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Case ReportsAbstract
Merkel cell carcinomas (MCCs) exhibit divergent molecular profiles, often categorized by their association with Merkel cell polyoma virus (MCPyV). MCPyV-associated MCCs typically display a low tumor mutational burden (TMB), lacking both somatic mutations and ultraviolet signature. In contrast, MCPyV-negative MCCs commonly arise in sun-exposed skin and frequently exhibit a high TMB, along with TERT promoter mutation (TPM) and somatic mutations, particularly in TP53 and RB1. Gene fusions are exceedingly rare in MCCs, and their specific frequency and fusion transcripts remain largely unexplored. Here, we present a unique case of MCPyV-associated MCC characterized by NSD3::FGFR1 fusion, representing a novel fusion transcript not previously reported in MCCs. A 72-year-old Caucasian man presented with a cyst-like nodule on the left elbow, which had progressively increased in size over a span of 6 months. Excisional biopsy revealed a neuroendocrine carcinoma diffusely expressing CK20 (perinuclear dot-like), synaptophysin, and MCPyV, consistent with MCC. Next-generation sequencing identified NSD3::FGFR1 fusion without any additional somatic mutations, including TP53 and RB1 mutations, or TPM. Subsequently, the patient underwent wide local excision and sentinel lymph node biopsy, revealing no residual MCC in the skin or nodal metastases (stage IIA, pT2pN0cM0). While NSD3::FGFR1 fusion has been sporadically reported in other solid tumors, including breast, pancreatic, and thyroid cancers, its identification in MCC is unprecedented to our knowledge. This novel finding not only underscores the uniqueness of our case but also contributes to the evolving understanding of the molecular landscape of MCCs, particularly MCPyV-associated MCCs.