Interobserver agreement in the diagnosis of endometrial atypical hyperplasia and the contribution of PTEN immunohistochemistry

Endometrial atypical hyperplasia (EAH) is a precancerous lesion whose distinction from non-atypical hyperplasia and endometrioid carcinoma carries major therapeutic implications, particularly in young women eligible for fertility-sparing treatment. Because diagnostic reproducibility remains limited, we assessed interobserver concordance for EAH and explored the contribution of PTEN immunohistochemistry, used here as a single, readily available ancillary marker. In this retrospective, multicenter study, 121 patients of reproductive age with an outside diagnosis of EAH, referred within the PREFERE registry (2017–2023), underwent independent histological re-evaluation by two expert gynecological pathologists according to the WHO 2020 classification; cytonuclear atypia criteria were further analyzed in the 55 cases with slides available for a second review, including 46 with PTEN immunohistochemistry. The concordance rate was 97.5% for the diagnosis of hyperplasia but only 71% for EAH specifically; in 29% of cases the diagnosis was revised after review, most often to non-atypical hyperplasia (62.8%) or adenocarcinoma (17%). Complex architecture was present in 94% of EAH versus 50% of non-atypical hyperplasias, and the diagnosis of EAH relied on the combination of several cytonuclear criteria rather than any single feature. PTEN loss was more frequent in EAH than in non-atypical hyperplasia (75% vs. 14%; P = 0.0045). Interobserver agreement for EAH remains only moderate, reinforcing the value of expert re-review for the fertility-sparing management of these young patients; confirmation in larger, multi-observer series using the complete recommended biomarker panel (PTEN, PAX2, β-catenin) is warranted.