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Case Reports

Abstract

Spitz nevi are melanocytic tumors, often characterized by spindled-to-epithelioid morphology, which are distinct from acquired melanocytic nevi as they do not harbor mutations in BRAF or NRAS. Rather, these lesions often demonstrate gene rearrangements in kinase proteins such as ALK, ROS1, and NTRK1. Herein, we present a case of a 38-year-old woman with a 0.3 cm slightly erythematous papule in the 4th web space of her right hand. A shave biopsy was decidedly performed which demonstrated a dermal melanocytic proliferation with spindled and Schwannian-type growth, including Verocay-like bodies. Peripheral nesting of melanocytes were present, resembling that of a more conventional nevus. Rare mitotic activity was noted. The tumor showed diffuse expression of Melan-A and S100 with weak HMB-45 reactivity. Notably, ALK and Pan-Trk stains were negative, and the Ki-67 proliferative index was approximately 1-2 percent. Due to the unusual morphology, next-generation sequencing was pursued which revealed a MYO5A-NTRK3 gene rearrangement with an overall tumor mutational burden of 2.1 m/MB, microsatellite stability (MSS), and no other potentially actionable/biologically relevant mutations. Given the molecular findings, this lesion was found to be most consistent with a Spitz nevus with MYO5A-NTRK3 gene fusion. The MYO5A-NTRK3 gene rearrangement is relatively uncommon, however has been reported in the formation of Spitz-lineage tumors often characterized by Schwannian-like growth. We present this case to raise awareness of this relatively rare tumor, its unusual morphology, and the possibility of negative expression upon screening with a Pan-Trk immunostain.