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Epithelioid sarcoma of the vulva
GYNECOLOGIC
ONCOLOGY
9,231-246
(1980)
CASE REPORT
Epithelioid
Sarcoma
of the Vulva1
DON J. HALL, M.D., FACOG,2 MARGARET M. GRIMES, M.D.,3 AND DEAN R. GOPLERUD, M.D., FACOG Gynecologic
Oncology Service, Department of Obstetrics and Gynecology Division of Surgicul Pathology, the Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298
and the
Received May 28, 1979 The authors present the third known case of an epithelioid sarcoma involving the vulva. This case illustrates the confusion that can occur in making a proper pathologic diagnosis. The histologic and electron microscopic characteristics of the tumor are presented. The natural history of the disease is discussed describing the propensity for local recurrence and the sites of metastases. Recommendations for management are discussed.
INTRODUCTION
Epithelioid sarcoma, a rare neoplasm, was first recognized in 1970 as a distinct tumor type 111. Since then more cases have been reported [2-81. The lesion has been commonly misdiagnosed as being either benign or another variety of malignant neoplasm [1,6,8]. This tumor occurs chiefly in young adults and is characterized by a slowly enlarging nodular growth with early necrosis and ulceration of the overlying skin. It is most commonly seen on the fascia and tendons of the extremities and may be present for many years before the patient seeks medical attention [1,6,8]. Only two previous cases of vulvar epithelioid sarcoma have been reported, both of which occurred in young white females [5,7]. The following presentation is believed to be the third reported case. CASE HISTORY
B.P. was a 31-year-old white female gravida 2, para 2 who initially saw her local physician in 1%8 with a small ulcerating lesion in the left anterolateral edge of the vulva of 2 years duration. An excisional biopsy was performed. The pathology report was atypical fibroxanthoma. The patient did well until 1974 when she presented with a lesion of the left labium majus and two nodular ulcerated lesions ’ This investigation was supported in part by Grant 5R25 CA 22032-02. 2 ACS Fellowship 3965, Fellow in Gynecologic Oncology. 3 ACS Fellowship 4216, Fellow in Surgical Pathology. 237
0090-8258/80/020237- 10$01.00/O Copyright @ 1980 by Academic Press, Inc. All rights of reproduction in any form reserved.
238
HALL,
GRIMES,
AND
GOPLERUD
in the left groin. Excision was again performed. A second pathologist interpreted the specimen as showing rhabdomyosarcoma of the vulva and groin. The patient was referred to the Gynecologic Onoclogy Service at the Medical College of Virginia. The slides were reviewed and reinterpreted as representing a malignant fibrous histiocytoma. In February 1974, a wide local excision and left inguinal and femoral node dissection was performed. The tissue specimen was again interpreted as malignant fibrous histiocytoma of the vulva with chronic lymphadenitis. During routine follow-up, the patient was found to be pregnant in September of 1974 and subsequently delivered a normal 7 lb 8 oz female infant in May 1975. In October 1976 the patient presented to the Thoracic Surgery Service with bilateral spontaneous pneumothorax requiring thoracotomy. One month later a left spontaneous pneumothorax recurred requiring chest tube management. In January 1977, the patient noted a 2-cm blue nodule of the left vulva in the area of the previous lesion. Multiple enlarged lymph nodes were palpable in the right groin. A biopsy was performed from the vulvar nodule. This was interpreted as malignant hemangioendothelioma. A radical vulvectomy with node dissection was recommended but was refused by the patient fearing disfigurement and loss of sexual function. The patient refused further follow-up until August 1977 when she presented to the MCV emergency room with hemoptysis. A chest radiograph and tomograms showed multiple metastatic lesions. A 2-cm blue raised, ulcerated lesion of the vulva was present. Combination chemotherapy consisting of adriamycin, dimethyltriazenoimidazole-carboxamide, Cytoxan, and vincristine was started. A repeat course of chemotherapy was given 4 weeks later. At that time the mass in the vulva measured 2 x 3 cm with surrounding subcutaneous induration and fixation. Because of side effects, the patient refused further chemotherapy and traveled to Mexico where she underwent Laetril treatment until May of 1978. Although she claimed a feeling of subjective improvement, the vulvar mass continued to grow. She was next seen in July of 1978 complaining of pain, bleeding, and foul odor. Satellite nodules were noted on the right vulva, both groins, and the medial aspect of the left thigh (Fig. 1). The patient was admitted for palliative excision and debridement of the lesion. The final pathology report was epithelioid sarcoma. A chest radiograph showed progression of the pulmonary lesions and a CT scan revealed liver metastases and retroperitoneal lymphadenopathy. The patient refused further chemotherapy. She received radiation therapy for local control of bleeding and pain. External beam therapy was given delivering 4500 t-ad to the pelvis and upper thighs. An additional boost of 1000 rad was planned but only 700 rad were completed because of radiation vulvitis and lack of response of the vulvar lesion. Triple chemotherapy consisting of a 5-day course of adriamycin-D, dimethyltriazenoimidazole-carboxamide, and vincristine was begun, however the patient refused further chemotherapy after the third day. The patient never returned for further therapy despite multiple attempts by physicians, nurses, and paramedical personnel. The patient expired at home on February 13, 1979.
EPITHELIOID
FIG.
1. Recurrent epithelioid
SARCOMA
OF THE VULVA
239
sarcoma of the vulva with multiple satellite nodules.
MATERIALS
AND METHODS
Biopsy tissue prepared at the Medical College of Virginia was stained with hematoxylin-eosin after fixation in Zenker’s solution. Material for electron microscopy was minced into l-mm pieces, placed in 4% glutaraldehyde in sodium cacodylate buffer for 2 hr, then postfixed in buffered 2% osmium tetroxide. Tissue was then dehydrated in graded alcohols and propylene oxide and embedded in Epon. Areas of study were selected from I- to 2-pm-thick sections stained with toluidine blue. Thin sections were stained with uranyl acetate and lead citrate. PATHOLOGIC
FINDINGS
Biopsy of the left groin lesion in 1968 was originally interpreted as an atypical fibroxanthoma, possibly arising from an inflamed epidermal cyst. Proliferating
240
HALL,
GRIMES,
AND GOPLERUD
fibroblasts, histiocytes, and giant cells appeared to surround degenerated squamous epithelium. Despite mitoses and bizarre nuclei, the process was believed to be benign. The lesion recurred in 1974 as “hard masses” in the left labia. Rhabdomyosarcoma was diagnosed at another hospital on the basis of eosinophilic staining of tumor cells, a suggestion of strap cells, and results of trichrome staining. The 1968 lesion in retrospect was believed to represent a granular cell myoblastoma. The sections of both lesions were reviewed at Medical College of Virginia. The first tumor was interpreted as an atypical fibrous histiocytoma. Sections of the recurrence showed a nonencapsulated, cellular growth, composed of pleomorphic cells within a fibrous stroma. Nuclei varied from spindled to plump, some having prominent nucleoli. Small clefts or spaces were lined by cells with abundant cytoplasm. The fibrous pattern predominated (Fig. 2). Because of the appearance, size, and recurrence of the lesion, the diagnosis of malignant fibrous histiocytoma was made. A subsequent reexcision and superficial inguinal lymph node dissection revealed a similar histologic appearance and absence of nodal metastases. In 1977, biopsy of a second recurrence was performed. Microscopically, the tumor had a distinct vascular pattern, with some papillary features (Fig. 3). The same large tumor cells with opaque eosinophilic cytoplasm were recognized, and these lined spaces filled with blood cells. In addition, there was necrosis and cystic degeneration. Occasional mitoses were seen. Because of the pattern seen on this biopsy, and the similarity noted upon review of the previous slides, the diagnosis was changed to malignant hemangioendothelioma. At excision of the third recurrence in 1978, the tumor was described as a U-mm,
FIG. 2. Biopsy of first recurrence, interpreted as malignant fibrous histiocytoma. “epitheloid” cells were present at this time. H&E, x192.
Clefts and
EPITHELIOID
SARCOMA
OF
THE
VULVA
241
FIG. 3. The tumor stimulated a vascular pattern at the second recurrence leading to a diagnosis of malignant hemangioendothelioma. H&E, x 160.
nodular, gray-tan mass having a hemorrhagic, gelatinous cut surface. The microscopic appearance was similar to that of the previous biopsy, with the exception that the clefts or spaces were now large, freely communicating channels filled with blood. The tumor cells lining these spaces were identical to those previously described (Fig. 4). The original impression was, again, malignant hemangioendothelioma. No intracellular mucin was found on special stains. Within the fibrous component of the tumor, reticulin appeared to surround individual cells. The reticulin surrounding the clefts was incomplete in most cases, with plump neoplastic cells lying on the luminal side. These cells could be seen adhering in small groups without intervening reticulin. There was no discrete elastic framework surrounding the clefts. Electron microscopic study of the tumor showed a monotonous pattern of loosely arranged, darkly staining mononuclear cells. Most cells demonstrated plentiful filopodia (Fig. 5). No desmosomes were seen. At higher power, some cells showed nuclei with prominent filamentous nucleolonema (Fig. 6), a few lysosomes, and plentiful rough endoplasmic reticulum. Mitochondria were sparse. In some areas it appeared that the cells lined true vascular spaces, in which polymorphonuclear leukocytes and lymphocytes were identified (Fig. 7). Weibel-Palade bodies were not identified in any of the tumor cells. These findings, and the clinical features of the case, were felt to be more consistent with epithelioid sarcoma than with malignant hemangioendothelioma, especially since
FIG. 4. Tumor cells with abundant eosinophilic cytoplasm filled “vascular channels” at the third recurrence. H&E, x400.
FIG. 5. Electron micrography showing tumor cells with numerous filopodia. x4015. 242
EPITHELIOID
SARCOMA
OF
THE
VULVA
243
FIG. 6. A neoplastic cell with filamentous nucleolonema in nucleus. Abundant rough endoplasmic reticulum and a lipid body are seen in the cytoplasm. Note prominent tilopodia. x9920.
the ultrastructural findings were similar to those reported in previous examples of epithelioid sarcoma [2,9, lo]. DISCUSSION
This case is believed to represent an example of epithelioid sarcoma involving the vulva of which only two other published reports were found [5,7]. This rare sarcoma is seen most commonly on the extremities of young patients in the third and fourth decades of life, It affects males more often than females (63. The lesions are usually asymptomatic at first resulting in patient delay in seeking medical care as illustrated by our case. The tumor starts as a slow-growing nodular lesion which ulcerates, and may be confused with a granuloma or a variety of infectious processes. The gross lesions are frequently purple-red in color. Although tumor growth is slow, it is relentless with a marked tendency for local recurrence when inadequately treated. Distant metastases often occur after repeated local recurrences. The primary
244
HALL,
GRIMES,
AND GOPLERUD
FIG. 7. Lymphocytes and polymorphonuclear leukocytes were seen in the channels lined by neoplastic elements. Weibel-Palade bodies were not identified in any of the tumor cells. X3575.
metastatic route is lymphatic with hematogenous spread being secondary [I I]. Direct tumor extension also occurs. Prat has noted a poor prognosis associated with local recurrence after excision, vascular invasion, and lymph node metastases [6]. The reported incidence of metastases varies from 30-45% [ 1,8,12,13]. In a recent series of 22 patients, 58% developed metastases with 42% of these going to regional lymph nodes and 47% to lungs. In addition to the regional lymph nodes and lung, the liver and peculiarly the scalp appeared to be other metastatic sites. Lung, liver, and regional nodes were involved in this case presentation. The vulva is a rare location for epithelioid sarcoma with only two previous cases reported [5,7]. Clinically all of these lesions started as an asymptomatic mass and all occurred in young white females. Our case was the only one to present with a draining ulcerative lesion. The original sites of the three cases were infraclitoral 151, left midvulvar [7], and left vulvar edge (present case). All patients presented with a history of previous excisional biopsy. The initial pathological interpretation
EPITHELIOID
SARCOMA
OF
THE
VULVA
245
in Gallup’s case was “poorly differentiated metastatic carcinoma.” In our case four other diagnoses were made (atypical fibroxanthoma, rhabdomyosarcoma, malignant fibrous histiocytoma and malignant hemangioendothelioma). The variety of diagnoses attached to the lesion in this case at various stages of its growth demonstrates well the difficulty that may be encountered. When Enzinger described the neoplasm in 1970, he emphasized its frequent confusion with other malignant as well as benign lesions, for example, squamous cell carcinoma, synovial sarcoma, or necrotizing granuloma [l]. Histologic features of the tumor which he thought characteristic were nodularity, frequent necrosis, and the acidophilia of the epithelioid cells. The tendency to form clefts, to the point of simulating a vascular neoplasm, was also noted. This has been ascribed to loss of cellular adhesion and/or fixation artifact. The cell of origin remains debatable. Various electron microscopic studies have suggested synovial, histiocytic, or fibrocytic derivation [2,9,10]. As previously noted by Gallup et al. [7], the best treatment for epithelioid sarcoma of the vulva is undetermined. All three cases had initial excisional biopsy. The first case, reported by Piver, was treated with a wide local excision (lo-cm area) and node biopsy, and remains disease-free at this writing [14]. No residual tumor was present in the surgical specimen. The second case reported by Gallup and co-workers was treated with radical vulvectomy and bilateral groin dissection. The specimen revealed several tumor nodules in the area of initial excision as well as one positive lymph node. Despite the metastasis, the patient was reported to be doing well 16 months post-treatment [ 111. The present case, as well as Gallup’s patient, illustrates the problem with a small local excision only, and the possibility of treatment failure with local recurrence and distant metastases. Our patient had a wide local excision and ipsilateral groin dissection following two small local excisions. Despite negative lymph nodes and clear surgical margins, the tumor recurred. Prat has shown no correlation between the incidence of nodal metastases and survival [6]. The patient illustrates a lack of radiosensitivity and implies radiation therapy does not appear to be beneficial at least for the vulvar lesions. Chemotherapy has been reported in the treatment of a number of patients with recurrent disease but no specific agent or combination appears to be superior as of this writing [3,4,6,10]. No conclusion regarding effectiveness of the chemotherapy can be made from this case. Delay in diagnosis may adversely affect outcome. The duration between onset of symptoms and definitive therapy was approximately 1.5 months [5], 4 months [71, and 2 years in our case. The influence of pregnancy on this tumor is unknown. We believe that early surgical management consisting of a very wide en bloc removal or radical vulvectomy with regional lymph node dissection is the best mode of initial therapy. Small local excision may lead to treatment failure. Regular and prolonged follow-up is desirable with frequent chest radiographs and careful inspection of the vulva and scalp [3]. Radiation therapy offers little hope for controlling recurrent vulvar disease. The role of chemotherapy is undetermined at present in the management of epithelioid sarcoma.
246
HALL,
GRIMES,
AND GOPLERUD
ACKNOWLEDGMENTS The authors wish to thank Dr. W. J. Frable and Dr. S. Kay for their help in the preparation of this manuscript.
REFERENCES 1. Enzinger, F. M. Epithelioid sarcoma, a sarcoma simulating a granuloma or carcinoma, Cancer 26, 1029-1041 (1970). 2. Frable, W. F., Kay, S., Lawrence, W., et al. Epithelioid sarcoma. An electron microscopic study, Arch. Parhol. 95, 9-12 (1973). 3. Lo, H. H., Kalisher, L., and Faix, J. D. Epithelioid sarcoma: Radiologic and pathologic manifestations, Amer. J. Radiol. 128(6), 1017-1020 (1977). 4. Peimer, C. A., Smith, R. J., Sirota, R. L., ef al. Epithelioid sarcoma of the hand and wrist: Patterns of extension, J. Hand Surg. 2(4), 275-282 (1977). 5. Piver, M. S., Tsukada, Y., and Barlow, J. Epithelioid sarcoma of the vulva, Obstet. Gynecol. 40, 839-842 (1972). 6. Prat, J., Woodruff, J. M., and Marcove, R. C. Epithelioid sarcoma. An analysis of 22 cases indicating the prognostic significance of vascular invasion and regional lymph node metastases, Cancer 41(4), 1472-1487 (1978). 7. Gallup, D. G., Abell, M. R., and Morley, G. W. Epithelioid sarcoma of the vulva, Obstef. Gvnecol. 48(1, Suppl.), 14S-17s (1976). 8. Santiago, H., Feinerman, L. K., and Lattes, R. Epithelioid sarcoma. A clinical and pathologic study of nine cases, Hum. Purhol. 3, 133-147 (1972). 9. Gabbiani, G., Fu, Y. S., Kaye, G. I., ef al. Epithelioid sarcoma. A light and electron microscopic study suggesting a synovial origin, Cancer 30, 486-499 (1972). 10. Bloustein, P. A., Silverberg, S. G., and Waddell, W. R. Epithelioid sarcoma: Case report with ultrastructural review, histogenetic discussion, and chemotherapeutic data, Cancer 38(6), 2390-2400 (1976). 11. Davos, I., and Abell, M. R. Soft tissue sarcomas of the vulva, Gynecol. Oncol. 4(l), 70-86 (1976). 12. McKenzie, D. H. Two types of soft tissue sarcoma of uncertain histiogenesis, Brit. J. Cancer 25, 458-461 (1971). 13. Bryan, R. S., Soule, E. G., Dobyns, J. H., et al. Primary epithelioid sarcoma of the hand and forearm. A review of 13 cases, J. Bone Joint Surg. Amer. Vol. 56-A(3), 458-65 (1974). 14. Barlow, J. Personal communication.
ONCOLOGY
9,231-246
(1980)
CASE REPORT
Epithelioid
Sarcoma
of the Vulva1
DON J. HALL, M.D., FACOG,2 MARGARET M. GRIMES, M.D.,3 AND DEAN R. GOPLERUD, M.D., FACOG Gynecologic
Oncology Service, Department of Obstetrics and Gynecology Division of Surgicul Pathology, the Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298
and the
Received May 28, 1979 The authors present the third known case of an epithelioid sarcoma involving the vulva. This case illustrates the confusion that can occur in making a proper pathologic diagnosis. The histologic and electron microscopic characteristics of the tumor are presented. The natural history of the disease is discussed describing the propensity for local recurrence and the sites of metastases. Recommendations for management are discussed.
INTRODUCTION
Epithelioid sarcoma, a rare neoplasm, was first recognized in 1970 as a distinct tumor type 111. Since then more cases have been reported [2-81. The lesion has been commonly misdiagnosed as being either benign or another variety of malignant neoplasm [1,6,8]. This tumor occurs chiefly in young adults and is characterized by a slowly enlarging nodular growth with early necrosis and ulceration of the overlying skin. It is most commonly seen on the fascia and tendons of the extremities and may be present for many years before the patient seeks medical attention [1,6,8]. Only two previous cases of vulvar epithelioid sarcoma have been reported, both of which occurred in young white females [5,7]. The following presentation is believed to be the third reported case. CASE HISTORY
B.P. was a 31-year-old white female gravida 2, para 2 who initially saw her local physician in 1%8 with a small ulcerating lesion in the left anterolateral edge of the vulva of 2 years duration. An excisional biopsy was performed. The pathology report was atypical fibroxanthoma. The patient did well until 1974 when she presented with a lesion of the left labium majus and two nodular ulcerated lesions ’ This investigation was supported in part by Grant 5R25 CA 22032-02. 2 ACS Fellowship 3965, Fellow in Gynecologic Oncology. 3 ACS Fellowship 4216, Fellow in Surgical Pathology. 237
0090-8258/80/020237- 10$01.00/O Copyright @ 1980 by Academic Press, Inc. All rights of reproduction in any form reserved.
238
HALL,
GRIMES,
AND
GOPLERUD
in the left groin. Excision was again performed. A second pathologist interpreted the specimen as showing rhabdomyosarcoma of the vulva and groin. The patient was referred to the Gynecologic Onoclogy Service at the Medical College of Virginia. The slides were reviewed and reinterpreted as representing a malignant fibrous histiocytoma. In February 1974, a wide local excision and left inguinal and femoral node dissection was performed. The tissue specimen was again interpreted as malignant fibrous histiocytoma of the vulva with chronic lymphadenitis. During routine follow-up, the patient was found to be pregnant in September of 1974 and subsequently delivered a normal 7 lb 8 oz female infant in May 1975. In October 1976 the patient presented to the Thoracic Surgery Service with bilateral spontaneous pneumothorax requiring thoracotomy. One month later a left spontaneous pneumothorax recurred requiring chest tube management. In January 1977, the patient noted a 2-cm blue nodule of the left vulva in the area of the previous lesion. Multiple enlarged lymph nodes were palpable in the right groin. A biopsy was performed from the vulvar nodule. This was interpreted as malignant hemangioendothelioma. A radical vulvectomy with node dissection was recommended but was refused by the patient fearing disfigurement and loss of sexual function. The patient refused further follow-up until August 1977 when she presented to the MCV emergency room with hemoptysis. A chest radiograph and tomograms showed multiple metastatic lesions. A 2-cm blue raised, ulcerated lesion of the vulva was present. Combination chemotherapy consisting of adriamycin, dimethyltriazenoimidazole-carboxamide, Cytoxan, and vincristine was started. A repeat course of chemotherapy was given 4 weeks later. At that time the mass in the vulva measured 2 x 3 cm with surrounding subcutaneous induration and fixation. Because of side effects, the patient refused further chemotherapy and traveled to Mexico where she underwent Laetril treatment until May of 1978. Although she claimed a feeling of subjective improvement, the vulvar mass continued to grow. She was next seen in July of 1978 complaining of pain, bleeding, and foul odor. Satellite nodules were noted on the right vulva, both groins, and the medial aspect of the left thigh (Fig. 1). The patient was admitted for palliative excision and debridement of the lesion. The final pathology report was epithelioid sarcoma. A chest radiograph showed progression of the pulmonary lesions and a CT scan revealed liver metastases and retroperitoneal lymphadenopathy. The patient refused further chemotherapy. She received radiation therapy for local control of bleeding and pain. External beam therapy was given delivering 4500 t-ad to the pelvis and upper thighs. An additional boost of 1000 rad was planned but only 700 rad were completed because of radiation vulvitis and lack of response of the vulvar lesion. Triple chemotherapy consisting of a 5-day course of adriamycin-D, dimethyltriazenoimidazole-carboxamide, and vincristine was begun, however the patient refused further chemotherapy after the third day. The patient never returned for further therapy despite multiple attempts by physicians, nurses, and paramedical personnel. The patient expired at home on February 13, 1979.
EPITHELIOID
FIG.
1. Recurrent epithelioid
SARCOMA
OF THE VULVA
239
sarcoma of the vulva with multiple satellite nodules.
MATERIALS
AND METHODS
Biopsy tissue prepared at the Medical College of Virginia was stained with hematoxylin-eosin after fixation in Zenker’s solution. Material for electron microscopy was minced into l-mm pieces, placed in 4% glutaraldehyde in sodium cacodylate buffer for 2 hr, then postfixed in buffered 2% osmium tetroxide. Tissue was then dehydrated in graded alcohols and propylene oxide and embedded in Epon. Areas of study were selected from I- to 2-pm-thick sections stained with toluidine blue. Thin sections were stained with uranyl acetate and lead citrate. PATHOLOGIC
FINDINGS
Biopsy of the left groin lesion in 1968 was originally interpreted as an atypical fibroxanthoma, possibly arising from an inflamed epidermal cyst. Proliferating
240
HALL,
GRIMES,
AND GOPLERUD
fibroblasts, histiocytes, and giant cells appeared to surround degenerated squamous epithelium. Despite mitoses and bizarre nuclei, the process was believed to be benign. The lesion recurred in 1974 as “hard masses” in the left labia. Rhabdomyosarcoma was diagnosed at another hospital on the basis of eosinophilic staining of tumor cells, a suggestion of strap cells, and results of trichrome staining. The 1968 lesion in retrospect was believed to represent a granular cell myoblastoma. The sections of both lesions were reviewed at Medical College of Virginia. The first tumor was interpreted as an atypical fibrous histiocytoma. Sections of the recurrence showed a nonencapsulated, cellular growth, composed of pleomorphic cells within a fibrous stroma. Nuclei varied from spindled to plump, some having prominent nucleoli. Small clefts or spaces were lined by cells with abundant cytoplasm. The fibrous pattern predominated (Fig. 2). Because of the appearance, size, and recurrence of the lesion, the diagnosis of malignant fibrous histiocytoma was made. A subsequent reexcision and superficial inguinal lymph node dissection revealed a similar histologic appearance and absence of nodal metastases. In 1977, biopsy of a second recurrence was performed. Microscopically, the tumor had a distinct vascular pattern, with some papillary features (Fig. 3). The same large tumor cells with opaque eosinophilic cytoplasm were recognized, and these lined spaces filled with blood cells. In addition, there was necrosis and cystic degeneration. Occasional mitoses were seen. Because of the pattern seen on this biopsy, and the similarity noted upon review of the previous slides, the diagnosis was changed to malignant hemangioendothelioma. At excision of the third recurrence in 1978, the tumor was described as a U-mm,
FIG. 2. Biopsy of first recurrence, interpreted as malignant fibrous histiocytoma. “epitheloid” cells were present at this time. H&E, x192.
Clefts and
EPITHELIOID
SARCOMA
OF
THE
VULVA
241
FIG. 3. The tumor stimulated a vascular pattern at the second recurrence leading to a diagnosis of malignant hemangioendothelioma. H&E, x 160.
nodular, gray-tan mass having a hemorrhagic, gelatinous cut surface. The microscopic appearance was similar to that of the previous biopsy, with the exception that the clefts or spaces were now large, freely communicating channels filled with blood. The tumor cells lining these spaces were identical to those previously described (Fig. 4). The original impression was, again, malignant hemangioendothelioma. No intracellular mucin was found on special stains. Within the fibrous component of the tumor, reticulin appeared to surround individual cells. The reticulin surrounding the clefts was incomplete in most cases, with plump neoplastic cells lying on the luminal side. These cells could be seen adhering in small groups without intervening reticulin. There was no discrete elastic framework surrounding the clefts. Electron microscopic study of the tumor showed a monotonous pattern of loosely arranged, darkly staining mononuclear cells. Most cells demonstrated plentiful filopodia (Fig. 5). No desmosomes were seen. At higher power, some cells showed nuclei with prominent filamentous nucleolonema (Fig. 6), a few lysosomes, and plentiful rough endoplasmic reticulum. Mitochondria were sparse. In some areas it appeared that the cells lined true vascular spaces, in which polymorphonuclear leukocytes and lymphocytes were identified (Fig. 7). Weibel-Palade bodies were not identified in any of the tumor cells. These findings, and the clinical features of the case, were felt to be more consistent with epithelioid sarcoma than with malignant hemangioendothelioma, especially since
FIG. 4. Tumor cells with abundant eosinophilic cytoplasm filled “vascular channels” at the third recurrence. H&E, x400.
FIG. 5. Electron micrography showing tumor cells with numerous filopodia. x4015. 242
EPITHELIOID
SARCOMA
OF
THE
VULVA
243
FIG. 6. A neoplastic cell with filamentous nucleolonema in nucleus. Abundant rough endoplasmic reticulum and a lipid body are seen in the cytoplasm. Note prominent tilopodia. x9920.
the ultrastructural findings were similar to those reported in previous examples of epithelioid sarcoma [2,9, lo]. DISCUSSION
This case is believed to represent an example of epithelioid sarcoma involving the vulva of which only two other published reports were found [5,7]. This rare sarcoma is seen most commonly on the extremities of young patients in the third and fourth decades of life, It affects males more often than females (63. The lesions are usually asymptomatic at first resulting in patient delay in seeking medical care as illustrated by our case. The tumor starts as a slow-growing nodular lesion which ulcerates, and may be confused with a granuloma or a variety of infectious processes. The gross lesions are frequently purple-red in color. Although tumor growth is slow, it is relentless with a marked tendency for local recurrence when inadequately treated. Distant metastases often occur after repeated local recurrences. The primary
244
HALL,
GRIMES,
AND GOPLERUD
FIG. 7. Lymphocytes and polymorphonuclear leukocytes were seen in the channels lined by neoplastic elements. Weibel-Palade bodies were not identified in any of the tumor cells. X3575.
metastatic route is lymphatic with hematogenous spread being secondary [I I]. Direct tumor extension also occurs. Prat has noted a poor prognosis associated with local recurrence after excision, vascular invasion, and lymph node metastases [6]. The reported incidence of metastases varies from 30-45% [ 1,8,12,13]. In a recent series of 22 patients, 58% developed metastases with 42% of these going to regional lymph nodes and 47% to lungs. In addition to the regional lymph nodes and lung, the liver and peculiarly the scalp appeared to be other metastatic sites. Lung, liver, and regional nodes were involved in this case presentation. The vulva is a rare location for epithelioid sarcoma with only two previous cases reported [5,7]. Clinically all of these lesions started as an asymptomatic mass and all occurred in young white females. Our case was the only one to present with a draining ulcerative lesion. The original sites of the three cases were infraclitoral 151, left midvulvar [7], and left vulvar edge (present case). All patients presented with a history of previous excisional biopsy. The initial pathological interpretation
EPITHELIOID
SARCOMA
OF
THE
VULVA
245
in Gallup’s case was “poorly differentiated metastatic carcinoma.” In our case four other diagnoses were made (atypical fibroxanthoma, rhabdomyosarcoma, malignant fibrous histiocytoma and malignant hemangioendothelioma). The variety of diagnoses attached to the lesion in this case at various stages of its growth demonstrates well the difficulty that may be encountered. When Enzinger described the neoplasm in 1970, he emphasized its frequent confusion with other malignant as well as benign lesions, for example, squamous cell carcinoma, synovial sarcoma, or necrotizing granuloma [l]. Histologic features of the tumor which he thought characteristic were nodularity, frequent necrosis, and the acidophilia of the epithelioid cells. The tendency to form clefts, to the point of simulating a vascular neoplasm, was also noted. This has been ascribed to loss of cellular adhesion and/or fixation artifact. The cell of origin remains debatable. Various electron microscopic studies have suggested synovial, histiocytic, or fibrocytic derivation [2,9,10]. As previously noted by Gallup et al. [7], the best treatment for epithelioid sarcoma of the vulva is undetermined. All three cases had initial excisional biopsy. The first case, reported by Piver, was treated with a wide local excision (lo-cm area) and node biopsy, and remains disease-free at this writing [14]. No residual tumor was present in the surgical specimen. The second case reported by Gallup and co-workers was treated with radical vulvectomy and bilateral groin dissection. The specimen revealed several tumor nodules in the area of initial excision as well as one positive lymph node. Despite the metastasis, the patient was reported to be doing well 16 months post-treatment [ 111. The present case, as well as Gallup’s patient, illustrates the problem with a small local excision only, and the possibility of treatment failure with local recurrence and distant metastases. Our patient had a wide local excision and ipsilateral groin dissection following two small local excisions. Despite negative lymph nodes and clear surgical margins, the tumor recurred. Prat has shown no correlation between the incidence of nodal metastases and survival [6]. The patient illustrates a lack of radiosensitivity and implies radiation therapy does not appear to be beneficial at least for the vulvar lesions. Chemotherapy has been reported in the treatment of a number of patients with recurrent disease but no specific agent or combination appears to be superior as of this writing [3,4,6,10]. No conclusion regarding effectiveness of the chemotherapy can be made from this case. Delay in diagnosis may adversely affect outcome. The duration between onset of symptoms and definitive therapy was approximately 1.5 months [5], 4 months [71, and 2 years in our case. The influence of pregnancy on this tumor is unknown. We believe that early surgical management consisting of a very wide en bloc removal or radical vulvectomy with regional lymph node dissection is the best mode of initial therapy. Small local excision may lead to treatment failure. Regular and prolonged follow-up is desirable with frequent chest radiographs and careful inspection of the vulva and scalp [3]. Radiation therapy offers little hope for controlling recurrent vulvar disease. The role of chemotherapy is undetermined at present in the management of epithelioid sarcoma.
246
HALL,
GRIMES,
AND GOPLERUD
ACKNOWLEDGMENTS The authors wish to thank Dr. W. J. Frable and Dr. S. Kay for their help in the preparation of this manuscript.
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