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

NTRK-rearranged spindle cell tumors represent a distinct entity among kinase fusion-driven mesenchymal neoplasms, as recognized in the 5th edition of the WHO Classification of Soft Tissue and Bone Tumors. Histologically, these tumors exhibit a spectrum of morphological features ranging from lipofibromatosis-like to malignant peripheral nerve sheath tumor-like patterns, encompassing both low- and high-grade morphologies. A diagnostically useful microscopic feature is the presence of prominent keloid-like hyalinized collagen bands, which are often arranged in perivascular rings. Immunophenotypically, these tumors typically co-express S-100 and CD34, and show diffuse pan-TRK positivity. Genetically, most cases involve fusions of NTRK1 or NTRK3 with partners, such as LMNA , TPM3 , or TPR ; rearrangements involving NTRK2 are far less common. Herein, we report a rare case of high-grade spindle cell sarcoma harboring a TRIM25::NTRK2 fusion in an 84-year-old male who presented with facial radiculoneuralgia and a right submandibular mass. Histopathological evaluation revealed a poorly differentiated neoplasm with infiltrative growth, marked nuclear atypia, frequent mitosis, and extensive necrosis. Immunohistochemical analysis demonstrated diffuse positivity for pan-TRK and S-100 as well as partial expression of CD34. Next-generation sequencing confirmed the presence of the TRIM25::NTRK2 gene fusion. 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 insight into potential clinical therapeutic targets.