Melanocytic proliferation with BAP-1 inactivated melanocytoma-like morphology in a patient with BRAC2 and CHEK2 germline mutations

Summary: BRCA1-associated Protein (BAP1)-inactivated melanocytoma (BIM) exhibit a unique, biphasic cellular composition. The tumor comprises two distinct melanocytic populations: a cytologically bland nevoid of aggregated nests and a more distinctive group of larger, epithelioid melanocytes with prominent eosinophilic cytoplasm. Both cell populations typically test positive for BRAF V600E, with the epithelioid component demonstrating biallelic BAP1 inactivation which can be demonstrated by loss of BAP1 nuclear expression by immunohistochemistry (IHC) within the epithelioid melanocytes. Most cases are sporadic; however, some patients have an underlying BAP1 germline mutation. We report a case of a 14-year-old female with a strong family history of breast cancer and a lifelong wrist lesion. A biopsy showed a dermal based melanocytic proliferation with features similar to those described in BAP-1 inactivated melanocytoma with BRAF V600E expression; however, BAP-1 expression was retained. Further, molecular testing of the lesion revealed BRAC2 and CHEK2 germline mutations. This case highlights that the histopathologic features of BAP-1 inactivated melanocytoma can be seen in the setting of an underlying germline mutation other than BAP-1 inactivation. Further study of melanocytic tumors showing BIMT-like histology but with normal BAP1 immunostaining is warranted, as some may contain clues to underlying germline mutations related to family cancer predisposition.