Abstract

BAP1-inactivated melanocytomas (BIMs) are rare melanocytic neoplasms characterized by loss of nuclear expression of BRCA1-associated protein-1 (BAP1), typically accompanied by BRAF mutation. These neoplasms occur sporadically or as part of a syndrome. Histologically, BIMs feature BAP1-deficient epithelioid melanocytes, often accompanied by a second population of ordinary-appearing nevomelanocytes. Despite these unusual features, BIMs rarely progress to melanoma, and BAP1 mutations are uncommon in melanomas. However, rare melanomas associated with germline or sporadic BAP1-inactivation have been reported. We present a case of a 51-year-old male with a lesion on the right thigh. Histopathological examination revealed a polypoid compound melanocytic proliferation with an expansile dermal nodule. The dermal component displayed two distinct populations: 1) spitzoid melanocytes with high-grade atypia and 2) moderately pleomorphic, large epithelioid melanocytes with eosinophilic cytoplasm and prominent cell borders. Both populations displayed loss of BAP1 expression. With array comparative genomic hybridization, the melanoma exhibited numerous chromosomal abnormalities consistent with genomic instability related to malignancy, whereas the BIM population displayed a profile consistent with a benign lesion. Interestingly, the two populations displayed disparate patterns of chromosome 3 loss (both encompassing BAP1) and no overlap in other chromosomal alterations. Our case demonstrates the utility of array comparative genomic hybridization to distinguish BAP1-deficient melanocytic neoplasms at a molecular level. Furthermore, the lack of cytogenetic similarity suggests that the BIM represented an independently evolved neoplasm rather than an intermediate step toward the melanoma. Our case thus raises broader questions about pathways of malignant progression for BAP1-deficient melanocytic neoplasms.