A high-grade sarcoma with TRIM25::NTRK2 rearrangements in the head and neck: case report

NTRK-rearranged spindle cell tumor is a newly identified pathohistological entity defined by molecular features in the 5th edition of the WHO classification of soft tissue and bone tumors. This tumor type most commonly arises in the superficial or deep soft tissues of the extremities, with approximately half of reported cases occurring in children and adolescents. Histologically, it exhibits two main morphological patterns: one resembling low-grade malignant peripheral nerve sheath tumors (neurinomatous type) and the other resembling lipofibromatosis-like neural tumors. Immunohistochemically, it is characterized by co-expression of S-100 and CD34, along with diffuse pan-TRK positivity. Genetically, most cases involve rearrangements of the NTRK1 or NTRK3 genes, often with fusion partners such as LMNA, TPM3, and TPR. Rearrangements involving NTRK2 are considerably rarer. Herein, we report a rare case of high-grade spindle cell sarcoma with a TRIM25::NTRK2 fusion located in the head and neck region, supported by clinicopathologic and molecular genetic analyses. The patient was an 84-year-old male who presented with facial radiculoneuralgia and subsequently underwent partial resection of a right submandibular mass. Microscopic examination at low magnification revealed ill-defined borders, infiltrative growth patterns, and extensive necrosis. At higher magnification, the tumor cells exhibited short spindle-shaped or ovoid morphology, with abundant cytoplasm, nuclear pleomorphism, prominent nucleoli, and frequent mitotic figures. Some tumor cells contained paranuclear vacuoles resembling univacuolated lipoblasts. The stroma showed collagen deposition, with focal lymphocytic infiltration and hemorrhage. Immunohistochemical analysis demonstrated diffuse positivity for pan-TRK and S-100, partial expression of CD34, and negative staining for CK-pan, SOX10, Desmin, SMA, ALK, P16, MDM2, CDK4, NUT, and other markers. INI-1 and BRG1 expression was preserved. Next-generation sequencing confirmed the presence of the TRIM25::NTRK2 gene fusion. Spindle cell tumors with NTRK2 gene rearrangements are rare. This case expands the morphological and genetic spectrum of NTRK-rearranged spindle cell tumors. Combined with its characteristic immunohistochemical and molecular pathological findings, this case provides insights into potential clinical therapeutic targets.