Clinicopathogenomic Characteristics of Primary and Metastatic Melanomas With RAF1 and BRAF Fusions

Point mutations in genes of the mitogen-activated protein kinase (MAPK) pathway are the most frequent oncogenic drivers of melanocytic neoplasms, whereas gene fusions are comparatively rare. Kinase fusions are among the molecular alterations that characterize Spitz neoplasms; however, not all melanocytic tumors that harbor one as the main oncogenic driver conform to clinical and/or histomorphologic parameters associated with Spitz neoplasms. In this study, we describe the clinical, histopathologic, and molecular characteristics of 7 RAF1 and 23 BRAF fusion-positive melanomas of patients who presented with or later developed regional and/or distant metastases. We report that most tumors in this series arose in adult patients and lacked Spitz-like microscopic features. Awareness of the varied clinical and histopathologic presentation of RAF1 and BRAF fusion-positive melanomas is important as the protein products of these kinase gene fusions constitute potentially actionable therapeutic targets.