Clark, Hannah E.Huang, Yuan Yu MichaelVance, Gail H.Alomari, Ahmed K.2023-09-072023-09-072022Clark HE, Huang YYM, Vance GH, Alomari AK. Fatal melanoma with a novel MYO5A-BRAF fusion and small associated conventional nevus: A case report and review of literature. J Cutan Pathol. 2022;49(9):808-812. doi:10.1111/cup.14263https://hdl.handle.net/1805/35404Kinase fusions play an important role in the pathogenesis of Spitz neoplasms and occasionally non-Spitz neoplasms. We report a case of a 19-year-old woman with a growing nodule on the scalp, morphologically consistent with a diagnosis of melanoma with epithelioid features arising in association with small nevus. This tumor aggressively metastasized and failed to respond to immunotherapy. Next-generation sequencing of a metastatic focus revealed an MYO5A-BRAF kinase fusion with a low mutational burden and fluorescence in situ hybridization (FISH) of the primary melanoma showed similar results. FISH testing of the associated nevus failed because of technical reasons. MYO5A has rarely been reported as the fusion partner with BRAF-rearranged melanocytic tumors. Moreover, this case raises speculations and contributes to the growing literature on the pathogenesis, nomenclature, and tumorigenic pathways in kinase-fusion melanomas. The patient succumbed to disease, which is in concordance with some literature suggesting aggressive behavior of BRAF fusion melanomas with TERT promoter mutations.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalGenomic analysisKinase‐fusion mutationSpitz melanomaSpitzoid neoplasmTERT‐promoter mutationArticle