A Distinct Subset of Atypical Spitz Tumors is Characterized by BRAF Mutation and Loss of BAP1 Expression

We recently reported that germline mutations in BAP1 cause a familial tumor syndrome characterized by high penetrance for melanocytic tumors with distinct clinical and histologic features. Melanocytic neoplasms in affected individuals harbored BRAF mutations, showed loss of BAP1 expression, and histologically resembled so-called "atypical Spitz tumors" (ASTs). ASTs are an ill-defined and probably heterogenous group of melanocytic tumors that display histologic features seen in both Spitz nevi and melanomas. Their biological behavior cannot be reliably predicted. In view of the histologic similarities of the familial tumors and ASTs, we hypothesized that a subset of ASTs might harbor genetic alterations seen in the familial tumors. To address this hypothesis, we analyzed 32 sporadic ASTs for BRAF mutations and for BAP1 expression. Nine (28%) sporadic ASTs showed loss of BAP1 expression, of which 8 (89%) had concomitant BRAF mutations. Only 1 of the BAP1-positive ASTs (4%) had a BRAF mutation (P