Track: Case Reports

Abstract:

Common acquired melanocytic nevi often harbor BRAF V600E mutations, while kinase gene fusions are a hallmark of Spitz neoplasms. To our knowledge, this is the first report of a combined melanocytic lesion with a BRAF V600E mutated conventional nevus in combination with a BRAF fusion driven atypical Spitz tumor (AST). We report a 78-year-old male who presented with a well-demarcated pink papule over the left neck measuring 3mm in diameter. Histopathologic evaluation revealed a predominantly intradermal, atypical, compound melanocytic proliferation composed of epithelioid melanocytes with abundant amphophilic cytoplasm and prominent nucleoli adjacent to a second population of banal nevoid melanocytes. The epithelioid lesional melanocytes displayed mild cytologic atypia and nuclear pleomorphism, without any apparent mitotic activity, in a background of fibrous stroma; a subset displayed close proximity to hyperplastic nerve bundles, raising the possibility of neurotropism. P16 and BAP1 expression were preserved throughout the lesion, while PRAME expression was not identified. BRAF V600E stain highlighted the conventional nevus component but was negative in the epithelioid lesional cells. Targeted DNA/RNA next generation sequencing performed on the epithelioid melanocytic component was negative for pathogenic single nucleotide variations in BRAF, NRAS, NF1, and TERT genes or copy number alterations; further whole RNA sequencing identified a pathogenic AKAP9::BRAF fusion. Molecular findings confirmed a BRAF fused AST in combination with a BRAF V600E mutated conventional nevus. Neurotropism has rarely been reported in other cases of AKAP9::BRAF fusion Spitz tumors. This case expands the known histopathologic and molecular spectrum of genetic alterations in combined melanocytic neoplasms.