Atlas of Uterine Pathology

By Oluwole Fadare and Andres A. Roma

This Atlas of Uterine Pathology is comprehensive overview of the major pathologic processes that may be encountered in the uterine corpus and cervix. Each section is lavishly illustrated and covers normal histology as well as neoplastic and non-neoplastic diseases. Emphasis is placed on presenting the full morphologic and immunophenotypic spectrum of entities, including classical and variant pathology, in a manner that maximizes the utility of the information in routine diagnostic practice.

• Language: English
• Publisher: Springer
• Release date: Jun 20, 2019
• ISBN: 9783030179311

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© Springer Nature Switzerland AG 2019

O. Fadare, A. A. RomaAtlas of Uterine PathologyAtlas of Anatomic Pathologyhttps://doi.org/10.1007/978-3-030-17931-1_1

1. Normal Histology of the Uterine Corpus

Oluwole Fadare¹   and Andres A. Roma¹

(1)

University of California, San Diego, La Jolla, CA, USA

Keywords

Normal histology of endometriumMenstrual cycleBlood vessels of uterusInflammatory cells of endometriumArtifacts of endometrial biopsy

1.1 Embryology and Normal Anatomy of the Uterine Corpus

The uterus is the fusion product of the embryologic paramesonephric (müllerian) ducts. By the second trimester, the endometrial lining is composed of columnar epithelium with surface ciliation, abundant nuclear pseudostratification, and occasional mitotic figures. The epithelium is mostly flat but may show undulations and gland-like invaginations into the underlying mesenchyme, in which a vague layering is often morphologically discernible (Figs. 1.1, 1.2, 1.3, 1.4, and 1.5).

The adult, non-gravid uterus is a pear-shaped structure that measures 7–9 cm on average along its long axis (Figs. 1.6 and 1.7). The caudal third of the uterus represents the cervix, and the proximal two thirds is the corpus [1–4]. The portion of the corpus cephalad to a line connecting the two fallopian tube origins is called the fundus . The body—the portion of the uterine corpus caudal to the same line—tapers into a lower uterine segment or uterine isthmus, which in turn is in continuity with the cervix. The uterine body is anteflexed on the cervix and the whole uterus is tipped slightly forward (anteversion). The hollow center of the uterus is a triangular space whose lining is continuous with the fallopian tube mucosa at the bilateral tubal cornu, and with the endocervical mucosa caudally. The endometrial cavity is lined by endometrium (comprising endometrial epithelium, endometrial mesenchyme, and vessels) and is surrounded by a myometrium composed of smooth muscle, vessels, and other mesenchymal elements. The myometrium comprises bundles of woven smooth muscle, which are arranged in two or three somewhat distinct layers, although this layering is not always clearly discernible. The outer portions of the myometrium are in continuity with the outer musculature of the fallopian tube, cervix, and vagina. The uterine musculature has a larger component of collagenous tissue at the level of the internal os and distally.

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Fig. 1.1

Uterus at 18 weeks . Note the central epithelium-lined uterine canal surrounded by uterine mesenchyme

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Fig. 1.2

Uterus at 22 weeks . The endometrial lining shows surface undulations and gland-like invaginations. Even at term, the endometrial lining is often simple and is devoid of the complex glandular architecture that may be encountered in the adult endometrium

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Fig. 1.3

(a, b) Uterus at 18 weeks . Endometrial epithelium shows ciliation and abundant pseudostratification. The surrounding mesenchyme shows vague layering and increased cellularity. Smooth muscle differentiation is demonstrable in the uterine mesenchyme at this stage

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Fig. 1.4

Uterine mesenchyme at 23 weeks . A muscular layer is well developed. An outer layer (lower field) and inner layer are discernible. The endometrium epithelium is seen in the upper right field

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Fig. 1.5

Myometrium in the second trimester . There is more cellularity than in the adult myometrium, and there is significantly less fascicular arrangement of cells

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Fig. 1.6

Primary components of the uterus

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Fig. 1.7

The anterior surface of the uterus (left) can be distinguished from the posterior surface (right) based on the fact that the anterior surface has a larger area that is devoid of peritoneal lining than the posterior, in its lower component. Additionally, the stump of the round ligament is anteriorly directed

1.2 Uterine Vasculature

The immediate arterial supply of the uterus comprises the right and left uterine arteries, which are subsidiaries of the internal iliac arteries [5, 6]. At the level of the uterine isthmus, the uterine artery on each side bifurcates into two branches, whose subsidiaries include the circumferentially arranged arcuate arteries, their myometrium-penetrating branches (radial arteries), basal branches of radial arteries, and ultimately, the spiral arterioles that terminate in the endometrium (Figs. 1.8, 1.9, 1.10, 1.11, and 1.12). Spiral arteries are hormone-sensitive, and their pericytes have been shown to be estrogen- and progesterone-receptor positive. The venous drainage of the uterus is largely comparable.

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Fig. 1.8

Uterine arteries . Thick-walled vessels of the outer myometrium include the lateral perforating branches of the uterine artery, from which branch the arcuate artery and then the radial arteries. These arteries not infrequently show atherosclerosis and calcification

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Fig. 1.9

Uterine arteries . Comparing this specimen to Fig. 1.8 highlights the fact the relative thickness and prominence of myometrial vessels may vary significantly between patients

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Fig. 1.10

Uterine arteries . Arteries at the endometrial basalis and at the myometrial/endometrial interface may also be prominent and notably clustered. These are basal branches of the radial arteries

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Fig. 1.11

Uterine arteries . Arterioles may occasionally be clustered in the endometrial functionalis; this is a clinically insignificant variation

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Fig. 1.12

Uterine arteries . Clustered arterioles in the functionalis at high magnification

1.3 Inflammatory Cells of the Endometrium

Leukocytes represent about 10–25% of all endometrial cells, and they vary in number and distribution during the menstrual cycle [7–9] (Figs. 1.13, 1.14, 1.15, 1.16, 1.17, 1.18, 1.19, 1.20, 1.21, 1.22, 1.23, 1.24, 1.25, 1.26, 1.27, 1.28, 1.29, 1.30, 1.31, 1.32, 1.33, 1.34, and 1.35). Table 1.1 summarizes the full distribution of inflammatory cells that may be encountered in the endometrium [8, 9]. Scattered lymphoid aggregates are essentially a normal finding, typically present in the stratum basalis (Fig. 1.32). However, the presence of large numbers of lymphocytic aggregates has been associated with chronic endometritis. There is some evidence that in the setting of chronic endometritis, there is a change in the distribution and ratio of lymphocytic subpopulations. Neutrophils are commonly present when the menstrual phase is well developed, typically around day 2 of the cycle [9, 10] (Fig. 1.35). Plasma cells may be associated with breakdown and menstruation, but may be pathologic when seen in significant populations outside of these settings.

Table 1.1

Relative distribution of inflammatory cells in the functional endometrium at three specific points of the normal menstrual cycle

Adapted from Salamonsen and Lathbury [8]; with permission

NK Natural killer

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Fig. 1.13

The endometrium is composed of a functional layer (stratum functionalis) and a basal layer (stratum basalis). The functional layer is generally of greater volume than the basal layer , especially in cycling, premenopausal patients. The functional layer shows significantly greater sensitivity to endogenous and exogenous hormones than the basal layer

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Fig. 1.14

The stratum functionalis in the secretory phase can be classified into a superficial compact layer (stratum compactum) and a deep spongy layer (stratum spongiosum), but in the early and mid parts of the secretory phase, as shown here, the stratum compactum is not apparent

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Fig. 1.15

The stratum compactum is the sub-surface epithelial zone that has the appearance of comprising mostly confluent predecidualization. The stratum spongiosum is the deeper zone of serrated glands. The stratum compactum/spongiosum layering is seen in the late secretory phase

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Fig. 1.16

The stratum basalis in a patient who has been treated with exogenous progestins. Even in this setting, the stratum basalis frequently shows less hormonal responsiveness than the stratum functionalis. In the second half of gestation, however, or after prolonged treatment with progestins, the stratum basalis may show alterations consistent with hormone responsiveness, including complete stroma precidualization/decidualization

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Fig. 1.17

Stratum basalis . The stroma typically appears more compact and cellular than the stratum functionalis with which it is associated. The stroma may also be spindled, especially near the myometrial/endometrial interface

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Fig. 1.18

Stratum basalis . Clusters of vessels are commonly present, representing the basal branches of the myometrial radial arteries

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Fig. 1.19

(a, b) Stratum basalis in a biopsy specimen. The stroma of the stratum basalis fragment is often distinct because of its increased stromal cellularity compared with the stratum functionalis fragments. The glands of the basalis are often simple or branched tubular glands lined with nonsecretory, pseudostratified cells with basophilic chromatin; mitotic figures are rare. The glands in the stratum basalis may show slight dilatation, which is most likely either a secretion retention or an atrophic phenomenon. Another feature that may be seen in the basalis is one or more lymphoid aggregates

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Fig. 1.20

(a, b) Stratum basalis in a biopsy specimen. The glands of the stratum basalis may display more dilatation than the glands of the stratum functionalis. This finding should not be mistaken for an anovulatory pattern (disordered proliferative endometrium). The concurrent presence of increased stromal spindling and cellularity are useful morphologic features that support the interpretation that the fragment that displayed such glands represents stratum basalis

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Fig. 1.21

(a, b) Surface epithelium overlying proliferative pattern endometrium. The surface epithelium is continuous with the underlying glands, but generally shows less cyclic variation. The epithelium is lined by cells that are columnar, variably pseudostratified, and frequently ciliated

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Fig. 1.22

(a, b) Surface epithelium overlying early secretory pattern endometrium. The surface epithelium shows less secretory change than the underlying glands. This dissonance is more appreciable in the early parts of the secretory phase

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Fig. 1.23

Surface epithelium overlying mid secretory pattern endometrium. The surface epithelium more closely resembles the underlying glands, with which it is contiguous

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Fig. 1.24

(a, b) The uterine isthmus (lower uterine segment) shows significantly reduced responsiveness to hormones, compared with the uterine corpus. Accordingly, the functional state of the lower uterine segment endometrium should not be used as an indicator for the functional state of the entire endometrium. The glands are typically lined by weakly proliferative columnar glands with prominent ciliation. The stroma is more spindled, more collagenous, and generally less cellular than the endometrial stroma in the upper uterine corpus

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Fig. 1.25

Endometrial epithelium . Proliferative-type glands are lined by cells with fusiform nuclei, variably dense chromatin, and inconspicuous nucleoli. During the proliferative phase, mitotic figures are easily identifiable in such glands in the stratum functionalis, and the nuclei appear to be pseudostratified

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Fig. 1.26

Endometrial epithelium . Proliferative-type glands frequently show ciliation. Ciliated cells are commonly identified in the surface epithelium and underlying endometrial glands, especially towards the cornu and the cervix. Ciliated cells become more prominent in conditions associated with estrogen excess

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Fig. 1.27

Endometrial epithelium . Clear cells (such as the one at the 9 o’clock position) are characterized by round nuclei and clear cytoplasm; they often have a cytoplasm diameter that appears to be significantly wider than adjacent non-clear cells. These cells are significantly less common than ciliated cells, but are almost invariably identified in association with the latter and are thought to be their precursors. Clear cells also show a more specific association with conditions of estrogen excess than ciliated cells

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Fig. 1.28

Endometrial epithelium . Secretory cells vary in appearance depending on the day of the menstrual cycle, as described in detail in subsequent sections

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Fig. 1.29

Endometrial stroma . The endometrial stroma in the proliferative phase comprises round to fusiform cells with scant cytoplasm, dense chromatin, and inconspicuous nucleoli. Mitotic activity is prominent during the proliferative phase

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Fig. 1.30

Endometrial stroma . At various points during the cycle, the endometrial stroma shows prominent interstitial edema, giving the cells a dispersed appearance

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Fig. 1.31

Endometrial stroma . Later in the menstrual cycle, the endometrial stroma shows increased eosinophilic cytoplasm, poorly defined cell membranes, nuclei with more vesicular chromatin, and variably discernible nucleoli. These changes define stroma pseudodecidualization or predecidualization [10]. Similar changes associated with pregnancy are termed decidualization

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Fig. 1.32

(a, b) Endometrial lymphocytes . Aggregates of lymphocytes are a common (and essentially normal) finding in the endometrium. They are more commonly identified in the stratum basalis than in the stratum functionalis

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Fig. 1.33

Endometrial foam cells show abundant vacuolated cytoplasm and oval or bean-shaped nuclei. They are associated with conditions of estrogen excess, such as endometrioid carcinomas and hyperplasias, but they are nonspecific and may be seen in other conditions, such as xanthogranulomatous endometritis. Various authors think them to be of either histiocytic origin or stromal origin

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Fig. 1.34

Stromal granulocytes (also known as granular/granulated lymphocytes, K cells, large granular lymphocytes, endometrial granulocytes, or decidual granulated lymphocytes) are present in large populations during the last days of the menstrual cycle. Stromal granulocytes display eosinophilic cytoplasmic granules; small, somewhat lobulated hyperchromatic nuclei; and a CD3−CD56brightCD16− phenotype. This phenotype distinguishes them from the natural killer (NK) cells of the peripheral blood, wherein CD56 expression is dim. These cells should not be mistaken for neutrophils

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Fig. 1.35

Neutrophils are commonly present when the menstrual phase is well developed, typically around day 2 of the cycle

1.4 Histology of the Premenopausal Endometrium During the Menstrual Cycle

The menstrual cycle during the reproductive years has traditionally been classified into proliferative (preovulatory/ovarian follicular) and secretory (postovulatory/ovarian luteal) phases, to which menstrual and interval phases may be added [1–5] (Figs. 1.36, 1.37, 1.38, 1.39, 1.40, 1.41, 1.42, 1.43, 1.44, 1.45, 1.46, 1.47, 1.48, 1.49, 1.50, 1.51, 1.52, 1.53, 1.54, 1.55, 1.56, 1.57, and 1.58). The proliferative phase accounts for most of the observed interpatient variability in the length of the menstrual cycle.