Primary Cutaneous Melanocytic Neoplasms

This chapter on primary cutaneous melanocytic neoplasms of the skin will discuss three major categories of benign melanocytic neoplasms: common acquired, congenital, and blue nevi. The predominant initiating genomic event in common acquired nevi is a mutation in BRAF, while a significantly smaller percentage have a mutation in NRAS. Mutations in NRAS occur far more frequently in congenital nevi; the ratio of NRAS to BRAF mutations in congenital nevi varies depending on the size of the congenital nevus. Giant congenital nevi are almost exclusively NRAS mutated. Blue nevi commonly have mutations in GNAQ and GNA11 and likely have a distinct melanocytic precursor cell compared to many, but not all, common acquired nevi. This chapter will highlight how specific mutations and melanocytic precursor cell types impact morphology of benign melanocytic nevi and how these factors can be integrated into a more reproducible classification system. The author also discusses two major subtypes of melanoma: those occurring on non-chronically sun-damaged skin, which have frequent BRAF mutations, and melanomas occurring in chronically sun-damaged skin, which have less frequent BRAF and NRAS mutations but have occasional mutations in c-Kit or NF1. Likewise, the author discusses how the mutation and cell of origin in these melanomas relate to morphology and ultimately can be used for a more robust classification system.