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Diagnosing Endometrial Hyperplasia: Why is it so Difficult to Agree?

Allison, Kimberly H. MD*; Reed, Susan D. MD, MPH† ‡ §; Voigt, Lynda F. PhD‡ §; Jordan, Carolyn D. MD*; Newton, Kathryn M. PhD‡ ∥; Garcia, Rochelle L. MD*

The American Journal of Surgical Pathology: May 2008 - Volume 32 - Issue 5 - p 691-698
doi: 10.1097/PAS.0b013e318159a2a0
Original Articles

Current World Health Organization classification of endometrial hyperplasia is problematic because of poor diagnostic reproducibility. We sought to determine factors that cause diagnostic disagreement in a review of 2601 endometrial specimens. Blinded random specimens of normal endometrium, hyperplasias, and carcinoma were reviewed by 2 pathologists, with review by a third pathologist in cases with disagreement. All cases of endometrial hyperplasia or carcinoma were scored for degree of glandular crowding, architectural complexity, and cytologic atypia. Sample adequacy, hyperplasia volume, presence of metaplasia, or endometrial polyp were also scored. The overall κ for agreement was 0.71, with a lower κ of 0.36 when cases called “no hyperplasia” were excluded. The percent specific agreement was 90.3% for no hyperplasia, 31.1% for simple hyperplasia, 51.1% for complex hyperplasia, 49.8% for atypical hyperplasia, and 57.5% for adenocarcinoma. Cases categorized as “low volume hyperplasia” had more diagnostic disagreement than “high volume,” (62% vs. 39%, P=0.003). Similarly, cases called “scant” had more diagnostic disagreement than “not scant” (65% vs. 57%, P=0.013). The histologic feature associated with the most diagnostic disagreement was cytologic atypia (P<0.0001). Architectural crowding, architectural complexity, or the presence of a polyp were all associated with diagnostic disagreement (P<0.0001). High diagnostic disagreement in endometrial hyperplasia is related to both sample adequacy and interpretation of histologic features present. Although obtaining additional tissue may increase diagnostic reproducibility, differences in interpretation of key histologic features like cytologic atypia remain major factors contributing to diagnostic disagreement.

Departments of *Pathology

Obstetrics and Gynecology

Epidemiology, University of Washington Medical Center

§Public Health Sciences Division, Fred Hutchinson Cancer Research Center

Group Health Center for Health Studies, Seattle, WA

Reprints: Kimberly H. Allison, MD, Department of Pathology, University of Washington Medical Center, 1959 NE Pacific, Box 356100, Seattle, WA (e-mail:

© 2008 Lippincott Williams & Wilkins, Inc.