Case Report: Molecularly Distinct Synchronous Uterine BRG1-Deficient and Ovarian p53- Mutant Endometrioid Carcinomas

Background Synchronous multiple primary malignancies (SMPMs) of the uterus and ovary are uncommon and diagnostically challenging, as they must be distinguished from metastatic spread of a single primary tumor. Accurate assessment of tumor clonality increasingly relies on integrated molecular profiling, which has important implications for staging, prognosis and therapeutic decision-making. Case Presentation We describe a 47-year-old woman presenting with abdominal distension and extensive peritoneal dissemination. Imaging revealed a uterine endometrial mass and bilateral adnexal lesions. After neoadjuvant chemotherapy, she underwent optimal cytoreductive surgery. Histopathology demonstrated a low-grade endometrioid carcinoma of the uterine corpus and a high-grade endometrioid carcinoma of the ovary. Immunohistochemistry and molecular work-up showed that the uterine tumor had wild-type p53 expression, complete loss of BRG1 and deficient mismatch repair (dMMR), whereas the ovarian tumor exhibited a p53-mutant phenotype with diffuse strong nuclear staining, retained BRG1 expression and proficient mismatch repair (pMMR). Multiple foci of endometriosis were also identified in the pelvis. Conclusions This pronounced molecular heterogeneity, particularly the distinct p53 and BRG1 profiles, provides compelling evidence for two independent primary malignancies rather than metastatic spread from a common origin. This case underscores the critical utility of comprehensive molecular profiling, emphasizing p53 and BRG1 status alongside MMR, in distinguishing genuinely independent synchronous primary gynecological tumors. Such an approach is indispensable for accurate diagnosis, prognostication, and guiding optimal personalized patient management.