Different clinico-pathological and prognostic features of vulvar, vaginal, and cervical melanomas.

Female genital tract melanoma (FGTM) is a rare and aggressive melanocytic malignancy, and its clinico-pathological and prognostic features at different anatomic sites have not yet been fully described. We retrospectively analyzed and compared the clinico-pathological data and survival outcomes of patients with primary lower genital tract melanoma enrolled between January 2005 and December 2020. We identified 95 patients with FGTM, of whom 46 had vulvar melanomas (VuM), 43 had vaginal melanomas (VaM), and six had cervical melanomas (CM). The clinical characteristics of all 95 cases, including symptoms, single or multiple primary lesions, clinical stage, surgery, and histopathological characteristics of 62 primary untreated cases, including pigmentation, predominant cytology, histological pattern, mitotic figures, and tumor-infiltrating lymphocytes of VuM, VaM, and CM, differed significantly. In comparison, only trend differences in molecular alternations were evident (p = 0.077). Disease-specific survival (DSS) was 30.7% at 5 years (46.5%, 25.6%, and 44.4% for VuM, VaM and CM, respectively). Seventy-one (85.5%) patients experienced FGTM recurrence. The median time to the first recurrence was 11 months, and VaM recurred earlier than VM and CM (16, 6, and 10 months for VuM, VaM, and CM, respectively, p = 0.038). A univariate analysis of 50 cases revealed the negative factors of disease-specific survival (DSS), including the location of the vagina and the presence of ulceration, and the negative factors of recurrence-free survival (RFS), including multiple lesions, the presence of ulceration, and the presence of lymphovascular invasion. Multiple lesions showed a borderline correlation with DSS. A multivariate Cox regression analyses of 50 cases revealed that the presence of ulceration was associated with shorter DSS and RFS (yes vs. no, Hazard Ratio = 2.400 and 2.716, respectively). Vaginal location showed a significant correlation with DSS (Hazard Ratio = 2.750, p = 0.024). In conclusion, vulval, vaginal, and cervical melanomas may differ in terms of their clinico-pathological features and associations with DSS and RFS. Ulceration and vaginal location were significantly associated with shorter DSS, and ulceration was associated with an increased risk of FGTM recurrence.

Primary malignant melanoma of uterine cervix treated with pembrolizumab as adjuvant immunotherapy.

This is the case report of primary malignant melanoma (MM) of uterine cervix treated by immune checkpoint inhibitor: the Pembrolizumab. Despite the merge of the novel drugs that has been strikingly improving prognosis of MM, we still struggle treatment of MM of uterine cervix that has aggressive characteristics with unknown etiology. We present our case to contribute its rarity of the disease case report, the primary MM of the uterine cervix that had poor response to pembrolizumab and had OS of 6 months. The treatment ineffectiveness is mainly considered for mucosal MM of low tumor mutation burden and its unusual type of pathology. Accumulation of retrospective studies exclusively on cervical melanoma needs to be proceeded to investigate on characteristics between poor and long survival to establish standardized treatment.

Combined immunotherapy and radiation for treatment of mucosal melanomas of the lower genital tract.

OBJECTIVE: To report our experience using ipilimumab, a monoclonal antibody targeting CTLA-4, combined with radiation therapy in women diagnosed with mucosal melanoma of the lower genital tract. METHODS: We retrospectively identified all patients who received ipilimumab with concurrent radiation treatment of mucosal melanoma of the lower genital tract at Memorial Sloan Kettering Cancer Center from 2012 to 2015. Various clinicopathologic data and treatment response were abstracted and analyzed. RESULTS: Four patients were identified. Median age was 61.5 years (range 44-68); 3 were diagnosed with vaginal melanoma, 1 with cervical melanoma. All would have required extensive surgical procedures to remove entirety of disease. Median size of lesions was 4.7 cm (range, 3.3-5.3); all were Ballantyne stage I. Median number of doses of upfront ipilimumab was 4 (range, 3-4). Two patients suffered CTCAE grade 3 adverse events (colitis, rash). All received external beam radiation: 3 to 3000 cGy, 1 to 6020 cGy. Post-radiation surgical resection was performed in 3 patients (75%); 1 (33%) of 3 patients achieved complete pathologic response. Complete local radiographic response was observed in all patients after completion of initial therapy and surgery. Two developed recurrence at 9 and 10 months post-diagnosis (mediastinum, lung); 2 remain disease-free at 20 and 38 months. CONCLUSIONS: Mucosal melanoma of the lower genital tract is rare, and data-driven treatment strategies limited. Immunotherapy has demonstrated durable efficacy in the treatment of cutaneous melanomas. Our small case series shows a favorable response to combined ipilimumab and radiation therapy. Larger studies are needed to validate these promising results.

Primary gynecologic melanoma: A report of two unusual cases.

BACKGROUND: Primary ovarian and cervical melanomas are extremely rare tumors with a poor prognosis. Diagnosis requires a high index of suspicion as presentation can mimic benign conditions clinically and other neoplasms histologically. CASES: A 41 year-old with an adnexal mass underwent surgical staging for a stage IA ovarian melanoma. Imaging revealed a brain metastasis treated with radiation. Subsequent nodal recurrence was treated with immune and targeted therapies. She is alive with disease at 61 months follow-up. A 54 year-old presented after endocervical melanoma was diagnosed with polypectomy. She underwent radical hysterectomy, lymphadenectomy, and adjuvant brachytherapy. Immediate post-treatment imaging revealed widespread liver and pulmonary metastasis, currently being treated with ipilimumab. CONCLUSION: Immunohistochemistry can facilitate the diagnosis of gynecologic melanoma, and multidisciplinary treatment is recommended.