Track

Case Reports

Abstract

BAP-1 inactivated melanocytoma (BIM) is a rare spitzoid-appearing intradermal melanocytic neoplasm characterized by loss of BAP-1 function. BAP-1 inactivation is usually sporadic, although germline inactivation is associated with development of multiple cancers, including uveal and cutaneous melanoma, mesothelioma, and renal cell carcinoma. Microscopically these tumors often demonstrate a biphasic melanocyte proliferation, with atypical epithelioid melanocytes showing loss of BAP-1 protein, with a second component of ordinary/conventional melanocytes. A concurrent genetic alteration, usually a mitogenic driver mutation involving BRAF, is also common. Although cases of melanoma arising from BIM are rare, BAP-1 loss combined with other oncogenic driver mutations may suggest increased progression risk. We identified a case of a 48-year-old male with BAP-1 inactivated melanocytoma and a unique combination of molecular features. The tumor presented as a nevoid nodule located on the right inferior helix. Histology demonstrated an intradermal proliferation of epithelioid melanocytes with loss of BAP-1 staining, variable loss of p16, and patchy PRAME positivity. BRAF V600E expression by immunostaining was also negative, an unusual finding in BAP-1 inactivated tumors. MART-1 and Ki-67 co-staining showed an elevated proliferation index in some of the more atypical appearing melanocytes. Molecular profiling demonstrated an HRAS Q61R mutation with RNF43 mutation. Although BIM with KRAS mutations have been previously described, to our knowledge, this is the first case reporting a combination of BAP-1 with an HRAS mutation. These findings contribute to the current understanding of the molecular profile of BIM and highlight features with the potential for therapeutic translation.