Track: Case Reports

Topic: Melanocytic Neoplasms

Abstract:

Unlike Spitz melanocytic neoplasms, which frequently exhibit chromosomal rearrangements resulting in recurrent gene fusions, non-Spitz melanomas typically lack such fusion events. Here, we present a unique case of melanoma characterized by RNF11::BRAF fusion, representing a novel fusion transcript not previously reported in non-Spitz melanomas. The patient, a 63-year-old man with a history of stage IB melanoma of the upper back (pT2apN0cM0), progressed to develop metastases in multiple sites, including lymph nodes, lung, liver, and brain, over the duration of approximately 40 months despite receiving systemic treatment with immunotherapies. Histopathologically, the tumor cells displayed epithelioid and prominent rhabdoid morphologies. Next-generation sequencing of a metastatic melanoma specimen identified RNF11::BRAF fusion, along with TERT promoter mutation. Notably, no other somatic mutations, including BRAF, NRAS, and NF1 mutations, or copy number variations were detected (triple wild-type). RNF11::BRAF fusion has previously been implicated as an oncogenic driver in histiocytic disorders, such as Erdheim-Chester disease and juvenile xanthogranuloma. Its occurrence has also been sporadically reported in certain solid tumors, including brain and pancreatic cancers. While BRAF fusions are predominantly observed in Spitz melanocytic neoplasms, the identification of RNF11::BRAF fusion in non-Spitz melanocytic neoplasms, particularly melanomas, is unprecedented. To the best of our knowledge, this case represents the first report of RNF11::BRAF fusion in melanoma, contributing to the expanding body of literature on BRAF-fused melanomas.

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Yan Gao, MD