Endometrial Mesonephric-like Carcinosarcoma With Shared KRAS, TP53, and RB1 Mutations: Report of a Rare Case Highlighting Diagnostic Challenges and Novel Molecular Insights, and Review of the Literature

Mesonephric-like carcinosarcoma (MLCS) is an uncommon gynecologic malignancy comprising mesonephric-like adenocarcinomatous (MLA) and high-grade (HG) sarcomatous elements. We describe an endometrial MLCS in a 63-yr-old woman showing divergent p53 immunohistochemical expression, with abnormal expression in the MLA component and normal expression in the sarcomatous component. Dedifferentiated carcinoma and uterine mesenchymal tumors are primary differential diagnoses when sarcomatous elements predominate or exhibit round-cell morphology. A review of 25 endometrial MLCS cases, including ours, showed advanced-stage presentation in 48% (12/25), recurrence in 60% (15/25) and disease-related death in 28% (7/25) of cases, underscoring its aggressive behavior. Heterologous differentiation occurred in 16% of cases but was not essential for diagnosis when unequivocal HG sarcomatous cells were present. Component-specific next-generation sequencing of our case revealed identical KRAS , TP53 , and RB1 mutations in both components, with additional PTPRT mutation and KLF5 amplification restricted to the MLA component, representing a novel molecular signature with potential therapeutic implications.