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Department of Pathology, Sinai Hospital of Baltimore Pathology, Baltimore, MD, USA
Keywords
EndometriumMyometriumInfertilityPregnancyLeiomyomaSerousEndometrioidThe endometrium is a cycling glandular and stromal layer overlying the myometrium of the uterus . The appearance varies widely across different phases of the menstrual cycle, pregnancy, and menopause. Common reasons for performing an endometrial biopsy include the following:
Abnormal vaginal bleeding
A “thickened endometrial stripe” found on ultrasound, suggesting hyperplasia or carcinoma
Part of an infertility workup
Follow-up study for women with a history of hyperplasia who have been conservatively treated with hormones
The reason for the biopsy will influence your approach to the slide. Regardless of history, start by differentiating between atrophic, inactive, proliferative, secretory, and hormone-treated endometrium. On low power, survey the epithelium to get a feel for the glands and stroma:
Atrophic endometrium (typically postmenopausal) has a low gland-to-stroma ratio, and the glands are thin, with an almost cuboidal epithelium, and no mitoses. In biopsy specimens, they tend to come off in thin strips that look like hair pins (Figure 17.1).
Figure 17.1.
Atrophic endometrium . When curetted, the epithelium typically comes off in thin strips resembling hairpins (arrow). The specimen is also scant.
Proliferative endometrium has a fuller, blue look to the stroma and a gland-to-stroma ratio of about 1:1. The glands are simple tubular structures that stand out as dark blue “donuts” with pseudostratified nuclei (slight variation in nuclear location, but predominantly basal) and columnar epithelium (Figure 17.2). Mitoses should be readily visible in the glands. A similar architecture with an absence of mitoses indicates an inactive endometrium.
Figure 17.2.
Proliferative endometrium . Multiple donut-shaped glands are visible, with dark oblong nuclei and frequent mitoses (arrow).
Secretory endometrium has prominent spiral arterioles and variably edematous stroma so that the stromal cells look like naked nuclei floating in water. The glands are notable for cytoplasmic secretory vacuoles and secretions in the lumen (Figure 17.3). Late-cycle secretory stroma begins to get decidualized (acquires pink cytoplasm), and the glands lose their vacuoles and show low cuboidal pink cells, ragged luminal edges, and a tortuous spiral shape. You should not see mitoses in secretory glands.
Figure 17.3.
Secretory endometrium , various phases. (a) In early secretory endometrium, the glands have become tortuous in shape, and prominent cytoplasmic vacuoles are present (subnuclear, in this example; arrow). (b) Later in the secretory phase, the cytoplasmic vacuoles are gone, and the epithelium is more cuboidal in shape, with small round nuclei (arrow). The stroma is edematous, and early decidualization (accumulation of pink cytoplasm) is beginning around the spiral arteries (arrowhead).
Progestin-treated endometrium , like gestational endometrium, has a very decidualized stroma (plump pink cells with visible cytoplasm) but is paired with attenuated, flattened gland epithelium (Figure 17.4). These changes are due to the unopposed progesterone exposure. Unopposed estrogen, on the other hand, has a proliferative effect and tends to promote hyperplasia or carcinoma. Tamoxifen, paradoxically, acts as an estrogen agonist in the endometrium.
Figure 17.4.
Progestin-treated endometrium . The glands are still tortuous in shape, like secretory endometrium, but the epithelium is markedly thinned (arrow). The stromal cells are decidualized (arrowhead), which means they have plump pink cytoplasm and distinct cell borders.
Why are the endometrial characteristics important? Secretory endometrium, almost by definition, is not hyperplastic. Once you have identified secretory phase, you (usually) do not need to agonize over crowded glands. Because progesterone pushes the endometrium toward secretory change, it is used as treatment for hyperplasia; if you can prod the endometrium to complete the cycle and shed, the hyperplasia may go away.
Next, within the biopsy fragments, look for possible causes of bleeding:
Benign endometrial polyp : Benign endometrial polyps are composed of fibrotic (pink and spindly) stroma, thick-walled vessels, and usually nonfunctional (atrophic) and/or cystically dilated glands (Figure 17.5).
Figure 17.5.
Benign endometrial polyp . This polyp shows cystic dilation of glands (1), secretory-type epithelium (2), and thickened arteries (3). The stroma is also pink, indicating a high collagen content.
Endometrial stromal breakdown : At the end of the secretory phase, the stroma takes on a blurry blue look as it condenses into small dense aggregates (“blue balls”). The associated surface epithelium shows eosinophilic metaplasia, becoming almost oncocytic in appearance. Fibrin thrombi in vessels and neutrophils are also common features (Figure 17.6). The background endometrium may be end-secretory (in normal menstrual bleeding) or proliferative (in dysfunctional bleeding).
Figure 17.6.
Endometrial stromal breakdown . The stroma is condensed into an extremely blue mass of tightly packed cells (arrow). The overlying epithelium is expanded into papillary tufts of pink cells, some with cilia, which is a metaplastic change (arrowhead).
Endometritis : The diagnosis of acute endometritis requires microabscesses and epithelial destruction; the presence of neutrophils alone may just indicate normal menstrual breakdown. Chronic endometritis is diagnosed by the presence of plasma cells, which are not found in normal endometrium. In general, the stroma takes on a blue spindly look, and there are increased numbers of lymphocytes; these features should prompt you to crawl around at 20× looking for plasma cells (Figure 17.7).
Figure 17.7.
Chronic endometritis . At low power, the diagnostic plasma cells are not visible, but the spindly, swirling blue stroma (arrow) should be a clue to look more closely. The epithelium here is proliferative (arrowhead).
Disordered proliferative endometrium : This is a diagnosis used when there is some glandular crowding that falls short of a diagnosis of hyperplasia. It is a mixture of cystically dilated, budding, and tubular glands in a proliferative setting. It typically occurs during anovulatory cycles.
Atrophy : Atrophy, described earlier, is responsible for about half of all cases of abnormal postmenopausal bleeding.
Hyperplasia
Hyperplasia is defined as an increase in the gland-to-stroma ratio, and you will notice it as “crowded glands” in a proliferative setting (Figure 17.8). Endometrial hyperplasia has been classified as simple vs. complex and atypical vs. non-atypical, but it appears to be only the presence of atypia that has prognostic significance, so it is acceptable (and easier) to simply classify it as either hyperplasia without atypia or atypical hyperplasia. The terms dysplasia and carcinoma in situ are not applied to endometrium.
