Virchows Archiv

, Volume 472, Issue 6, pp 907–917 | Cite as

Benign endometrial proliferations mimicking malignancies: a review of problematic entities in small biopsy specimens

  • Philip Pun-Ching Ip
Review and Perspectives


Benign proliferations that mimic malignancies are commonly encountered during the course of assessment of small and fragmented endometrial samples. Although benign, endometrial epithelial metaplasias often coexist with premalignant or malignant lesions causing diagnostic confusion. The difficulty with mucinous metaplasia lies in its distinction from atypical mucinous glandular proliferations and mucinous carcinomas, which are associated with significant interobserver variability. Papillary proliferation of the endometrium is commonly associated with hormonal drugs and endometrial polyps and is characterised by papillae with fibrovascular cores covered by epithelial cells without cytologic atypia. They are classified into simple or complex papillary proliferations depending on the architectural complexity and extent of proliferation. Complex papillary proliferations are associated with a high risk of concurrent or subsequent hyperplasia with atypia/carcinoma. Papillary proliferations may have coexisting epithelial metaplasias and, most commonly, mucinous metaplasia and syncytial papillary change. Those with striking mucinous metaplasia overlap morphologically with papillary mucinous metaplasia. The latter has been proposed as a precursor of endometrial mucinous carcinoma. Misinterpreting the Arias-Stella reaction as a malignant or premalignant lesion is more likely to occur if the pathologist is unaware that the patient is pregnant or on hormonal drugs. Endometrial hyperplasia with secretory changes may occasionally be difficult to distinguish from the torturous and crowded glands of a late secretory endometrium. Endometrial polyps may have abnormal features that can be misinterpreted as endometrial hyperplasia or Mullerian adenosarcoma. Awareness of these benign endometrial proliferations and their common association with hormonal medication or altered endogenous hormonal levels will help prevent the over-diagnosis of premalignant and malignant lesions.


Endometrium Papillary proliferation Mucinous Mucinous metaplasia Arias-Stella reaction Endometrial polyp Endometrial hyperplasia Mullerian adenosarcoma 



The author thanks Dr. Philip B. Clement who offered constructive criticism of the manuscript that was most helpful.

Compliance with ethical standards

Ethics approval

Ethics approval is not applicable to review article.

Conflict of interest

The author declares that there is no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PathologyThe University of Hong KongPok Fu LamHong Kong SAR

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