Acral Mesenchymal Spindle Cell Neoplasm With a Novel HMGA2::NCOA2 Fusion

Molecular profiling has revolutionized the field of soft tissue pathology, enhancing diagnostic precision and treatment strategies. The integration of molecular analysis and immunohistochemistry has been crucial for classifying diagnostically challenging acral mesenchymal neoplasms. Herein, we report the first documented case of an acral mesenchymal spindle cell neoplasm harboring an HMGA2::NCOA2 fusion. The neoplasm presented as a slow-growing verrucous papule on the right thumb of an 18-year-old female. Histological examination revealed spindled cells of varying cellularity with intervening sclerotic collagen and dilated vasculature. The cells had patchy S100 and focal GLUT-1 reactivity but were negative for CD34, EMA, Sox-10, Pan-TRK, p63, CKAE1/3, MUC4, ALK, Factor 13A, actin, desmin, and ERG. Given the unusual morphology and non-diagnostic immunohistochemical profile, the specimen was sent for additional molecular profiling. Next-generation sequencing revealed a novel in-frame HMGA2::NCOA2 fusion. The tumor was likely benign, with 4 mitoses per 10 high-powered fields (HPF), but was excised due to the unpredictable behavior of the fusion. As the first known case to date with this fusion, these findings contribute to the emerging research on genomic testing in acral soft tissue tumors. Additional cases and longer clinical follow-up are needed to better characterize the novel HMGA2::NCOA2 fusion.