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Hertig and Beyond: A Systematic and Practical Approach to the Endometrial Biopsy

Crum, Christopher P. MD; Hornstein, Mark D. MD; Nucci, Marisa R. MD; Mutter, George L. MD

Advances in Anatomic Pathology: November 2003 - Volume 10 - Issue 6 - pp 301-318
Review Articles

Evaluation of the endometrial biopsy is a challenge to practicing pathologists, largely due to the wide range of morphologic patterns resulting from both normal and abnormal cyclic changes, exogenous hormones, infections, and intrauterine tumors. Successfully addressing these challenges requires that the practitioner (i) understand the clinical questions being asked, (ii) have a realistic expectation for answering these questions, and (iii) have a systematic approach to resolving these questions in the context of these expectations. The approach outlined begins with the subdividing of women with endometrial alterations into three general categories: (i) women in their fourth decade undergoing evaluation for infertility, (ii) women in their fifth decade who experience abnormal uterine bleeding, and (iii) women in their sixth decade and beyond who experience postmenopausal bleeding. The clinical expectations for each group are unique, as are the morphologic patterns most commonly encountered. Algorithms for the laboratory management of cyclic changes, dysfunctional bleeding, and mixed-pattern endometria are provided, as are pitfalls in interpretation and exclusion of neoplasia.

In 1950, Noyes, Hertig, and Rock 1 published the first comprehensive treatise on evaluating the endometrial cycle. This work reflected their keen interest in reproductive biology and took advantage of a repository of pathologic material derived from women whose cycles they had meticulously documented. Since this sentinel work was published, major advances in the understanding of the menstrual cycle have been made including the identification of specific entities, the recognition of which are essential to reproductive care.

Pathologists routinely evaluate endometrial biopsies, which account for at least 20% of gynecologic specimens requiring pathology consultation. However, the clinically relevant questions that should be answered or clinical information necessary to assess the question at hand varies for each individual case (Table 1). For women of reproductive age seeking to bear children, the principal question is whether ovulation occurred and if so, if the luteal phase has progressed normally. Addressing the latter issue may entail determining (i) if the cycle day of the endometrium appears normal and (ii) has an appearance that is consistent with a cycle day that is at least 2 days earlier than expected based upon the patient's last menstrual period. Alternatively a conspicuous disturbance in secretory maturation may be present (ie, the glands and stroma appear discordant enough with respect to the cycle day to warrant intervention). For women in their fifth decade, the questions are typically focused on causes of unscheduled (intermenstrual bleeding), unusually heavy uterine bleeding (metrorrhagia), or both (menometrorrhagia) rather than nuances of ovulation. In the six and seventh decades, the questions shift to causes of bleeding in patients receiving hormonal replacement therapy, or if the patient is not receiving hormones, other causes of unexpected bleeding, particularly the possibility of a neoplastic process.

Several excellent chapters are available on the interpretation of benign endometrium; this literature introduced improvements in the original scheme put forth by Noyes et al. 2,3 Nevertheless, the wide range of alterations seen in the endometrium during reproductive and menopausal years poses a challenge to many practitioners. This review proposes a framework on which to superimpose the histologic images that are encountered when reviewing the endometrial biopsy. The goal of this review is to provide 3 overlapping templates to facilitate interpretation of the endometrium, including age group, diagnostic categories, and pitfalls in interpretation.

From the Division of Women's and Perinatal Pathology, Department of Pathology, and the Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Reprints: Christopher P. Crum, Department of Pathology, Brigham and Women's Hospital, Boston, 75 Francis St., Boston, MA 02115 (e-mail:

© 2003 Lippincott Williams & Wilkins, Inc.