Integrated histological parameters define prognostically relevant groups in atypical endometrial hyperplasia / endometrioid intraepithelial neoplasia

Background: The risk of endometrial cancer (EC) in atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AEH/EIN) is highly variable among different series. Recent studies suggested that histological criteria may subdivide AEH/EIN into prognostically relevant groups. Objective: To assess the risk of EC in AEH/EIN patients stratified according to integrated histological parameters. Methods: All women with AEH/EIN undergoing hysterectomy within 1 year from diagnosis without undergoing progestin treatment were included. AEH/EINs were subdivided into 3 study groups, based on nuclear atypia and on the presence of focal (<2 mm) stromal disappearance (FSD): low-grade (LG)-AEH/EIN, high-grade (HG)-AEH/EIN, and FSD-AEH/EIN. The rate of EC on the subsequent hysterectomy was assessed in each study group, and differences between study groups were assessed using Fisher’s exact test, with a significant p-value<0.05. Reproducibility was assessed by using Cohen’s k. Results: Ninety-six patients were included. Overall, 36/96 patients (37.5%) had EC on the subsequent hysterectomy. The number of EC was 4/42 (9.5%) in LG-AH/EIN, 14/28 (50%) in HG-AH/EIN, and 18/26 (69.2%) in FSD-AEH/EIN. The rate of EC was significantly higher in HG-AH/EIN than in LG-AEH/EIN (p<0.001), while it did not significantly differ between HG-AEH/EIN and FSD-AEH/EIN (p=0.176). The reproducibility among pathologists was moderate for LG-AEH/EIN vs HG-AEH/EIN (k=0.58) and substantial for FGD-AEH/EIN vs LG-AEH/EIN (k=0.63) and HG-AEH/EIN (k=0.63). Conclusion: AEH/EIN can be stratified into prognostically relevant groups based on integrated histological parameters, with a possible major impact on patient management.