VAGINAL MALIGNANT MELANOMA IN TREATED PATIENT OF CARCINOMA CERVIX- AN UNUSUAL CLINICALENTITY

Divyesh Kumar 1 , Anindya Mukherjee 1 , Manish Rohilla 2 , Nalini Gupta 2 , Bhavana Rai 1 and Sushmita Ghoshal 1 . 1. Department of Radiotherapy, PGIMER, Chandigarh. 2. Department of Cytopathology, PGIMER, Chandigarh. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History

Vaginal melanoma is a rare gynecological malignancy, with no clearly defined risk factor. It presents mostly in postmenopausal women as a painless lump in lower vagina. Surgical excision with or without adjuvant radiotherapy is the treatment of choice. Despite all treatment modalities, it is characterized by its poor survival outcome. There isn"t yet any conclusive evidence on the possibility of radiation induced carcinogenesis.

Case Presentation:-
A 66 year post-menopausal female resident of Punjab, P 3+0, was referred to our clinic for cervical brachytherapy in early August 2009. She was a diagnosed case of squamous cell carcinoma of cervix, FIGO stage IIB and had received external beam radiotherapy by Cobalt-60 to a dose of 46Gy in 23 fractions, completed in July, 2009. On local examination, a 2 x 1cm residual was seen at cervix with thickened medial one-third of right parametrium;left parametriumand rectal mucosa were free. We treated her with 35 Gy Low Dose Rate (LDR) equivalents by Medium Dose Rate (MDR) Selectron applicator. Post treatment patient had clinically complete response. Hence, she was kept on periodic follow-up and was asymptomatic till December, 2015 when she developed swelling around her genitalia. Local examination revealed a 3.5 x 2.5 cm ulcerated growthover upper two-thirds of anterior vaginal wall which bled to touch. The cervix was completely flushed with no evidence of any disease recurrence and bilateral parametrium were fibrosed. Contrast enhanced computed tomography (CECT)chest, abdomen and pelvis showed a well-defined heterogeneous mass 3.5 x 3.5 cm involving upper two-thirds of vagina causing circumferential wall thickening [Fig 1] . Three well defined heterogeneously enhancing masses along right external and internal iliac vessels were also seen, suggestive of metastatic lymphadenopathy Her general condition was not considered fit for surgery hence palliative radiotherapy (30Gy in 10 fractions) to the primary and inguino-pelvic regions was planned. She tolerated radiotherapy well and vaginal bleeding stopped. Thereafter, she was started on three weekly palliative chemotherapy with cisplatin (30mg/m 2 Day 1-3) and dacarbazine(375mg/m² Day 1-3). She completed chemotherapy uneventfully. Her last clinical examination showed a marginal decrease in size of of the vaginal mass post treatment.

Discussion:-
VMM accounts for less than 3% of all vaginal malignancies [1] .They occur mostly in post-menopausal women in their fifth and sixth decades and commonly present with vaginal bleeding and discharge or with lump in the lower third of vagina or its anterior wall [1,3,4] .Macroscopically, VMM are mostly polypoid and ulcerated with a pigmented appearance [3,5] . The non-pigmented ones look like epithelial tumors of the vagina [3,5] .The most common histopathological variants of VMM are epitheloid (55%), mixed (28%) and spindle (17%) [3,5] . In our case, the tumor was ulcerated with a pigmented appearance, located in upper two-thirds of vagina and pathologically it belonged to the mixed variant.
Vaginal melanomas are better staged surgically using the AJCC system, which incorporates Breslow and Clark micro staging [6] . Wide local excision (WLE) with negative margins is the standard surgical procedure for VMM [4] . Lymph node dissection is not recommended because of the low rate of lymph nodal metastases in such patients [4] . Hence, sentinel lymph node biopsy has gained popularity [7] . Pelvic exenteration has fallen out of place because of its accompanying morbidity and very modest survival benefit over WLE and adjuvant radiotherapy [4,8] . Immunotherapy with interferon (IFN) or interleukin-2 (IL-2) has shown survival benefit in VMM, but toxicity of the therapy often excludes its application in elderly patients [9] . Combining immunotherapy with chemotherapy (known as "biochemotherapy") has shown improved response rates over chemotherapy alone in cutaneous melanomas, but its role in VMM is yet to be proved and its toxicity is a major concern [9] . Our patient was 66 years old and her general condition was not fit for any surgery or immunotherapy. Hence we treated her with palliative radiotherapy to vagina and inguino-pelvic regions followed by palliative chemotherapy with reduced doses of cisplatin and dacarbazine, even knowing the little benefits these cytotoxic agents had in VMM [10] .
Regardless of the treatment modality, the prognosis of VMM is very poor with a 5 year survival estimate of only 5-25%, becausemost of the cases are diagnosed at a late stage [1, 11 and 12] . The rich vascular and lymphatic network is thought to contribute to early tumor spread and metastases [4] . Tumor size less than 3 cm is supposedly the most important prognostic factor for survival, irrespective of the treatment delivered [13] . In our case the vault primary was more than 3 cm and the disease had already spread to external iliac nodes by the time it was detected. Hence palliative treatment was chosen keeping in mind the dismal prognosis of the patient.
The etiology of VMM is not clearly defined and there are no significant racial or ethnic differences in its incidence [2] . Exposure to Ultraviolet radiation has been clearly linked with cutaneous melanomas [14] ; however, whether therapeutic radiotherapy can be a risk factor for melanomas has not yet been documented clinically. With extensive search, we could find only one molecular medicine research article reporting that radiotherapy induced decrease in substance P may potentiate melanoma growth [15] . We are not sure whether radiotherapy induced changes in immune