Synchronous multiple primary malignancies (SMPMs) involving the uterus and ovary pose significant diagnostic challenges, particularly in distinguishing independent primary tumors from metastatic disease when tumors exhibit overlapping or divergent morphologic and molecular features. Accurate assessment of tumor clonality increasingly relies on integrated clinicopathologic and molecular profiling, which has important implications for staging, prognosis, and therapeutic decision-making. 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. Following neoadjuvant chemotherapy, she underwent optimal cytoreductive surgery. Histopathologic examination demonstrated a FIGO stage IA low-grade endometrioid carcinoma of the uterine corpus and a SMARCA4-deficient undifferentiated carcinoma of the ovary. Immunohistochemistry showed that the uterine tumor exhibited wild-type p53 expression, retained BRG1 expression, hormone receptor positivity, and proficient mismatch repair (pMMR) status. In contrast, the ovarian tumor demonstrated a p53-mutant phenotype with diffuse strong nuclear staining, complete loss of BRG1 expression, and pMMR status. Multiple foci of endometriosis were also identified in the pelvis. The marked molecular heterogeneity observed in this case, particularly the discordant p53 and BRG1 expression patterns, supports the interpretation of two independent primary malignancies rather than metastatic spread from a common origin. This case highlights the value of integrated clinicopathologic and immunohistochemical assessment, including evaluation of p53, BRG1, and MMR status, in the diagnostic work-up of synchronous gynecologic tumors. Such an approach may contribute to more accurate diagnosis, risk stratification, and individualized treatment planning.
Sun et al. (2026) studied this question.