Amplification of mutant NRASin melanocytic tumors with features of Spitz tumors

NRASactivating mutations are prevalent in melanocytic neoplasia, occurring in a subset of common acquired melanocytic nevi and approximately 30% of cutaneous melanomas. In this study, we describe a cohort of seven distinctive melanocytic tumors characterized by activating point mutations in codon 61 of NRASwith amplification of the mutant NRASallele and shared clinicopathologic features. These tumors occurred predominantly in younger patients, with a median age of 20 years (ranging from 6 to 56). They presented as papules on the helix of the ear (four cases) or extremities (three cases). Microscopically, the tumors were cellular, relatively well-circumscribed, compound or intradermal proliferations. The tumor cells often extended into the deep reticular dermis, and involved the superficial subcutaneous fat in some cases. The melanocytes were epithelioid to spindled with moderate amounts of cytoplasm and conspicuous nucleoli. They were arranged in short plexiform fascicles, nests, and cords. Some cases had occasional pleomorphic and multinucleated melanocytes. Rare dermal mitotic figures were present in all cases. The dermis contained thick collagen bundles and minimal solar elastosis. Follow-up data were available for five patients, with a median period of 4.2 years (ranging from 1 to 9 years), during which no recurrences or metastases were reported. Our series highlights a clinicopathologically and molecularly distinctive subset of NRAS-mutated tumors with amplification of the mutant NRASallele.