[Precursor lesions of endometrial carcinoma]

The 2014 WHO classification distinguishes between endometrial hyperplasia without atypia (EH) and atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AEH/EIN). AEH/EIN is characterized by crowded glands with cytologically atypical epithelium separated by little intervening stroma. Cellular atypia is characterized by nuclear enlargement and rounding, pleomorphism, loss of polarity, and presence of nucleoli. The diagnosis of atypia is facilitated by comparison with areas of adjacent normal and non-atypical glands, respectively. AEH/EIN is often associated with squamous but also secretory and mucinous metaplasia. Loss of PTEN and/or PAX2 immunoreactivity occurs in up to two thirds of AEH/EIN. In contrast, invasive low-grade endometrioid carcinoma shows confluent growth with loss of stroma and formation of labyrinth-like or cribriform structures. Differential diagnosis includes different forms of metaplasias, papillary proliferations, and hyperplastic polyps. Epithelial metaplasia may be present in various benign endometrial lesions as well as in endometrioid adenocarcinoma. AEH/EIN may also occur in endometrial polyps. Progestin therapy of AEH/EIN has low level of evidence but frequently leads to complete regression. Serous intraepithelial carcinoma (SEIC) is characterized by high-grade cellular atypia and polymorphism, detachment of cells, a mutant immunoreactive pattern for the P53 and an increased Ki67 labeling index. Although designated as precursor of serous carcinoma of the endometrium, biologically it is considered a non-invasive serous carcinoma since it may already be associated with massive extrauterine spread.