Congenital melanocytic nevi initiated by BRAF fusion oncogene with firmness, pruritus, and desmoplastic stroma.

Background: Large and giant congenital melanocytic nevi present a risk for developing melanoma or neurocutaneous melanosis. Most are caused by NRAS or, less commonly, BRAF mutations.

Objective: We present a series of patients with large to giant congenital melanocytic nevi with BRAF fusion genes as driver alterations and describe their unique clinical presentation.

Methods: We retrospectively identified five patients with giant congenital melanocytic nevi harboring BRAF fusion genes, from three academic institutions. We analyzed tumor DNA using capture-based next-generation sequencing.

Results: Four of five patients with giant congenital melanocytic nevi harboring a BRAF fusion gene exhibited thousands of satellite nevi, 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 nevi with BRAF fusion genes. Notably, one case responded to the MEK inhibitor trametinib, demonstrating the potential therapeutic advantage of genetic characterization of these lesions.

Conclusions: Congenital melanocytic nevi with BRAF fusion genes appear to have unique clinical features and may be associated with numerous satellite lesions. Marked desmoplasia is a histopathologic feature that can point towards an underlying BRAF fusion gene.