Abstract

ALK fusions are common abnormalities detected in Spitz tumors. Various fusion partners have been described. Here, we describe a lesion from the upper back of a 20-year-old woman that showed a novel NME7::ALK fusion. Histologic sections showed a symmetric, wedge-shaped lesion. The lesional melanocytes were epithelioid to spindled with ovoid nuclei, open chromatin, frequent small nucleoli, and a moderate amount of pale, eosinophilic cytoplasm. The cells were arranged in nests, cords, and as single cells infiltrating through the dermis, tracking deeply along adnexal structures, and encircling small nerves. Mitotic activity was not identified. There was a moderate amount of melanoderma. By immunohistochemistry, expression of p16 was retained, the Ki-67 index was low, HMB45 expression mildly diminished with dermal descent, and PRAME was entirely negative. An ALK (D5F3) stain was strongly positive. Next-generation sequencing revealed an NME7::ALK fusion, as well as a tumor mutation burden of 4.1 / Mb and microsatellite stable status. This lesion displayed the epithelioid to spindled cytomorphology, wedge-shaped silhouette, and infiltrative growth pattern frequently reported in ALK-fused Spitz tumors. There was less cytologic atypia than is often reported in these lesions. The lesion extended to the biopsy margins, and a conservative re-excision was recommended. With only one month of follow up to date, further observation will be required to track the long-term behavior of this lesion.