Prolonged disease-free survival with immunotherapy combined with chemotherapy in a patient with advanced stage large cell neuroendocrine carcinoma of the uterus.

BACKGROUND: Large Cell Neuroendocrine Carcinoma (LCNEC) is a rare and aggressive high-grade neuroendocrine malignancy that only infrequently arises in the uterus. Owing to its rarity, there are no standardized treatment guidelines, and management is generally extrapolated from neuroendocrine carcinomas of the lung or cervix. Data on the role of immune checkpoint inhibition in uterine LCNEC are lacking. We report, to our knowledge, the first case of mismatch repair (MMR)-deficient endometrial LCNEC treated with multimodal therapy including adjuvant chemotherapy, radiation, and maintenance immunotherapy, resulting in prolonged disease-free survival.

CASE PRESENTATION: A 62-year-old woman presented with postmenopausal bleeding. Endometrial biopsy showed poorly differentiated endometrial adenocarcinoma. Computed tomography revealed a uterine mass, prominent left adnexa, and retroperitoneal, para-aortic, and right external iliac lymphadenopathy. She underwent exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy with radical debulking, right pelvic lymph node dissection, and para-aortic lymphadenectomy, achieving no gross residual disease. Histopathology demonstrated a mixed carcinoma with a predominant LCNEC component (∼95%) and focal endometrioid adenocarcinoma (∼5%), with full-thickness myometrial and cervical invasion, parametrial involvement, extensive lymphovascular invasion, and metastases to multiple pelvic and para-aortic nodes, consistent with FIGO 2023 stage IIIC2. The tumor was MMR-deficient with loss of MLH1 and PMS2, p53 wild type, HER2-negative, FOLR1-negative, and PD-L1 combined positive score of 10. Post-operatively, she received six cycles of carboplatin, paclitaxel, and dostarlimab every three weeks, followed by maintenance dostarlimab. Given the extent of local disease, she also received vaginal brachytherapy and external beam radiation to the pelvis and para-aortic regions. At 29 months post-operation, she remains on maintenance immunotherapy with excellent functional status and no radiographic evidence of disease.

CONCLUSIONS: This case illustrates that aggressive multimodal therapy including immune checkpoint inhibition may achieve durable disease control in advanced-stage MMR-deficient uterine LCNEC. While the relative contributions of surgery, chemotherapy, radiation, and immunotherapy cannot be separated, the favorable outcome supports further investigation of immunotherapy in rare high-grade endometrial neuroendocrine carcinomas and underscores the importance of including these histologies in clinical trials.