Spitz Spindle Cell/Reed Nevus With SQSTM1::NTRK2 Fusion and Atypical Features in an Older Male Patient: A Case Report and Review of Literature.

Abstract

Spitz lesions display a set of genetic alterations that differ from classical melanocytic lesions: examples include mutations in HRAS and fusions involving ALK, ROS1, MET, MAP3K8, BRAF, and the NTRK genes. We present a Spitz spindle cell/Reed nevus with atypical junctional features and an NTRK2 translocation in a patient of unusual age. The patient was a 61-year-old man with a pigmented brown flat 6 mm lesion growing on the skin over the left scapula. The lesion was composed of spindled and epithelioid melanocytes and was arranged in nests with some scattered focal pagetoid cells as well as intraepidermal nests at the center of the lesion and occasional mitotic figures. The melanocytes showed diffuse staining for pan-Trk antibodies. p16 staining was focally and weakly positive. The cells showed staining for HMB-45, MART-1, and tyrosinase, whereas they were negative for PRAME, ALK-1, and ROS-1 immunostaining. BAP-1 was preserved. Next-generation sequencing detected a SQSTM1::NTRK2 fusion and showed no alterations of ALK, ROS1, RET, NTRK1, and NTRK3 genes, as well as no pathogenic variants of BRAF. Fluorescent in situ hybridization showed NTRK2 translocation in all melanocytes evaluated. This case presents a Spitz nevus with a rare translocation in an older patient.