Abstract
BACKGROUND: Large and giant congenital melanocytic naevi (CMN) present a risk for developing melanoma or neurocutaneous melanosis. Most CMN are caused by NRAS or, less commonly, BRAF mutations. OBJECTIVES: To present a series of patients with large-to-giant CMN with BRAF fusion genes as driver alterations and describe their unique clinical presentation. METHODS: We retrospectively identified five patients, from three academic institutions, with giant CMN harbouring BRAF fusion genes. We analysed tumour DNA using capture-based next-generation sequencing. RESULTS: Four of five patients with giant CMN harbouring a BRAF fusion gene exhibited thousands of satellite naevi, many with significant pruritus, nodularity and firmness. One patient developed neurocutaneous melanosis. Histopathology showed marked stromal desmoplasia, akin to the changes observed in acquired melanocytic naevi with BRAF fusion genes. Notably, one patient responded to the MEK inhibitor trametinib, demonstrating the potential therapeutic advantage of genetic characterization of these lesions. CONCLUSIONS: CMN with BRAF fusion genes appear to have unique clinical features and may be associated with numerous satellite lesions. Marked desmoplasia is a histopathological feature that can point to an underlying BRAF fusion gene.