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Epithelioid sarcoma
Original Artiele
EPITHELIOID SARCOMA A Clinical and Pathologic Study of Nine Cases Hector Santiago, MD.,* Lois K. Feinerman, M.D.,t and Raffaele Lattes, M.D.t
Abstract This is a report of nine cases of epitheloid sarcoma, a term introduced recently to designate a special variant of malignant soft tissue tumor generally involving tendons, aponeuroses, and more superficial tissues of the extremities. The histologic features of this tumor, which consists of a mixture of polygonal epithelioid cells and elongated fibroblastic cells with necrotizing foci, have often misled the pathologist into diagnoses of necrotizing granuloma, malignant melanoma, angiosarcoma, or metastatic carcinoma. The tumor is definitely malignant, is difficult to eradicate by local surgical excision, and often metastasizes to lymph nodes and via the blood. The histogenesis of this tumor is still controversial, but some light and electron microscopic features suggest a possible synovial origin.
Enzinger- in 1970 reviewed a series of 62 cases of an unusual type of sarcoma that is often confused clinically and pathologically with a variety of granulomatous and neoplastic diseases. He has called this tumor "epithelioid sarcoma." Other probable examples of this tumor type have been described previously in the literature with different classifications. Black" in 1936, Berger in 1938, and De Santo et a1. 4 in 1941 described similar cases, which they included in the general group of synovial sarcomas. Bliss and Reed" in 1968 described four cases of "large cell sarcomas of tendon sheath" thought to
represent the malignant counterpart of the benign giant cell tumor of tendon sheaths. In their discussion of soft tissue tumors of the penis, Dehner and Smith" in 1970 described a "fascial sarcoma," which closely resembles the epithelioid sarcoma of Enzinger and represents the only such lesion known to have been observed on the penis. Epithelioid sarcoma is most often found in adult males as a subfascial or subcutaneous lesion originating on the limbs. Microscopically the tumor has a characteristic nodular appearance and is composed of both spindle cells resembling
*Pathologist, Hospital Infantil Irnan, Mexico City, Mexico. tAssociate Professor of Dermatology, Albert Einstein College of Medicine. Staff, Hospital of Albert Einstein College of Medicine, Bronx, New York. :j:Professor of Surgical Pathology, College of Physicians and Surgeons, Columbia University. Attending Pathologist, Presbyterian Hospital, New York, New York.
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HUMAN PATHOLOGY-VOLUME 3, NUMBER I-lvlarch 1972
Figure 1. Case 8, male, 45. Recurrent tumor of forearm treated by amputation. Note extensive infiltration of tendons and surrounding tissues.
fibroblasts and polygonal or epithelioid acidophilic cells. Areas of focal necrosis are common, and there may be more or less abundant collagen associated with the tumor cells. The tumor grows slowly, often as multiple nodules, frequently along fibrous structures such as tendons and fascia (Fig. 1). In spite of apparently adequate local removal, the tumor recurs frequently and may metastasize widely. The purpose of this report is to record the study of the clinical and histologic findings in nine patients with epithelioid sarcoma. Two illustrative typical case histories are presented in detail.
MATERIAL AND METHODS The nine cases include material submitted for consultation to the Division of Surgical Pathology, College of Physicians and Surgeons, as well as from patients treated at the Columbia Presbyterian Medical Center. Hematoxylin and eosin stain was used in all cases. In selected cases
134
hematoxylin-phloxin-safranin, Laidlaw reticulin, Masson's trichrome, PAS mucicarmine, and alcian blue stains were employed. Follow-up information was obtained whenever possible.
TWO TYPICAL CASE HISTORIES Case 5
A 31 year old male was first seen in Florida in 1957 because of stiffness, pain, and swelling, which began in the left index finger and later involved the left hand and forearm. Nodular and ulcerated lesions subsequently developed over the affected limb. Multiple cultures for fungi were negative. Several biopsies were performed, the diagnoses ranging from malignant melanoma and squamous cell carcinoma to sarcoidal or fungal granuloma. He was treated unsuccessfully with various antibiotics. In May 1959 he was admitted to The Columbia-Presbyterian Medical Center. The left index finger, webspace, and
EPITHELIOID SARCOMA -SANTIAGO
ET AL.
J
Figure 2. Case 5, male, 31. Tumor of index finger with multiple superficial satelIite ulcerated nodules in forearm. Finger and metacarpal were amputated (see inset) and interscapulothoracic amputation performed subsequently. Patient died four years after onset of disease with extensive metastases. Note deep seated tumor on dorsum of index finger and the multiple skin nodules in finger and forearm.
second metacarpal were excised along with three axillary lymph nodes. The pathologic diagnosis was that of a malignant tumor, most probably malignant melanoma (Fig. 3). One of three axillary lymph nodes was involved with tumor. A forequarter amputation and axillary node dissection were performed (Fig. 2). Five months after surgery the patient developed metastatic nodules on the left cheek, nuchal region, left alveolar ridge, and below the scar at the amputation site. These lesions were excised and the patient was discharged to have radiotherapy in Florida. In September 1961, four years after the onset of symptoms, he died in Florida, presumably as a result of metastatic disease. Case 6
R.H., a 29 year old female, was seen in January 1960 because of subcutaneous nodular lesions of her left forearm and wrist that had been present for three
years. A biopsy one year earlier had been interpreted as an inflammatory lesion of the flexor tendons. Some of the nodules and several axillary lymph nodes were excised for examination. The tumor was diagnosed as a malignant hemangioendothelioma (angiosarcoma); no tumor was found at this time in the axillary lymph nodes (Fig. 4). A left interscapulothoracic amputation was performed in February 1960. At this time tumor metastatic to the axillary lymph nodes was found (Fig. 5). The patient remained free of disease until June 1965, when a metastatic nodule of the scalp was excised. Radiotherapy was given after new scalp nodules had appeared. In July 1966 she developed pulmonary metastases, which regressed after radiotherapy, but one year later new pulmonary metastases developed. A short course of methotrexate was temporarily effective, but she died in February 1968 with cutaneous and pulmonary metastases, 11 years after the onset of her tumor.
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Figure 3. Case 5. Photomicrograph from section of an ulcerated skin nodule. Note resemblance to malignant melanoma. (Hematoxylin and eosin stain. X 215.)
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EPITHELIOID SARCOMA-SANTIAGO ET AL.
Figure 4. Case 6, female, 29. Tumors in tendons of wrist, followed by multiple nodules in forearm. Axillary and scalp metastases developed, followed by lung metastases. Patient died 11 years after onset of disease. Original biopsy. Note pseudoangiosarcomatoLlS pattern caused by shrinkage artefact. (Hematoxylin and eosin stain. x 250.)
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HUMAN PATHOLOGY-VOLUME 3, NUMBER I-March 1972
Figure 5. Case 6. Axillary lymph node metastasis. Note the epithelioid appearance of the tumor cells. (Hematoxylin and eosin stain. x 250.)
CLINICAL DATA
138
The ages of the patients at the time of biopsy ranged from 21 to 64 years, with a median of 33 years. Seven were males and two females. Four of the patients had had signs or symptoms eight to 18 months before a diagnosis was made, and in two patients signs and symptoms occurred three years prior to therapy. In one patient the diagnosis was made nine years after the onset of the disease; in two patients this information is not known. Five of the lesions were located on the lower limb (leg 2, knee 1, heel 1, gluteal region 1). Four tumors were located on the upper limb (forearm 2, finger 1, wrist 1). The original diagnoses for these nine cases are listed in Table 1.
TABLE 1.
DIAGNOSES SUGGESTED FOR NINE CASES OF EPITHELIOID SARCOMA*
Synovial sarcoma Malignant histiocytoma Rhabdomyosareo rna Sweat gland carcinoma Mesothelioma Atypical giant cell sarcoma of tendon sheath Fibrosarcoma Atypical fibrous xanthoma Fibrous histiocytoma Sporotrichosis Malignant melanoma Sarcoidal granuloma Squamous cell carcinoma Malignant hemangioendothelioma (angiosarcoma) *For some of these cases more than one diagnosis was formulated during the course of the disease.
TABLE 2. Case
SUMMARY OF CLINICAL DATA ON NINE PATIENTS REPORTED
Duration from Onset to Diagnosis
Age
Sex
Location
I. P&S 87422 2. P&S 86166
53 64
M M
Gluteal region Lower leg
I year 8 months
3. P&S 87443
32
M
Heel
9 years
4. P&S 70792
33
M
Wrist
Not known
A 77561
31
M
Index finger
3 years
5.
Follow-up Therapy
Local excision. Local excision, radiotherapy. Three local excisions followed by recurrence. Ampuration 9 years after onset of disease.
Duration
Not known. 10 months 9 years
Alive and well. Alive and well (7 months after amputation).
Forearm amputation, axillary metastases noted; upper arm amputation I year later for recurrence.
7 years
Death presumably from metastatic disease.
Interscapulo-
2 years
Metastases to cheek and alveolar ridge in 5 . months. Death presumablv from metastatic disease 4 years after onset of disease. Metastases to scalp and lungs. Death from metastic disease 11 years after onset.
thoracic amputation. Axillary metastases noted.
6. P&S 84712
29
F
Forearm
3 years
Local excision followed by recurrence.
8 years
Interscapulothoracic
7. P&S 87194
21
M
Leg
Not known
8.
45
M
Forearm
10 months
B 91165
9. P&S 78147
........ C,)O
.o
41
F
Knee
18 months
Result
amputation six months later. Axillary metastases noted. Above knee amputaNot known tion. Local excision fol2 years lowed by local recurrence. Supracondylar amputation. Local excision and 12 years radiotherapy. Recurrenee 6 years later. Above knee amputation.
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Local recurrence Alive and well.
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Metastases to lungs. Pneumonectomy 12 years after onset.
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HUMAN PATHOLOGY-VOLUME 3, NUMBER I-lV/arch 1972
One lesion was treated solely by local excision. One patient had local excision and radiotherapy. Seven patients had amputations of the involved limbs. Four of these patients had local excision initially, but because of local recurrences the involved limb was amputated. Four patients were followed for more than five years; of these, two died of metastatic disease, one is alive with metastases, and one is alive and well. Two other patients were followed for over one year; one is alive and well and one died with metastatic disease. For the remaining three patients, no significant follow-up is available at this time. Six patients have had at least one local recurrence. One patient has had three local recurrences. The principal sites of metastasis were the lungs and the regional lymph nodes.
140
In addition, metastases to the scalp, cheek, and alveolar ridge occurred. The clinical data from all the patients are summarized in Table 2. PATHOLOGIC FINDINGS
The gross appearance of the lesion varied according to its location. When it involved the dermis or subcutis, there were usually several nodules measuring up to 1 to 2 em. in diameter that 'occasionally became ulcerated (Fig. 2). When the lesion was located near the tendons, there were firm irregular deep masses along these structures with infiltration of the surrounding soft tissues (Fig. 1). When 'the lesion was located deep in the soft tissues not in direct contact with tendons or
Figure 6. Case 6. Section of a recurrent. skin nodule in forearm. Note granuloma-like necrotizing foci in deep dermis and subcutaneous tissue. (Hematoxylin and eosin stain. X 50.)
EPITHELIOID SARCOMA-SANTIAGO ET AL.
Figure 7. Necrotizing focus in a recurrent skin nodule. Note in the center a vascular space plugged with tumor cells. (Hematoxylin and eosin stain. X 126.)
jomts. there was a fibrotic, irregularly shaped infiltrating mass.
Microscopic Examination The following main microscopic patterns were present in different proportions in every case: a granuloma-like pattern (Figs. 6, 7), a pseudocarcinomatous pattern (Fig. 8), a melanoma-like pattern (Figs. 3, 5, and 10), an angi.osarcoma-like pattern (Figs. 4, 9), and an undifferentiated sarcomatous pattern (Fig. 9). Cytologically, the most cons picuous elements were large, round, or polygonal cells with abundant eosinophilic cytoplasm and round or oval nuclei with prominent nucleoli. Multinucleated cells were seldom seen. In addition, poorly differentiated spindle cells resembling immature fibroblasts and associated with collagenous ground substance were present.
The granuloma-like lesions with central areas of necrosis sometimes showed blood vessel walls infiltrated by tumor cells. This massive vascular invasion was probably responsible for the ischemic changes and necrosis (Fig. 7). The angiosarcomatous type of pattern is probably an artifact due to imperfectfixation with shrinkage resulting in gTOUpS of tumor cells attached to the surrounding hyalinized compact stroma and giving the impression of vascular channels lined by neoplastic "endothelial" cells. When there are dermal nodules, especially if they are ulcerated, the subepidermal clusters of large acidophilic cells can be mistaken for malignant melanoma. The pseudocarcinomatous pattern was seen mainly in those cases in which the tumor grew along tendons or fascia. Also here, occasional pseudoglanclular lumens, probably a shrinkage artifact, were sometimes seen. (Text continued on pctge 145.J
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HUMAN PATHOLOGY-VOLUME 3, NUMBER I-March 1972
Figure 8. Case 8. Note aggregates of tumor cells of epithelium-like appearance, exhibiting a pseudoglandular pattern. The gland-like spaces are artefactual and result from lack of cohesiveness and shrinkage. (Hematoxylin and eosin stain. x 240.)
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EPITHELIOID SARCOMA-SANTIAGO
ET AL.
Figure 9. Case 9, female, 4]. Tumor of knee. Local excision followed by x-ray therapy. Amputation above knee 18 months later for recurrence. Lung metastasis 12 years later treated by pneumonectomy. Note mixture of epithelioid and spindle shaped cells, and the arte factual clefts mimicking vascular channels. (Hematoxylin and eosin stain. X 160.)
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Figure 10. Case 4. male. 33. Tumor of wrist. Forearm amputated one year after diagnosis of malignant tumor. Patient died six years later with clinical evidence of metastases. Note the large pleomorphic acidophilic cells, sometimes mistaken for malignant melanoma or rhabdomyosarcoma. (Hematoxylin and eosin stain. X 160,)
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EPITHELIOID SA RCO MA- SANTIAGO ET AL.
Figure 11. Case 8. Note the biphasic pat tern co ns isting of a fibrosarcomatous str o ma and epithelioid cells arranged in ne sts a nd cords and in pseudoglandul a r fa sh ion . (Hema to x ylin and eos in stain . x 2 50.)
DISCUSSION Table 3 summarizes the 70 reported cases of this entity found in the lite rature , as well as th e cases re po r ted here. Most of the cases occurred in ad u lt mal es and in vol ved the upper limb, often in association with tendon sheath lesions. O f note are two case s origin atin g in the scalp reported by Enzinge r! and Dehner and Smith's case" involving the pe nis . Pe rhaps as thi s en tity gains wider recogn ition , fu rther cases in volving sites other than the e xtremities will be r eported. The frequency with which thi s tumor both rec urs and metastasizes, despi te rad ical the rapy , is evident. Only on e autopsy is reponed in the literature , th at of Bliss and Reeds (case 3). Here metastases to the lungs, mediastinal lymph nodes , and liver wer e discovered. The tumors recurred in 85
per cen t of Enzinger' s ca ses- and metastasized in 30 per cent. Of ou r nine patients, six had local recu rre nces an d three of th ese also had lymph nod e or b loo d borne metastases . Ultrastructural obse rvatio ns of these tumors ha ve d escribed the p r esence of two different types of cells' : " consisting of immature fibr oblasti c and histiocytelike elements and epithelium-like cells, simi lar to the biphasic pattern fou n d in no rmal synovi al m embranes," gian t cell tumors of tendon sheaths," and synovial
sarcoma." In a re ce n t study st ill unpublished, describing th e ultrastructure o f two of these tumors, certain feature s consistent with a possible synovial origin have been noted." Presumably these tu mol'S ar e sarcomas originating from undifferentiated
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TABLE 3.
SUMMARY OF
79
CASES OF EPITHELIOID SARCOMA REPORTED IN THE LITERATURE
Age
Sex
Black, 1936
36
M
Berger, 1938 (Case IV) DeSanto, 1941
75
F
Web of thumb, tendon sheath Wrist, tendon sheath
30
F
4th finger
46
M
44
M
Left 4th finger, tendon sheath Wrist, tendon sheath
44
M
Palm, tendon sheath
24
M
3rd finger, tendon sheath
M-49 F-13
38 22 2 13
Author and Year
No. Cases
Bliss and Reed. 1968
Enzinger
4
62
Median 23
Location
upper extremity lower extremity scalp tumors involved
Tendon or tendon sheath
Santiago et al.
Dehner and Smith. 1970
146
9
Median 33
35
M-7
5 lower extremity
F-2
4 upper extremity
M
Ventral shaft of penis
Follow-up No recurrence considered benign. Local recurrence in 3 weeks. Recurrence following local excision; alive without recurrence following amputation. Local recurrence; death with lung metastasis. Six months postexcision, metastasis to axilla. Death in 5 months. Autopsy revealed pulmonary pleural, mediastinallymph node, and liver metastases. Local recurrence; death in 20 months presumably from metastatic disease. 54 patients followed 12 alive with recurrence 3 alive with metastases 2 alive with recurrence and metastases 11 died from metastasis 25 alive and well I dead of intercurrent disease 3 patients alive and well 1 patient alive with local recurrence 3 patients dead from metastatic disease I patient alive with metastasis Lost to follow-up
EPITHELIOID SARCOMA-SANTIAGO
mesenchymal cells of tendons, aponeuroses, and synovial tissues. This might explain their biphasic pattern (epithelioid and fibroblastic cell types) analogous to that of the typical synovial sarcoma (Fig. 11). The most important practical point, however, is that the pathologist must learn to recognize this entity as a variant of the highly malignant soft tissue sarcomas that require prompt and adequate radical treatment, and to avoid confusing it with metastatic carcinoma, malignant melanoma, or inflammatory granulomatous lesions. REFERENCES 1. Enzinger, F. M.: Epithelioid sarcoma: A sarcoma simulating a granuloma or a carcinoma. Cancer, 26:1029-1041, 1970. 2. Black, W. C;. Synovioma of the hand. Report of a case. Arner. J. Cancer, 28:481-484, 1936.
ET AL.
3. Berger, 1.: Synovial sarcomas in serous bursae and tendon sheaths. Amer. J. Cancer, 34: 501-538, 1938. 4. De Santo, D. A., Tennant, R., and Rosahn, P. D.: Synovial sarcomas in joints, bursae and tendon sheaths. Surg. Gynee. Obstet., 72:951-981, 1941. 5. Bliss, B. 0., and Reed, R. J.: Large cell sarcomas of tendon sheath: malignant giant cell tumors of tendon sheath. Amer, J. Clin. Path., 49: 776-781, 1968. 6. Dehner, 1. P., and Smith, B. H.: Soft tissue tumors of the penis. Cancer, 25:1431-1447, 1970. 7. Fu, Y, Cabbiani, G., Kaye, G., Lattes, R., and Majno, G.: Unpublished data. 8. Grinley, P. M., and Sohologg, 1.: Synovial giant cells in rheumatoid arthritis. Amer, J. Path., 49:931,1966. 9. Eisenstein, R.: Giant cell tumors of tendon sheath; its histogenesis studied by the electron microscope. J. Bone Joint. Surg., 50:476486,1968. 10. Gabbiani, G., Kaye, G., Lattes, R., and Majno, G.: Synovial sarcoma. Electron microscopic study of a typical case. Cancer, 28: 1031-1039, 1971. Surgical Pathology College of Physicians and Surgeons 630 West 168th Street New York, New York 10032 (Dr. Lattes)
147
EPITHELIOID SARCOMA A Clinical and Pathologic Study of Nine Cases Hector Santiago, MD.,* Lois K. Feinerman, M.D.,t and Raffaele Lattes, M.D.t
Abstract This is a report of nine cases of epitheloid sarcoma, a term introduced recently to designate a special variant of malignant soft tissue tumor generally involving tendons, aponeuroses, and more superficial tissues of the extremities. The histologic features of this tumor, which consists of a mixture of polygonal epithelioid cells and elongated fibroblastic cells with necrotizing foci, have often misled the pathologist into diagnoses of necrotizing granuloma, malignant melanoma, angiosarcoma, or metastatic carcinoma. The tumor is definitely malignant, is difficult to eradicate by local surgical excision, and often metastasizes to lymph nodes and via the blood. The histogenesis of this tumor is still controversial, but some light and electron microscopic features suggest a possible synovial origin.
Enzinger- in 1970 reviewed a series of 62 cases of an unusual type of sarcoma that is often confused clinically and pathologically with a variety of granulomatous and neoplastic diseases. He has called this tumor "epithelioid sarcoma." Other probable examples of this tumor type have been described previously in the literature with different classifications. Black" in 1936, Berger in 1938, and De Santo et a1. 4 in 1941 described similar cases, which they included in the general group of synovial sarcomas. Bliss and Reed" in 1968 described four cases of "large cell sarcomas of tendon sheath" thought to
represent the malignant counterpart of the benign giant cell tumor of tendon sheaths. In their discussion of soft tissue tumors of the penis, Dehner and Smith" in 1970 described a "fascial sarcoma," which closely resembles the epithelioid sarcoma of Enzinger and represents the only such lesion known to have been observed on the penis. Epithelioid sarcoma is most often found in adult males as a subfascial or subcutaneous lesion originating on the limbs. Microscopically the tumor has a characteristic nodular appearance and is composed of both spindle cells resembling
*Pathologist, Hospital Infantil Irnan, Mexico City, Mexico. tAssociate Professor of Dermatology, Albert Einstein College of Medicine. Staff, Hospital of Albert Einstein College of Medicine, Bronx, New York. :j:Professor of Surgical Pathology, College of Physicians and Surgeons, Columbia University. Attending Pathologist, Presbyterian Hospital, New York, New York.
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HUMAN PATHOLOGY-VOLUME 3, NUMBER I-lvlarch 1972
Figure 1. Case 8, male, 45. Recurrent tumor of forearm treated by amputation. Note extensive infiltration of tendons and surrounding tissues.
fibroblasts and polygonal or epithelioid acidophilic cells. Areas of focal necrosis are common, and there may be more or less abundant collagen associated with the tumor cells. The tumor grows slowly, often as multiple nodules, frequently along fibrous structures such as tendons and fascia (Fig. 1). In spite of apparently adequate local removal, the tumor recurs frequently and may metastasize widely. The purpose of this report is to record the study of the clinical and histologic findings in nine patients with epithelioid sarcoma. Two illustrative typical case histories are presented in detail.
MATERIAL AND METHODS The nine cases include material submitted for consultation to the Division of Surgical Pathology, College of Physicians and Surgeons, as well as from patients treated at the Columbia Presbyterian Medical Center. Hematoxylin and eosin stain was used in all cases. In selected cases
134
hematoxylin-phloxin-safranin, Laidlaw reticulin, Masson's trichrome, PAS mucicarmine, and alcian blue stains were employed. Follow-up information was obtained whenever possible.
TWO TYPICAL CASE HISTORIES Case 5
A 31 year old male was first seen in Florida in 1957 because of stiffness, pain, and swelling, which began in the left index finger and later involved the left hand and forearm. Nodular and ulcerated lesions subsequently developed over the affected limb. Multiple cultures for fungi were negative. Several biopsies were performed, the diagnoses ranging from malignant melanoma and squamous cell carcinoma to sarcoidal or fungal granuloma. He was treated unsuccessfully with various antibiotics. In May 1959 he was admitted to The Columbia-Presbyterian Medical Center. The left index finger, webspace, and
EPITHELIOID SARCOMA -SANTIAGO
ET AL.
J
Figure 2. Case 5, male, 31. Tumor of index finger with multiple superficial satelIite ulcerated nodules in forearm. Finger and metacarpal were amputated (see inset) and interscapulothoracic amputation performed subsequently. Patient died four years after onset of disease with extensive metastases. Note deep seated tumor on dorsum of index finger and the multiple skin nodules in finger and forearm.
second metacarpal were excised along with three axillary lymph nodes. The pathologic diagnosis was that of a malignant tumor, most probably malignant melanoma (Fig. 3). One of three axillary lymph nodes was involved with tumor. A forequarter amputation and axillary node dissection were performed (Fig. 2). Five months after surgery the patient developed metastatic nodules on the left cheek, nuchal region, left alveolar ridge, and below the scar at the amputation site. These lesions were excised and the patient was discharged to have radiotherapy in Florida. In September 1961, four years after the onset of symptoms, he died in Florida, presumably as a result of metastatic disease. Case 6
R.H., a 29 year old female, was seen in January 1960 because of subcutaneous nodular lesions of her left forearm and wrist that had been present for three
years. A biopsy one year earlier had been interpreted as an inflammatory lesion of the flexor tendons. Some of the nodules and several axillary lymph nodes were excised for examination. The tumor was diagnosed as a malignant hemangioendothelioma (angiosarcoma); no tumor was found at this time in the axillary lymph nodes (Fig. 4). A left interscapulothoracic amputation was performed in February 1960. At this time tumor metastatic to the axillary lymph nodes was found (Fig. 5). The patient remained free of disease until June 1965, when a metastatic nodule of the scalp was excised. Radiotherapy was given after new scalp nodules had appeared. In July 1966 she developed pulmonary metastases, which regressed after radiotherapy, but one year later new pulmonary metastases developed. A short course of methotrexate was temporarily effective, but she died in February 1968 with cutaneous and pulmonary metastases, 11 years after the onset of her tumor.
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Figure 3. Case 5. Photomicrograph from section of an ulcerated skin nodule. Note resemblance to malignant melanoma. (Hematoxylin and eosin stain. X 215.)
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EPITHELIOID SARCOMA-SANTIAGO ET AL.
Figure 4. Case 6, female, 29. Tumors in tendons of wrist, followed by multiple nodules in forearm. Axillary and scalp metastases developed, followed by lung metastases. Patient died 11 years after onset of disease. Original biopsy. Note pseudoangiosarcomatoLlS pattern caused by shrinkage artefact. (Hematoxylin and eosin stain. x 250.)
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HUMAN PATHOLOGY-VOLUME 3, NUMBER I-March 1972
Figure 5. Case 6. Axillary lymph node metastasis. Note the epithelioid appearance of the tumor cells. (Hematoxylin and eosin stain. x 250.)
CLINICAL DATA
138
The ages of the patients at the time of biopsy ranged from 21 to 64 years, with a median of 33 years. Seven were males and two females. Four of the patients had had signs or symptoms eight to 18 months before a diagnosis was made, and in two patients signs and symptoms occurred three years prior to therapy. In one patient the diagnosis was made nine years after the onset of the disease; in two patients this information is not known. Five of the lesions were located on the lower limb (leg 2, knee 1, heel 1, gluteal region 1). Four tumors were located on the upper limb (forearm 2, finger 1, wrist 1). The original diagnoses for these nine cases are listed in Table 1.
TABLE 1.
DIAGNOSES SUGGESTED FOR NINE CASES OF EPITHELIOID SARCOMA*
Synovial sarcoma Malignant histiocytoma Rhabdomyosareo rna Sweat gland carcinoma Mesothelioma Atypical giant cell sarcoma of tendon sheath Fibrosarcoma Atypical fibrous xanthoma Fibrous histiocytoma Sporotrichosis Malignant melanoma Sarcoidal granuloma Squamous cell carcinoma Malignant hemangioendothelioma (angiosarcoma) *For some of these cases more than one diagnosis was formulated during the course of the disease.
TABLE 2. Case
SUMMARY OF CLINICAL DATA ON NINE PATIENTS REPORTED
Duration from Onset to Diagnosis
Age
Sex
Location
I. P&S 87422 2. P&S 86166
53 64
M M
Gluteal region Lower leg
I year 8 months
3. P&S 87443
32
M
Heel
9 years
4. P&S 70792
33
M
Wrist
Not known
A 77561
31
M
Index finger
3 years
5.
Follow-up Therapy
Local excision. Local excision, radiotherapy. Three local excisions followed by recurrence. Ampuration 9 years after onset of disease.
Duration
Not known. 10 months 9 years
Alive and well. Alive and well (7 months after amputation).
Forearm amputation, axillary metastases noted; upper arm amputation I year later for recurrence.
7 years
Death presumably from metastatic disease.
Interscapulo-
2 years
Metastases to cheek and alveolar ridge in 5 . months. Death presumablv from metastatic disease 4 years after onset of disease. Metastases to scalp and lungs. Death from metastic disease 11 years after onset.
thoracic amputation. Axillary metastases noted.
6. P&S 84712
29
F
Forearm
3 years
Local excision followed by recurrence.
8 years
Interscapulothoracic
7. P&S 87194
21
M
Leg
Not known
8.
45
M
Forearm
10 months
B 91165
9. P&S 78147
........ C,)O
.o
41
F
Knee
18 months
Result
amputation six months later. Axillary metastases noted. Above knee amputaNot known tion. Local excision fol2 years lowed by local recurrence. Supracondylar amputation. Local excision and 12 years radiotherapy. Recurrenee 6 years later. Above knee amputation.
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Local recurrence Alive and well.
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Metastases to lungs. Pneumonectomy 12 years after onset.
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HUMAN PATHOLOGY-VOLUME 3, NUMBER I-lV/arch 1972
One lesion was treated solely by local excision. One patient had local excision and radiotherapy. Seven patients had amputations of the involved limbs. Four of these patients had local excision initially, but because of local recurrences the involved limb was amputated. Four patients were followed for more than five years; of these, two died of metastatic disease, one is alive with metastases, and one is alive and well. Two other patients were followed for over one year; one is alive and well and one died with metastatic disease. For the remaining three patients, no significant follow-up is available at this time. Six patients have had at least one local recurrence. One patient has had three local recurrences. The principal sites of metastasis were the lungs and the regional lymph nodes.
140
In addition, metastases to the scalp, cheek, and alveolar ridge occurred. The clinical data from all the patients are summarized in Table 2. PATHOLOGIC FINDINGS
The gross appearance of the lesion varied according to its location. When it involved the dermis or subcutis, there were usually several nodules measuring up to 1 to 2 em. in diameter that 'occasionally became ulcerated (Fig. 2). When the lesion was located near the tendons, there were firm irregular deep masses along these structures with infiltration of the surrounding soft tissues (Fig. 1). When 'the lesion was located deep in the soft tissues not in direct contact with tendons or
Figure 6. Case 6. Section of a recurrent. skin nodule in forearm. Note granuloma-like necrotizing foci in deep dermis and subcutaneous tissue. (Hematoxylin and eosin stain. X 50.)
EPITHELIOID SARCOMA-SANTIAGO ET AL.
Figure 7. Necrotizing focus in a recurrent skin nodule. Note in the center a vascular space plugged with tumor cells. (Hematoxylin and eosin stain. X 126.)
jomts. there was a fibrotic, irregularly shaped infiltrating mass.
Microscopic Examination The following main microscopic patterns were present in different proportions in every case: a granuloma-like pattern (Figs. 6, 7), a pseudocarcinomatous pattern (Fig. 8), a melanoma-like pattern (Figs. 3, 5, and 10), an angi.osarcoma-like pattern (Figs. 4, 9), and an undifferentiated sarcomatous pattern (Fig. 9). Cytologically, the most cons picuous elements were large, round, or polygonal cells with abundant eosinophilic cytoplasm and round or oval nuclei with prominent nucleoli. Multinucleated cells were seldom seen. In addition, poorly differentiated spindle cells resembling immature fibroblasts and associated with collagenous ground substance were present.
The granuloma-like lesions with central areas of necrosis sometimes showed blood vessel walls infiltrated by tumor cells. This massive vascular invasion was probably responsible for the ischemic changes and necrosis (Fig. 7). The angiosarcomatous type of pattern is probably an artifact due to imperfectfixation with shrinkage resulting in gTOUpS of tumor cells attached to the surrounding hyalinized compact stroma and giving the impression of vascular channels lined by neoplastic "endothelial" cells. When there are dermal nodules, especially if they are ulcerated, the subepidermal clusters of large acidophilic cells can be mistaken for malignant melanoma. The pseudocarcinomatous pattern was seen mainly in those cases in which the tumor grew along tendons or fascia. Also here, occasional pseudoglanclular lumens, probably a shrinkage artifact, were sometimes seen. (Text continued on pctge 145.J
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Figure 8. Case 8. Note aggregates of tumor cells of epithelium-like appearance, exhibiting a pseudoglandular pattern. The gland-like spaces are artefactual and result from lack of cohesiveness and shrinkage. (Hematoxylin and eosin stain. x 240.)
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ET AL.
Figure 9. Case 9, female, 4]. Tumor of knee. Local excision followed by x-ray therapy. Amputation above knee 18 months later for recurrence. Lung metastasis 12 years later treated by pneumonectomy. Note mixture of epithelioid and spindle shaped cells, and the arte factual clefts mimicking vascular channels. (Hematoxylin and eosin stain. X 160.)
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Figure 10. Case 4. male. 33. Tumor of wrist. Forearm amputated one year after diagnosis of malignant tumor. Patient died six years later with clinical evidence of metastases. Note the large pleomorphic acidophilic cells, sometimes mistaken for malignant melanoma or rhabdomyosarcoma. (Hematoxylin and eosin stain. X 160,)
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EPITHELIOID SA RCO MA- SANTIAGO ET AL.
Figure 11. Case 8. Note the biphasic pat tern co ns isting of a fibrosarcomatous str o ma and epithelioid cells arranged in ne sts a nd cords and in pseudoglandul a r fa sh ion . (Hema to x ylin and eos in stain . x 2 50.)
DISCUSSION Table 3 summarizes the 70 reported cases of this entity found in the lite rature , as well as th e cases re po r ted here. Most of the cases occurred in ad u lt mal es and in vol ved the upper limb, often in association with tendon sheath lesions. O f note are two case s origin atin g in the scalp reported by Enzinge r! and Dehner and Smith's case" involving the pe nis . Pe rhaps as thi s en tity gains wider recogn ition , fu rther cases in volving sites other than the e xtremities will be r eported. The frequency with which thi s tumor both rec urs and metastasizes, despi te rad ical the rapy , is evident. Only on e autopsy is reponed in the literature , th at of Bliss and Reeds (case 3). Here metastases to the lungs, mediastinal lymph nodes , and liver wer e discovered. The tumors recurred in 85
per cen t of Enzinger' s ca ses- and metastasized in 30 per cent. Of ou r nine patients, six had local recu rre nces an d three of th ese also had lymph nod e or b loo d borne metastases . Ultrastructural obse rvatio ns of these tumors ha ve d escribed the p r esence of two different types of cells' : " consisting of immature fibr oblasti c and histiocytelike elements and epithelium-like cells, simi lar to the biphasic pattern fou n d in no rmal synovi al m embranes," gian t cell tumors of tendon sheaths," and synovial
sarcoma." In a re ce n t study st ill unpublished, describing th e ultrastructure o f two of these tumors, certain feature s consistent with a possible synovial origin have been noted." Presumably these tu mol'S ar e sarcomas originating from undifferentiated
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TABLE 3.
SUMMARY OF
79
CASES OF EPITHELIOID SARCOMA REPORTED IN THE LITERATURE
Age
Sex
Black, 1936
36
M
Berger, 1938 (Case IV) DeSanto, 1941
75
F
Web of thumb, tendon sheath Wrist, tendon sheath
30
F
4th finger
46
M
44
M
Left 4th finger, tendon sheath Wrist, tendon sheath
44
M
Palm, tendon sheath
24
M
3rd finger, tendon sheath
M-49 F-13
38 22 2 13
Author and Year
No. Cases
Bliss and Reed. 1968
Enzinger
4
62
Median 23
Location
upper extremity lower extremity scalp tumors involved
Tendon or tendon sheath
Santiago et al.
Dehner and Smith. 1970
146
9
Median 33
35
M-7
5 lower extremity
F-2
4 upper extremity
M
Ventral shaft of penis
Follow-up No recurrence considered benign. Local recurrence in 3 weeks. Recurrence following local excision; alive without recurrence following amputation. Local recurrence; death with lung metastasis. Six months postexcision, metastasis to axilla. Death in 5 months. Autopsy revealed pulmonary pleural, mediastinallymph node, and liver metastases. Local recurrence; death in 20 months presumably from metastatic disease. 54 patients followed 12 alive with recurrence 3 alive with metastases 2 alive with recurrence and metastases 11 died from metastasis 25 alive and well I dead of intercurrent disease 3 patients alive and well 1 patient alive with local recurrence 3 patients dead from metastatic disease I patient alive with metastasis Lost to follow-up
EPITHELIOID SARCOMA-SANTIAGO
mesenchymal cells of tendons, aponeuroses, and synovial tissues. This might explain their biphasic pattern (epithelioid and fibroblastic cell types) analogous to that of the typical synovial sarcoma (Fig. 11). The most important practical point, however, is that the pathologist must learn to recognize this entity as a variant of the highly malignant soft tissue sarcomas that require prompt and adequate radical treatment, and to avoid confusing it with metastatic carcinoma, malignant melanoma, or inflammatory granulomatous lesions. REFERENCES 1. Enzinger, F. M.: Epithelioid sarcoma: A sarcoma simulating a granuloma or a carcinoma. Cancer, 26:1029-1041, 1970. 2. Black, W. C;. Synovioma of the hand. Report of a case. Arner. J. Cancer, 28:481-484, 1936.
ET AL.
3. Berger, 1.: Synovial sarcomas in serous bursae and tendon sheaths. Amer. J. Cancer, 34: 501-538, 1938. 4. De Santo, D. A., Tennant, R., and Rosahn, P. D.: Synovial sarcomas in joints, bursae and tendon sheaths. Surg. Gynee. Obstet., 72:951-981, 1941. 5. Bliss, B. 0., and Reed, R. J.: Large cell sarcomas of tendon sheath: malignant giant cell tumors of tendon sheath. Amer, J. Clin. Path., 49: 776-781, 1968. 6. Dehner, 1. P., and Smith, B. H.: Soft tissue tumors of the penis. Cancer, 25:1431-1447, 1970. 7. Fu, Y, Cabbiani, G., Kaye, G., Lattes, R., and Majno, G.: Unpublished data. 8. Grinley, P. M., and Sohologg, 1.: Synovial giant cells in rheumatoid arthritis. Amer, J. Path., 49:931,1966. 9. Eisenstein, R.: Giant cell tumors of tendon sheath; its histogenesis studied by the electron microscope. J. Bone Joint. Surg., 50:476486,1968. 10. Gabbiani, G., Kaye, G., Lattes, R., and Majno, G.: Synovial sarcoma. Electron microscopic study of a typical case. Cancer, 28: 1031-1039, 1971. Surgical Pathology College of Physicians and Surgeons 630 West 168th Street New York, New York 10032 (Dr. Lattes)
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