CHAPTER 24
General Principles of
Tumor Management
Chapter Contents
Tumors of the Musculoskeletal System     999
Tumors of the Musculoskeletal System
Tumors of the musculoskeletal system present a variety of
challenges. The pediatric orthopaedist manages many benign
tumors easily with a good outcome, but occasionally seri-
ous complications develop. Surgeons with specific expertise
in oncology provide the best treatment for patients with
malignant tumors. Inexperience may lead to fatal treatment
errors even at the stage of primary biopsy. Modern survival
rates far exceed those of 20 years ago, largely because of
development of the field of orthopaedic oncology and the
armamentarium of surgical and adjuvant therapies.
Classification
Benign tumors are classified as latent, active, or aggressive.
A latent benign tumor (stage 1) is intracapsular, is usually
asymptomatic, and never metastasizes. An active benign
tumor (stage 2) is also intracapsular and rarely metastasizes
but is actively growing and often symptomatic. An aggres-
sive benign tumor (stage 3) often breaks through its cap-
sule and extends into an adjacent compartment. Rarely do
these tumors metastasize.22 Oliveira and co-­workers have
provided an overview of the principles and problems of his-
tologic grading of tumors.15
Enneking has classified sarcomas of bone and soft tissue
into various stages according to their histologic grade, the
location of the tumor relative to anatomic compartments,
and the presence of metastases.7 A low-­grade tumor has
well-­differentiated cells, few mitotic figures, few or no
atypical cells, little necrosis, and no vascular invasion. High-­
grade tumors have frequent mitoses; are poorly differen-
tiated; have atypical cells, necrosis, and little matrix; and
show vascular invasion.
The ability to treat malignant tumors successfully with
limb salvage depends on understanding sarcoma behavior.
As stated by Enneking,7 “A sarcoma grows centrifugally
like a spreading ripple on a pond. However, as it expands
it follows the path of least resistance.” If a tumor remains
within its compartment, either osseous or fascial, it can be
removed successfully by resecting the entire compartment.
A bone is considered to be a compartment, as is a muscle
or a joint. Tumors may invade adjacent compartments and
become extracompartmental. The Enneking staging system
is shown in Table 24.1.
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John A. Herring
As tumors grow, they compress surrounding tissues into
structures that resemble fibrous capsules. This surround-
ing tissue contains tumor cells, known as satellites. In addi-
tion, there may be tumor cells in surrounding normal tissue,
called skips.7 Within a bone there may also be skip metasta-
ses, with intramedullary tumor extending well proximal to
the apparent extent of the primary tumor.
Clinical Features
The clinical manifestations in a patient with a musculoskel-
etal tumor are often a useful clue to the diagnosis. A child
with a pathologic fracture and no previous symptoms most
often has a benign lesion of bone that has gradually weak-
ened the cortex and resulted in a fatigue fracture through a
cystic lesion. In contrast, a gradually enlarging mass accom-
panied by increasing pain, especially at night, suggests a
diagnosis of primary malignancy. Soft tissue tumors are
most often painless and come to a medical provider’s atten-
tion because the patient or parent notices a mass. The more
aggressive the tumor, the shorter and more alarming the
period of onset.
The presence of a palpable mass is an important finding
on physical examination. The examiner should determine
its size, consistency, and mobility and whether it is painful
on palpation. A rapidly growing lesion is more likely to be
malignant than benign. In taking the history, it is helpful to
compare the size of the mass with a dime, nickel, quarter, or
half-­dollar, or, if the tumor is larger, with a tennis ball, foot-
ball, and so on. It is important to measure and record the
size of the tumor as accurately as possible for comparison
and subsequent examinations.
The consistency of the mass is determined next. Is it
firm or soft? Does it feel cystic or bony and hard? A cys-
tic or fluid-­filled mass should be examined with a flashlight
to determine whether it transilluminates. In general, fluid-­
filled masses are commonly benign, whereas large, hard
masses are more likely to be malignant. Is there a distinct
change from normal to abnormal at the margins of the mass?
Does the mass have the same consistency as the surrounding
normal tissue? Malignant swellings usually invade adjacent
tissues. An increase in local temperature is more suggestive
of a malignant than a benign lesion.
Mobility of a mass is of great help in ascertaining its
nature. When the mass is fixed, it is either attached to bone
or intraosseous. An osseous tumor is unaffected by muscle
contraction. Intramuscular tumors are usually mobile when
the muscle is relaxed and become fixed when the muscle
contracts. Deep, mobile lesions that are extramuscular are
beneath the deep fascia and extramuscular. Tumors that are
superficial and can be moved have not invaded deep fascia
and are probably benign.
999
1000 SECTION IV Musculoskeletal Tumors

Table 24.1    Enneking’s Classification of Sarcomas of Box 24.1 Common Anatomic Sites of
Bone or Soft Tissue. Primary Bone Tumors
Stage Grade Site Metastases SPINE Ribs
IA Low Intracompartmental None In children and adolescents
Posterior Elements
Fibrous dysplasia
(Spinous Process, Lamina,
IB Low Extracompartmental None Ewing sarcoma
Pedicles)
Metastases
IIA High Intracompartmental None Aneurysmal bone cyst
In adults
Osteoma
IIB High Extracompartmental None Ewing sarcoma
Osteoblastoma
Chondrosarcoma
III Low or high Intracompartmental or Yes Anterior Elements Fibrous dysplasia
extracompartmental (Vertebral Body) Multiple myeloma
In a child Metastases
From Enneking W, Spanier S, Goodman M. A system for the surgical stag-
ing of musculoskeletal sarcoma. Clin Orthop Relat Res. 1980;153:106–120. Histiocytosis X (“vertebra
Pelvis
plana”)
In children
Hemangioma
Ewing sarcoma
Tenderness on palpation indicates an active process and is In an adult
Fibrous dysplasia
a result of an inflammatory response. An abscess or infection Metastases
Aneurysmal bone cyst
Multiple myeloma
is very painful and is usually accompanied by other signs of Osteoblastoma
Paget disease
inflammation, such as erythema, edema, lymphangitis, and In adults
Hemangioma
adenopathy, whereas moderate tenderness is indicative of Chordoma Ewing sarcoma
an active neoplastic process, and the absence of tenderness Chondrosarcoma
suggests a quiescent lesion. One should, however, be wary LONG BONES (PHYSES Paget disease
OPEN) Multiple myeloma
because rapid growth and necrosis of a malignant tumor
Metastases
may mimic infection. This may be a problem, for example, Epiphysis
in distinguishing between Ewing sarcoma and osteomyelitis. Chondroblastoma Scapula
When a rapidly growing malignant tumor is subcutaneous, Eosinophilic granuloma Ewing sarcoma
(epiphyseal osteomyelitis)a Osteoblastoma
it may cause vascular dilation, increased local heat, and skin
Aneurysmal bone cyst
turgor; such a tumor may be mistaken for thrombophle- Metaphysis
bitis or an infectious process. A firmer feeling and lack of Multiple benign lesions such Multiple Lesions
local pitting edema, as well as the cutaneous tissue being as a unicameral bone cyst In children
Common site for osteogenic Multiple hereditary
not as red as in infection, however, characterize a neoplas-
sarcoma exostoses
tic inflammatory response. Point tenderness is indicative of
Diaphysis Fibrous dysplasia (Albright
lesions such as osteoid osteoma or a neural or glomus tumor.
Fibrous dysplasia syndrome)
Joint range of motion may be limited because of muscle Histiocytosis X
Histiocytosis X
spasm or mechanical interference. There may be reactive Enchondroma (Ollier
Ewing sarcoma
synovitis when the lesion is adjacent to a joint or if the joint disease)
Osteoblastoma
is directly involved. Muscle atrophy is not uncommon, and Adamantinoma Multiple hemangiomatosis
an antalgic limp may be present. Lymphoma Metastases—
A vascular tumor is suspected if elevation or steady, neuroblastoma, hyper-
Parosteal nephroma
firm pressure causes a diminution in its size; if the size is
Myositis ossificansa Lymphoma
increased by the use of a venous tourniquet; or if a thrill Osteosarcoma In adults
or palpable pulsation is present. A pathologic fracture may Chondrosarcoma Multiple myeloma
occur in primary or metastatic malignant tumors, or one Enchondroma
may complicate a benign process such as a unicameral bone
aNot a tumor.
cyst.
Invasion of a nerve will cause neurologic symptoms and
signs, such as stabbing pain, paresthesia, hypoesthesia, or Anatomic Site of the Lesion
motor weakness. Pathologically, the nerve may be encased The location of a bony lesion is an important diagnostic
by the lesion or trapped against bone or rigid fascia. Neuro- clue (Box 24.1). Epiphyseal lucent lesions are usually a
logic dysfunction is uncommon except when tumors are in chondroblastoma, infection, or occasionally an eosinophilic
anatomic areas where nerves are unable to move freely, such granuloma. Epiphyseal lesions after growth plate closure are
as the sciatic notch or neural foramina. generally giant cell tumors. The metaphysis is a common
site for benign tumors, unicameral cysts, osteoid osteomas,
Radiographic Findings and osteosarcomas. Diaphyseal lesions include fibrous dys-
plasia, Ewing sarcoma, and adamantinoma.
Evaluation of the Initial Radiograph The portion of the skeleton involved is of diagnostic
The initial radiographic study of a lesion in bone should be importance. Anterior vertebral lesions in children are usu-
evaluated systematically, with the examiner first consider- ally eosinophilic granulomas or infection, whereas posterior
ing the character of the lesion itself, the reaction of the sur- element lesions are often aneurysmal bone cysts or osteoid
rounding bone, the location of the lesion, and the possibility osteomas. Pelvic lesions are frequently Ewing sarcoma or
of lesions in other sites. fibrous dysplasia.

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Character of the Lesion
A lesion in bone may be completely radiolucent, suggestive
of a cystic disorder; may have soft tissue density; or may
have bony or calcific density. Ossification within a lesion
has some elements that resemble mature bone, whereas
calcifications are usually more haphazard and of greater
density. Some lesions, such as fibrous dysplasia, alter the
bony architecture so that the cortices become indistinct and
the bony trabecular pattern is replaced by a ground-­glass
appearance. A soft tissue mass adjacent to a bony lesion sug-
gests malignancy.
Reaction of Surrounding Bone
Often the nature of a bony lesion is clear from the response
of the adjacent bony tissue. A benign process such as a
unicameral bone cyst has a sharp margin between the cys-
tic cavity and the adjacent bone. The cortex is thinned
and expanded, which suggests gradual enlargement from
a pressure phenomenon. An irritative lesion such as oste-
oid osteoma produces a vigorous response of bone forma-
tion and cortical thickening in adjacent areas. Eosinophilic
granulomas produce punched-­ out lesions with no host
reaction. Malignancies may be permeative without evi-
dent margins between the tumor and surrounding bone.
When a tumor breaks through a cortex, it elevates the
adjacent periosteum, thereby resulting in new bone for-
mation along that cortex. The apex of this elevation is
seen as a triangle of periosteal bone formation, the so-­
called Codman triangle. A large area of periosteal bone
formation is termed a sunburst pattern. These periosteal
reactions are indicative of aggressive processes, which
may occur with benign tumors and infections, as well as
malignancies.
Staging Studies
Staging studies are studies that define the location,
extent, activity, and probable treatment of musculoskel-
etal lesions.18,25 Obviously, benign lesions (a term to be
used cautiously) may be treated on the basis of plain
radiographs alone. Examples include unicameral cysts,
osteochondromas, and fibrous dysplasia. Any lesion that
could be malignant should be staged before a biopsy is
performed.22 One reason for this order is that a biopsy
may alter the findings on later studies. As mentioned pre-
viously, the plain radiograph offers the greatest amount of
information at the lowest cost and inconvenience, and it
should be carefully evaluated before further studies are
ordered.
Computed Tomography
Computed tomography (CT) is a vital tool for determin-
ing the character and boundaries of bony lesions.2,6,24
The extent of tumor within the bone may be accurately
determined with CT.20 Soft tissue masses may also be
evaluated for size, location, and relationship to bone.
Although magnetic resonance imaging (MRI) has sup-
planted CT for soft tissue imaging, CT remains the best
modality for evaluating cortical disruption and fractures.
CT-­guided biopsies have become a standard approach to
many lesions.28
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CHAPTER 24 General Principles of Tumor Management 1001
Magnetic Resonance Imaging
In the staging of tumors of the musculoskeletal system, MRI
is almost indispensable. Soft tissue lesions are demonstrated
in exquisite detail, and the relationship of surrounding struc-
tures is clearly evident.17,27 Many of these lesions can be
definitively diagnosed by MRI. Other lesions are indeter-
minate, especially sarcomas, and biopsy is necessary for a
definitive diagnosis.9 In many instances MRI is superior to
CT in demonstrating the extent of tumor involvement within
a long bone.3,10,23,29 Skip lesions within the bone might be
seen only with MRI. Gadolinium-­enhanced imaging is often
used to assess tumor necrosis secondary to chemotherapy.30
Diffusion-­weighted imaging has been found helpful in analysis
of tumor tissue. Necrotic tumor tissue shows a higher degree
of diffusion of water protons than viable tissue does.1 Scintig-
raphy technetium scanning is used to detect bone formation
and blood flow, and it demonstrates bone lesions nonspecifi-
cally. Scintigraphy is more sensitive and more cost-­effective
for demonstrating bone metastases than is a plain radiography.
Normal scan findings strongly suggest that a lesion is benign,
but an abnormal scan does not distinguish a benign from a
malignant lesion.23 Benign tumors that affect more than one
bone may be evaluated with this modality. Benign lesions that
are “hot” on scan include osteoid osteoma, osteoblastoma,
aneurysmal bone cyst, and fibrous dysplasia. “Cold” lesions
include eosinophilic granuloma and myeloma. Intraoperative
scintigraphy may be used to locate osteoid osteoma lesions.
Gallium scintigrams are obtained to evaluate soft tissue
tumors. Sarcomas usually cause increased uptake of gal-
lium, whereas noninflammatory benign tumors have normal
uptake.12
Angiography
Angiography is not commonly used in tumor staging today
because of the information available noninvasively with
MRI. When detailed study of the vasculature is necessary in
planning a limb-­sparing procedure, angiography may be nec-
essary. In addition, angiography is performed when a lesion
is to be embolized before treatment to decrease vascular-
ity. At times angiography is used to instill cytotoxic agents
directly into the vasculature of the tumor.
Positron Emission Tomography
Positron emission tomography (PET and PET/CT) using
2-­deoxy-­2-­fluoro-­d-­
glucose and other agents is a modality
which is useful in determining metabolic activity of various tis-
sues. As such it is very useful in identifying metastatic disease
and identifying types of cellular components within a tissue.
Liu and co-­workers found PET/CT scan to be 96% accurate
in differentiating primary bone sarcomas from benign lesions.
The scan had a sensitivity of 92% in detecting recurrence of
tumor.13 Liu and others have shown that evaluation of texture
analysis and tissue patterns with PET/CT scanning can differ-
entiate between benign and malignant bone tumors.32 Cam-
panile and coworkers were able to use PET scans to detect
different types of osteosarcoma in a mouse model.4
Biopsy
A biopsy is required in treating all malignant tumors, and
in many cases it is necessary in managing benign lesions.
1002 SECTION IV Musculoskeletal Tumors
Table 24.2   Types of Excision of Tumor as Related to Surgical Margins.a
Type Plane of Dissection
Intralesional Debulking or curettage
Marginal Pericapsular reactive zone
Wide Normal cuff of tissue (intracompartmental)
Radical Whole bone or muscle outside compartment
aNeeds surgical and pathologic verification.
Radiographic diagnoses without a biopsy are often made
safely for a variety of benign lesions, including unicameral
bone cyst, aneurysmal cyst, fibrous cortical defect, fibrous
dysplasia, chondroblastoma, osteochondroma, and osteoid
osteoma. If malignancy is suspected, a tissue diagnosis is
required. When the appearance of the lesion is typical for a
certain diagnosis and all staging studies support that diagno-
sis, a biopsy may be performed as part of the definitive sur-
gical procedure. In all other cases an incisional biopsy before
treatment is recommended.
The rules of biopsy for musculoskeletal lesions have been
well established for a number of years, yet poorly done
biopsies continue to cause harm to patients. In most cases,
biopsy of a probable malignant lesion should be deferred
to an individual who is capable of definitively treating that
patient. Bad biopsies can preclude the use of limb salvage
and may increase the risk for tumor recurrence and death.
To quote Enneking,7 “The optimal chance for an adequate
local procedure is in the virgin, unbiopsied state.”
Needle biopsies are often used, and in centers with
appropriate expertise they frequently provide definitive
diagnoses. At times they are performed in radiology suites
under CT guidance.24 Fine-­ needle aspiration cytology is
useful in certain tumors and, with proper clinical and radio-
logic correlation, may approach open biopsy in accuracy.21
A recent study of a large number of cases found that CT-­
guided needle biopsies provided a correct diagnosis 77% of
the time, with 20% indeterminate, and 3% with an insuf-
ficient sample material.19 Another technique, needle biopsy
with sonographic guidance, has been shown to be reliable
in the diagnosis of soft tissue tumors and bone lesions with
extraosseous masses in the appendicular skeleton.26 The
volume of tissue obtained is limited, and pathology and
radiology consultations should be obtained before biopsy.14
Welker and colleagues31 analyzed 173 cases and showed a
higher degree of accuracy and lower complication rate with
needle biopsy than with open biopsy. Only 7% of patients
required open biopsy to obtain more material.
Open incisional biopsies are most often used for bone and
soft tissue sarcomas. The incision should be longitudinal and
placed so that the incision tract can be completely excised
at the time of tumor excision without undue compromise of
function. Hemostasis must be meticulous because bleeding
into tissues spreads tumor. Retraction must also be gentle;
sharp rakes can spread tumor cells. Closure of each com-
partment should be complete and a bone plug may be rein-
serted or replaced with methacrylate to seal the bone.7,14
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Result
Leaves macroscopic disease
Likely to leave microscopic disease
May leave “skip” or “satellite” disease
No residual
Before biopsy the surgeon should consult radiologists and
pathologists so that the biopsy produces the most diagnosti-
cally useful tissue.
Treatment
Treatment of tumors of the musculoskeletal system should
be undertaken only by surgeons who possess understand-
ing of and training in the basic principles of tumor manage-
ment.5 Some benign lesions, such as osteoid osteoma, can
be treated with radiofrequency ablation, while others such
as aneurysmal bone cysts may be managed with injection or
embolyzation.16 The margins of excision, as defined by Dr.
William Enneking many years ago, are vitally important to
provide the best chance of curing the disease, whether limb
salvage or amputation is chosen (Table 24.2, see also Video
24.1).7
An intracapsular margin of tumor removal leaves gross
tumor behind and is appropriate only for certain benign
lesions. An example is curettage of an aneurysmal bone
cyst.
A marginal excision is performed by removing the tumor
and its pseudocapsule. Because the capsule contains tumor
cells, this excision by definition leaves viable tumor in the
surrounding local tissues. Marginal excision is inadequate
for local removal of a malignancy.
A wide margin is defined as one that is free of tumor.
It requires removal of tissue beyond the reactive pseudo-
capsule so that a cuff of normal tissue surrounds the tumor
and capsule. This is sufficient for the primary tumor, but
intracompartmental skip lesions may remain.
A radical margin implies removal of the primary lesion
and all normal tissue within the compartment. Such surgery
ensures removal of the tumor and any skip or satellite lesions.7
Whenever possible, limb-­sparing procedures are preferred,
but the surgeon must adhere to the principles of tumor exci-
sion.11 A recent review compared “Enneking appropriate”
excisions with “Enneking inappropriate” surgery and found
considerably higher risks of local recurrence and greater fre-
quency of mortality when Dr. Enneking’s rules were not fol-
lowed.8 Amputations often achieve a radical margin and are
necessary when limb sparing cannot be safely performed. The
principles of compartment involvement and staging apply
equally to amputations and limb-­salvage surgery.
References
For references, see expertconsult.com.

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