposterior and, B: lateral radiographs of the left knee show
patchy areas of lucency and sclerosis in the distal femur and proximal tibia compatible with multi-
ple bone infarcts involving the medullary canal and subchondral regions. C: Sagittal proton density
magn etic reson ance image of th e kn ee an d, D: Coronal T2-weigh ted magnetic resonance image of
the tibia with fat suppression shows typical imaging features of medullary infarcts with irregularly
margin ated lesions th at h ave fat-sign al in ten sity cen trally.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 371

F igu r e 26.145. O steoblastic osteosarcoma associated with

an infarct involving the distal femur in a 60-year-old woman.
Th e in traosseous compon en t h as th e well-circumscribed
appearance of an infarct. The soft-tissue mass is irregularly
min eralized. An infarct also is presen t in th e proximal tibia.
( Case provided by Dr. Gerson Paull, Crawford Long Hospital
at Emory University, Atlanta, Georgia.)

F igu r e 26.144. A an d B: Necrotic osseous trabeculae with

empty osteocytic lacunae surrounded by amorph ous mineral-
ization of fi brotic degenerated marrow.

artifactual, produced by over-decalcifi cation. Infarcts,

however, also show changes in the marrow in the form
of fat necrosis. In later stages, the necrotic fat is replaced
by amorphous calcifi cation ( Fig. 26.144) . Infarcts of
bone may be associated with secondary aneurysmal
bone cyst. The radiographic appearance may suggest a
sarcomatous change an d infarct.
Several examples of sarcoma in association with an
infarct have been described. The Mayo Clinic fi les con-
tain seven examples of sarcoma arising in association F igu r e 26.146. Malignant fi brous histiocytoma associated
with an infarct involving the proximal tibia in a 65-year-old
with infarcts: two osteosarcomas, three fi brosarcomas, woman. The infarct has mineralization at the periphery. ( Case
and two malignant fi brous histiocytomas ( Figs. 26.145 & provided by Dr. Donald J. Schreiber, Marshfi eld Medical Cen-
26.146) . ter Laboratory, Marshfi eld, Wisconsin.)
372 Chapter 26 ■
F igu r e 26.147. A: Bon e islan d in volvin g th e ilium. Th e lesion is extremely den se an d h as regular
margin s. B: Bon e islan d in volvin g th e femoral h ead. Th is was an in ciden tal fi n din g. Th e lesion h as
the appearance of dense bone and has an irregular outline.
BON E ISLAN D
Bone islands ( enostosis) are manifested as an area of
density on radiographs. They are usually small, densely
sclerotic, and have a tendency to have spiculated edges,
producing a thornlike appearance ( Fig. 26.147) . They
generally are positive on bone scans. Although usually
small, large examples have been described. The appear-
ance may be mistaken for blastic metastasis. However,
the radiographic appearance is characteristic en ough
to preclude this mistake. If biopsy is per formed, corti-
cal-appearing bone is seen within the medullary cavity.
Osteopoikilosis, a condition in which multiple areas of
sclerosis are seen within bone, has the same histologic
appearance as bone islands.
H AMARTOMA (MESEN CH YMOMA)
OF TH E CH EST WALL
This extremely rare lesion has been known by several
names, including chest wall hamartoma in infancy, mes-
enchymal hamartoma of the chest wall, and vascular and
cartilaginous hamartoma of the ribs. Unfortunately, these
lesions have also been mistaken for, and called, malig-
nant mesenchymoma.
The lesion always occurs in infancy and always on the
chest wall. Hamartoma of the chest wall may be diag-
nosed in utero. The infants have an obvious chest wall
mass, and its size may affect breathing. The lesion may
also cause mechanical problems with delivery.
Radiographs show an extrapleural mass that is almost
always mineralized ( Fig. 26.148) . One or more ribs in
the center of the lesion are destroyed, and those at the
periphery appear deformed by the lesion.
Grossly, there are cystlike areas and islands of carti-
lage. Microscopically, there is proliferation of cartilage,
which is frequently hypercellular. However, the lesions
also have enchondral ossifi cation, giving rise to an epi-
physeal platelike appearance. Trabeculae of bone with
spindle cells are also present. Very characteristically,
areas that resemble aneurysmal bone cysts are also seen
( Fig. 26.149) .
The prognosis is good, and the lesion should regress.
It is important not to overtreat these lesions.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone 373

F igu r e 26.148. Computed tomogram showing a

large mesenchymal hamartoma involving the chest
wall in a 10-month-old girl.

F igu r e 26.149. Mesenchymal hamartoma of the chest wall.

A: Proliferatin g cartilage with a column ar arran gemen t of th e
cells an d maturation to bon y trabeculae simulate th e appearan ce
of an epiph yseal plate. B: Area domin ated by proliferatin g spin -
dle cells without cytologic atypia. C: Cavernous spaces and septa
like those of aneurysmal bone cyst.
374 Chapter 26 ■

STERN OCLAVICU LAR H YPEROSTOSIS

Sternoclavicular hyperostosis, an uncommon condi-

tion, was fi rst described in Japan. Although much more
common in that country, it has been described in other
parts of the world. Patien ts present with swelling and
pain in the upper chest wall. Plain radiographs show
sclerosis and swelling in the area involving the fi rst
rib, th e medial end of the clavicle, and the sternum.
Mineralization may be present in the space between
the medial end of the clavicle and the fi rst rib. These
appearances may suggest a bone-forming neoplasm.
The cause is unknown, and sections merely show thick-
ened bony trabeculae.
A promin en t costoch on dral jun ction , especially of
th e secon d rib, may also simulate a n eoplasm clin ically.
F igu r e 26.150. Calcifyin g pseudon eoplasm of th e n euraxis.
Radiograph s are typically n egative. A segmen t of th e Nodules of blue-gray calcifi cation surroun ded by h istiocytes
costoch on dral jun ction may be removed surgically. and multinucleated giant cells impart a granulomatous
Microscopically, th e cartilage stain s pale blue an d is appearance.
h ypocellular. Th e presen ce of cartilage in th e ch est
wall may suggest th e diagn osis of ch on drosarcoma.
H owever, th e cartilage in a n ormal costoch on dral
jun ction is very h ypocellular an d lacks th e features lack of in nervation of the joint and repeated trauma.
of a n eoplasm. Kn owledge of th e con dition an d th e Patients may presen t with a pain less swellin g that may
fact th at th e plain radiograph s do n ot sh ow a mass mimic a soft-tissue sarcoma. Radiograph s show swellin g
lesion sh ould h elp to avoid th e mistaken diagn osis of of soft tissue and a rapid destruction of th e segment
ch on drosarcoma. of bon e next to the joint. Th ere may be complete loss
of the h umeral head or femoral h ead, almost as if th e
bon e has been tran sected with a kn ife. Radiograph s
also sh ow calcifi c debris in th e distended join t capsule
CALCIFYIN G PSEU D ON EOPLASM
( Fig. 26.151) . The h istologic ch an ges of neuropath ic
OF TH E N EU RAL AXIS
joint are n ot specifi c. Fragmen ts of articular cartilage
an d bon e are embedded in th e syn ovium ( Fig. 26.152) .
Bertoni and coauthors described 14 patients with a
Th ese ch anges are similar to th ose in degen erative join t
neoplasm-like lesion that involved predominantly the
disease. Th e key to diagn osis is correct radiograph ic
neural axis. The lesions tended to involve the spinal
in terpretation.
cord, usually in the adjacent soft tissue at the level of
the intervertebral disk. Some of the lesions involved the
skull or even the brain. Patients complained of pain or
PIGMEN TED
other neurologic symptoms. Radiographs show a cal-
VILLON OD U LAR SYN OVITIS
cifi ed mass in an extradural location. Microscopically,
there are nodules of calcifi cation with a granuloma-
Pigmented villonodular synovitis is a disease of major
tous appearance. Th e calcifi ed material is surrounded
joints of unknown cause. It almost always is mon oarticu-
by epithelioid histiocytes and benign giant cells
lar. Patients usually have a long history of painful swell-
( Fig. 26.150) . The lesion appears to be nonneoplastic
ing of the joint. Radiographs may show distention of the
and may be related to synovial cysts of the facet joint of
joint, with erosion into bones on both sides. Lucencies
a degenerated intervertebral disk.
in bones on either side of a joint are very typical of pig-
mented villodonular synovitis.
Grossly, th e synovium is thickened and brown.
N EU ROPATH IC JOIN T Microscopically, villous hyperplasia of the synovium
is seen. The villi con sist of proliferating synovial cells
Neuropathic join t ( Ch arcot join t) may in volve major admixed with benign giant cells. Foam cells and hemo-
joints such as the h ip or th e sh oulder or small join ts of siderin pigmentation are also identifi ed ( Fig. 26.153) .
th e foot. Th e lesion is produced by a combin ation of Hyperplasia of the synovium may be seen in various
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone
F igu r e 26.151. Lateral radiograph ( A) an d sagittal T1-weigh ted,
sagittal in version recovery ( B) an d coron al T1-weigh ted ( C) mag-
netic resonance images of the left foot sh ow advanced destructive
ch an ges in volvin g multiple join ts of th e midfoot an d h in dfoot,
with associated joint subluxations, fragmentation and increased
density of the bones, joint effusions, and extensive periarticular
soft tissue swellin g an d osseous debris. Th e imagin g features are
ch aracteristic of neuropath ic join t disease.
condition s, including degenerative join t disease. H ow-
ever, in these condition s, there is no proliferation of the
synovial cells. The involvement of bone may suggest the
diagnosis of sarcoma.
PERIOSTEALLY LOCATED TU MORS
A wide variety of tumors involve bone by coaption or
erosion from without. Some of these may begin in the
periosteum, but many arise from the periosseous tis-
sues. Desmoid tumors often secondarily involve bone,
375
especially in the region of the forearm. Giant cell
tumors of tendon sheath origin occasion ally erode,
sometimes extensively, into small bones of the hands
and feet. Some tumors, for example, synovial sarcoma
and epithelioid sarcoma, frequently invade nearby
bone. Some juxtaosseous tumors such as hemangiomas
and lipomas produce confusingly prominent reactive
changes in nearby bone. Tumoral calcinosis may pro-
duce a huge mineralized mass juxtaposed to skeletal
structures, especially at the hip and elbow. The lesion is
composed of amorphous calcifi c masses with associated
foreign body giant cell reaction.
376 Chapter 26 ■

F igu r e 26.152. Neuropathic joint. A: Fragments of bone and cartilage are embedded in the syno-
vium. B: Pieces of cartilage and calcifi ed bone are often admixed with fi brinous debris.

F igu r e 26.153. Pigmented villonodular synovitis. A: Low-power

view of the lesion shows a villonodular growth pattern. Hemo-
siderin deposition is also visible. B: Other areas of the lesion
contained sheets of foamy histiocytes merging with immature
synovial cells. C: High-power view of the diagnostic synovial cells
with round nuclei surrounded by eosinophilic cytoplasm.
 ■ Conditions T hat Commonly Simulate Primary Neoplasms of Bone
MISLEAD IN G RAD IOGRAPH S
Although radiographs nearly always show the lesion and
indicate whether it is benign or malignant, sometimes
they are misleading. Infections of bone may simulate
neoplasm; a benign process may mimic malignant dis-
ease. Rarely, radiographic fi ndings are suggestive of dis-
ease that is not present. Correct interpretation demands
skilled analysis. Magnetic resonance images may be too
sensitive and show chan ges where no disease exists. This
is especially true around neoplasms, where edema or
some other kind of reaction may suggest extensions of
the tumor.
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Odontogenic and Related Tumors
Th e jawbon es are susceptible to special tumors th at
derive from th eir den tal structures. Th ese lesion s
sim u late n eoplasm s of osseous derivation . Th e fol-
lowin g tabulation of th ese special tum ors, sh ort an d
som ewh at sim plifi ed, sh ould be useful to th e gen -
eral path ologist. Th is sh ort list in cludes m ost of th e
special lesion s th at th e gen eral path ologist is likely
to en coun ter: am eloblastom a, calcifyin g epith elial
odon togen ic tum or ( Pin dborg tum or) , am eloblastic
fi brom a, ameloblastic odon tom a, complex odon tom a,
m yxom a ( fi brom yxom a) , an d aden om atoid odon to-
gen ic tum or ( am eloblastic aden om atoid tum or) . Sev-
eral years ago, th e term odontogenic mixed tumor was
suggested an d in cluded am eloblastic fi brom a, am elo-
blastic odon tom a, an d com plex an d com poun d odon -
tom a. Th is design ation ackn owledges th at h istologic
overlap is seen am on g m em bers of th is group an d
suggests th at th ey are h am artom atous m alform ation s
of th e odon togen ic an lage. Peculiarly, th e fi brous
portion of th ese tum ors m ay becom e m align an t an d
produce a rare odon togen ic sarcom a, in cludin g
am eloblastic sarcom a.
Bone tumors generally found in the other areas of
the skeleton may occur in the jaws; hence, pathologists
interested in bone tumors become involved with lesions
of odontogenic origin and, therefore, peculiar to the
jawbones.
Some special ch aracteristics of tumors of th e jaws
must be recogn ized. O steoch on dromas practically
n ever occur in th e jaws. Ben ign ch on droblastomas an d
ch on dromyxoid fi bromas in th ese bon es are path o-
logic curiosities, an d th e few recorded cases ten d to
be atypical. Th e h istopath ologic features of osteoblas-
tomas overlap th ose of so-called cemen toblastomas
( see Ch apter 10) . Gian t cell tumors of th e type foun d
in oth er bon es occur rarely, if ever, in th e jaws, with
th e possible exception of th ose few th at develop in
Paget disease. Ch on drogen ic n eoplasms of th e jaws
are n early always malign an t; on e must be aware, h ow-
ever, of ch on droid differen tiation in a callus or in
h eterotopic ossifi cation in th is region . O steosarcoma
C H APT ER
27
h as been easier to cure wh en it arises in th e jaws th an
wh en it arises in oth er skeletal sites; in th ese small
bon es, th e lesion develops in somewh at older patien ts
an d sh ows better ( an d often more) ch on droid differ-
en tiation . Adaman tin oma of lon g bon es is a differen t
tumor from ameloblastoma, alth ough h istologic simi-
larities exist.
Giant cell ( reparative) granuloma is distinctively
a tumor of the jaw, but a similar process occasionally
affects the supramaxillary region and, on rare occasions,
even bones at other sites. Aneurysmal bone cyst is prob-
ably closely related to giant cell reparative granuloma
of the jaw, and a classic example is sometimes found
there. Synovial chondromatosis occasionally affects the
temporomandibular joint. Metastatic carcinoma can
simulate a primary tumor of the jaw.
Although included in many classifi cations, dentino-
mas are probably variants of some of the above hama-
rtoma-like tumors, such as ameloblastic odontomas.
Cementifying fi broma ( periapical fi brous dysplasia)
derives from specialized bone around the dental roots
and, thus, is not strictly odontogenic. Bulbous masses of
densely ossifi ed material surrounding dental roots are
considered to be cementomas.
Cysts of th e jaws are usually lin ed by squamous
epith elium. Referen ce to th e h istory an d radiograph s
is n ecessary for determin in g wh eth er th ese cysts are
related to un errupted teeth or to residual epith elial
islan ds after den tal extraction or wh eth er th ey h ave
some oth er gen esis. Keratocyst h as become recogn ized
as th e correct design ation for a cyst of th e jaw th at
typically h as a th in n er epith elial lin in g, lacks sign ifi -
can t basal zon e irregularity like th at of rete pegs, an d
sh ows keratin ization at th e sur face ( Figs. 27.1–27.2) .
Th ese cysts h ave an an n oyin g capability to recur, are
often multicen tric, an d may be associated with various
abn ormalities of basal cell n evus syn drome. Th ese are
sometimes referred to as primordial cysts. O ccasion ally,
degen erative alteration with calcifi cation of th e epith e-
lium produces wh at h as been called calcifying epithelial
odontogenic cyst. Th ese cysts an d th e h emorrh agic or
381
382 Chapter 27 ■
F igu r e 27.1. Keratocyst of th e man dible. A: Radiograph ic
appearance ( arrowheads indicate outline of cyst) . B: In this
area, the keratocyst epithelial lining is partially detached and
sh ows sign s of degen eration of th e epith elial cells, some of
which have become mineralized.
traumatic cysts of th e jaw, wh ich h ave n o lin in g, pose
little diagn ostic problem for th e h istopath ologist.
Benign fi bro-osseous lesions of the jaws are relatively
common. They have such a wide variation in the amount
of osseous component that they defy strict classifi cation
( Fig. 27.3) . Pathologically, the lesions fi t into the general
category of fi brous ( fi bro-osseous) dysplasias. Benign,
densely collagenous, fi broblastic tissue contains a vari-
able amount of bone that typically arises as a metaplastic
change in the tissue. Occasional lesions are large expan-
sile masses that may bulge into and destroy the sinuses,
for which the term fi brous osteoma or osteofi broma is pre-
ferred by some. Most are centrally originating lesions
that vary greatly in size and radiopacity. On radiographs,
the lesion may be noted incidentally or may greatly
distort the bone. A small proportion of the lesions are
F igu r e 27.2. A: Keratocyst with regular border alon g
underlying connective tissue, no infl ammatory component,
and a thin epithelial cell layer with keratinization at the sur-
face. B: The squamous epithelial lining becomes thin and
ulcerated because of a prominent infl ammatory component.
part of the polyostotic fi brous dysplasia complex. Even
cherubism, with its fi brous expansion of the jaws of chil-
dren, that is characteristically familial and bilateral and
tends toward spontaneous resolution, is often called
fi brous dysplasia. The least conspicuous end of the spec-
trum is periapical fi brous dysplasia. All these fi bro-
osseous lesions are benign, although they may recur.
Conservative surgical management is indicated. Unless
exposed to radiation therapy, the lesions have little ten-
dency to malignant change. Some osteosarcomas of the
jaws are so lacking in overt anaplasia that they are diffi -
cult to differentiate from fi brous dysplasia. Fibrous dyspla-
sia and fi bro-osseous lesion were the terms applied to the
various members of this group by Waldron and Gian-
santi, who concluded that although similarities exist, the
lesions generally can be separated into these two families
 ■ Odontogenic and Related Tumors 383

F igu r e 27.3. A: Fibrous dysplasia of th e jaw. Th is ch aracteristic pattern may occur in lesion s of th e
jaw in patien ts with polyostotic in volvemen t, even in Albrigh t syn drome. B: Fibro-osseous “lesion .”
Because such tumors may resemble those of fi brous dysplasia, radiographic and surgical fi ndings
are essen tial to in terpretation .

of diseases. Fibrous dysplasias tend to be diffuse, whereas

benign fi bro-osseous lesions tend to be extremely well
demarcated. Benign fi bro-osseous lesions also appear
more active in having osteoblastic and osteoclastic
activity. The World Health Organization classifi cation,
although relatively elaborate, is useful because it is reli-
able and valid and most of the lesions encountered can
be assigned to an appropriate grouping.
This chapter is not meant to supplant standard texts
on this complex subject. Some of the lesions are rare;
for instance, only one melanotic progonoma has been
recognized in the Mayo Clinic series.

AMELOBLASTOMA F igu r e 27.4. Ameloblastoma formin g a solid an d partially

Ameloblastoma is the most common of the odontogenic
tumors in the Mayo Clinic series; yet, it comprises only
about 1% of the cysts and tumors seen in the region of
the maxilla and mandible. There were approximately
230 ameloblastomas in the Mayo Clinic series through
2003. During this same period, there were 137 osteosar-
comas that involved the jawbones.
Females predominated by a ratio of 4:3. Most
patients with ameloblastoma are young adults. The
youngest patient with an ameloblastoma in the Mayo
Clinic fi les was 7 years old. Only 10 patients were in
the fi rst two decades of life. More than 60% of the
patients were in the third through fi fth decades of
life. About 80% of the lesions arose in the mandible,
most commonly in the molar-angle region ( Fig. 27.4) .
Being slow growing, the tumor is usually painless. Swell-
ing is the usual symptom. Radiographs typically show
a coarsely trabeculated zone of osseous destruction
cystic mass in the man dible of a 37-year-old woman wh o pre-
sen ted with th e complain t of loose teeth .
that has the appearance of a multilobular cystic cavity
( Fig. 27.5) . The bone often appears to be replaced
by several well-defi ned radiolucent areas that give the
lesion a honeycomb or soap-bubble confi guration. The
tumor may be so predominantly cystic that a squamous
epithelial-lined cyst with incidental nonneoplastic
ameloblastic elements in its wall becomes a differential
consideration. The histologic appearance of amelo-
blastoma is typical but variable. The predominant fea-
ture is the proliferation of epithelial cells with varying
amounts of surrounding fi brous tissue. Some lesions
are quite cellular, with little fi brous connective tissue,
whereas others show widely separated epithelial islands
with fi brous connective tissue. The epithelial cells char-
acteristically have what have been termed a follicular
384 Chapter 27 ■
F igu r e 27.5. Recurren t multilocular ameloblastoma of th e
anterior part of the mandible.
pattern, in which the epithelial cells are arranged in a
palisading pattern at the periphery with central, more
loosely arranged tissue suggesting a stellate reticulum
( Figs. 27.6A & 27.7) . The cells at the periphery are
columnar and have the appearance of basal cells. They
do not show any signifi cant cytologic atypia. The term
plexiform pattern is used when epithelial cells tend to
form an astomosing chords ( Fig. 27.6B) . Occasionally,
a cellular variant may resemble spindle cell sarcoma.
Squamous metaplasia is relatively frequent and may
be so extensive as to suggest a diagnosis of squamous
cell carcinoma. However, the squamous cells do not
show cytologic atypia ( Fig. 27.8) . Some ameloblastomas
have a trabecular pattern and resemble ameloblastic
fi broma ( Fig. 27.9) . Rare ameloblastomas contain cells
that are granular; such cells may comprise the entire
tumor. At times, ameloblastomas are so vascular that
they have been called ameloblastohemangiomas. By defi -
nition, ameloblastoma does not produce recognizable
mature dental substances. One of the ameloblastomas
occurred in a patient with basal cell nevus syndrome.
The histogenesis of melanoameloblastomas ( melanotic
progonoma, retinal anlage tumor) is obscure, but this
rare tumor of infancy is nearly always found in the jaws,
especially in the maxilla.
O ccasion ally, an ameloblastoma h as con n ection s
with th e overlyin g oral mucosa. Th is con n ection prob-
ably results from th e growth of th e tumor up to th e sur-
face an d does n ot in dicate an origin from th e mucosa
( Fig. 27.10) .
F igu r e 27.6. Typical low-power appearan ce of ameloblas-
toma. A: Th is example of a follicular pattern sh ows variably
sized n ests of epith elial cells separated by fi brous tissue. B:
Th is plexiform pattern con tain s larger dilated spaces sur-
rounded by anastomosin g cords of odon togen ic epithelium
and less intervening stroma.
Ameloblastomas are locally aggressive tumors, and
conservative but total removal is indicated. A cystic
variant of ameloblastoma has been suggested to have a
better prognosis.
Distant metastases are extremely uncommon with
ameloblastoma. We have seen 4 examples of metastatic
ameloblastoma to the lung. The histologic features
were typical of ameloblastoma, with no cytologic fea-
tures suggesting malignancy. Laughlin reported on a
case of ameloblastoma with widespread metastasis and
found 42 other previously reported cases. Ameloblasto-
mas with malignant change and ameloblastic carcino-
mas have also been reported. The distinction may be
diffi cult to make on a histologic basis. Epithelial tumors
with clear cells and an aggressive course have also been

F igu re 27.7. A: Epithelial cells are arranged in a palisading
fashion at the periphery of an island containing central loosely
arranged stellate cells. B: The center of this island contains a
more cellular population of plump spindle cells. Cystic change
is also present.
F igu r e 27.8. Squamous metaplasia is often seen in amelo-
blastoma.
■ Odontogenic and Related Tumors 385
F igu r e 27.9. A: Trabecular pattern occasion ally seen in
ameloblastomas mimics somewhat the histologic appearance
of ameloblastic fi broma. Th e ch aracteristic fi brous compo-
n ent of the latter lesion is lacking. B: Gran ular cells such as
the ones seen here compose part of an ameloblastoma in rare
instances.
F igu r e 27.10. Ameloblastoma erodin g to an d approach in g
th e gin gival epithelium.
386 Chapter 27 ■

described. Salivary gland carcinomas such as mucoepi-

dermoid carcinoma have been reported to arise primar-
ily within jawbones.

CALCIFYIN G EPITH ELIAL

OD ON TOGEN IC TU MOR
(PIN D BORG TU MOR)

Calcifyin g epith elial odon togen ic tum or m ay be a

varian t of am eloblastom a. Th e clin ical features are
sim ilar to th ose of am eloblastom a. Th ere h ave been
11 exam ples of Pin dborg tum or in th e Mayo Clin ic
fi les. Th ese tumors occur in adulth ood an d grow
slowly to become m an ifest as a swellin g of th e jaw.
Radiograph s sh ow a well-defi n ed defect th at may be
calcifi ed ( Fig. 27.11) .
As the name indicates, the predominant feature is
a cellular proliferation. Th e cells appear epithelial and F igu r e 27.11. Pin dborg tumor ( calcifyin g epith elial odon -
have abundant eosinophilic cytoplasm. The nucleoli togen ic tumor) of extremely slow growth .
may be prominent, suggesting a metastatic carcinoma.
Calcifi c foci, in the form of tiny spherules, are typical.
Eosinophilic amorphous material that stains like amy-
loid is commonly seen ( Fig. 27.12) . Occasionally, the
tumor contains large amounts of this material, with only
tiny foci of epithelial islands. In addition, we have seen
one example with an associated carcinoma.

AD EN OMATOID OD ON TOGEN IC
TU MOR (AMELOBLASTIC
AD EN OMATOID TU MOR)

Th is tumor, also called adenoameloblastoma, sh ould be

distin guish ed from ameloblastoma because it respon ds
to con ser vative surgical removal an d h as little ten den cy
to recur. It is much less common th an ameloblastoma.
Th rough Jan uary 1, 2004, th e Mayo Clin ic fi les con -
tain ed on ly 11 examples. Most of th e patien ts are in
th e secon d decade of life. Approximately two-th irds
of th e tumors in volved th e maxilla, an d n early all of
th em were located an terior to th e fi rst th ree molars.
Patien ts usually complain of swellin g or th e lesion may
be an in ciden tal radiograph ic fi n din g.
Radiograph ically, th e tumor produces a cystlike
zon e th at may display calcifi c material in a stippled
pattern ( Fig. 27.13) . Th e cyst often con tain s an
un errupted tooth an d resembles a den tigerous cyst.
Grossly, th e lesion is often cystic, an d th e solid tissue
may fi ll on ly a fraction of th e cavity. Microscopically,
th e tumor is ch aracterized by tubular, ductlike struc-
tures lin ed with column ar or cuboidal epith elium.
Th e cen tral spaces in some of th ese ductlike struc- F igu r e 27.12. Pindborg tumor. A: Mineralized portion asso-
tures are empty, oth ers are fi lled with acidoph ilic ciated with epithelial cells. B: The nodular acellular pale pink
material, an d still oth ers are lin ed by a layer of pin k material is amyloid an d stain ed positive with Con go red.

F igu r e 27.13. Ameloblastic aden omatoid tumor. Cystlike
lesion contains upper right premolar tooth.
h yalin e material ( Fig. 27.14) . Small calcifi ed sph er-
ules or even larger min eralized masses may be foun d,
sometimes with in th e tubular spaces. Masses of cells
th at produce wh orllike structures are foun d amon g
th e glan dular-appearin g elemen ts ( Fig. 27.15) . Th ese
epith elial cells sometimes resemble th e stellate reticu-
lum of ameloblastomas, but th ey usually are distin ctly
spin dle sh aped. Th ese n ests of cells lie outside th e
glan dular compon en t, wh ich is in strikin g con trast to
th eir location with in th e palisade of column ar cells in
ameloblastoma. Alth ough th e cells are closely packed,
th ey are regular in size an d sh ape an d do n ot appear
to be an aplastic. Th e progn osis is excellen t, with local
curettage bein g curative.
AMELOBLASTIC FIBROMA
This lesion, also called soft mixed odontoma, is rare.
Only 14 examples are found in the Mayo Clinic fi les.
Eight of the patients were males. This lesion affects
young patients, with half of the patients being younger
than 10 years. Three patients, however, were older
than 30 years. Of the 14 tumors, 11 involved the man-
dible, usually the bicuspid-molar region. Generally,
there is painless swellin g, and the lesion may be found
incidentally on radiographs, where it produces a well-
circumscribed cystlike radiolucent zone. Occasion-
ally, an unerrupted tooth is associated with th e tumor.
■ Odontogenic and Related Tumors 387
F igu r e 27.14. A: An oth er example of aden omatoid odon -
togen ic tumor con tain in g n umerous tubular or ductlike
structures. B: Th e tubular structure con sists of a cen tral
space surroun ded by cuboidal to column ar cells. A th in
h yalin e-appearin g lin in g is presen t.
Grossly, the tissue is a soft fi brous mass. Proliferation
of mesenchymal and epithelial odontogenic elements
characterize this tumor. In contrast to ameloblastoma,
in which the connective tissue is not part of the neoplas-
tic process, ameloblastic fi broma contains an actively
proliferating fi broblastic component with plump nuclei
that show little variation in size and shape. There are
buds, chords, and islands of epithelial cells that usually
are only a few cell layers thick ( Fig. 27.16) . Peripheral
cells tend to become columnar, as in ameloblastoma. If
many sections of an ameloblastic fi broma are studied,
one may fi nd evidence of hard dental structures such as
dentin and enamel. Hence, this tumor overlaps histo-
logically with ameloblastic odontoma, and both lesions
probably should be regarded as hamartomas of a more
primitive type than of the composite and compound
odontomas.
388 Chapter 27 ■
Figure 27.15. Adenomatoid odontogenic tumor. A: Whorled
masses of plump spin dle cells con tain in g n umerous small
ductular structures adjacent to a zone containing smaller
round- to oval-shaped cells with dilated cystic spaces. B: High -
power appearance of larger ductular structures. C: Nodular
masses of calcifi cation with in th e lesion .
F igu r e 27.16. Ameloblastic fi broma A: Branching nests of
ameloblastic cells and associated fi broblastic proliferation. B:
Fibrous tissue containing short spindle-shaped cells surround-
ing epithelial nests.
Nearly all ameloblastic fi bromas are easily cured with
conservative surgical means, but there is a malignant
counterpart in which fi brosarcoma arises in stroma.
There are two such cases in the Mayo Clinic fi les, and
several other cases have been documented.
AMELOBLASTIC OD ON TOMA
This tumor occupies a place between ameloblastic
fi broma and compound and complex odontomas. It
contains foci of proliferating ameloblastic cells, which
introduce the hazard of mistaking the lesion for amelo-
blastoma. Dentin and enamel, which are present in a
poorly organized state, differentiate ameloblastic odon-
toma from ameloblastoma and indicate the former’s
 ■ Odontogenic and Related Tumors 389

F igu r e 27.17. Low-power ( A) and high-power ( B) appearance of ameloblastic fi bro-odontoma.

In addition to areas th at resemble ameloblastic fi broma, th e lesion con tain s foci of en amel an d
dentin matrix.

F igu r e 27.18. Complex odon toma. A: Th e lesion h as poorly formed but recogn izable den tal
structures. B: High er magn ifi cation sh ows irregular masses of den tin .

basically hamartomatous nature ( Fig. 27.17) . Parts of COMPLEX OD ON TOMA

ameloblastic odontoma may resemble ameloblastic
fi broma. The Mayo Clinic fi les contain 11 cases of this
rare tumor; all patients were younger than 20 years.
An y part of either jaw may be affected; only 4 of the
11 tumors were in the maxilla. Gorlin and coworkers,
in 1961, found a predilection for the premolar and
molar areas. This tumor may cause delayed eruption or
irregular position of teeth and swelling of the alveolar
process. The cystlike zones seen on radiographs may
contain small or large radiopaque bodies. Nearly all
these well-circumscribed tumors are readily cured with
conservative surgical means, but sarcomatous change in
the connective tissue has been observed on very rare
occasions.
This tumor lacks ameloblastic tissue, corresponding to
a later stage of development of teeth than does amelo-
blastic odontoma. A disorderly mixture of h ard, dental
elements characterized this lesion ( Figs. 27.18 & 27.19) .
Well-formed toothlike structures are not found.
Although it is considered to be somewhat more com-
mon in females, such a predilection was not found
among the 26 patients whose cases are in the Mayo
Clinic fi les. Complex odontoma is found most often in
older children and in young adults. The lesion has a
predilection for the molar portion of the lower jaw. The
lesion is usually an incidental radiographic fi nding and
is readily cured with simple removal.
390 Chapter 27 ■

F igu r e 27.19. An oth er example of complex odon toma situ-

ated in soft tissue.

F igu r e 27.20. Compoun d odon toma. Differen tiation

toward teeth is defi n ite.

COMPOU N D OD ON TOMAS

These tumors are composed of grossly recognizable

teeth, although the teeth tend to be small and deformed
( Fig. 27.20) . The number of teeth vary from three
or four to many hundred. Complex and compound
odontomas merge with one another, being arbitrarily
differentiated on the basis of the degree of morphodif-
ferentiation of the teeth. Both lesions are completely
benign. Compound odontoma tends to occur in the
incisor-cuspid region; there were 14 examples in the
Mayo Clinic fi les.

F igu r e 27.21. A: Expan din g “multicystic” myxoma th at

MYXOMA (FIBROMYXOMA)
Myxomas of bone nearly always occur in the jaws, which
suggests they are probably of odontogenic origin. This
extended from the second bicuspid to the coronoid process
of th e righ t man dible. B: Myxoma with scan ty, small cells an d
ch aracteristic slightly fi brillar an d almost tran sparen t matrix.
C: More cellular myxomas such as this have not been associ-
ated with poorer prognosis.

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suggestion is supported by the resemblance of these
tumors to the mesenchymal portion of the tooth germ.
Some chondrosarcomas and even fi brosarcomas of the
rest of the skeleton show such prominent myxomatous
alteration, probably as a result of degeneration, that they
have been classifi ed erroneously among the myxomas
an d myxosarcomas. There are 42 examples of myxomas
of the jawbones in the Mayo Clinic fi les. There is a slight
male predilection. Although any age may be affected,
most patients are young adults. The youngest patient in
our series was 1.5 years old and the oldest was 56 years.
The upper and lower jaws are affected about equally.
This slowly growing lesion is usually painless but causes
gradually progressive swelling; at times, severe facial
deformities result. The tumors may be seen on radio-
graphs as multilobular and unilocular. They cannot be
distinguished from other cystlike rarefying expansile
lesions of the jaws ( Fig. 27.21A) .
Grossly, th e tumor is soft an d semitran slucen t an d
may h ave a glisten in g sur face. Loose stellate cells
domin ate th e h istologic pattern ( Fig. 27.21B) . Th e
cells h ave lon g an astomosin g cytoplasmic processes.
Th e in tercellular substan ce may be somewh at gran u-
lar an d basoph ilic. Some myxomas are h ypocellular
an d obviously ben ign . O th ers con tain relatively large
an d bizarre n uclei, fi n din gs th at suggest th ey are more
active, but follow-up studies in dicate n o correlation
between cytologic abn ormality an d ability of th e tumor
to recur. O ccasion ally, zon es with in myxomas sh ow
con siderable fi bromatous quality, but th is does n ot
appear to affect th eir clin ical beh avior ( Fig. 27.21C) .
Th e stromal elemen ts of tooth buds may be mistaken
for myxomas h istologically. H owever, th ese tooth buds
are ch aracterized by sh arp circumscription an d th e
presen ce of epith elial cells at th e periph er y.
The available eviden ce suggests that myxoma of the
jaw has the capacity to recur, similar to that of amelo-
blastoma, but does not metastasize. The therapeutic
goal should be total local removal of the lesion. Chon-
drosarcomas, osteosarcomas, and even fi brosarcomas
with myxoid features can simulate myxoma and must
be carefully differentiated from it.
■ Odontogenic and Related Tumors 391
BIBLIOGRAPH Y
1961 Gorlin, R. J., Chaudhry, A. P., and Pindborg, J. J.: Odon-
togenic Tumors: Classifi cation, Histopathology, and Clinical
Beh avior in Man and Domestic An imals. Can cer, 14:73–101.
1975 Waldron, C. A., Giansanti, J. S., and Browand, B. C.:
Sclerotic Cemen tal Masses of the Jaws ( So-called Ch ron ic
Sclerosin g Osteomyelitis, Sclerosin g Osteitis, Multiple En osto-
sis, an d Gigan tiform Cemen toma) . Oral Surg, 39:590–604.
1985 Hansen, L. S., Eversole, L. R., Green, T. L., and Powell,
N. B.: Clear Cell Odon togen ic Tumor: A New H istologic Vari-
ant With Aggressive Potential. Head Neck Surg, 8:115–123.
1985 Takahashi, K., Kitajima, T., Lee, M., Iwasaki, N., Inoue,
S., Matsui, N., Ohki, K., Nagao, K., Akikusa, B., and Matsu-
zaki, O .: Granular Cell Ameloblastoma of the Mandible With
Metastasis to th e Th ird Th oracic Vertebra: A Case Report. Clin
Orth op, 197:171–180.
1985 Waldron, C. A., Small, I. A., and Silverman, H.: Clear
Cell Ameloblastoma: An Odon togen ic Carcin oma. J Oral
Maxillofac Surg, 43:707–717.
1988 Dorner, L., Sear, A. J., and Smith, G. T.: A Case of Amelo-
blastic Carcin oma With Pulmon ary Metastases. Br J Oral Max-
illofac Surg, 26:503–510.
1989 Bang, G., Koppang, H. S., Hansen, L. S., Gilhuus-Moe,
O., Aksdal, E., Persson, P. G., and Lundgren, J.: Clear Cell
Odontogenic Carcinoma: Report of Three Cases With Pul-
mon ary an d Lymph Node Metastases. J O ral Path ol Med,
18:113–118.
1989 Kahn, M. A.: Ameloblastoma in Young Persons: A
Clin icopath ologic An alysis an d Etiologic In vestigation . Oral
Surg Oral Med Oral Path ol, 67:706–715.
1989 Laughlin, E. H .: Metastasizing Ameloblastoma. Cancer,
64:776–780.
1989 McClatchey, K. D., Sullivan, M. J., and Paugh, D. R.:
Periph eral Ameloblastic Carcin oma: A Case Report of a Rare
Neoplasm. J Otolaryngol, 18:109–111.
1989 Ueda, M., Kaneda, T., Imaizumi, M., and Abe, T.:
Man dibular Ameloblastoma With Metastasis to th e Lun gs an d
Lymph Nodes: A Case Report an d Review of th e Literature. J
Oral Maxillofac Surg, 47:623–628.
1990 Waldron, C. A. and Koh, M. L.: Central Mucoepidermoid
Carcin oma of th e Jaws: Report of Four Cases With An aly-
sis of th e Literature an d Discussion of th e Relation sh ip to
Mucoepidermoid, Sialodon togen ic, an d Glan dular Odon to-
gen ic Cysts. J Oral Maxillofac Surg, 48:871–877.
1993 Milles, M., Doyle, J. L., Mesa, M., and Raz, S.: Clear Cell
Odontogenic Carcinoma With Lymph Node Metastasis. Oral
Surg Oral Med Oral Path ol, 76:82–89.
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 Index

ERRNVPHGLFRVRUJ
A osseous sh ell, 335
Adamantinoma, 2, 5, 7, 286–293
age, 286
basaloid pattern , 292
distal tibia, 288
fi brous dysplasia, 290
fi bula, 287, 288
foamy histiocytes, 290
gross path ologic features, 287–288
histopathologic features, 288–293
in ciden ce, 286
keratin formation, 291
localization, 286–287
magn etic reson an ce imagin g, 289
osteofi brous dysplasia, 287, 292
ph ysical fi n din gs, 287
progn osis, 293
radiograph ic features, 287
sex, 286
spin dle cell pattern , 292
squamous differen tiation , 292
symptoms, 287
tibia, 288–290
treatment, 288–293
Adenoameloblastoma, 386–387
Adenomatoid odontogen ic tumor, 386–387
Aggressive ch on droblastoma, 48
Aggressive osteoblastoma, 112
Albrigh t’s syn drome, 328
fi broblastic osteosarcoma, 326, 327
Alveolar soft part sarcoma, 303
Ameloblastic adenomatoid tumor, 386–387
Ameloblastic fi broma, 387–388
Ameloblastic odontoma, 388–389
Ameloblastoma, 383–386
basal cell n evus syn drome, 384
follicular pattern, 384
man dible, 383, 384
plexiform pattern , 384
squamous metaplasia, 384, 385
Amyloid, myeloma, 194, 196,–198
An aplastic myeloma, 197
Aneurysmal bone cyst, 333–340
age, 333
ben ign chondroblastoma, 44–46
ben ign osteoblastoma, 123–124
bon e formation , 335, 340
cervical spin e, 334
ch on dromyxoid fi broma, 55
computed tomograph y, 334, 335
differen tial diagn osis, 161
fi brous dysplasia, 319, 321
giant cell tumor, 233–234
gross path ologic features, 334–335, 338
heterotopic ossifi cation, 333, 337
histopathologic features, 335–240
in ciden ce, 333
localization, 333–334
lumbar spin e, 337
magn etic reson an ce imagin g, 336, 337
malign an t tran sformation , 340
calcifi c deposits, 46
path ologic fracture, 334, 340 calcifi cation , 45, 46, 48
ph ysical fi n din gs, 334 ch on droid differen tiation , 46
primary vs. secon dary, 333 computed tomograph y, 43, 44, 48
progn osis, 340 cystic ch an ge, 45
proximal h umerus, 336 distal femur, 41, 48
radiograph ic features, 334–338 epithelioid, 46
recurren ce, 336, 340 epithelioid-like cells, 47
rib, 338 greater trochanter of femur, 42
secon dary, 57 gross pathologic features, 43–45
sex, 333–334 h istopathologic features, 45–48
symptoms, 334 in ciden ce, 41
treatment, 340 localization, 41–42
An giomatosis, 266 magn etic reson an ce imagin g, 43–45
An giosarcoma, 272–282. See also metastasis, 48
Hemangioendothelioma; mitotic fi gures, 46, 47
Hemangiosarcoma mon on uclear cells, 46, 47
age, 272 n ecrosis, 47
epithelioid h eman gioendoth elioma, 282 ph ysical fi n din gs, 42
gross path ologic features, 273–277 progn osis, 48
h istopath ologic features, 277–282 proximal femur, 41
immun oh istoch emical markers, 281 pubic bon e, 114
in ciden ce, 272 radiation th erapy, 48
localization , 272 radiographic features, 42–43
ph ysical fi n din gs, 273 recurren ce, 48
progn osis, 282 secon dary an eurysmal bone cyst, 44–47
radiograph ic features, 273 sex, 41
sex, 272 soft-tissue, 42
stages, 274, 276–279 soft-tissue recurren ce, 48
symptoms, 273 symptoms, 42
terminology issues, 272 temporal bone, 44, 47
treatment, 282 treatment, 48
Apoph ysis, clear cell ch on drosarcoma, 85–86 vascular invasion, 47
Avulsion fracture, 352 Ben ign fi bro-osseous lesion , jaw, 383
Ben ign osteoblastoma, 112–121
age, 112
B aggressive osteoblastoma, 112, 120
Bacillary an giomatosis, 282 an eurysmal bon e cyst, 119
Ben ce Jon es protein uria, myeloma, 193 bon y trabeculae, 114, 115
Benign fi brous h istiocytoma, 179–183 cartilage, 117
age, 179–180 cemen toblastoma, 112, 116
epiph ysis, 181 cervical vertebra, 121
gross pathologic features, 181 computed tomograph y, 114
h istopath ologic features, 181–182 distal femur, 116, 118
h ypoph osphatemic osteomalacia, 180, 181 gross pathologic features, 114, 117–118
ilium, 180–182 h istopathologic features, 114–120
in ciden ce, 179 in ciden ce, 112
localization , 179 localization , 113
ph ysical fi n din gs, 180 lumbar vertebra, 114
progn osis, 183 malign an t ch an ge, 120
pulmon ary metastasis, 180 malign an t osteoblastoma, 112, 120
radiograph ic features, 180–181 mitotic activity, 115
recurren ce, 179 multifocal growth pattern , 117
sacrum, 180 n eurologic disorders, 113
sex, 179 n idus, 114
symptoms, 180 osteomalacia, 113
treatment, 183 osteosarcoma, differen tiation , 117, 120
Benign ch on droblastoma, 41–48 ph ysical fi n din gs, 113
age, 41 pleomorph ic n ucleus, 117
aneurysmal bon e cyst, 44–46 prognosis, 120–121
apoph ysis, 43 proximal femur, 117

393
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Ben ign osteoblastoma (Continued ) focal myxoid change, 15 radiograph ic features, 51–54
proximal tibia, 120 magn etic reson an ce imagin g, 11 recurren ce, 57, 58
pubic bon e, 114 subun gual exostoses, 9 ribs, 53
radiation therapy, 120, 121 Cavern ous h eman gioma, 269 secon dary an eurysmal bon e cyst, 57
radiograph ic features, 113–117 Cemen toblastoma, 112, 113, 116 sex, 50
reactive sclerosis, 118 Cervical vertebra, 303 symptoms, 51
recurren ce, 120 an eurysmal bon e cyst, 334 treatment, 57
regression, 112 ben ign osteoblastoma, 113 Ch on drosarcoma, 60–89, 253, 255, 257
rib, 113 ch on drosarcoma, 23 acetabulum, 64, 81
sacrum, 115, 117, 120 computed tomograph y, 65 age, 61
sex, 112 Ch arcot’s join t, 374 calcifi cation , 65
symptoms, 113 Ch emodectomas. See Paragan glioma cervical vertebra, 65
systemic toxicity, 113 Ch erubism, 382 ch emoth erapy, 81
thoracic vertebra, 120 Ch est wall clear cell, 84–88
tooth root, 116 h amartoma, 372–373 clusterin g of th e ch on drocytes, 73
treatment, 120 in in fan cy, 372 computed tomograph y, 65, 71
Ben ign vascular tumors, 262–270 mesenchymoma, 372–373 cortical th icken in g, 64, 72
age, 262–263 Ch on droblastic osteosarcoma, 133, 134, 139 dedifferen tiated, 76–83
in ciden ce, 262 age, 123 distal femur, 65, 66, 77, 78
localization , 263 distal femur, 125, 126 distal h umerus, 76
sex, 262–263 jaw, 137–139 vs. en ch on droma, 73
treatment, 267–270 magn etic reson an ce imagin g, 129 en dosteal erosion , 66
Bilateral retin oblastoma, osteosarcoma, 123 proximal femoral sh aft, 150 en dosteal scallopin g, 66
Bizarre parosteal osteoch on dromatous pulmon ary metastasis, 130 femur, 88
proliferations, 18–20 Ch on drodysplasias, radiograph ic features, fi brous dysplasia, 60, 61
Bloom syn drome, osteosarcoma, 123, 132 26 fi rst metatarsal, 68, 72
Bon e islan d, femoral h ead an d ilium, 372 Ch on droid ch ordoma, 255, 258 Gardn er syn drome, 61, 64
Bon e scan Ch on droma, 22–39 grading, 74
ch on droma, 24 age, 22 gross path ologic features, 66–72
in suffi cien cy fracture, 352 cartilagin ous tumors, 34–36 h istopathologic features, 70–76
malign an t lymph oma, 203 great toe, 34 in ciden ce, 60
myeloma, 193 gross path ologic features, 27–28 in vasive pattern , 74, 76
osteoid osteoma, 104 h istopath ologic features, 28–31 irradiation , 85
osteosarcoma, 127 in ciden ce, 22 isch ium, 67, 80
Paget’s disease, 364 isotope bon e scan , 24 liquefaction , 66
Bon e tumor, 1–8 localization , 22–24 localization , 61–62
classifi cation myxoid ch an ge in matrix, 31 magn etic reson an ce imagin g, 80, 86
ch on drogen ic, 6 Ollier’s disease, 32–34 metacarpal, 72
fi brogenic, 6 pain , 36 metastasis, 88
h ematopoietic, 6 path ologic fracture, 26, 34 mitotic fi gures, 74
h istiocytic, 6 progn osis, 31 multicen tric, 66
lipogen ic, 8 proximal h umerus, 25, 27 myxoid ch an ge of matrix, 74
n eurogenic, 8 radiograph ic features, 24–27 n ecrosis, 71, 82
n otochordal, 8 sarcomas, 34 Ollier disease, 68, 81
osteogen ic, 6 sex, 22 osteochon droma, 68–70
vascular origin, 8 soft tissue, 34–36 pain , 70
core n eedle biopsy, 3 synovial chon dromatosis, 36–39 periosteal, 76–77
fi ne-needle aspiration meth ods, 3 treatment, 31 permeation , 74
grading, 4 Ch on dromatous tumor, 18–20 ph ysical fi n din gs, 64
h istologic diagnosis Ch on dromyxoid fi broma, 50–58 pleomorph ism of n uclei, 76
decalcifi cation meth ods, 2 age, 50 primary, 60–76
fresh frozen sections, 2 bon e sur face, 56–57 progn osis, 89
margin s, 3 calcifi cation , 51, 55, 56 proximal femur, 64, 78, 85, 88
imagin g modalities, 2 cellular atypia, 55, 57 proximal h umerus, 76, 81
laboratory studies, 1 ch on droblastoma, 56 proximal ph alan x of fi n ger, 68
skeletal an d age distribution , 7–8 computed tomograph y, 53 radiation th erapy, 61, 85
stagin g, 4 distal femur, 54 radiograph ic features, 64–69
symptoms, 1 distal fi bula, 57 recurren ce, 63, 71, 88
team management, 1 femur, 54 secon dary. See Secon dary ch on drosarcoma
Brodie’s abscess, 102, 116 gross path ologic features, 51–55 sex, 61
h istopath ologic features, 55–57 soft tissue, 65, 67–73, 76, 81, 86, 88
ilium, 53, 58 surgical tech n iques, 85
C in ciden ce, 50 symptoms, 62–63
Calcan eus, lipoma, 301 liquefaction , 57 syn ovial ch on dromatosis, 61, 71
Calcifi ed malign an t syn ovioma, 374 localization , 50–51 thigh, 71
Calcifyin g epith elial odon togen ic cyst, 381 magn etic reson an ce image, 53 treatment, 85–89
Calcifyin g epith elial odon togen ic n ecrosis, 55 variants, 61
tumor, 386 permeation , 57 vertebral column, 65
Calcifyin g pseudon eoplasm of th e n eural ph ysical fi n din gs, 51 Ch ordoid men in gioma, 259
axis, 374 pleomorph ic n ucleus, 57 Ch ordoma, 142, 248–260
Cartilage cap, 14–17 progn osis, 57–58 age, 248
ch on drocytes, 14, 15 proximal fi bula, 52 calcifi cation , 251
computed tomograph y, 3 proximal tibia, 52, 55 carcin oma, 257

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ch on drosarcoma, 254, 255, 257, 259 ch on drosarcoma, 65, 71 localization , 175

coccyx, 254 ch ordoma, 251 magn etic reson an ce imagin g, 177
computed tomograph y, 251 con den sin g osteitis, 356 ph ysical fi n din gs, 176
cytoplasm, 256, 257, 259 dedifferen tiated ch on drosarcoma, 81 progn osis, 176
dedifferen tiated, 258 Ewing tumor, 216 radiographic features, 176–177
differen tial diagn osis of metastatic, 258 fi brosarcoma, 171 scapula, 177
distal sacrum, 249 fi brous dysplasia, 322, 323 sex, 175
eosinophilic cytoplasm, 257 giant cell tumor, 228 spin dle cells, 177
epithelial appearan ce, 255 h eman gioma, 264 symptoms, 176
fi brosarcoma, 169–170 h eterotopic ossifi cation , 347 treatment, 176
giant notochordal rest, 258 in n omin ate bon e, 317 Diabetes in sipidus, Erdh eim-Ch ester disease,
gross path ologic features, 253–255 juxtacortical osteosarcoma, 160, 163 361–362
histopathologic features, 255–259 malign an t lymph oma, 204 Differen tiated adaman tin oma, 292
immun operoxidase stain in g, 259 myeloma, 194–195 Differen tiated ch on drosarcoma, 70, 71, 75
in ciden ce, 248 osteoch on droma, 13
lobulated growth pattern , 258 osteoid osteoma, 104
localization , 248 osteosarcoma, 128, 138, 140 E
magn etic reson an ce imagin g, 251, 252 parosteal osteosarcoma, 160, 163 Ecchondrosis physaliphora, 248
metastasis, 253, 260 Con den sin g osteitis, 356 Elbow joint, synovial chondromatosis, 61
myxopapillary epen dymoma, 258 Con gen ital fi bromatosis. See Myofi bromatosis En ch on droma, 25, 26, 28–30
notochordal hamartoma, 258 Cortical desmoid age, 24
nuclei, 257 distal femur, 316 vs. ch on drosarcoma, 73
ph ysaliferous cell, 255 femoral shaft, 317 fi bula, 28
ph ysical fi n din gs, 249 Cran ial ch ordoma, 251 middle ph alan x, 26
pleomorph ic n uclei, 257 Crush artifact, lymph oma, 206 ph alan x, 30, 31
prognosis, 259–260 Cuboid, osteoid osteoma, 108 proximal fi bula, 28
radiographic features, 249–253 Cyst of degen erative join t disease, 343 proximal tibial sh aft, 25
sacrum, 250, 251, 254, 258 distal femur, 345 sex, 24
secon d cervical vertebra, 255 Cystic an giomatosis, 266 Enchondromatosis, 9
secon d lumbar vertebra, 253 Cystic lesion s, 333–347 Enostosis, 372
sex, 248 Eosin oph ilic gran uloma, 358–361
spin dled n uclei, 256 Ependymomas, 304
symptoms, 248–249 D Epidermoid cyst, 343–346
treatment, 259 Dedifferen tiated ch on drosarcoma, 76–83 an teroposterior, 344
Chron ic osteomyelitis, tibial medulla, 202 age, 77–78 fi n ger, 346
Clavicle computed tomograph y, 80 path ologic features, 345–346
hemangioen dothelioma, 281 distal femur, 78 radiographic features, 344–345
traumatic osteolysis, 369 femur, 78, 81, 83 skull, 343
Clear cell carcin oma, xan th oma of bon e, fi brosarcoma, 76 Epiphyseal plate, fi brocartilaginous
differen tial diagn osis, 317 gross pathologic features, 79 mesen ch ymoma, 330
Clear cell chondrosarcoma, 83–89 h istopath ologic features, 79–81 Epithelioid angiosarcoma, 281
age, 83–84 h umeral sh aft, 79 Epithelioid hemangioendothelioma, 276,
ch on droblastoma, 84 inciden ce, 76–77 280–282
cystic ch an ge, 70, 86 localization , 83 ilium, 276
femoral head, 84 magn etic reson an ce imagin g, 80 liver, 275
gross pathologic features, 84, 86 malign an t fi brous h istiocytoma, 77, 79 lun g, 275
histopathologic features, 85, 87 vs. mesen ch ymal ch on drosarcoma, 77 vertebral body, 275
in ciden ce, 83 metastasis, 73 Epithelioid osteoblast, 119, 120
localization , 83 multiple ch on drosarcoma, 77 Epithelioid-appearing osteoblastoma, 120
magn etic reson an ce imagin g, 65, 68, 78, multiple exostoses, 77 Epithelioid-appearing osteosarcoma, 136, 137
80, 84, 86 osteosarcoma, 76, 79 distal femur, 125–127
metastasis, 88 periph eral, 77 pulmon ary metastasis, 138
osteoblastoma, 83 progn osis, 81 Erdh eim-Ch ester disease, 361–362
progn osis, 89 proximal femur, 78 diabetes in sipidus, 361
proximal femur, 64, 77, 86, 88 proximal h umerus, 76, 82 tibia, 362
radiographic features, 84–85 radiograph ic features, 78–79 Ewin g tumor, 211–222
recurrence, 71, 79, 88 rh abdomyosarcoma, 81 age, 211–212
rib, 70 sex, 77–78 bon y trabeculae, 216
sex, 83–84 symptoms, 77 cell lobulation , 218
symptoms, 84 treatment, 81 ch romosomal tran slocation , 221–222
treatment, 85 Dedifferen tiated ch ordoma, 258 computed tomograph y, 216
Clear cell sarcoma, 303 Dedifferen tiated clear cell ch on drosarcoma, delin eation of cytoplasm of cells, 219
Collagen , desmoplastic fi broma, 178 64, 72, 75, 78 distal femur, 217
Complex odontoma, 389–390 Degen erative join t disease, 343, 345 distal h umerus, 213
Compoun d odon tomas, 390 distal femur, 345 fi bula, 218
Computed tomograph y juxta-articular bon e, 343 fi ligree pattern , 219
acetabulum, 283 Desmoplastic fi broma, 175–178 genetics, 220
an eurysmal bon e cyst, 335, 337 age, 175–176 gross path ologic features, 214–216
ben ign ch on droblastoma, 42, 44, 48 collagen , 178 histopathologic features, 206–209, 216–222
ben ign osteoblastoma, 115 distal femur, 177 ilium, 214
cartilage cap, 11 gross path ologic features, 176–177 immun operoxidase stain s, 220
cervical vertebra, 303 h istopath ologic features, 176–178 in ciden ce, 211
ch on dromyxoid fi broma, 53 in ciden ce, 175 laboratory fi n din gs, 212

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Ewing tumor (Continued )
large cell varian t, 218
localization , 212
lun g, 218
magnetic reson an ce imagin g, 214–217
malign an t lymph oma, n uclei compared,
218–219
medullary compon en t, 213
metastasis, 212, 216, 220
MIC-2 gen e, 218
mid h umerus, 217
n eural markers, 221
vs. n euroblastoma, 212
n uclei, 218–219
on ion skin appearan ce, 213
ph ysical fi n din gs, 212
postradiation sarcoma, 222
prognosis, 221–222
proximal h umeral metaph ysis, 213
radiograph ic features, 213–214
recurren ce, 217, 218
reticulum cell sarcoma, glycogen stain for
differen tiation , 221
rib, 222
rosettes, 221
saucerization of cortex, 217
scapula, 218
sex, 211–212
vs. small cell osteosarcoma, 219
symptoms, 212
treatment, 222
Exuberant callus, 350–352
F fi broma, 320
Femoral epiph ysis, distal, ben ign
chon droblastoma, 41–42
Femoral h ead
bon e islan d, 372
clear cell ch on drosarcoma, 85
myeloma, 195
Femoral metaph ysis, distal
osteosarcoma, 130
periosteal ch on droma, 27
Femoral n eck
osteoid osteoma, 102
tuberculosis, 356
Femoral sh aft
distal
ch on drosarcoma, 79
cortical desmoid, 317
malign an t fi brous h istiocytoma, 188
juxtacortical osteosarcoma, 165
massive osteolysis, 266, 268
myeloma, 195
osteoch on droma, 166
osteosarcoma, 126
parosteal osteosarcoma, 150, 159, 165
proximal
ch on droblastic osteosarcoma, 147
massive osteolysis, 266
mesen ch ymal ch on drosarcoma, 94
periosteal osteosarcoma, 150
Femur
ch on dromyxoid fi broma, 54
ch on drosarcoma, 64
dedifferen tiated ch on drosarcoma, 79
distal
an eurysmal bon e cyst, 233
ben ign ch on droblastoma, 45
ben ign osteoblastoma, 118
ch on droblastic osteosarcoma, 146
ch on dromyxoid fi broma, 53
ch on drosarcoma, 65, 72, 77, 78 spin dle cells, 331
cortical desmoid, 316 Fibrodysplasia ossifi can s progressiva, 349
cyst of degen erative join t disease, 345 Fibrogen ic tumor, 6
dedifferen tiated ch on drosarcoma, 78 Fibroh istiocytic n eoplasm, 179
degen erative join t disease, 345 spin dle cells, 237
desmoplastic fi broma, 177 storiform pattern , 237
epith elioid-appearin g osteosarcoma, Fibroma
136, 137 See also Metaph yseal fi brous defect
Ewing tumor ( sarcoma) , 213, 217 an kle, 344
fi brosarcoma, 169, 171 distal tibia, 344
giant cell tumor, 227, 231, 234 femur, 342
giant osteoid osteoma, 116, 118 fi broblastic conn ective tissue, 342
h emangioendoth elioma, 273 foam cell, 325
in farct, 370 foci of osteoid, 350
irregularities simulatin g malign an cy, mitotic fi gures, 339
316–317 tibia, 344
juxtacortical osteosarcoma, 160–165 Fibromyxoma. See Myxomas
lipoma, 302 Fibro-osseous dysplasia, 317–319
low-grade cen tral osteosarcoma, 146 vs. men in gioma, 325
malign an t fi brous h istiocytoma, 185, skull, 325
186, 188 Fibro-osseous lesion , jaw, 383, 391
malignan t gian t cell tumor, 245–246 Fibro-osseous pseudotumor of digits, 383
mesen ch ymal ch on drosarcoma, 95 Fibrosarcoma, 169–175
multicen tric osteoblastoma, 116 age, 169
n onosteogenic fi broma, 181 computed tomograph y, 171
osteoblastic osteosarcoma, 371 dedifferen tiated ch on drosarcoma, 170
osteoblastoma, 116, 118 distal femur, 169, 171
osteoch on droma, 12 grading, 170, 171
osteoid osteoma, 102 gross path ologic features, 172–173
osteosarcoma, 125–127, 131, 144, 146 h istopathologic features, 172–175
parosteal osteosarcoma, 160–165 in ciden ce, 169
periosteal ch on droma, 27 in farct, 169, 172
sarcoma, 164, 303 localization , 169–170
telangiectatic osteosarcoma, 144, 188 myxoid matrix, 172
ph ysical fi n din gs, 170
fi brous dysplasia, 323 predisposin g con dition s, 170
greater trochanter, 42, 127, 234 progn osis, 175
ben ign ch on droblastoma, 42 proximal femur, 173
fi broblastic osteosarcoma, 127 proximal fi bula, 172
giant cell tumor, 234 proximal tibia, 171–173
malign an t lymph oma, 204 radiograph ic features, 170–171
massive osteolysis, 268 sex, 169
osteosarcoma, 116 spin dle cell, 173, 174
proximal symptoms, 170
ben ign ch on droblastoma, 41 treatment, 175
ben ign osteoblastoma, 117 Fibrous cortical defect. See Metaph yseal
ch on drosarcoma, 64, 79, 85, 88 fi brous defect
clear cell ch on drosarcoma, 88 Fibrous dysplasia, 317–326
dedifferen tiated ch on drosarcoma, 79 age, 318–319
dedifferen tiated clear cell Albrigh t syn drome, 318
ch on drosarcoma, 88 an eurysmal bon e cyst, 319, 321
fi brosarcoma, 173 cartilage islan ds, 319
fi brous dysplasia, 320, 323 Ch in ese ch aracters, 320
giant cell tumor, 230 ch on drosarcoma, 326
malign an t lymph oma, 204 computed tomograph y, 322, 323
myeloma, 193 femur, 320
osteosarcoma, 142 foam cells, 325
Paget’s disease, 366 giant cell, 320
postradiation sarcoma, 142 gross pathologic features, 319, 323
Fibroblastic osteosarcoma, 139 histopathologic features, 320–321, 324–326
age, 112–113 in ciden ce, 318
Albrigh t’s syn drome, 327 jaw, 318
distal radius, 163 localization , 318
distal tibia, 129, 145 myxoid ch an ge in matrix, 320
greater trochanter of femur, 127 orbital bon e, 322
pagetoid bon e, 141 osteoblastic rimmin g, 320
polyostotic fi brous dysplasia, 323 Paget’s disease, 325
proximal tibia, 245, 371 pelvis, 323
pulmon ary metastasis, 167 ph ysical fi n din gs, 319
Fibrocartilagin ous dysplasia, 30 polyostotic, 320
Fibrocartilagin ous mesen chymoma, 330–331 postradiation , 326
epiph yseal plate, 330 progn osis, 326
proximal fi bula, 330 proximal femur, 320, 323

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psammoma bodies, 320 localization , 226 diffuse cystic an giomatosis, 266

radiographic features, 319–323 magn etic reson an ce imagin g, 227 fi bula cortex, 267
rib, 323, 324, 326 metacarpal bon e, 227, 234 fi bula shaft, 265
sarcoma, 326 metaph ysis, 229 gross path ologic features, 267–268
computed tomograph y, 326 metastasis, 240 vs. h eman gioen doth elioma, 262
postradiation , 326 multicen tric, 226 h istopathologic features, 267, 269–270
sex, 318 ossifi cation , 227, 234, 240 in ciden ce, 262
storiform pattern , 320 Paget’s disease, 227 localization , 263
symptoms, 319 ph ysical fi n din gs, 227 massive osteolysis, 263, 266–270
thigh, 323 progn osis, 238–239 multiple primary h eman giomas, 266
treatment, 321, 326 proximal femur, 231 n asal bon e, 267
Fibrous h istiocytoma, 5, 7 proximal h umerus, 232, 233 polka-dot appearan ce, 264
See also Malign an t fi brous h istiocytoma proximal ph alan x of fi n ger, 234 radiographic features, 263–267
vs. gian t cell tumor, 238 proximal tibia, 229, 235 sex, 262–263
Fibrous lesions, 310–333 pubis, 239 skeletal muscle, 267
Fibrous osteoma, 382 pulmon ary metastasis, 226 skull, 268
Fibula radiograph ic features, 227–232 symptoms, 263
adaman tin oma, 288 reactive bon e formation , 238 treatment, 267–270
distal recurren ce, 231 vertebra, 264, 269
ch on dromyxoid fi broma, 57 sacrum, 228, 233 vertebral body, 264
ganglion cyst, 343 sex, 225–226 Hemangiomatosis, 262, 265
enchondroma, 28 soft tissue, 228, 231–232, 233, 234, 238 Heman giopericytoma, 282–284
Ewing’s sarcoma, 218 symptoms, 227 acetabulum, 283
proximal thigh, 234 age, 282–283
ch on dromyxoid fi broma, 52 treatment, 236, 238 features, 282
en chondroma, 28 vascular channels, 239 lesion site, 283
fi brocartilagin ous mesen chymoma, 330 Gian t n otoch ordal rest, 258 vs. myeloma, 196
fi brosarcoma, 172 Gian t osteoid osteoma. See Osteoblastoma peak in ciden ce, 282
simple cyst, 342 Glomus tumor, 267, 270 sex, 282–283
Fine-n eedle aspirate, bon e tumor, 3 distal ph alan x, 270 stern um, 284
Finger, epidermoid cyst, 346 Gorh am’s disease, 262 Hemangiosarcoma, 262. See also
Florid reactive periostitis, 349 Gran ulomatous osteomyelitis, proximal An giosarcoma;
Foam cell, fi broma, 316 tibia, 357 Hemangioendothelioma
Freezin g microtome, 3 terminology issues, 272
Fron tal bon e, osteosarcoma, 140 Hematopoietic tumor, 6
Fron tal sin us, osteoma, 99 H Heterotopic ossifi cation , 347–350
Hamartoma computed tomograph y, 347
ch est wall, 372–373 forms, 349
G Hand gross pathologic features, 347
Ganglion cyst, 343–346 Maffucci’s syn drome, 33 h istopathologic features, 348–350
an teroposterior, 344 multiple ch on dromas, 27 magn etic reson an ce imagin g, 348
degen erative join t disease, 343 soft tissue, cartilagin ous tumors, 34–36 malign an t tran sformation , 350
distal fi bula, 343–344 Hemangioendothelial sarcoma ph ysical fi n din gs, 347
Gardn er’s syn drome, 104 terminology issues, 272 progn osis, 349–350
ch on drosarcoma, 64 Hemangioendothelioma, 8, 262, 272, radiographic features, 347–349
Gian t cell 275, 276, 278 , 280– 282. See also thigh, 348
fi brous dysplasia, 320 An giosarcoma; Heman giosarcoma treatment, 349
metaph yseal fi brous defect, 315 acetabulum, 283 zonation, 348
nonossifying fi broma, 181 age, 262–263 High -grade sur face osteosarcoma, 147–153
nuclei, 236 clavicle, 277 age, 148
osteosarcoma, 135 distal femur, 273 lesion site, 148
spin dle cell, 55 femoral neck, 268 magn etic reson an ce imagin g, 152
syn ovial ch on dromatosis, 36 foot, 276 progn osis, 150
Gian t cell reaction, 354–355 grading, 281, 282 proximal h umerus, 150
Gian t cell reparative granulomas, 352–353 gross path ologic features, 267–268 radius sh aft, 152
man dible, 353 vs. h eman gioma, 269 sex, 148
Gian t cell tumor, 225–240 h istopath ologic features, 267, 269–270 Hip, synovial chondromatosis, 38
age, 225–226 immun operoxidase markers, 281 Histiocytic tumor, 6
an eurysmal bon e cyst, 233, 239 in ciden ce, 262 Histiocytic xanthogranuloma, 179
ben ign , 229, 230, 239 , 240 localization , 263 Histiocytosis X. See Langerhans cell histiocytosis
bon e matrix, 238 multiple lytic lesion s, 273 Hodgkin disease, 207
computed tomograph y, 228 osteoblastoma, compared, 267 ilium, 204
differen tial diagn osis, 230 ph ysical fi n din gs, 263 immun operoxidase stain in g, 206
distal femur, 227, 230, 233 progn osis, 282 pleomorph ic n uclei, 197
distal radius, 232 radiograph ic features, 263–267 Humeral shaft
distal tibia, 235 reactive n ew bone formation, 280 dedifferen tiated ch on drosarcoma, 79
fi brous histiocytoma, 233 sex, 262–263 metastatic ren al cell carcin oma, 306
grading, 227, 235 symptoms, 263 simple cyst, 341
greater trochanter of femur, 234 terminology issues, 272 Humerus, distal
gross pathologic features, 230 treatmen t, 267–270 ch on drosarcoma, 76
histopathologic features, 230–236 Hemangioma, 262–270 Ewing’s sarcoma, 213
in cidence, 225–226 age, 262–263 parosteal osteoch on dromatous
in farct-like n ecrosis, 237 computed tomograph y, 264 proliferation , 18–20

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Hyperparathyroidism, 364–368 L primary, 201

gross specimen, 368 Langerhans cell granulomatosis. See progn osis, 209
parath yroid tumor, 367 Langerhans cell histiocytosis proximal femur, 204
renal disease, 364 Langerhans cell histiocytosis proximal tibia, 205
rib, 372 Birbeck gran ules, 361 radiograph ic features, 202–204
gross pathologic features, 359 rib, 205, 207, 208
h istopath ologic features, 359–361 sex, 201
I man dible, 359 stern um, 205
Ilium ph ysical fi n din gs, 358–359 subclassifi cation , 206, 207
ben ign fi brous h istiocytoma, 180–182 progn osis, 361 symptoms, 202
bon e islan d, 372 radiograph ic features, 359 treatment, 209
ch on dromyxoid fi broma, 53, 58 S-100 protein, 360
epithelioid h emangioen dothelioma, 276 skull, 359–360
Ewing’s sarcoma, 214 treatment, 361 M
Hodgkin disease, 204 Leiomyosarcoma, 174 Maffucci’s syn drome
myeloma, 195 magn etic reson an ce imagin g, 171 h and, 33
osteoblastic metastasis, 305 proximal tibia, 171 radiographic features, 26
secon dary ch on drosarcoma, 13, 70 Letterer-Siwe disease, 358 thumb, 33
xanthoma of bone, 317 Leukemic infi ltrate, 207 Magn etic reson an ce imagin g
Infarct, 369–371 Li-Fraumeni syndrome, osteosarcoma, 132 adaman tin oma, 288
distal femur, 370 Lipogenic tumor, 8 an eurysmal bon e cyst, 333
magn etic reson an ce imagin g, 370 Lipoma, 298–302 ben ign ch on droblastoma, 43–45
malign an t fi brous h istiocytoma, 371 age, 298 cartilage cap, 11–12
proximal tibia, 370 calcan eus, 301 ch on drosarcoma, 80, 86
In n omin ate bon e, computed distal femur, 303 ch ordoma, 250, 252
tomography, 64 gross pathologic features, 299 dedifferen tiated ch on drosarcoma, 67,
In suffi cien cy fracture, bon e scan , 352 h istopath ologic features, 299–302 78, 80
In tracortical osteosarcoma, 106 in ciden ce, 298 Ewin g tumor, 214–217
In traosseous gan glion , 345 in traosseous lipoma, 301 giant cell tumor, 227
Isch ial apoph yseolysis, 352 localization , 298–299 h eterotopic ossifi cation , 347
Isch ium, ch on drosarcoma, 33 ph ysical fi n din gs, 299 h igh -grade sur face osteosarcoma, 150
radiograph ic features, 299 in farct, 369
sex, 298 juxtacortical osteosarcoma, 161
J soft tissue, 299 lymph oma, 205
Jaffe-Campan acci syn drome, 312 symptoms, 299 myositis ossifi can s, 349
Jaw Liposarcoma osteoblastoma, 115
ben ign fi bro-osseous lesion , 383 h umerus, 298, 299 osteoch on droma, 11
ch on droblastic osteosarcoma, 138, 139 Liver, epithelioid hemangioendothelioma, osteofi brous dysplasia, 328
fi bro-osseous lesion, 383 279 osteosarcoma, 129, 152
fi brous dysplasia, 383 Low-grade cen tral osteosarcoma, 145–147 parosteal osteosarcoma, 161
osteosarcoma, 139 age, 145 periosteal osteosarcoma, 150
traumatic cyst, 382 dedifferen tiation , 146, 147 telangiectatic osteosarcoma, 144
Juxta-articular ch on droma, 36, 37 distal femur, 146 Malign an t ch on droblastoma, 41
Juxtacortical ch on drosarcoma, 61, 145 lesion site, 145 Malign an t fi brous h istiocytoma, 184–189
Juxtacortical osteosarcoma, 158–168 metastasis, 146 age, 184
age, 159 progn osis, 145 dedifferen tiated ch on drosarcoma, 184
bon y trabeculae, 164 recurren ce, 145 distal femur, 185, 186, 188
cartilage islan d, 163 sex, 145 gross pathologic features, 187
computed tomograph y, 161, 163 Lumbar vertebra h istopathologic features, 187–189
dedifferen tiation , 192 ben ign osteoblastoma, 114 in ciden ce, 184
differen tial diagn osis, 161 ch ordoma, 254 in farct, 185, 186
distal femur, 160–162, 164, 165 Lung localization , 184
femoral shaft, 165 epith elioid h eman gioen doth elioma, 280 vs. lymph oma, 187
giant cells, 166 Ewing’s sarcoma, 218 malign an t gian t cells, 187
gross path ologic features, 164–165 Lymph oma, 201–209 Paget’s disease, 185, 187
h istopathologic features, 165–167 age, 201 ph ysical fi n din gs, 185
h ypocellular spindle cell stroma, bon e scan , 204 pleomorph ic, 187
165, 166 computed tomograph y, 204 progn osis, 189
in ciden ce, 158 crush artifact, 206 proximal tibia, 187
localization , 159 Ewing’s sarcoma, nuclei compared, 207 pulmon ary metastasis, 185
magn etic reson an ce imagin g, 161 femur, 204–205, 206 radiograph ic features, 185–186
medullary in volvemen t, 162, 163 gross path ologic features, 204–205 secon dary, 185
metastasis, 165, 167 h istopath ologic features, 206–209 sex, 184–185
vs. parosteal osteoma, 163 immun oh istoch emical stain s, 206 storiform pattern , 184
ph ysical fi n din gs, 159 in ciden ce, 201 symptoms, 185
prognosis, 167–168 localization , 202 total hip arthroplasty, 185
proximal h umerus, 160 magn etic reson an ce imagin g, 204 treatment, 189
pulmon ary metastasis, 165, 167 vs. malign an t fi brous h istiocytoma, 205 Malign an t giant cell tumor, 243–247
radiograph ic features, 159–163 vs. myeloma, 196 age, 243, 244
sex, 158–159 vs. osteomyelitis, 203 distal femur, 245–246
spin dle cells, 165, 166 Paget’s disease, 204 gross path ologic features, 244–246
symptoms, 159 periosteal n ew bon e formation , 203 h istopathologic features, 246–247
treatment, 167 ph ysical fi n din gs, 202 in ciden ce, 243, 244

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localization , 244
ph ysical fi n din gs, 244
progn osis, 247
proximal tibia, 245
pulmon ary metastasis, 245
radiograph ic features, 244
secon dary, 245
sex, 243, 244
symptoms, 244
treatment, 247
Malign an t osteoblastoma, 112, 120
Malign an t periph eral n erve sh eath
tumor, 295
Man dible
ameloblastoma, 383, 384
giant cell reparative granuloma, 353
Langerhans cell histiocytosis, 359
mesen ch ymal ch on drosarcoma, 94
mixed capillary an d cavern ous
h emangioma, 269
myxoma, 390
osteosarcoma, 138, 139
sch wan n oma, 296
Massive osteolysis, 266–270
femoral shaft, 266, 268
femur, 268
path ologic features, 267
proximal femoral sh aft, 266
radiograph ic features, 266
rib, 263
skull, 266
Mastocytosis, 362–364
humerus, 363
pelvic bon e, 363
Maxilla, osteosarcoma, 138
Medullary bon e
juxtacortical osteosarcoma, 163
parosteal osteosarcoma, 163
Men in gioma
vs. fi bro-osseous dysplasia, 325
osteoma, 98, 99
Mesen chymal chondrosarcoma, 92–96
age, 92, 93
calcifi cation , 93, 95, 96
dedifferen tiated vs. differen tiated
ch on drosarcomas, 96
distal femur, 95
gross pathologic features, 93
hemangiopericytomatous pattern , 93
histopathologic features, 93–96
in ciden ce, 92
localization , 92
man dible, 94
metastasis, 96
osteoid, 96
progn osis, 96
proximal femoral sh aft, 94
radiographic features, 93–95
sex, 92, 93
small cell osteosarcoma, 96
symptoms, 92
treatment, 96
vascular pattern, 96
Mesen ch ymal h amartoma of ch est
wall, 373
Mesen chymoma, chest wall, 372–373
Metacarpal
ch on drosarcoma, 70
giant cell tumor, 227, 234
Metaph yseal fi brous defect, 310–316
age, 311
fi brous defects, 310–311
giant cell, 315
gross pathologic features, 312, 314
h istopath ologic features, 314
in ciden ce, 311
localization , 311–312
path ologic fracture, 311, 312
ph ysical fi n din gs, 312
polyostotic in volvemen t, 312
progn osis, 315
radiograph ic features, 312–314
sex, 311
symptoms, 312
treatmen t, 314–315
Metastasis
ben ign ch on droblastoma, 48
carcinomas, 305–310
ch on drosarcoma, 88
ch ordoma, 253, 260
clear cell ch on drosarcoma, 88
dedifferen tiated ch on drosarcoma, 83
Ewing’s sarcoma, 212, 216
giant cell tumor, 240
juxtacortical osteosarcoma, 165, 167
low-grade cen tral osteosarcoma, 145
mesen ch ymal ch on drosarcoma, 96
osteosarcoma, 132, 152
multifocal origin of sarcoma, 132
parosteal osteosarcoma, 165, 167
sarcomatoid carcin oma, 309, 310
Multicen tric gian t cell tumor, 226
Multicen tric osteoblastoma
distal femur, 116
Multicen tric osteosarcoma, 123, 127
Multifocal osteomyelitis, 356
Multiple ch on dromas
dysplasia, 22
h and, 32
Maffucci syn drome, 34
Ollier disease, 32–34
sarcomas, 34
Multiple exostoses
dedifferen tiated ch on drosarcoma, 16
sarcoma, 16
Multiple osteoch on dromas
developmen tal abn ormalities, 9
risk of ch on drosarcomatous ch ange, 9
Multiple primary h eman giomas, 266
Myeloma, 191–200
age, 191
amyloid, 194, 196–198
amyloidosis, 196
Ben ce Jon es protein uria, 193
bon e scan s, 193
computed tomograph y, 194–195
diffuse demin eralization , 193
femoral head, 195, 199
femoral shaft, 195
globulin fraction, 193
gross path ologic features, 194–196
vs. h eman giopericytoma, 196
h istopath ologic features, 196–199
h ypercalcemic crisis, 192
ilium, 195
immun oh istoch emical stain s, 198
in ciden ce, 191
laboratory fi n din gs, 192–193
localization , 192
vs. lymph oma, 196
osteosclerotic form, 192
periph eral polyn europath y, 192
ph ysical fi n din gs, 192–193
POEMS syn drome. See Myeloma,
osteosclerotic form
progn osis, 199
■ In dex 399
proximal femur, 193
radiographic features, 193–194
sex, 191
solitary, 194, 196
symptoms, 192
treatment, 199
Myofi bromatosis, 331–333
h eman giopericytomatous vascular
pattern , 333
radiograph ic appearance, 332
skeleton , 332, 333
Myositis ossifi can s, 347, 349
computed tomograph y, 347
forms, 349
gross pathologic features, 347
h istopathologic features, 348–349
magn etic reson an ce imagin g, 348
malign an t tran sformation , 350
ph ysical fi n din gs, 347
progn osis, 349–350
radiograph ic features, 347
treatment, 349
zonation, 348
Myositis ossifi can s progressiva, 349
Myxoid ch on drosarcoma, 57
Myxoid fi brosarcoma, 169
Myxoid matrix, 58, 169, 172, 174, 258,
280, 304
Myxomas, man dible, 390–391
Myxopapillary epen dymoma, 258, 304
N
Needle biopsy, bon e tumor, 3
Neurilemmoma. See Scwan n oma
Neuroblastoma vs. Ewin g sarcoma, 220
Neurofi bromatosis, 295–297
Neuropath ic join t, sh oulder, 374
Non -ossifyin g fi broma. See Metaph yseal
fi brous defect
Nora’s lesion , 18–19
Notoch ordal h amartoma, 258
Notoch ordal tumor, 6
O
Odontogenic mixed tumor, 381
Odontogen ic tumors, 381–391
aden oameloblastoma, 386–388
ameloblastic fi broma, 387–388
ameloblastic odon toma, 388–389
ameloblastoma
multilobular cystic cavity, 383
squamous metaplasia, 385
calcifyin g epith elial odon togen ic
tumor, 386
complex odon toma, 389
compoun d odon tomas, 389–390
h istologic typin g, 384–385
myxomas, 390–391
Odontoma, 388–390
Ollier’s disease, 26, 32–34
cartilagin ous lesion , 33
ch on droma, 33–34
ch on drosarcoma, 67, 80
radiographic features, 24–27
Orbital bone, fi brous dysplasia, 322
Ossifying fi broma, 112
Osteoblastic metastasis
ilium, 317
sacrum, 304
vertebra, 305
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Osteoblastoma, 112–121. See also Gian t bon e scan , 104 femur, 126, 136
osteoid osteoma bon y trabeculae, 108, 109 frontal bone, 140
age, 112 cartilage, 105 genetic abnormality, 123
bon y matrix, 238 computed tomograph y, 104 giant cell, 135
vs. clear cell ch on drosarcoma, 85 cuboid bon e, 108 gross examination of postchemotherapy,
distal femur, 116, 118 differen tial diagn osis, 109 132
gross pathologic features, 114, 117–118 distal femur, 102 gross pathologic features, 130–132
vs. h eman gioen doth elioma, 278, 281 femoral neck, 102 h igh -grade sur face osteosarcoma,
h istopathologic features, 114–120 fl exion con tractures, 103 147–150
in ciden ce, 112 gross path ologic features, 105, 107–109 h istopathologic features, 132–137
localization , 113 growth disturbances, 103 in ciden ce, 123
vs. osteosarcoma, 117 h istopath ologic features, 105–110 in farcts, 125, 237
ph ysical fi n din gs, 113 in ciden ce, 102 jaw, 137–139
prognosis, 120–121 localization , 102–103 Li-Fraumeni syndrome, 123, 132
proximal tibia, 120 lumbar disk syn drome, 103 localization, 123–124
radiograph ic features, 113–116 multicen tric, 102 low-grade cen tral osteosarcoma, 145–147
sex, 112 osteoch on dritis dissecan s, 102 magn etic reson an ce imagin g, 129, 152
symptoms, 113 osteomyelitis, 102 man dible, 138, 139
treatment, 120 pain , 103 maxilla, 138
Osteoblastoma-like osteosarcoma, 137 ph alan x, 102 metastasis, 152
Osteocartilagin ous exostosis, 9–20. See also ph ysical fi n din gs, 103 myasth en ia gravis, 125
Osteochondroma progn osis, 110 n ecrosis, 140, 154
Osteocartilaginous loose body, synovial prostaglan din s, 103 on cogen ic osteomalacia, 125
chon dromatosis, compared, 36–39 radiograph ic features, 103–107 vs. osteoblastoma, 137
Osteochondritis dissecans vs. osteoid recurren ce, 110 osteoid matrix, 134, 140
osteoma, 102 sex, 102 osteomyelitis, 123, 125, 142
Osteoch ondroma, 9–20 symptoms, 103 osteopoikilosis, 123, 132, 142
after radiation , 9 technetium Tc 99m methylene Paget’s disease, 139–141
age, 10 diph osph on ate, 110 path ologic fracture, 125, 127, 142
bin ucleated cartilage cells, 14 tetracycline, 110 periosteal osteosarcoma, 147–150
bizarre parosteal proliferation , 18–20 treatment, 110 permeation , 135
bursa, 13 Osteolysis, path ologic features, 267–270 ph ysical fi n din gs, 125
cartilage th ickn ess, 11 Osteoma, 98–101 postradiation , 141–142
ch on drosarcoma, 13 den se parosteal, 98 prognosis, 153–155
computed tomograph y, 13 differen tial diagn osis, 98 proximal femur, 142
cystic ch an ge, 14 frontal sinus, 99 proximal tibia, 129–131, 149
dedifferen tiated ch on drosarcoma, 16 h istological features, 98, 102 proximal tibial metaph ysis, 129–130
distal femur, 12 men in gioma, 98, 99 pulmon ary metastasis, 130
distal tibia, 12 proximal femur, 100 radiograph ic features, 125–130
distribution by age and sex, 9–10 symptoms, 98, 99 recurren ce, 137, 146
femoral shaft, 16 Osteomyelitis, 354–358 Roth mun d-Th omson syn drome, 123, 132
gross pathologic features, 11–14 gross pathologic features, 355 sex, 123
h istopathologic features, 14–16 h istopath ologic features, 355–357 skip areas, 131
inciden ce, 9–10 h umerus, 355, 356 small cells, 136
localization , 10 vs. lymph oma, 357 symptoms, 124–125
magn etic reson an ce imagin g, 11 vs. osteoid osteoma, 355, 356 telan giectatic osteosarcoma, 142–145
multiple exostoses, sarcoma, 16 ph ysical fi n din gs, 354 trauma, 122
osteocartilagin ous loose bodies, 10 radiograph ic features, 354–355 treatment, 153
ph ysical fi n din gs, 10 vs. sarcoma, 354 types, 137
progn osis, 16 sclerosin g, 356
proximal h umerus, 12 sequestrum, 354
radiograph ic features, 11–12 treatment, 356–358 P
sarcoma, 16 Osteopoikilosis, 372 Pagetoid bon e, fi broblastic osteosarcoma,
sex, 10 osteosarcoma, 123, 132, 142 141
solitary osteoch on droma, sarcoma, 16 Osteoporosis, transient, 368 Paget’s disease, 364, 366–367
spon tan eous regression , 9 Osteosarcoma, 122–154 bon e scan , 364
subungual exostoses, 17–18 age, 123–124 cemen t lin es, 364
symptoms, 10 vs. ben ign osteoblastoma, 123–124 fi brous dysplasia, 138
syn ovial ch on dromatosis, 10 bilateral retin oblastoma, 123 giant cell tumor, 364
treatment, 16 Bloom syn drome, 123, 132 ivory vertebra, 364
Osteoclastoma. See Gian t cell tumor bon e scan , 127 vs. lymph oma, 364
Osteofi broma, 318, 382 bon y matrix, 140 malign an t fi brous h istiocytomas, 371
Osteofi brous dysplasia, 327–330 ch emoth erapy, 130, 131, 153 osteosarcoma, 364
bon e trabeculae, 329 vs. ch on droblastoma, 135, 137 proximal femur, 366
magn etic reson an ce image, 328 ch ordoma, 142 vertebral body, 358
path ologic fracture, 329 computed tomograph y, 128, 138, 140 Paraganglioma, 303–304
tibia, 328–329 dedifferen tiated ch on drosarcoma, Parath yroid osteopath y, 366–367
Osteoid matrix, osteosarcoma, 134, 140 152–153 Parosteal osteoch on dromatous
Osteoid vs. mesen ch ymal diaph yseal, 124 proliferation s, 18–20
ch on drosarcoma, 93 distal femoral metaph ysis, 130 distal h umerus, 19
Osteoid osteoma, 102–110 distal femur, 125–127, 131, 144, 146 distal uln a, 20
age, 102 exuberant callus, 137 Nora’s lesion , 18
arth ritis, 103 femoral shaft, 148, 150, 153 recurren ce, 18, 19

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Parosteal osteoma, 98–100 Postradiation sarcoma h umerus sh aft, 341

vs. juxtacortical osteosarcoma, 158–168 age, 124 ph ysical fi n din gs, 340
vs. parosteal osteosarcoma, 164, 165 Ewing’s sarcoma, 142 progn osis, 342
Parosteal osteosarcoma, 158–168. See also pelvis, 142 radiographic features, 340–341
Juxtacortical osteosarcoma proximal femur, 142 treatment and prognosis, 342
age, 159 scapula, 141 Sinus histiocytosis with massive
bon y trabeculae, 164 sex, 124 lymph aden opath y, 364
cartilage islan d, 163 site of lesion , 124 Skull
computed tomograph y, 161, 163 Primitive n euroectodermal tumor, 221 cavern ous h eman gioma, 265
differen tial diagn osis, 161 Prostaglan din , osteoid osteoma, 103 epidermoid cyst, 346
distal femur, 160–162, 164, 165 Pseudomalign an t osteoblastoma, 120 Langerhans cell histiocytosis, 359
femoral shaft, 165 massive osteolysis, 266
giant cells, 166 myofi bromatosis, 331–333
gross path ologic features, 163–165 R Small cell osteosarcoma, 136
histopathologic features, 165–167 Radius, distal vs. Ewin g’s sarcoma, 136
in ciden ce, 158 fi broblastic osteosarcoma, 139 vs. mesen ch ymal ch on drosarcoma, 95
localization , 159 giant cell tumor, 232 Solid aneurysmal bone cyst, 336
magn etic reson an ce imagin g, 161 osteoid osteoma, 7 Solitary myeloma, 193, 199
medullary in volvemen t, 163 Ren al disease, h yperparath yroidism, Spheno-occipital chondroid chordoma,
metastasis, 165, 167 364–368 251, 253
vs. parosteal osteoma, 163 Rib Spine, dedifferentiated chondrosarcoma, 92
ph ysical fi n din gs, 159 ch on dromyxoid fi broma, 57 Squamous cell carcinoma, 346, 357, 358
prognosis, 167–168 clear cell ch on drosarcoma, 77 tibial medulla, 358
proximal h umerus, 160 Ewing’s sarcoma, 222 Sternoclavicular hyperostosis, 374
pulmon ary metastasis, 165, 167 fi brous dysplasia, 323, 324, 326 Sternum
radiographic features, 159–163 malign an t lymph oma, 205, 208 h eman giopericytoma, 284
sex, 158 ph an tom bon e disease, 262 lymph oma, 205
spin dle cells, 165, 166 Rickets, 51, 125 Stress fracture, 351, 352
symptoms, 159 Rosai-Dor fman disease, 364 Subperiosteal ossifi cation, 349
treatment, 167 Subun gual exostoses, 9, 17–18
Path ologic fracture, 203, 205 cartilage cap, 17
Periosteal ch ondroma, 22–31 S distal ph alan x, 17
age, 22–23 Sacrum Subun gual keratoacan thoma, 346–347
distal femoral metaph ysis, 27 ben ign fi brous h istiocytoma, 179 distal ph alan x, 347
distal femur, 26, 28 ben ign osteoblastoma, 115, 117 keratin, 346
gross path ologic features, 27–28 ch ordoma, 250, 251, 254, 258 Subungual osteogenic melanoma, 18
histopathologic features, 28–31 distal, ch ordoma, 248, 249 Surgical margin
localization, 22–23 giant cell tumor, 228 radical margin, 4
proximal h umerus, 25, 27 osteoblastic metastasis, 303 reactive zon e, 4
radiographic features, 24–27 sch wan n oma, 297 wide margin , 4
sex, 22 Sarcomatoid carcinoma, 309, 310 Synovial ch ondromatosis, 36–39
Periosteal ch on drosarcoma, 76 Scapula cellular atypia, 36
in vasion , 74, 77 desmoplastic fi broma, 177 ch on drosarcoma, 38–39
proximal h umerus, 76 Ewing’s sarcoma, 218 clusterin g pattern , 36, 39
radiograph s, 76 postradiation sarcoma, 141 elbow join t, 61
Periosteal desmoid, 316–317 Schüller-Christian syndrome, 358, 359 giant cell, 35
Periosteal fi brosarcoma, 169 Schwan n oma, 295–298 h ip, 38
Periosteal osteosarcoma, 145–147 age, 295–296 malign an t tran sformation , 37
age, 146, 148 An ton i A an d B, 298 monon uclear cells, 35–36
femoral shaft, 148 computed tomograph y, 297 osteocartilagin ous loose body, compared,
lesion site, 148 gross path ologic features, 296–297 36–39
magn etic reson an ce imagin g, 149 h istopath ologic features, 297–298 Systemic mastocytosis. See Mastocytosis
microscopic appearan ce, 147 in ciden ce, 295
progn osis, 147 localization , 295
proximal femoral sh aft, 150 man dible, 296 T
proximal tibial sh aft, 350 ph ysical fi n din gs, 296 Telangiectatic osteosarcoma, 142–145
radiograph ic appearance, 147 progn osis, 297 age, 145
sex, 148 radiograph ic features, 296 criteria, 142–143
tibia, 149 sacrum, 297 distal femur, 144
tibial shaft, 350 sex, 295–296 lesion site, 143
Periosteally located tumors, 375–376 symptoms, 296 magn etic reson an ce imagin g, 146
Ph an tom bon e disease, 269. See also Massive treatment, 297 progn osis, 144
osteolysis Sclerotic osteosarcoma, 133 sex, 143
rib, 263 Secondary chondrosarcoma, 10, 11 Temporal bon e, ben ign ch on droblastoma,
Ph osph aturic mesen ch ymal tumor, age, 61 44, 47
181, 302 ilium, 70 Thoracic vertebra, benign osteoblastoma, 120
Ph ysaliferous cell, ch ordoma, 255 localization , 61–62 Tibia
Pigmen ted villonodular syn ovitis, 374–375 sex, 61 adaman tinoma, 288–290
Pin dborg tumor, 386. See also Calcifyin g Simple cyst, 340–343 distal
epithelial odontogenic tumor cemen tum, 342 an eurysmal bon e cyst, 340
Polyostotic fi brous dysplasia, fi broblastic fi bula, 343 giant cell tumor, 236
osteosarcoma, 320 gross pathologic features, 341 osteoch on droma, 10
Postradiation osteosarcoma, 139–141 h istopath ologic features, 341–343 osteosarcoma, 129, 145

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Tibia (Continued ) Torus mandibularis, 98 V

fi broma, 169 Torus palatinus, 98 Vascular an d cartilagin ous h amartoma of
osteofi brous dysplasia, 328–329 Total hip arthroplasty, malignant fi brous ribs, 372
periosteal osteosarcoma, 149 h istiocytoma, 185 Vertebra
proximal Traumatic cyst, jaw, 382 h eman gioma, 269
ch on dromyxoid fi broma, 52, 55 Traumatic osteolysis, 368–369 osteoblastic metastasis, 305–310
fi brosarcoma, 171–173 clavicle, 369 Paget’s disease, 364
giant cell tumor, 229, 233 Tuberculosis, osteomyelitis, 356 von Recklinghausen’s disease,
in farct, 371 170, 295
leiomyosarcoma, 173
malign an t fi brous h istiocytoma, 187 U
malign an t gian t cell tumor, 245 Uln a, distal, parosteal osteoch on dromatous X
malign an t lymph oma, 206 proliferation , 20 Xan th oma of bon e, 317
osteoblastic osteosarcoma, 135 Un icameral cyst, 340–343. See also Simple clear cell carcin oma, differen tial
osteoblastoma, 120 cyst diagn osis, 317
osteosarcoma, 129–131, 149 Urticaria pigmen tosa, 362 ilium, 317

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