Poor Prognosis and High Recurrence in NTRK3 Fusion Cervical Sarcoma: A Series of 3 Cases and Literature Review

This study aimed to expand the morphologic and molecular spectrum of NTRK-rearranged uterine tumors by reporting 3 cases of NTRK3-fusion cervical sarcoma and conducting a literature review, thereby strengthening the understanding of their clinicopathologic features, differential diagnosis and treatments. We collected 3 cases of NTRK3-fusion cervical sarcoma and reviewed their clinical presentation, histomorphology, immunohistochemistry, fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) findings. Previously reported cases were identified from the English-language literature in PubMed, and the differential diagnosis of uterine spindle cell tumors was discussed. The tumors in all 3 cases were composed of uniform spindle cells with mild to moderate atypia and focal lymphocytic infiltration. Mitotic activity varied from 10 to 30 per 10 high-power fields. Immunohistochemically, all cases showed CD34 and pan-TRK positivity, and 2 cases showed patchy to diffuse S-100 staining. NGS identified NTRK3 fusions in all cases (SPECC1L::NTRK3, ETV6::NTRK3, KHDRBS1::NTRK3). All 3 patients experienced recurrence, and 2 remained stable after receiving TRK inhibitor therapy. Integration of our cases with 68 previously reported cases revealed that NTRK3-fusion uterine tumors tend to be larger, with higher mitotic counts, a higher proportion of cases with International Federation of Gynecology and Obstetrics (FIGO) stage above IB, higher recurrence rates, and increased disease-specific mortality. NTRK3-fusion cervical sarcomas represent a rare but clinically significant subset of NTRK-rearranged tumors characterized by their potential for recurrence and metastasis. The molecular identification of NTRK-rearranged neoplasms is highly significant, as patients may benefit from TRK inhibitor therapy.