Abstract

Introduction: BRCA1-Associated Protein 1 (BAP1) is a deubiquitylase that functions as a tumor suppressor, regulating multiple cellular processes including cell cycle control, differentiation, cell death, and DNA repair. BAP-1 inactivated melanocytic tumors have recently been described and are characterized by epithelioid cytomorphology, are often clonal in appearance, and typically do not recur or demonstrate malignant transformation on follow-up. Herein we describe a series of five cases of BAP-1 inactivated malignant melanomas. Methods: The archives at three separate institutions were retrospectively analyzed for tumors classified as melanoma with loss of BAP-1 via immunohistochemistry. Five cases were identified and reviewed by two independent dermatopathologists. Genomic analysis for all cases was performed via OncoScan. Results: The five reviewed cases consisted of four females and one male ranging from 29 to 71 years in age. All cases were classified as malignant melanoma based on cytomorphology as well as immunohistochemical and molecular features. Three out of the five melanocytic tumors were found on the head and neck whereas two lesions were located on the back and thigh. Microarray assay demonstrated that out of the five, four cases (80%) had a complete deletion of 3p and three cases (60%) demonstrated BRAF V600E missense mutation. All cases showed malignant copy number alterations. Conclusions: Herein we describe five cases of BAP-1 inactivated melanomas, all of which demonstrate a malignant clinical course with molecular studies confirming the genetic profile of these tumors. This is the first known copy number examination of this subset of tumors to our knowledge.

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