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Life sciences · Journal article
Medicine · September 18, 2026
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Rationale: Dedifferentiated endometrial carcinoma (DEC) is a rare and aggressive subtype of endometrial cancer comprising undifferentiated carcinoma and a low-grade endometrioid component. Although POLE -mutated tumors usually show favorable outcomes owing to their ultramutated and immunogenic nature, the clinical relevance of POLE mutations in DEC remains unclear. In particular, the therapeutic effects of immune checkpoint inhibitors in POLE -mutated DEC with brain metastases have not been well characterized. Patient concerns: Here, we report the case of a 58-year-old woman with POLE -mutated DEC who presented with headache, dizziness, and generalized weakness due to multiple brain and pulmonary metastases. The clinical course, pathological and genomic findings, multidisciplinary treatment, and treatment outcomes were evaluated. Diagnoses: Endometrial biopsy confirmed dedifferentiated carcinoma. Genomic profiling identified a pathogenic POLE exonuclease domain mutation (V411L) and a high tumor mutational burden (49.7 mutations/Mb). Interventions: The patient underwent urgent cerebellar resection, followed by radiotherapy, during which a new intracranial lesion developed. Outcomes: Systemic therapy with carboplatin, paclitaxel, and pembrolizumab resulted in marked regression of uterine and pulmonary lesions. Her symptoms resolved completely, and the Eastern Cooperative Oncology Group performance status improved from 2 to 0. During maintenance pembrolizumab therapy, further tumor regression was observed, and durable disease control was maintained thereafter. At 14 months, the patient remained progression-free without significant adverse events. Lessons: This case demonstrated a dramatic and sustained response following multidisciplinary treatment, including surgery, radiotherapy, chemotherapy, and immune checkpoint inhibitor therapy, in POLE -mutated DEC with brain metastases. This highlights the importance of molecular profiling in identifying patients who may benefit from immunotherapy, even in aggressive and widely metastatic disease.