Abstract

Spitzoid melanocytic neoplasms range from Spitz nevus to malignant Spitz tumor with an intermediate category termed “atypical Spitz tumor”. They are composed of large epithelioid and/or spindled cells with distinctive architecture. About 20% of Spitz nevi harbor activating HRAS mutation. In about 55% of Spitz nevi and atypical Spitz tumors, there are chromosomal rearrangement-induced fusions involving the kinase genes ROS-1, ALK, BRAF, NTRK1, NTRK3, MET, and RET, resulting in chimeric proteins. Agminated Spitz tumors represent a rare entity, where multiple lesions arise in a segmental distribution. Herein, we present a case of a 4-year-old male who presented with several scattered pink-brown papules on the right malar cheek, right medial brow, and right glabella. Lesions had developed over last several months and were asymptomatic on presentation. Biopsies showed atypical Spitz tumors on all lesions. RNA sequencing was performed, which showed no evidence of kinase fusions. Rather, there was overexpression of fibroblast growth factor 2 (FGF-2) and ERBB2 (HER2) by next gene sequencing. An inactivating HRAS mutation was also revealed during genetic analysis. Expression of FGF-2 and HER2 have not been reported in Spitz tumors in the literature. Multiple Spitz nevi arranged in clusters (agminated Spitz nevi) are very rare and very few cases have been described in the literature thus far. We review the genomic features of Spitz tumors and how it contributes to classification of Spitzoid melanocytic lesions. We present a case of a child with agminated Spitz tumors with a novel genetic profile, and we discuss potential clinical significance of these mutations in Spitz tumors.

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