Benign endometrial hyperplasia sequence and endometrial intraepithelial neoplasia.

Endometrial "hyperplasia," as currently diagnosed, includes the changes caused by an abnormal hormonal state and those caused by a separate category of monoclonal premalignant disease. The appearance of the disease in these 2 functional categories is discontinuous, permitting more specific diagnosis of the condition using the terms "benign endometrial hyperplasia" and "endometrial intraepithelial neoplasia" (EIN), respectively. Benign endometrial hyperplasia involves the entire endometrial compartment and, with protracted estrogen exposure, shows the progressive development of cysts, remodeled glands, vascular thrombi, and stromal microinfarcts. They are best construed as a sequence of changes whereby the appearance at any single time point is uniquely dependent on the preceding combination and the duration of hormonal exposures. In contrast, the premalignant clone of an EIN lesion is characteristically offset from the background endometrium by its altered cytology and crowded architecture. The use of an internal standard for cytology assessment, combined with the distinctive topography of a clonal process, enables the diagnosis of EIN lesions with a long-term cancer risk 45-fold greater than that of their benign endometrial hyperplasia counterparts. The resolution of hormonal and premalignant subsets of traditional "endometrial hyperplasias" is possible using redefined diagnostic criteria, enabling patient therapy to be appropriately matched with the underlying disease mechanisms.