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Case Reports

Abstract

Mucosal melanomas are a rare, aggressive class of melanoma associated with poor prognostic outcome and limited response to immunotherapy. Unlike cutaneous melanomas, they carry numerous genetic structural aberrations rather than point mutations. While gene fusions are rarely drivers of melanoma, activating MAP3K8 rearrangements have been found as oncogenes in Spitz nevi and melanomas. BRAF and ALK fusions have also been identified infrequently in mucosal melanoma. Here, we report a 55-year-old woman with sinonasal mucosal melanoma demonstrating a MAP3K8 rearrangement. Tumor microscopic features upon re-excision revealed invasive sheets of mitotically active, pleomorphic, discohesive epithelioid cells with Sox-10 and MelanA positivity and did not demonstrate unique histopathologic characteristics or spitzoid cytomorphology. In situ melanoma was also present. Tumor tissue testing using the UCSF500 Gene Panel revealed a MAP3K8::PAK2 gene fusion. Mucosal melanomas remain difficult to treat due to their considerable genetic heterogeneity and relative lack of targetable drivers as compared to cutaneous melanomas. This case demonstrates a unique, previously undescribed gene rearrangement in mucosal melanoma, further illustrating the complex genetic landscape behind this intractable malignancy.