Precursor Lesions of Endometrial Carcinoma

Abstract

Endometrial hyperplasia often precedes the development of endometrioid carcinoma, the most common type of endometrial carcinoma. More recently, studies have found that the risk of endometrial hyperplasia is associated with increasing body mass index and nulliparity [24]. In addition, obesity, anovulatory cycles, and exogenous hormones are associated with both endometrioid carcinoma and hyperplasia. All of these factors are thought to result in unopposed estrogen stimulation of the endometrium. The role of unopposed estrogen stimulation in the development of endometrial hyperplasia and carcinoma is further supported by studies demonstrating elevated serum estrogen levels in patients with endometrioid carcinoma [14, 72]. However, other histologic types of endometrial carcinoma appear to be unrelated to hormonal factors and hyperplasia [81]. Serous carcinoma is the prototypic endometrial carcinoma that is not related to estrogenic stimulation or hyperplasia. It usually arises in atrophic endometrium through a precursor lesion called endometrial intraepithelial carcinoma (EIC). Over the past 3 decades, clinicopathologic, immunohistochemical, and molecular genetic studies have provided data to support the development of a dualistic model of endometrial carcinogenesis. In this model, two types of precursor lesions precede the two most common types of endometrial carcinoma. Atypical hyperplasia (AH) is recognized as the precursor for endometrioid carcinoma and endometrial intraepithelial carcinoma (EIC) is recognized as the precursor for serous carcinoma. The following discussion summarizes current knowledge about these precursor lesions including their differential diagnosis, treatment, and relationship to endometrial carcinoma.