Arch Gynecol Obstet (2009) 280:819822 DOI 10.

1007/s00404-009-1009-0

C A S E RE P O RT

Primary malignant melanoma of the vagina

Ali Baloglu Incim Bezircioglu Burcu Cetinkaya Ali Yavuzcan

Received: 17 December 2008 / Accepted: 10 February 2009 / Published online: 26 February 2009 Springer-Verlag 2009

Abstract Background Primary vaginal melanoma is a rare, highly malignant, and poor prognostic disease. Case The 51-year-old patient with diagnosis of vaginal malignant melanoma was referred to our clinic. Since detection of pervasive brown lesions in the vagina total vaginectomy was performed. At pathological investigation melanoma was not determined. Immunotherapy was administered adjuvantly. Paraaortic lymph node metastasis was seen on the ninth month after total vaginectomy and the metastatic lymph nodes were excised. Cisplatin and tremozolamide chemotherapy was administered for six cycles after surgery. The patient is alive and disease-free at 18th month of the diagnosis of the disease. Conclusion The impact of therapy on outcome of primary vaginal malign melanomas is poorly understood. Improved clinical outcomes were associated with surgical removal of gross disease whenever possible. Because of the low rate of lymph node metastasis, elective pelvic lymph node dissection is not mandatory. We presented a case of FIGO stage I primary vaginal malignant melanoma, which metastasized to the paraaortic lymph nodes 9 months after the primary operation.

Keywords Vaginal malignant melanoma Vaginectomy Colpectomy

Introduction Vaginal malignant melanoma is a rarely encountered noncutaneous form of melanoma. Non-cutaneous melanomas develop multifocally on the locations which are not exposed to ultraviolet rays, and their incidence is less than that of cutaneous melanomas. Genital malignant melanomas constitute 1.6% of the melanomas presented in women. Vaginal melanomas are the second common genital melanomas. Vaginal malignant melanomas constitute 0.3% of all malignant melanomas and less than 3% of all vaginal carcinomas [1]. Although the age interval of the disease is reported as 3890 years, it is predominantly observed in the sixth and seventh decades of life. It aVects postmenopausal women and does not have any known risk factors. Most of the patients apply with the complaint of vaginal bleeding and the disease is usually locally advanced at the time of admission [2]. An appropriate and eVective treatment protocol for vaginal melanoma has not been deWned yet. Wide local excision, radical surgery, radiotherapy, chemotherapy, and immunotherapy are recommended for treatment. These melanomas have a more aggressive course than vulvar melanomas. Among the vaginal malignancies, malign melanomas are the group of tumors with the worst prognosis. Five-year survival independent of treatment is reported to be between 0 and 25% [3]. In the present study, we present a case of FIGO stage I primary vaginal malignant melanoma located in the upper half of the vagina, which metastasized to the paraaortic lymph nodes 9 months after the operation.

A. Baloglu I. Bezircioglu B. Cetinkaya A. Yavuzcan 1st Department of Obstetrics and Gynecology, Izmir Ataturk Training and Research Hospital, Izmir, Turkey I. Bezircioglu (&) Basin Sitesi, Gazeteci Hasan Tahsin Highroad, 253 Street, Number:43, 35360 Izmir, Turkey e-mail: drincimbezircioglu@yahoo.com

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Arch Gynecol Obstet (2009) 280:819822

Fig. 1 The appereance of brown lesions in the upper half of the vagina

Fig. 2 Under the normally vaginal squamous epihelium the presence of highly atpiycal melanocytes in clusters (H&E 120)

Case report The 51-year-old multiparous (P4, L4) patient who had applied to a secondary care hospital with the complaint of postmenopausal bleeding was diagnosed a tumoral mass on her anterior vaginal wall. After the tumoral mass excised and pathologically diagnosed as nodular malignant melanoma, she was referred to our hospital. Local examinations revealed an atrophic vulva, an incision scar beneath the urethra, and diVuse brown lesions in the upper half of the vagina (Fig. 1). The pelvic organs were evaluated as normal with bimanual examination and transvaginal ultrasonography. Metastasis or tumor inWltration was not determined by cervical and endometrial biopsy, computerised tomography, rectosigmoidoscopy, and cystoscopy. Nodular malignant melanoma had been determined in histopathological examination of previous speciemen section, which had been performed in the health center, from where the patient was referred (Figs. 2,3). Since we could not get access to previous vaginal biopsy speciemen, surgical margin was not evaluated. We thought that surgical margin was attached because of vaginal brown lesions. Since the lesions were diVuse and distant metastasis was not present, total vaginectomy was applied to the patient. The vaginectomy specimen is shown in Fig. 4. The histopathological examination of the vaginectomy specimen revealed prominent melanophage and dense lymphocytic inWltration, but melanoma was not determined. Clinical staging of the tumor was FIGO stage I. Adjuvant Interferon- was administered at a dose of three million units and three times a week. In the examination of the patient performed on the ninth month, a 4 cm solitary mass located at the renal hilus level was detected via computed thomography. The patient was admitted again for radical hysterectomy, bilateral salphingoooopherectomy, and pelvic-paraaortic

Fig. 3 Neoplastic melanocytes have large nuclei and nucleoli; abundant pale cytoplasm. Melanin is within both neoplastic melanocytes and melanophages (H&E 240)

Fig. 4 Macroscopic view of the vaginectomy specimen

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lymph node dissection. In the histopathologic investigation of the 4 cm paraaortic mass, lymph node metastasis of malignant melanoma was revealed. The patient underwent six cycles of the cisplatin and temozolamide therapy. Cisplatin (80 mg/m2) was administered by intravenous infusion, Tremozolamide (150 mg/m2) 5 days once in 28 days. The patient is alive and disease-free at 18th month of the diagnosis of the disease.

Discussion Vaginal primary malignant melanoma is a rare neoplasia. Less than 300 cases have been reported throughout the world. Since it is a rare disease, the number of case series and case reports related to the disease is limited [25]. The potential prognostic factors including age, FIGO stage, tumor location, tumor size, invasion depth, pigmentation, ulceration, histology, cell type, number of mitoses, vein invasion, type of the surgical procedure, adjuvant radiotherapy, and chemotherapy have been investigated in terms of survival. Vaginal primary malignant melanoma mostly occurs at the sixth and seventh decades of life. Nearly all patients are postmenopausal [2, 3]. Although our 51-yearold patient was younger than the patients reported in the literature, she was in the postmenopausal period. Malignant melanoma is mostly located in the lower onethird of the vagina and appears as a locally advanced disease. At the time of diagnosis, more than half of the patients are determined to be at FIGO stage I [3]. The FIGO staging system has been reported to be inadequate for the determination of prognosis in these patients. Most of the vaginal malignant melanomas are nodular [2]. The cell type is epithelioid in 5558% of the cases and spindled and mixed in the rest [2, 3]. No relation could have been shown between survival and any of the aforementioned factors. The tumor in our case was FIGO stage I, melanotic and epithelioid. Tumor size has been deWned as the most imortant prognostic factor determining survival in vaginal primary malignant melanoma cases [6, 7]. In the meta-analysis of Buchanan et al. evaluating 67 cases, median survival was reported as 41 months in patients with a tumor size <3 cm and 12 months in those with a tumor size 3 cm [4]. In our case, a 4 cm primary tumor had been reported in the records of the referring health center. DiVuse vaginal melanosis has been reported in 21% of the vaginal malignant melanoma cases [3]. In our case, total vaginectomy was decided because pervasive brown lesions were determined in the upper half of the vagina after the removal of the primary tumor and no information regarding surgical margins could be obtained from the referred pathological sample.

Wide local excision, radical surgery, radiotherapy or wide local excision accompanied by radiotherapy, chemotherapy, and immunotherapy are recommended treatments for vaginal malignant melanoma. Since it is a rare disease, the studies conducted with a limited number of patients could not show a relationship between survival and whether the primary treatment is conservative or radical [4, 6]. The prognosis is poor regardless of the applied treatment. In the series of Miner et al. consisting of 35 cases, the median survival was calculated as 20 months [3]. Survival was 25 months in 24 patients on whom primary surgery was performed while it was 13 months in 11 patients on whom primary radiotherapy was performed. The complete removal of the macroscopic tumor and negative surgical margins were found to be eVective in ensuring local control during survival. The authors reported that surgical removal of the macroscopic tumor improves clinical outcome [3]. The patients with a locally advanced melanoma can also be treated by colpectomy or wide local excision [8]. It was determined that elective lymph node sampling does not contribute to survival as far as the morbidity of the procedure itself is considered. Since the rate of lymph node metastasis is low, lymph node dissection is not recommended in vaginal malignant melanomas [3]. Hence, lymph node dissection was not performed in our patient during vaginectomy. Radiotherapy can be applied adjuvantly after surgery or primarily for tumors that can not be removed surgically [3]. The eVect of chemotherapy as primary or rescue treatment on survival could not be determined. In one study, partial response could be obtained in 36% of the 11 patients treated with systemic chemotherapy and median survival was 10 months [9]. Regional chemotherapy has also been tried out to downsize the tumor and improve local control [10]. Five-year survival has been reported to range between 0 and 25% [47]. As the patients who survived longer than 5 years were reviewed, radical surgery was performed in 27%, wide local excision in 27%, radiotherapy in 27%, wide local excision plus radiotheraphy in 14% of the patients. No treatment has been specifed in 5% of the patients [6]. Since suYcient data regarding the primary tumor was not present in our case and no tumor was determined in the vaginectomy material, immunotherapy instead of radiotherapy was applied using Interferon alpha-2b. The paraaortic lymph node metastasis was surgically excised. Adjuvant chemotheraphy was applied for six cycles. The patient is alive and disease-free at 18th month of the diagnosis of the disease. Hence the disease is so rarely seen, no consensus is reached about the treatment of vaginal malignant melanoma. However, surgery and chemotherapy are considered as the appropriate treatment methods for the disease.

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822 ConXict of interest statement None.

Arch Gynecol Obstet (2009) 280:819822 5. Petru E, Nagele F, Czerwenka K et al (1998) Primary malignant melanoma of the vagina: long-term remission following radiation therapy. Gynecol Oncol 70:2326. doi:10.1006/gyno.1998.4982 6. Tjalma WA, Monaghan JM, s Lopes A et al (2001) Primary vaginal melanoma and long-term survivors. Eur J Gynaecol Oncol 22:2022 7. Piura B, Rabinovich A, Yanai-Inbar I (2002) Primary malignant melanoma of the vagina: case report and review of literature. Eur J Gynaecol Oncol 23:195198 8. Schmidt M, Honig A, Schwab M, Adam P, Dietl J et al (2008) Primary vaginal melanoma: a case report and literature review. Eur J Gynaecol Oncol 29:285288 9. Harting MS, Kim KB (2004) Biochemotherapy in patients with advanced vulvovaginal mucosal melanoma. Melanoma Res 14:517520. doi:10.1097/00008390-200412000-00012 10. Beg MH, Muchmore JH, Carter RD, Krementz ET (1993) Vaginal melanoma and the role of regional chemotherapy. J Surg Oncol 53:133135. doi:10.1002/jso.2930530217

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