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Case Reports

Abstract

A 10-year-old male with family history of melanoma presented to dermatology for a growing, pink, smooth, 5 mm dome-shaped papule on the posterior neck. Histopathology revealed a biphasic compound melanocytic neoplasm with a conventional component and a second population of enlarged epithelioid melanocytes with abundant cytoplasm, occasional mitotic activity and moderate to focally severe nuclear atypia. A BRCA1-associated protein (BAP1)-inactivated melanocytic tumor (BIMT) was suspected, however, a BAP1 immunohistochemical stain failed to show the characteristic loss of nuclear expression in the epithelioid component. Further immunohistochemistry showed positive staining for BRAF V600E and p16, and PRAME was negative. Molecular sequencing was performed and showed pathogenic variants in BRAF p.V600E and BAP1 c.505C>T p.H169Y, confirming the diagnosis of a BIMT. The patient underwent genetic testing which was negative for germline BAP1 mutation. When BIMTs demonstrate classic histologic features, loss of nuclear expression of BAP1 by immunohistochemistry is considered diagnostic. Rarely, BIMTs may be caused by mutations that result in a BAP1 protein that is nonfunctional, but that can still be detected by immunohistochemistry. Our case highlights the importance of correlating morphology, immunohistochemical and molecular studies in the diagnosis of melanocytic neoplasms. This is especially important in the case of BIMTs with retained BAP1 immunohistochemical expression to avoid overdiagnosis as melanoma, allow for accurate diagnosis, and prompt genetic testing for germline mutation and the BAP1 tumor predisposition syndrome when appropriate.