EPITHELIOID SARCOMA

A Sarcoma Simulating a Granuloma OY a CaYcinoma

F. M. ENZINGER,
MD

This article reviews the pathologic features and the behavior of 62 cases of a
peculiar form of sarcoma that has repeatedly been confused with a chronic in-
flammatory process, a necrotizing granuloma, and a squamous cell carcinoma.
The tumor occurs chiefly in young adults (median age 23 years) and most com-
monly affects the soft tissues of the hand, the forearm, and the pretibial region.
I t tends to grow in a nodular or multinodular manner along fascial structures
and tendons, often with central necrosis of the tumor nodules and ulceration
of the overlying skin. Most of the tumors grow slowly, and many of our cases
had been present for months or years prior to surgery. Microscopically, the tu-
mor consists of irregular nodular masses of large, deeply acidophilic polygonal
cells merging with spindle cells, frequently associated with large amounts of
hyalinized collagen. Follow-up information on 54 patients (87%) revealed slow,
relentless clinical course with frequent recurrence (85%) and late metastasis
(30%). Cure may be achieved by wide local excision at early stage of disease.

T H I S IS A REVIEW OF O U R EXPERIENCE WlTH forearm. De Santo et al.4 reported a similar-

1 a distinctive but rare type of sarcoma that
is likely to be confused with a variety of be-
nign and malignant conditions, especially a
granulomatous process, a synovial sarcoma, or
an ulcerating squamous cell carcinoma. T h e
characteristic nodular arrangement and the
epithelioid appearance of the tumor cells, the
early necrosis, and the frequent involvement
of tendons and fascial structures were the
the principal features of the neoplasm that
led to errors in evaluation and diagnosis.
Initially we were under the impression that
a tumor of this type had not been previously
described, but a search of the literature re-
vealed similar cases among reviews of synovial
sarcoma. I n 1938, Rerger2 described a “distinc-
live and peculiar” variant of synovial sarcoma
affecling the common extensor tendon of the
right wrist. Although follo~r-upwas incom-
plete, the tumor recurred rapidly after enuc-
leation and necessitated amputation of the
From the Armed Forces Institute of Pathology, Wash-
ington, D. C.
Address for reprints: F. M. Enzinger, MD, Armed
Forces Institute of Pathology, Washington, D. C. 20305.
The opinions or assertions contained herein are the
private views of the author and are not to be construed
as official or as reflecting the views of the Department
of the Army or the Department of Defense.
Received for publication April 18, 1970.
1029
appearing tumor in the flexor tendon of the
ring finger that was interpreted as an atypical
synovial sarcoma with “polygonal and poly-
hedral cells bearing a strikin? resemblance to
epithelium.” A group of related or identical
tumors designated by Bliss and Reed“ as “large
cell sarcomas of tendon sheath,” has recently
been reported. Their tumors were attached
to the tendons of the hand and wrist and clin-
ically and histologically showed “a remarkable
resemblance to benign giant cell tumors of
tendon sheath.”
MATERIALS
AND METHODS
Clinical records and microscopic sections of
62 tumor cases submitted to the Armed Forces
Institute oE Pathology (AFIP) b y military, Vet-
erans Administration, and civilian hospitals
over a period of 25 years (1945 through
1969) and coded under a number of different
diagnoses were reviewed and analyzed (Table
1A, 1B). Follow-up information was obtained
on 54 of the 62 patients. T h e follow-up pe-
riod ranged from l year to 26 years and aver-
aged 7 years (median 5 years). In all cases,
hematoxylin-eosin stains were available. I n
selected cases, the following staininq tech-
niques were utilized: the Masson trichrome,
1030 No7?ember 1970
CANCER Vol. 26

TABLE1A. Benign Diagnoses Suggested for 62 volved than other sites, with the exception of
Epithelioid Sarcomas the fingers, hands, and feet.
No. of Signs and symptoms: When located in the
Diagnosis cases subcutis the lesion usually presented as a firm
Granulomatous inflammation 16 nodule or nodules of callus-like consistency
Nodular tenosynovitis 8 described as small “woody hard knots,”
Nodular fasciitis 6 “lumps,” or “warts” that “grew slowly but
Chronic ulcer or inflammation 6
Fibromatosis, fibroma 4
steadily” and usually caused no limitation of
Reactive fibrosis 4 function. Nodules situated in the dermis were
Histiocytoma, histiocytosis 3 often elevated above the skin surface and fre-
Fibrous xanthoma or sclerosing hemangioma 3 quently became ulcerated 2 or 3 months after
Benign synovioma 3 the nodule was first noted. Such lesions were
Benign adnexal tumor 2 commonly diagnosed as an “indurated ulcer,”
Granular cell myoblastoma 1 a “draining abscess,” or a n “infected wart” that
failed to heal in spite of intensive therapy
(Fig. 1). Deep-seated lesions fixed to the su-
perficial fasciae or tendons were generally of
the Movat and the Snook reticulum stains for larger size, were less well defined, and often
the demonstration of collagen, the periodic manifested as a firm area of induration or as
acid-Schiff (PAS) preparation with and with- a multinodular, lumpy mass, sometimes mov-
out diastase digestion for glycogen, the alcian ing slightly with motion of the extremity
blue, colloidal iron (AMP), aldehyde-fuchsin (Fig. 2). Pain or tenderness, mentioned spe-
and PAS-alcian blue for mucopolysaccharides, cifically in 15 of the 62 cases, were usually
Mallory’s (PTAH) stain for muscle fibrils, mild; severe pain, associated with numbness
the Congo red, crystal violet, and Sirius red and other sensory changes, was present in 3
(Sweat-Puchtler) stains for amyloid, the oil patients in whom the tumor had grown along
red 0 (ORO) for lipid, and the Gomori a large nerve trunk. I n 2 patients, nerve in-
method for iron. volvement caused severe muscular atrophy.
Electron microscopic studies were done on T h e median duration of symptoms prior to
tissue of 3 tumors fixed in 10% formalin and
later post-fixed in 1% osmium tetroxide and
stained with uranyl acetate and lead citrate.
TABLE1B. Malignant Diagnoses Suggested for 62
Epithelioid Sarcomas
RESULTS No. of
Diagnosis cases
Age, sex, and race: T h e age of the 62 pa-
tients at the time of surgery ranged from 4 to Synovial sarcoma 15
58 years, with 70% of the cases occurring be- Fibrosarcoma 4
tween the ages of 10 and 34 years. T h e median Malignant melanoma 4
age at onset of the lesion was 23 years, and at Angiosarcoma 3
the first surgical procedure, 26 years (Table Carcinoma, unspecified 3
2). There were 49 male and 13 female pa- Kaposi’s sarcoma
tients. Male patients also outnumbered female Glomoid sarcoma
in the 39 cases submitted by civilian hospitals Myotendon junction sarcoma
(26 male, 13 female). There were 58 Cau- Rhabdom yosarcoma 2
casian patients and 2 Negro patients. I n 2 pa- Liposarcoma 2
tients, the race was not stated. Chondrosarcoma 2
Anatomical location: With the exception Ulcerating squamous cell carcinoma 2
of 2 cases, both of which occurred in the scalp, Adnexal carcinoma 2
all tumors originated in the extremities-38 Giant cell fascia1 sarcoma 1
in the upper extremities and 22 in the lower. Malignant giant cell tumor of tendon sheath 1
T h e most common sites were the volar sur- Neurogenic sarcoma
face of the fingers, the palm, the extensor sur- Malignant mesothelioma
face of the forearm, and the anterior tibia1 sur- Osteogenic sarcoma
face of the lower leg (Table 3). I n general, the Sweat gland carcinoma
extensor surfaces were more commonly in- Malignant mixed tumor 1
No. 5 EPITHELIOID
SARCOMA * Enzinger 1031
surgery was 9 months (44 cases: range 1 TABLE
3. Anatomical Distribution (62 Cases)
month to 6 years). Anatomic site No. of patients
T h e recorded clinical data as to the size of Head and neck
the tumor varied substantially, ranging from Scalp 2
a small nodule or nodules measuring 2 or 3 Upper extremity
mm to a mass measuring 5 cm in diameter. Fingers 13
Since many lesions were multinodular when Hand 8
first examined, determination of the size of Wrist 7
the tumor was often impossible. Forearm 7
Roentgenographic examination, reported Elbow , 2
in 20 patients, revealed fine flecks of calcium Upper arm 1
in the tumors of 2 patients and cortical thick- Lower extremity
ening and superficial erosion of the underly- Buttock 4
Thigh 4
ing bone in 1. Osteoporosis of the adjacent Knee 4
bone was mentioned twice. T h e remainder of Lower leg 7
the patients showed no roentgenographic ab- Foot 3
normality except for the presence of a soft tis- -
sue mass. TOTAL 62
___--
Previous injury at the site of the tumor was
reported in 14 cases and specifically denied in
5. Only 6 of the 14 patients noted trauma to or the corium. Attachment to a fascia or ten-
the area within 5 years prior to the first a p don was suggested microscopically in 11 of
pearance of the tumor. T w o patients claimed these cases.
enlargement of a previously existing tumor Gross inspection usually revealed the pres-
nodule after injury. ence of one or more firm nodules surrounded
Operative and gross obsel-oations: At opera- by fibrous tissue and fat. T h e individual no-
tion, the tumor was found to be closely as- dules ranged from 0.5 to 5.0 cm in greatest
sociated with a tendon or tendon sheath in diameter, with two thirds of them measuring
13 patients, with the fascia in 11, with a nerve 1.5 cm or less. T h e tumors attached to ten.
or vascular sheath in 6, and with the perios- dons or the fascia lata were somewhat larger
teum in 5 . Six of the fascia1 tumors involved and averaged 2.5 cm in greatest diameter. T h e
the palmar fascia, and 4 the fascia lata. cut surfaces had a glistening grayish-white or
Three of the 5 tumors affecting the perios- grayish-tan appearance, commonly with yel-
teum were located in the pretibial region. One low or brown flecks or mottling.
additional tumor affected the interdigital lig- Microscopic findings: T h e prinicpal char-
ament between thumb and index finger in a acteristics, common to all tumors of this ser-
multinodular manner. Association with any
particular structure was not mentioned in
the operative report of the remaining pa-
tients, but most were situated in the subcutis

TABLE
2. Age Distribution a t the Time of Biopsy
or Excision (62 Patients)
Contributing hospitals
Total Military and
Age prolip no. of Veterans
(Years) case; Administration Civilian
0-9 3 3
10-19 16 2 14
20-29 24 15 9
30-39 13 4 9 FIG. 1. Multinodular tumor involving pretihial re-
40-49 5 2 3 gion, with ulceration of the skin, in a 21-year-old man.
Although the tumor recurred repeatedly over a 12-year
50-59 1 1 period, the patient is living and well 16 years after the
- - -
initial excision. Same case as Fig. 4 (AFIP Ncg. 69-
TOTAL
CASES 62 23 39 5321-1).
1032 November 1970
CANCER
ies, were the nodular arrangement of the t i i -
mor cells, their tendency to undergo degenera-
tion and necrosis, and the deep acidophilia of
FIG. 3. Characteristic nodular growth with central
necrosis, closely simulating a granulomatous process.
T h e patient was a 16-year-old boy with recurrent
tumor affecting the biceps region of the upper arm (H
and E, x20, AFIP Neg. 68-6474).
Vol. 26
FIG.2. Tumor surrounding and
infiltrating a flexor tendon of
the right hand in a 28-year-old
man (AFIP Neg. 68-14782).
the tumor tissue when examined with the he-
matoxylin-eosin stain (Figs. 3-8).
T h e nodular pattern, probably the most
conspicuous feature of this entity, varied con-
siderably in appearance. I n some cases, the
nodule or nodules were well circumscribed
(Figs. 3, 4); in others, they were less well de-
fined and had fused into irregular lobulated
masses involving large portions of the subcutis
and the corium (Fig. 5). Multiple nodules
were rare in tissue obtained at the initial
operation but were common in recurrent le-
sions. Necrosis was a characteristic feature in
virtually all cases; it was most prominent in
the center of larger nodules, and occasionally
was associated with hemorrhage, deposition of
fibrin, and cystic changes (Figs. 3-6, 8). Fu-
sion of several necrotizing tumor nodules re-
sulted in “geographic” lesions that, when
confined to tendons or fasciae, produced ir-
regular festoon- or garland-like bands of viable
tumor tissue separated by areas of necrosis
(Fig. 6).
As previously noted, the tumor displayed a
marked tendency to invade or grow along
dense fibrous structures such as tendons, fas-
ciae, or the periosteum. I n several patients, it
spread in a multinodular manner along the
connective tissue sheaths, investing large ves-
sels and nerves. I n one patient, it formed a
chain of small nodules in the interdigital liga-
ment between thumb and index finger. Le-
sions undergoing enlargement and necrosis
and growing in areas with little subcutaneous
fat tended to ulcerate through the overlying
skin, simulating an ulcerating squamous cell
No. 5 EPITHELIOID
SARCOMA 0 Enzingel- 1033

FIG. 4. Subcutaneous
necrotizing, multinod-
ular growth involving
the pretibial region.
Same case as Fig 1 (H
and E, x11, AFIP Neg.
68-6474).

carcinoma. This process occurred most fre- the result of the extensive desmoplasia, espe-
quently in the pretibial, the prepatellar, and cially the deposition of large amounts of bire-
the elbow regions. Unlike squamous cell car- fringent, hyalinized collagen about the tumor
cinoma, the skin surrounding the sarcoma
lacked dyskeratotic changes and showed only
a moderate degree of acanthosis.
T h e cellular elements of the tumor nodules
ranged from plump spindle cells to large
round or polygonal cells with deeply acido-
philic cytoplasm bearing a close resemblance
to epithelioid cells or squamous cells (Figs 7-
14). Cellular pleomorphism was always mini-
mal. Binucleated cells occurred, but multi-
nucleated giant cells were rare. Although
spindle and polygonal cells were often pres-
ent in different portions of one and the
same tumor, the spindle cells tended to be
more conspicuous in earlier lesions while the
polygonal or epithelioid cells predominated
in recurrent or metastatic tumors. T h e vari-
ous cell types always merged imperceptively,
and there was never the sharp separation of
the 2 cell types, as in synovial sarcoma (Figs.
10, 11). Irregular spaces and clefts and loss of
cellular cohesion were common and resulted
from focal necrosis and from a shrinkage arti-
fact secondary to fixation (Fig. 12). Hemor-
rhage into these spaces occasionally raised the
question of an angiosarcoma. Mitotic figures
were common and averaged from 2 to 6 per
10 high-power fields. FIG. 5 . Characteristic multinodular growth with cen-
T h e striking acidophilia of the tumor tis- tral necrosis. T h e tumor affected the flexor tendon of
the index finger of a 24-year-old man. I t occurred 2
sue was not exclusively clue to the staining years after the initial excision (H and E, x10, AFIP
characteristics of the cytoplasm but was also Neg. 69-9030).
1034 CANCERNovember 1970
cells. T h e cellular boundaries in some cases
were, in fact, completely obliterated by the
hyalinized material, and the tumor was seem-
ingly composed of haphazardly arranged nu-
clei within a dense mass of hyalinized colla-
gen (Figs. 12, 13). I n other cases, the deeply
acidophilic interstitial collagen sharply out-
lined the cellular boundaries, creating a pic-
ture reminiscent of plant cells. Infiltrating
tumors located in tendons or thick fascia1
structures often displayed arrangement of the
cells in a cordlike or chainlike pattern (Fig.
14).
Calcification was present in necrotic por-
tions of the primary or recurrent tumor of 8
patients, osteoid or bone formation in 5.
Cartilage formation was not observed. Sider-
ophages and aggregates of chronic inflam-
matory cells, chiefly lymphocytes, were fre-
quently encountered at the margin of the tu-
mor (Figs. 7, 8).
Metastatic tumors differed from primary or
recurrent tumors by a lesser degree of cellular
differentiation and, perhaps, by more exten-
sive necrosis. Nodular metastatic growth in-
volving the pleural and peritoneal surfaces
and the outer wall of large vessels and the
esophagus was observed at autopsy.
Special staining techniques: T h e cytoplasm
of the tumor cells stained a deep brownish
red o r brick red with the Masson trichrome
stain. Intracellular mucin was never seen, but
varying amounts of mucin were present about
Vol. 26
FIG.6. Tumor tissue
of characteristic ap-
pearance growing
within the fascia lata
in a festoon-like man-
ner. T h e patient, a
27-year-old man, died
with widespread me-
tastasis 7 years after
the onset of the lesion
(H and E, x11, AFIP
Neg. 69-4638).
the tumor cells in close association with a
more or less dense meshwork of collagen fib-
ers. Five of 15 cases in which AMP, alcian
blue, or mucicarmine stains were prepared
showed large amounts of hyaluronidase-sensi-
tive extracellular mucinous material, 6
showed moderate amounts, and 4 were nega-
tive. Intracellular glycogen, as demonstrated
with the PAS preparation before and after di-
gestion with diastase, was prominent in 2 of
the 10 cases in which this stain was prepared.
I n the remainder, little or no intracellular
glycogen was demonstrable. Fontana prepara-
tions failed to reveal any intracellular pig-
ment, but small amounts of intracellular iron
and ORO-positive lipid were noted in a few
cases. Amyloid preparations were negative.
Electyon microscopic findings: Most cells
contained an ovoid irregular and sometimes
indented nucleus with scanty, finely scattered
chromatin and 1 or 2 small nucleoli. Occasion-
ally small amounts of condensed chromatin
were distributed in small clumps or as a nar-
row band along the periphery. T h e cytoplasm
was always abundant and had a moderate
number of mitochondria and variable
amounts of rough-surfaced endoplasmic reti-
culum. Interspersed between these organelles
were small clusters of free ribosomes and a
meshwork of randomly oriented filaments
without condensation or bundling. T h e
amount of the filaments varied greatly and
appeared to be inversely proportional to the
No. 5 EPITHELIOID SARCOMA * Enzinger 1035

FIG. 7. Typical nod-

ular growth from the
palmar surface of the
wrist of a 38-year-old
man. T h e lesion re-
curred twice within a
3-year period (H and
E, x90, AFIP Neg.
68-9868).

FIG. 8. Necratizing
nodule consisting of
polygoual cells sug-
gestive of epitheliod or
squamous cells. T h e
tumor involved the
tendon sheath of the
left index finger of a
24-year-old man; it re-
curred 2 years after
simple excision (H and
E, x90, AFIP Neg.
69-9035).

amount of endoplasmic reticulum. Vacuolar
structures, micropinocytotic vesicles, and lyso-
somes were scarce. T h e cytoplasmic surface
had numerous blunt processes or filopodia,
which in one of the cases formed watertight
junctions or interdigitations with the neigh-
boring cells but without terminal bars or
desmosomes at the line of attachment (Fig.
15). Interposed between viable tumor cells
were degenerating cells showing varying de-
grees of swelling and loss of organelles. Thick
bundles of collagen, often intimately related
to the cytoplasmic surface, amorphous
ground substance of variable density, and ne-
crotic cellular debris of high electron opacity
occupied the extracellular spaces.
Follow-up data: At the end of the follow-
u p period, 42 of the 54 patients with follow-
1036 Nouernber 1970
CANCER
up data were alive, I:! with evidcnce ol rectir-
rence, 3 with metastasis, and 2 with recurrence
and metastasis (Table 4). Eleven had died
as a direct result of the disease. One additional
patient had died of “pulmonary hemorrhage,
shock and cavitation,” presumably as tlie re-
sult of metastasis. During the follow-up pe-
riod, which averaged 7 years, the tumor re-
curred in 46 patients; it recurred once in 14
patients, twice in 19, and 3 or more times in
Vol. 26
FIG. 9. Gradual transition be-
tween spindle and polygonal
cells occurring in a tumor of
the right middle finger of a
27-year-old man. T h e patient
died of metastatic tumor 17
years after the initial therapy
(H and E, ~ 1 6 5 ,AFIP Neg.
69-5547).
FIG. 10. Epithelioid elements
associated with spindle cells and
abundant collagen in a tumor
of the right forearm of a 26-
year-old man (H and E, x165,
AFIP Neg. 69-8093).
I3 patients. Recurrence was usually noted
within 6 months after the initial surgery. T h e
tunior did not recur in 8 of the 54 patients, but
4 of tlie 8 were recent cases that had been fol-
lowed for only one year. I t is likely that longer
follow-up would result in a slightly higher
rate of recurrence, since only 2 of the 30 pa-
tients who were followed for 5 years or more
were free of recurrence after initial therapy.
I n 16 patients, the tumor produced metasta-
No. 5 EPITHELIOID
SARCOMA - Enzingel- 1037

FIG. 11. Recurrent growth affecting the plantar surface of the left foot in a 21-year-old pa-
tient. T h e foot was amputated 10 years after the onset of the lesion, after it had recurred 5
times. A (left). Spindle cell pattern (H and E, ~ 1 9 5 AFIP
, Neg. 69-7207). B (right). Epithelioid
pattern (H and E, ~ 1 9 5AFIP
, Neg. 69-7208).

sis, virtually always after repeated local recur- inon metastatic sites were the pancreas, the gas-
rence. T h e lungs o r the pleurae were the sites trointestinal tract, the liver, the kidneys, and
of metastasis in 10 cases and the skin i n 8, 5 the vertebrae. Metastatic lymph node involve-
of which were located in the scalp. Less corn- ment was observed in 6 patients. T h e period

FIG. 12. Loss of cell-

nlar cohesion with for-
mation of irregular tis-
sue spaces in a tumor
exhibiting extensite
dcsmoplasia and hyali-
niration. T h e tumor
recurred twice within
a 3-year period (H and
E, x195, AFIP Neg.
68.9877).
1038 CANCERNovember 1970 VOl. 26

FIG. 13. Recurrent

tumor affecting the ex-
tensor tendon of the
little finger. Note the
large amounts of hy-
alinized collagen inter-
spersed between the
tumor cells. Eight years
after the onset of the
lesion, the patient is
living with recurrence
in the amputation
stump of the lower
forearm. See also Fig.
14 (H and E, x210,
AFIP Neg. 69-5550).

FIG. 14. Cords of

polygonal tumor cells
infiltrating tendon tis-
sue. Same case as Fig.
13 (H and E, x195,
AFIP Neg. 69-4623).

between initial diagnosis and metastasis
ranged from 3 months to 17 years, with a me-
dian of 5 years. Survival after the first manifes-
tation of metastasis ranged from a few months
to 8 years, with 5 patients surviving more than
one year after the metastasis became first ap-
parent.
Treatment: Of the 38 patients who were
alive with or without evidence of recurrence
at the end of the foIlow-up period or who
had died from intercurrent disease, 19 had
been treated by simple excision on one or
more occasions, 8 by wide local excision and
11 by amputation, usually after the tumor
had been repeatedly excised locally. TWO of
the 11 patients had received chemotherapy
and/or radiotherapy as an adjuvant to sur-
gery. Of the 16 patients who were alive with
metastatic lesions or who had died as a direct
result of the disease, 6 were treated by simple
No. 5 EPITHELIOID
SARCOMA* Enzinger 1039

FIG.15. Electron mi-

crograph showing the
filamentous material
within the hyaloplasm
and the interdigitation
and “watertight” junc-
tion between neigh-
boring cells (post-fixa-
tion of formalin-fixed
material in 1% os-
mium tetroxide; stain-
ing with uranyl acetate
a n d lead citrate,
~ 1 2 , 1 0 0 , AFIP Neg.
70-2384).

excision, 3 by wide local excision, and 7 by am-
putation. Three received radiotherapy and 3
chemotherapy as an adjunct to surgery.
DISCUSSION
T h e frequency with which the tumor was
mistaken for a benign process was due chiefly
to its deceptively harmless appearance during
the initial period of the disease. I n the aver-
age patient, the tumor presented as an indur-
ated, painless nodule in the subcutis, was ex-
ceptionally slow growing, and rarely measured
more than 1 cm in diameter after weeks and
months of development. Clinically, it was
nearly always thought to be an inflammatory
process and was treated accordingly, at least
until the complete lack of a response cast some
doubt upon the inflammatory nature of the
lesion.
than those of a granuloma and the constituent
cells were much less mature in appearance,
with large vesicular nuclei and a sizable num-
ber of mitotic figures. Other benign diagno-
ses suggested by the contributing patliologist
were fibromatosis, nodular fasciitis, nodular
tenosynovitis, and foreign body granuloma
(Table IA).
Neoplasms of larger size, frequently arising
from tendons or fascia1 structures, were more
readily recognized as a potentially malignant
tumor, but interpretation as to their histo-
logic type varied considerably. As Table 1B il-
lustrates, the long list of suggested diagnoses,
led by synovial sarcoma, included fibrosar-
coma, angiosarcoma, malignant melanoma,
and a great variety of other malignant neo-
___ TABLE
4. Follow-up Status

But even after biopsy and microscopic exam- No. of

patients Percent
ination, the malignant potential of the tu-
mor was not always evident. I n fact, a granulo- Alive and well 25 40
matous process was frequently considered Alive with recurrence 12 19
because of the characteristic nodular or multi- Alive with recurrence and
metastasis 2 3
nodular growth pattern-often associated with Alive with metastasis 3 5
central necrosis and ulceration of the overly- Dead with metastasis 11 18
ing skin-and the presence of large acido- Dead of intercurrent disease 1 2
philic cells closely resembling epithelioid Lost to follow-up 8 13
cells. Yet, in nearly all cases, the individual - -_
TOTAL 62 100
tumor nodules were more sharply defined
1040 November 1970
CANCER
plasms of mesenchymal and epithelial ori-
gin.
While the deep location of some tumors
and their intimate association with tendon:;
and fascial structures clearly established me-
senchymal origin, the exact cell type re-
mained debatable. Undoubtedly, the large
polygonal tumor cells and the focal loss of
cohesion were suggestive of synovial sarcoma,
but against this diagnosis were the constant
absence of a distinctly biphasic cellular pat-
tern and the total lack of well-defined mucin-
containing pseudoglandular spaces. Stainable
mucin was occasionally present about the tu-
mor cells, but-unlike the m u c h found in
synovial sarcoma-it was completely depoly-
merized by prior treatment of the sections
with testicular hyaluronidase. Moreover, only
a small number of tumors affected the re-
gion of the knee and hip joints, the 2 most
common sites of synovial sarcoma.0 I n fact,
the most frequent locations of the 62 tumors
of this series were the soft tissues of the fing-
ers, the hand, and the distal forearm, where
more than half of the tumors were located.
Other aspects of the tumor suggested a neo-
plasm of primitive mesenchymal cells dif-
ferentiating along 2 basic lines: 1. a fibroblas-
tic element, as implied by the prominent spin-
dle cell component and the elaboration of
large amounts of collagen, and 2. a histiocy-
tic component, as intimated by the abundant
eosinophilic cytoplasm and the epithelium-
like arrangement of the tumor cells. A tumor
developing along these lines-and perhaps
originating from newly formed adventitial
mesenchyme-was further implied by the
striking tendency of the tumor cells to grow
within various fibrous structures, including
structures completely devoid of a potential
synovial lining such as the superficial fascia,
the fascia lata, and the fascial sheath invest-
ing large vessels and nerves. I n regard to a
possible histiocytic component, it must be
added, however, that in none of the cases of
this series were lipid-carrying histiocytes or
multinucleated giant cells a conspicuous cell-
ular element.
Preliminary studies of 3 cases with the elec-
tron microscope also failed to provide an un-
equivocal answer as to the basic cell type.
The predominating cell possessed various ul-
trastructural features common to synovio-
blasts and histiocytes, including large amounts
of filamentous structures within the hyalo-
plasm, varying amounts of rough-surfaced en-
Vol. 26
doplasmic reticulum, and numerous filopodia
at the cell surface.’, 7-8 Unlike these cells, how-
ever, the intracytoplasmic vacuolar structures
were less prominent, and the filopodia were
shorter and, in one of the 3 cases, formed
“watertight” junctions or interdigitation as
described in epithelioid cells.5, 3 Transitions
between the large cells with a conspicuous fil-
amentous cytop!asm and smaller fibroblast-
like cells were observed in each of the 3 cases.
Although the problem of histogenesis re-
mains obscure, the malignant potential of
the tumor is convincingly demonstrated by
the available follow-up information: the tu-
mor recurred in 85% of the cases and pro-
duced metastasis in 30%. I n most patients, i t
recurred repeatedly over many years, necessi-
tating numerous surgical procedures of in-
creasing severity. For example, one of the pa-
tients, a 21-year-old man, was treated for re-
current tumor growth in the left pretibial re-
gion on 11 occasions during a 16-year period.
Another, a 27-year-old man with a tumor of
the middle finger of the hand, had more than
20 surgical procedures for recurrent growth;
he died, presumably of metastasis, 18 years
after onset of symptoms. I n earlier stages of
the disease, treatment tended to be conserva-
tive, chiefly because of the harmless clinical
appearance and the small size of the tumor;
in later stages, when it became evident that
simple excision was of only limited value,
treatment became more radical and consisted
chiefly of wide local excision and amputation.
This trend in the mode of therapy is illus-
trated by the fact that radical surgery-wide
local excision or amputation-was employed
in only 4% of the patients initially but in 74%
after the second recurrence.
As in practically all sarcomas, the lung was
the principal site of metastasis. It is note-
worthy, however, that the second most com-
mon site was the scalp, where the tumor was
present in 5 of the 16 cases with metastasis.
Three of the 5 patients with metastasis to
the scalp died subsequently of widespread me-
tastasis, but 2 are still alive 3 and 1 years, re-
spectively, after the first appearance of the le-
sion. Metastasis to regional lymph nodes oc-
curred but was observed in only 6 of the 62
cases of this series.
I t is obvious from the above data that a cor-
rect diagnosis and vigorous surgical therapy
at an early stage of the disease is imperative
in order to lower the high recurrence rate
and, it is hoped, the incidence of metastasis.
No. 5 EPITHELIOID
SARCOMA
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