Mixed clear cell/endometrioid and clear cell/serous carcinoma of the uterus are clinicopathologically similar to pure clear cell carcinoma: An NRG Oncology/Gynecologic Oncology Group (GOG-210) study of 311 women

Objectives: Clear cell carcinoma is a high-risk subtype of endometrial cancer. Some patients have a mixture of clear cell carcinoma with other histologic types (endometrioid or serous) or cannot be neatly assigned to one of these types. Protocol GOG-8032 within GOG-210 was designed to determine whether these tumors differ from pure clear cell carcinoma in stage at diagnosis, initial pattern of spread, or patient survival. Methods: The term “mixed” was applied to tumors with multiple identifiable components, and “indeterminate” was applied to tumors with features intermediate between different histologic types. Three hundred eleven women with pure, mixed, or indeterminate clear cell carcinoma were identified in a larger cohort of patients undergoing hysterectomy for endometrial cancer in GOG-210. Histologic slides were centrally reviewed by expert pathologists. Baseline and follow-up data were analyzed. Results: One hundred thirty-six patients had pure clear cell carcinoma and 175 had a mixed or indeterminate clear cell pattern. Baseline clinicopathologic characteristics were similar except for a small difference in age at presentation. Univariate survival analysis confirmed the significance of typical endometrial cancer prognostic factors. Patients in the mixed categories had disease-free and overall survival similar to pure clear cell carcinoma, but the indeterminate clear cell/endometrioid group had longer survival. Conclusion: In clear cell endometrial cancer, the presence of a definite admixed endometrioid or serous component did not correlate with a significant difference in prognosis. Patients whose tumors had indeterminate clear cell features had better prognosis. Some of these tumors may be endometrioid tumors mimicking clear cell carcinoma.