Diagnosis of premalignant endometrial disease

Modern molecular methods for precancer diagnosis have expanded the range of detectable disease to a preclinical level and provided material for histopathological correlation. The precancer scenario begins with sporadic acquisition of rare PTEN mutation bearing glands, which are morphologically unremarkable, and progresses to discrete foci of cytologically altered glands, readily visible on routinely stained sections. Clinical outcome studies of women with endometrial lesions have established threshold diagnostic features that confer increased cancer risk. This class of high risk lesions has been designated endometrial intraepithelial neoplasia (EIN). EIN is diagnosed by presence of cytological demarcation, crowded gland architecture, minimum size of 1mm, and careful exclusion of mimics. Most EIN lesions have been diagnosed as atypical endometrial hyperplasias in the World Health Organisation system. Specialised molecular and morphometric analyses have been extremely useful in redefining clinically relevant premalignant endometrial disease, but translation to improved patient care requires the informed participation of pathologists.