Medical Oncology, vol. 21, no. 4, 367–372, 2004 © Copyright 2004 by Humana Press Inc. All rights of any nature whatsoever reserved. 1357-0560/04/21:367–372/$25.00
Case
Epithelioid Sarcoma of Vulva A Case Report and Review of the Literature
Kadri Altundag,1 Oguz Dikbas,1 Basak Oyan,1 Alp Usubutun,2 and Alev Turker1 1Hacettepe 2Hacettepe
University Faculty of Medicine Department of Medical Oncology and University Faculty of Medicine Department of Pathology, Ankara, Turkey
Abstract Epithelioid sarcoma of vulva is an extremely rare and aggressive tumor. In most patients it is asymptomatic, and the lesions are usually mistaken for benign processes, leading to diagnosis at later stages. We report a case of vulvar epithelioid sarcoma in a 51-yr-old woman presenting with a nodularity of vulva. Left hemivulvectomy with bilateral inguinal lymph node dissection was performed. There was no evidence of distant metastasis at the time of diagnosis. Following adjuvant chemoradiotherapy and three cycles of chemotherapy, the patient developed lung metastasis 4 mo after surgery and died of disseminated disease after 6 mo of diagnosis. Vulvar epithelioid sarcoma is rare; showing different behavior changing from an extremely aggressive tumor to behaviors like low-grade tumors. It is best treated by early diagnosis and initial eradication. Definitive surgery provides excellent local control and survival in low-grade tumors. The role of adjuvant treatment remains to be determined. Key Words: Epithelioid sarcoma; vulva; vulvectomy; chemotherapy; radiotherapy.
reported in the English literature (2–17) (Table 1). We report a case of vulvar epithelioid sarcoma and review the current literature with special emphasis on the biological behavior and treatment of this rare tumor.
Introduction Sarcomas account for approx 1% of all cancers (1). Among the neoplasms of the urogenital system, malignancies of the vulva are relatively uncommon. The incidence of primary sarcoma of the vulva is rare and accounts for about 1.5–5% of all vulvar carcinomas. It occurs most frequently in the labia majora, followed, in decreasing order, by the Bartholin gland area, clitoris, and labium minus (2). Primary epithelioid sarcoma of vulva is extremely rare tumor and up to now only 19 cases were
Case Report A 51-yr-old postmenopausal female patient presented with the complaint of nodularity in left labia majora and left superficial inguinal lymph node swelling of 3-mo duration. Excisional biopsy was taken from the primary lesion. The initial pathology report indicated the diagnosis of epithelioid sarcoma. Evaluation of the biopsy revealed nodular neoplastic growth. Nodular growth was prominent in some areas and some of them had necrosis in the
Received 05/10/04; Accepted 06/22/04. Corresponding author and reprint requests to: Kadri Altundag, MD 8181 Fannin Street, No. 728 Houston, TX 77054, USA. E-mail:
[email protected]
367
Radical vulvectomy
30 21 21
49
5. Ulbright et al., 1983 (6) 6. Tan et al., 1989 (7) 7. Perrone et al., 1989 (8) 8. Wevers et al., 1989 (9) 9. Weissmann et al., 1990 (10) 10. Konefka et al., 1994 (11)
Wide local excision Local excision Radical vulvectomy Wide local excision Hemivulvectomy Local excision Hemivulvectomy
20.6 57 49 45 23 23 29
42 51
19. Ulutin et al., 2003 (2) 20. Our case
No Yes
No Yes Yes Yes No No No
No
No
No No No No No
No
No No No
Radiotherapy
No No No Yes-recurrence No No Yes-recurence Ifosfamide–adriamycine four cycles No Yes-adjuvant Cisplatin-VP-16 three cycles
Yes-Adjuvant CyVADICone cycle No
No No No No No
No
No No No
Chemotherapy
None Lung
None None None None None Local, lymph node Lung
Local, lung
Local, lymph node, lung, scalp, liver, kidney Lung
None None Local, Lymph node, Lung Local, Lung Abdominal wall Local, Lung None None
Recurrent site
4
17
11
5
14
1.5
8
35
Interval to recurrence (mo)
NED 146 DOD 6
NED 105 DOID 52 NED 22 NED 21 NED 48 NED 96 DOD 6.5
DOD 12
DOD 8
AWD 78
DOD 8 NED 36 NED 56
DOD 15
NED 108 NED 16 DOD 70
Outcome follow-up (mo)
a NED = no evidence of disease; DOD = dead of disease; DOID = dead of intercurrent disease; and AWD = alive with disease. CyVADIC: cyclophosphamide, vincristine, doxorubicin, dacarbazine.
Radical vulvectomy Hemivulvectomy
Radical vulvectomy
51
Local excision
11. Hernandez-Ortiz, et al., 1995 (12) 12. Ross et al., 1996 (13) 13. Guillou et al., 1997 (14) 14. Guillou et al., 1997 (14) 15. Guillou et al., 1997 (14) 16. Tjalma et al., 1999 (15) 17. Kasamatsu et al., 2001 (16) 18. Moore et al., 2002 (17)
26
Wide local excision Wide local excision Local excision No details Local excision
55
4. Ulbright et al., 1983 (6)
Wide local excision Radical vulvectomy Wide local excision
27 31 31
1. Piver et al., 1972 (3) 2. Gallup et al., 1976 (4) 3. Hall et al., 1980 (5)
Surgery
Age
Author, Year (Ref. no.)
Table 1 Reported Cases of Vulvar Epithelioid Sarcomaa
Epithelioid Sarcoma of Vulva
369
Fig. 1. Some nodules resembling a granuloma (H&E, ×400)
Fig. 2. Most of the neoplastic cells are anaplastic and resemble rhabdoid cells (H&E, ×400).
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370 center. A few nodules resemble granulomas (Fig. 1). Most of the neoplastic cells were anaplastic with large eosinophilic cytoplasm and bizzare nucleus. Some of them resemble rhabdoid cells (Fig. 2). In the any of the sections examined no connection was found between the neoplasm and surface epithelium. Neoplastic cells had the features of severe anaplasia. Immunohistochemically, tumor cells were positive for cytokeratin, EMA, and vimentin; but negative for SMA, HMB-45, and desmin and, did not stain for mucicarmin. The focal positivity with CD 34 stain led to the diagnosis of epithelioid sarcoma instead of sarcomatoid carcinoma. Left hemivulvectomy with bilateral inguinal lymph node dissection was performed. The tumor measured was 3.5×2.5 cm in size and 13 mm in depth. The surgical margins were free of neoplasm. The lesion had an irregular border with an ulceration in the center. Two of 37 inguinal lymph nodes were metastatic. Thoracal-abdominal computerized tomography did not show distant metastasis. Following surgical treatment, adjuvant chemoradiotherapy was planned. External radiotherapy was applied concomitantly with weekly cisplatin 35 mg/m2. She received a total dose of 45 Gy external radiotherapy (1.6 Gy/d) without treatment break. Echocardiography revealed 48% ejection fraction contraindicating doxorubicin administration. Then she received adjuvant chemotherapy regimen consisting of cisplatin 80 mg/m2, d 1 and etoposide (VP16) 120 mg/m2 d 1–3, repeated every 21 d. While receiving the third cycle of chemotherapy, she developed lung metastasis 4 mo after surgery. Six months after the initial diagnosis, she died of disseminated neoplastic diseases
Discussion Epithelioid sarcoma was first recognized by Enzinger in 1970, and is generally an aggressive malignant soft tissue tumor, usually originating in distal and proximal extremities, of young, particularly male, adults (18). It represents a special entity due to its characteristic pathological appearance and clinical behavior. The mean age of presentation is 35 yr (range 21–57), similar to other sarcomas (14,19). Primary soft tissue sarcomas of vulva are rare neoplasms comprising approx 1% of all vulvar malignancies (2). Vulva is a rare site of presentation
Medical Oncology
Altundag et al. for primary epithelioid sarcoma and frequently misdiagnosed as benign lesions such as infectious granuloma, Bartholin’s cysts, fibroma, fibrous histiocytoma, fasciitis, lipoma, dermoid cysts, viral warts, or squamous cell carcinoma (20,21). Slowly growing relatively painless mass in labia majora is the most common initial symptom of vulvar epithelioid sarcoma. Tumor originates either from deep or superficial tissues. Macroscopically, tumor consists of single or multiple nodules. Superficial lesions have a tendency to cause ulceration of the overlying epidermis (18,22). The tumor nodules are frequently surrounded by chronic inflammatory cells. This appearance may sometimes lead to a misdiagnosis of chronic inflammation or granuloma (10). A striking feature of epithelioid sarcomas is the occurrence of satellite lesions between the primary tumor and the regional lymph nodes (19). The neoplasm probably arises from primitive mesenchymal cells showing both fibroblastic and histiocytic differentiation. Immunohistochemistry reveals cytoplasmic immunoreactivity for cytokeratin, vimentin, and epithelial membrane antigen. CD 34, desmin, and HMB reactivity can be seen focally in some tumors. S100 and CD31 staining are negative in epithelioid sarcoma. These immunohistochemical findings are useful for differentiating epithelioid sarcoma from the other malignant soft tissue tumors of epithelioid appearance, including synovial sarcoma, extrarenal malignant rhabdoid tumor, epithelioid malignant peripheral nerve sheath tumor, melanoma, rhabdomyosarcoma, and undifferentiated carcinoma (14,18). In our case immunohostochemical studies supported the diagnosis of epithelioid sarcoma. The focal positivity with CD 34 stain also led to the diagnosis of epithelioid sarcoma instead of sarcomatoid carcinoma. Kasamatsu et al. (16) stated that vulvar epithelioid sarcoma seems to be more aggressive than the ordinary distal type as in our case. But some tumors grow more slowly than the ordinary distal type and had a more indolent course. Locoregional lymph node involvement, vascular invasion, tumor size larger than 2 cm, deep localization, presence of necrosis, and a high mitotic index in excess of 2 per 10 high power fields are the poor prognostic factors (19,20,23,24). In the view of prognostic factors, our case also had poor prognostic features showing
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Epithelioid Sarcoma of Vulva anaplasia, larger tumor size, and lymph node metastases. The high incidence of lymph node metastasis in epithelioid sarcoma contrasts with most other sarcoma types, which tend to spread hematogenously. Many of the recurrences occur within the 6 mo of the initial treatment. Many authors prefer local wide excision to radical vulvectomy (4,26–28). In a study by Curtin et al. (28), only one of the seven patients with low-grade leiomyosarcoma recurred locally by this treatment. Excision should include 2 cm from the margin of tumor. As the tumor has a tendency to form satellite lesions, radical excision sometimes means hemivulvectomy in vulvar region (4). In recent clinical study, Ulutin et al. (2) described seven cases with vulvar sarcoma treated with vulvectomy. They revealed excellent control without adjuvant treatment in patients with low-grade tumor and clear surgical margins. They stated that definitive surgery, and perhaps adjuvant radiotherapy, provide excellent local control survival in low-grade sarcomas. But tumors with high-grade or close surgical margins, as in our case, should be treated further with adjuvant treatment. Locoregional lymph node dissection for staging should only be considered when they are clinically suspicious or enlarged, because there is no evidence of the beneficial effect of lymph node resection on local or distant relapse rate, although in some cases it may have a palliative effect (18). In our case inguinal lymph node dissection was performed because of clinically enlarged lymph lodes at presentation. The roles of adjuvant radiotherapy and chemotherapy are not clear. The tumor is relatively insensitive to radiotherapy, although favorable effects of radiotherapy have been advocated by some authors to decrease local recurrence, but the effect of this on long-term survival is not yet clear (20). In a review article by Standers, it is stated that similar local control rates are achieved with external beam radiotherapy and low-dose-rate brachytherapy for high-grade soft tissue sarcoma and radiosensitizers may improve local control in the use of radiotherapy for inoperable soft tissue sarcomas, but do not seem to be of any benefit in the adjuvant setting (29). When surgery and radiotherapy are combined, better local control can be achieved. Despite local control, 40–60% of patients with high-grade sarcomas will die of metastatic disease. As a group, soft tissue sar-
Medical Oncology
371 comas respond poorly to chemotherapy. Only a few cytotoxic agents have relevant activity against these tumors. Chemotherapy has been used both in adjuvant situations and in locally advanced or metastatic disease. Agents with the most documented cytotoxic effect are doxorubicin, dacarbazine, ifosfamide, cyclophosphamide, etoposide, vincristine, and methotrexate (30). Cisplatin has a demonstrated activity at soft tissue sarcomas (31). Doxorubicin is described as the most active single agent for patients with soft tissue sarcomas, inducing overall response rates (RRs) of 15–35% (32). In our case, we planned to give doxorubicin-based chemotherapy, but low ejection fraction contraindicated its use and the other effective agents, cisplatin and etoposide, were used. In conclusion, vulvar epithelioid sarcoma is rare; showing different behavior changing from an extremely aggressive tumor to behaviors like lowgrade tumors. It is best treated by early diagnosis and initial eradication. Early diagnosis is not always possible, as it is frequently mistaken for benign lesions. Generally, there is a 2-yr interval between the onset of symptoms and diagnosis (20). Therefore, the correct diagnosis is not made until the tumor is in a late stage. A possible diagnosis of epithelioid sarcoma should always be in mind upon presentation of a slowly growing nodular lesion in vulva.
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