High-Grade Endometrial Stromal Sarcoma with NTRK Fusion and Response to Larotrectinib: A Case Report

Background: High-grade endometrial stromal sarcoma (HGESS) is a rare and aggressive uterine mesenchymal tumor with a significant potential for recurrence and metastasis. Advances in molecular pathology have identified recurrent gene fusions involving the neurotrophic tyrosine receptor kinase (NTRK) genes, which are crucial for tumorigenesis. The identification of NTRK fusions has significant therapeutic implications, as targeted therapies such as Larotrectinib, a selective tyrosine receptor kinase (TRK) inhibitor, have demonstrated remarkable efficacy in NTRK fusion-positive tumors across various tumor histologies. Case Presentation: This report depicts the case of a 42-year-old woman with HGESS harboring an NTRK fusion diagnosed by histopathology and immunohistochemistry after undergoing a vaginal myomectomy. She subsequently underwent a robotic total hysterectomy, bilateral salpingo-oophorectomy, and bilateral lymph node dissection. Following a four-year disease-free interval, HGESS relapsed. The patient received three cycles of gemcitabine plus docetaxel. Subsequent CT imaging indicated progression of the pelvic mass. Molecular testing identified an NTRK fusion. Accordingly, larotrectinib was initiated in the setting of progressive disease. After three months, imaging demonstrated a significant decrease in the pelvic mass and near-complete radiographic resolution of the pulmonary nodules. The patient remained on larotrectinib, with January 2024 imaging showing no evidence of recurrence. Conclusions: The case presented highlights a personalized approach based on molecular profiling, and the successful use of larotrectinib, a TRK inhibitor, after the identification of an NTRK fusion-positive HGESS, emphasizing the importance of molecular diagnostics and targeted therapy in managing this rare malignancy.