Molecular Alterations in Vaginal Melanomas: Report of 4 Cases and Literature Review

Melanomas of the female gynecological tract comprise approximately 18% of mucosal melanomas, a rare subtype of melanoma. Within the female genital tract, 70% of primary melanomas of the gynecological tract are from the vulva with the remainder occurring in the vagina and rarely, in the cervix. We investigate molecular alterations by next-generation sequencing-based molecular tests targeting 99 cancer genes and translocation/fusion assays in 4 and 3 vaginal melanomas, respectively. The ages of the 4 patients range from 65 to 90 years. Postmenopausal bleeding was the most common presenting symptom. Tumor size ranged from 0.5 to 6.6 cm. KIT L576P mutation was documented in case 1, whereas TP53 mutation was seen in cases 2 and 3 (L130F and Y163C). Case 2 also harbored NF2 E204Q and ATRX D1719H mutations. A number of gene copy alterations were noted in case 4, which included GNA11 loss, MYC gain, RET loss, SMO loss, SUFU loss, and TSC2 loss. No gene fusion was detected in any of the 3 tested cases. In conclusion, in addition to KIT, TP53, and ATRX mutations, which have been previously reported, our cases harbor NF2 mutation and multiple gene copy alterations that have not previously been documented in vaginal melanomas. These findings highlight the potential role of targeted therapy in this rare melanoma subtype.