Mapping evidence and gaps in diagnostic characteristics of endometrial carcinomas of the uterine corpus: implications for the WHO Classification of tumours, research, and clinical practice

Objective
The project “Mapping the Evidence for the World Health Organization (WHO) Classification of Tumours: a Living Evidence Gap Map by Tumour Type, WCT EVI MAP” pioneered use of Evidence Gap Maps (EGMs) in pathology to support future WHO Tumour Classification (WCT) editions. In this study, we generated an EGM for endometrial carcinomas of the uterine corpus (ECUC).

Methods
Structured PubMed and Ovid Embase searches and title and abstract screening identified peer-reviewed primary studies and systematic reviews addressing diagnostic characteristics, pathogenesis, diagnostic imaging, histopathology including cytopathology, diagnostic molecular pathology, prognosis, and prediction of therapy response for endometrioid, serous, clear cell, undifferentiated/dedifferentiated, mixed, and other endometrial carcinomas, and carcinosarcomas of the uterine corpus published between 01/01/2020 and 27/08/2024. Eligible abstracts reported sufficient methodological detail and effect measures disaggregated by WCT-aligned tumour type. Purely preclinical, qualitative, in silico, omics database-derived, treatment-effectiveness, and relapse/recurrence/metastasis studies were excluded. Included studies were coded by tumour characteristics, tumour types, and study design-related evidence levels according to a predefined hierarchy (1–highest, 5–lowest).

Results
Of 11,165 screened studies, 698 were included, yielding 1,134 map entries. Histopathology was most frequently investigated (44.4%), followed by prognosis (29.5%), whereas prediction studies were rare (0.8%). Level 1–2 evidence was concentrated in prognosis (60.3%), while other domains were mainly supported by level ≤ 3 evidence. Systematic reviews represented 0.7% of included studies, and 70% focused on prognosis.

Conclusions
Histopathology is the best-supported ECUC characteristic. Evidence on treatment-response prediction remains limited, even for endometrioid carcinomas. For non-endometrioid ECUC, evidence on pathogenesis and diagnostic imaging is sparse, and molecular pathology studies are more common but mostly low-level. Major synthesis gaps remain, with systematic reviews largely restricted to prognosis. High-level primary studies and systematic reviews are needed, particularly for pathogenesis, diagnostic imaging, predictive biomarkers, and rare ECUC subtypes, to inform WCT updates and improve diagnosis.