Endometrial hyperplasia and the risk of progression to carcinoma

The primary presenting symptom of endometrial neoplasia is abnormal uterine bleeding, which typically prompts an endometrial biopsy to rule out carcinoma. Approximately 70% of women with abnormal uterine bleeding are diagnosed with benign findings and 15% are diagnosed with carcinoma. The remaining 15% receive a diagnosis of endometrial hyperplasia (EH), which includes a broad range of lesions, from mild, reversible proliferations to the immediate precursors of carcinoma. The widely used World Health Organization (WHO) system classifies EH according to four combinations of glandular crowding and nuclear atypia: simple (SH), complex (CH), simple atypical (SAH), or complex atypical hyperplasia (CAH), although the two forms of atypical hyperplasia (AH) are often collapsed into one category. Diagnoses of EH raise three issues. First, the low interobserver reproducibility-less than 50% in almost all studies-hinders the ability of WHO-based classification to effectively guide clinical management. Second, approximately 50% of women diagnosed with AH have concurrent carcinoma. Not surprisingly, most women with AH undergo hysterectomy as primary treatment, but non-surgical management can be effective. Third, data on progression risks for women with EH who retain their uterus are extremely limited. Emerging data indicate the long-term risk among women with SH or CH is less than 5%, but the risk among women with AH is approximately 30%. These data highlight priority areas for future research, such as increasing the diagnostic reproducibility of EH, improving the discrimination between AH and carcinoma, and identifying biomarkers to stratify risks or serve as indicators of response to clinical treatment.