A Novel PDZRN3::BRAF Fusion as Potential Driver Mechanism in BAP1-inactivated Melanocytoma

BAP1 (BRCA 1–associated protein 1)-inactivated melanocytic tumor (BIMT) is a melanocytic neoplasm characterized histologically by large epithelioid cells and is commonly associated with a conventional nevus component. The defining molecular alteration is inactivation of the BAP1 gene. Initiating mutations in BIMT include BRAF p.V600E, or less commonly RAS mutations and fusions involving RAF1 . In this article, we report a case of BIMT with a BAP1 mutation and a novel PDZRN3::BRAF fusion. Histologic examination revealed an intradermal melanocytic neoplasm with nests and single units of large, atypical epithelioid cells with abundant amphophilic–eosinophilic cytoplasm, well-defined cell borders, large vesicular nuclei, and prominent nucleoli. Frequent binucleated and multinucleated melanocytes were present. There was no associated conventional nevus component. Scattered mitotic activity were identified. No evidence of maturation, necrosis, or lymphovascular or perineural invasion was seen. The lesional cells were immunoreactive for SOX10, Melan A, and HMB45 (focal, minimal, and weak), and were negative for PRAME. There was patchy loss of expression of p16 and complete loss of BAP1 expression. Molecular analysis demonstrated BAP1 mutation and a novel fusion involving PDZRN3::BRAF . Our finding expands our current understanding of the molecular landscape and pathogenesis of BIMT.