Track: Case Reports

Abstract:

A 20-year-old woman presented since early childhood with multiple pigmented lesions in a congenital segmental depigmented patch on her left trunk and leg. Histopathology for biopsied lesions showed epithelioid melanocytes on a background of common nevus. Immunohistochemistry revealed BAP1 loss in the epithelioid component, characteristic of BAP1-inactivated melanocytic tumors (BIMTs). Germline genetic testing revealed a BAP1 pathogenic variant (PV) (c.375+2T>A). Immunohistochemistry for BRAF V600E was performed in five lesions and was notably negative in four, while positive in one. Germline PVs in BAP1 predispose individuals to a spectrum of tumors including BIMTs, uveal melanoma, cutaneous melanoma, mesothelioma, and renal cell carcinoma—defining the BAP1 tumor predisposition syndrome. BIMTs occur in 75% of individuals with germline BAP1 PVs. Histopathologically, they are characterized by a dermal proliferation of large epithelioid melanocytes, often in association with a conventional nevus. These tumors exhibit loss of heterozygosity of BAP1 in the context of an activating driver mutation—primarily BRAF V600E, present in 67-89% of cases. On immunohistochemistry, this corresponds to loss of nuclear BAP1 expression in the epithelioid cells and BRAF V600E positivity in both components. BIMTs without BRAF V600E mutations are rarely described and may instead harbor NRAS mutations, RAF1 fusions, or ALK fusions. We report segmentally distributed BIMTs within a congenital hypopigmented patch in a patient with a germline BAP1 mutation. The presence of multiple lesions lacking BRAF V600E PVs underscores that alternative molecular pathways are implicated in BIMTs. The patient is being followed for other syndromic manifestations by a multidisciplinary team.

Elisa Scandiuzzi Maciel

Affiliation

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(303) Segmentally Distributed BAP1-Inactivated Melanocytic Tumors Without BRAF V600E Pathogenic Variants in a Patient with BAP1 Tumor Syndrome