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11/1/2019

Interpretation of benign endometrial biopsy report when evaluating abnormal uterine bleeding

The primary role of endometrial sampling is to ascertain existence of premalignant or malignant intrauterine pathology; however, further information can be gained from reviewing pathology results in the clinical setting of abnormal uterine bleeding (AUB).  Endometrial biopsy (EMB) is recommended for AUB in patients >45 years of age, younger patients with significant risk factors for endometrial intra-epithelial neoplasia (EIN)  or cancer, and patients with postmenopausal bleeding.

An adequate endometrial biopsy specimen contains both glandular and stromal tissue and has a high accuracy for detecting diffuse endometrial processes, even though only a small portion of the endometrium is sampled.  The detection rate for endometrial cancer is approximately 99.6% in postmenopausal patients, 91% in premenopausal patients, and 81% for EIN. An “insufficient” EMB result should always be viewed cautiously, especially in the setting of persistent postmenopausal bleeding. Approximately 20% of postmenopausal patients have endometrial pathology discovered during a secondary investigation following an insufficient or non-diagnostic initial EMB with as many as 3% of those patients having cancer.

The sensitivity of EMB is influenced by the lesion type and size, presence of uterine malformation or scarring, endometrial surface area, and number of lesions present. Endometrial lesions that are diffuse, multiple, and larger are more likely to be detected than a smaller, isolated lesion, such as a polyp. Scar tissue or synechiae (post-ablation or curettage) or fibroids that distort or enlarge the endometrial cavity may make obtaining a representative endometrial sample more difficult. History, physical findings, and clinical suspicion must be correlated with the EMB result, especially when an unexpected benign result is reported.

EMB results can reveal important information regarding the menstrual cycle. Proliferative endometrium indicates the follicular phase; whereas, secretory endometrium indicates luteal phase. The last menstrual period should be correlated with EMB results. Disordered or dyssynchronous endometrium suggests ovulatory dysfunction. A result of disordered or crowded glands is common with anovulatory cycles due to prolonged estrogen stimulation without postovulatory progesterone exposure. Use of contraceptive steroids or other hormones can cause alterations, such as decidual change or endometrial gland atrophy.

Secretory endometrium in a patient reporting menopausal symptoms would suggest she is not yet menopausal. A benign, proliferative EMB result in a postmenopausal patient suggests excess estrogen.  This can result from several sources including exogenous hormones taken as hormone replacement therapy, dietary supplements, peripheral conversion of normal levels of androgens by adipose tissue or an ovarian lesion that stimulates ovarian androgen production.

Endometrial polyps can be diagnosed by an EMB revealing endometrial glands and stroma with a central vascular channel. Most polyps are benign.  Removal is recommended for postmenopausal patients.  For patients not yet menopausal, observation may be an option but removal is usually preferred in the setting of AUB or in patients with risk factors for EIN. The glandular epithelium of a polyp is often dyssynchronous from the adjacent endometrium.

An EMB revealing plasma cells within the endometrial stroma suggests chronic endometritis which can cause AUB; whereas, lymphocytes are commonly found in normal endometrial tissue. Many cases of chronic endometritis have no known infectious etiology but respond to antibiotic treatment. Acute endometritis usually has physical examination findings and is often preceded by PID, STD, or an invasive gynecologic procedure; EMB often detects the abnormal presence of neutrophils within the endometrial glands.

Benign, premalignant, and malignant EMB results can be diagnostic and helpful in the clinical management of patients especially when used in conjunction with the entire clinical scenario.

 

Further Reading:

American College of Obstetricians and Gynecologists. Committee on Practice Bulletins—Gynecology; Practice bulletin no. 136: management of abnormal uterine bleeding associated with ovulatory dysfunction. Obstet Gynecol. 2013 Jul;122(1):176-85. doi: 10.1097/01.AOG.0000431815.52679.bb.

Dijkhulzen, FP, Mol, BW, Brolmann, HA, Heintz, AP. The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer. 2000 Oct 15;89(8):1765-72.

Silverberg, SG. The endometrium. Arch Pathol Lab Med. 2007 Mar;131(3):372-82.

Initial Approval September 2019, Minor revision May 2021.  Reaffirmed March 2023.

 

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