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Arch Pathol Lab Med. 2011 Apr;135(4):464-70. doi: 10.1043/2010-0139-OA.1.

International Internet-based assessment of observer variability for diagnostically challenging endometrial biopsies.

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Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.



Endometrial carcinoma of endometrioid histology is frequently preceded by endometrial hyperplasia, from which localized, premalignant lesions called endometrial intraepithelial neoplasia (EIN) emerge. Diagnostic criteria for EIN have been developed by histopathologic correlation with clinical outcome, molecular changes, and objective computerized histomorphometry. However, several benign mimics of EIN continue to cause diagnostic confusion.


To better understand the diagnostic pitfalls of EIN.


An online quiz of 18 endometrial biopsies considered difficult by a gynecologic pathologist was constructed. Each case contained clinical history and at least 2 microscopic images. Answer choices included the following: (1) EIN, (2) polyp, (3) benign endometrium (proliferative, secretory, disordered, tubal metaplasia, and lower uterine segment), and (4) adenocarcinoma. Online tutorials were offered at the start, and the authors' diagnosis and clinical follow-up were provided at the end.


The quiz was completed by 78 participants from 13 countries. Agreement with the authors ranged from 17% to 100% (mean, 55%). For analysis, polyp and benign responses were grouped. The mean percentage of agreement was highest in cases of polyp with no special features (88%), tubal metaplasia (87%), and secretory change (75%). Poorer agreement was seen with cases containing mucinous metaplasia (38%), extensive morular metaplasia (28%), and EIN arising in a polyp (53%). The mean percentage of agreement for EIN without these features was 63%.


Although the reproducibility of EIN criteria was good, a subset of biopsies with morular metaplasia and EIN in polyps was problematic and likely required consensus review.

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