Abstract

Primary vaginal melanomas are rare tumors that represent approximately 0.2% of all melanomas and characterized by their more aggressive clinical course. Since these tumors often present at an advanced stage, there is an increased need for identifying potential therapeutic targets through molecular studies. We report a case of an NF1 driven primary vaginal melanoma. A 51 year-old women presented to clinic with intermittent vaginal spotting and was found to have a circumferential pigmented mass on speculum examination. Biopsies of the mass showed a dermal proliferation of highly atypical and mitotically active melanocytes with abundant pigment deposition and varying morphology ranging from spindled to epithelioid. Melanoma in situ was present in the overlying vaginal epithelium. The tumor extended to and invaded the deep subcutaneous tissue, consistent with a pT4b melanoma. By immunohistochemistry, the malignant melanocytes expressed SOX10 and Melan-A. Additionally, there was a loss of p16 expression and p53 exhibited a null phenotype. Next generation sequencing showed copy number losses of NF1, MTAP, CDKN2A and CDKN2B. Additionally, a copy number gain of MDM2 was identified. The tumor had an overall mutation burden of 2.6 m/MB and was microsatellite stable. No mutational variants in BRAF, NRAS, or KIT were detected. This case demonstrates a unique molecular signature for primary vaginal melanomas and provides insight into the molecular genetics of a rare tumor. The views expressed in this abstract are those of the author(s) and do not necessarily reflect the official policy of the Department of Defense or the U.S. Government.

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