Atypical Spitz Tumor/Spitz Melanocytoma Revealing a VIM::NTRK3 Gene Fusion: Clinicopathological Correlation of a Unique Molecular Finding
Mario Della Mura, Joana Sorino, Anna Colagrande, Giuseppe Ingravallo, Alessio Giubellino, Francesco Fortarezza, Richard K. Yang, Woo Cheal Cho, Gerardo Cazzato
Abstract
ABSTRACT: Spitz tumors are a heterogeneous group of melanocytic neoplasms ranging from benign Spitz nevi to malignant Spitz melanomas, with atypical Spitz tumors/Spitz melanocytoma occupying an intermediate position within this biological spectrum. A hallmark of all these lesions is the presence of specific genetic alterations, distinct from those seen in common nevi, that include, among others, receptor tyrosine kinase fusions. NTRK3 gene rearrangements are rare, with only a few fusion partners described in the existing literature ( ETV6 , MYO5A , MYH9 , and SQSTM1 ). We report the first case of an atypical Spitz tumor/Spitz melanocytoma harboring a novel VIM::NTRK3 gene fusion, occurring in a 10-year-old girl. Histopathology revealed a compound melanocytic proliferation composed of both epithelioid and spindle-shaped melanocytes, that displays atypical features, including increased number of single junctional elements, evident pagetoid spread, and lack of maturation. Immunohistochemistry showed diffuse pan-TRK positivity, with a peculiar granular cytoplasmic and perinuclear dot-like pattern, the latter possibly reflecting the microtubule organizing center/centrosome. This case expands the spectrum of known NTRK3 fusion partners and underscores the importance of molecular characterization through next-generation sequencing for accurate diagnosis and potential therapeutic implications in challenging lesions.