Fatal melanoma with a novel MYO5A‐BRAF fusion and small associated conventional nevus: A case report and review of literature

Abstract

Kinase 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.

Reconsideration of the pathogenic significance of kinase gene fusion in melanocytic tumors based on a case of melanoma with non‐in‐frame BICD1::BRAF fusion

“…This case of aggressive melanoma with BICD1::BRAF fusion demonstrates that melanocytic tumors with kinase gene fusion are not always Spitz neoplasms and that kinase gene fusion is not always a pathogenic gene alteration. The MYO5A::BRAF fusion seen in the case of melanoma with a conventional nevus component described by Clark et al 1 might also have been a non‐pathogenic gene alteration. The pathogenic significance of kinase gene fusion in clinically or morphologically unusual melanocytic tumors should be evaluated with Sanger sequencing, because panel sequencing, including FoundationOne, does not provide the information.…”

“…We have read with great interest the recently published paper, titled “Fatal melanoma with a novel MYO5A‐BRAF fusion and small associated conventional nevus: a case report and review of literature,” 1 which reported a case of biologically aggressive melanoma with BRAF fusion. The authors of that paper reported that a small conventional nevus may have transformed into a fatal melanoma with a secondary genetic event of MYO5A::BRAF fusion 1 …”