High-grade uterine cancer with ambiguous features - a clinicopathological study

Endometrial endometrioid carcinoma FIGO grade 3 (EC3) and endometrial serous carcinoma (SEC), sometimes present diagnostic challenges due to overlapping and ambiguous features. The prognostic significance of assigning histological subtype remains debatable due to conflicting clinical outcome data. This study examined definite and ambiguous EC3 and SEC cases to compare clinicopathologic characteristics and prognosis.

This is a retrospective study of 129 patients diagnosed with EC3 and SEC at a single tertiary center between 2006-2022. Pathological slides were revised and classified as definite or ambiguous for EC3 and SEC. Survival, progression-free survival, and associations between tumor histologic type and clinicopathologic characteristics were analyzed.

Definite SEC displayed higher mortality compared to definite EC3 (68.2 % vs. 41.4 %, p = 0.023) as well as a non-significant trend towards lower 5-year survival (p = 0.096). Ambiguous SEC also showed higher mortality compared to ambiguous EC3 (68.8 % vs. 37.5 %, p = 0.020) and a non-significant trend towards lower 5-year survival (p = 0.098). Several parameters suggest that ambiguous cases are intermediate between the definite EC3 (lower) and definite SEC (higher) groups. Rates of lymph node metastases (EC3 6.9 %; ambiguous 16.4 % and SEC 29.5 %; p = 0.013), broad ligament involvement (EC3 0 %; ambiguous 1.8 % and SEC 11.4 %; p = 0.016), and omental involvement (EC3 3.4 %; ambiguous 10.9 % and SEC 29.5 %; p = 0.002). A similar trend was observed for ovarian involvement, but it did not reach statistical significance (EC3 6.9 %; ambiguous 12.7 % and SEC 22.7 %; p = 0.055).

Ambiguous cases may represent an intermediate group that displays clinicopathologic features which are more aggressive than in EC3, yet more favorable than in SEC. These results hold implications for managing patients with high-grade endometrial carcinomas, as identifying an intermediate group may inform treatment strategies and prognostic evaluations.