Uterus

Myometrium has rich network of blood vessels; arteries are sometimes found within dilated venous channels, AJSP 2002;26:232; myometrium is PLAP positive

Before puberty: endometrial tissue is inactive and composedof tubular glands, dense fibroblastic stroma, thin bloodvessels

After menopause: inactive (no proliferation or secretion), thin, often with cystic cavities lined by flat or cuboidal cells, fibrotic stroma

Normal uterus: anterior; posterior; secretory endometrium

Micro: may have lymphoid follicles

Micro images: normal endometrium and cyclin D1 (figures 1A/1B)

AFIP images: early proliferative phase #1 - small, round, regular glands are widely separated by a stroma without edema, which contains small, regularly distributed blood vessels; #2 - (same patient) glands have slight pseudostratification, occasional mitotic figures, and a few clear cells; the stromal cells are uniform and small, with round-to-ovoid nuclei and occasional mitotic figures

Anatomical divisions of uterus

Fundus: cephalad to line connecting the insertion of fallopian tubes

Cornua: lateral regions of fundus associated with intramural fallopian tubes

Isthmus/lower uterine segment: portion of corpus connecting with cervix

Cervix: lower 1/3 of uterus; at and below level of internal cervical os

Uterine cavity: 6 cm long, triangular shape, lined by endometrial mucosa / endometrium, then myometrium, then serosa, which extends to peritoneal reflection

Basalis layer is retained; functionalis layer (superficial 1/2 to 2/3) is shed monthly

Functionalis is divided into spongiosum (near basalis) and compactum (near surface)

Stroma is composed of stromal cells, vessels, stromal granulocytes (T cells, macrophages), foamy cells

Drains to parametrial, paracervical, internal iliac, external iliac, common iliac, periaortic and inguinal lymph nodes

Note: menstruating tissue is replaced by cells from basalis, isthmus and ostio of tubes

Bifid uterus

Gross images: image1

ENDOMETRIUM, LATE PROLIFERATIVE PHASE

This endometrium from day 10-12 shows glands that are more tortuous and crowded than those in figure 2. Intraglandular nuclear pseudostratification and mitotic activity are more prominent (see inset) and the stroma is edematous and mitotically active.

ENDOMETRIUM, EARLY SECRETORY PHASE
In this illustration, the glands exhibit a regular tortuosity and are clearly oriented from the base to the surface of the endometrium. Subnuclear glycogen vacuoles are clearly visible at this magnification.

ENDOMETRIUM, EARLY SECRETORY PHASE
The glands of this day-17 endometrium contain prominent subnuclear glycogen vacuoles underlying a single row of nuclei in the endometrial glands.

ENDOMETRIUM, MIDSECRETORY PHASE
These regularly tortuous glands in this day-20 endometrium contain secretions that are largely intracellular apical, and partially intraluminal.

ENDOMETRIUM, LATE SECRETORY PHASE
In this endometrium from day 23-24, the glands are beginning to show regressive changes. Spiral arterioles are present and are most prominent in the lower left portion of the illustration. They are beginning to be surrounded by cuffs of predecidua. Predecidual stromal change is not yet apparent in the superficial compacta.

ENDOMETRIUM, LATE SECRETORY PHASE
The glands of this day-25 endometrium are markedly regressed, and the superficial compacta has a diffusely predecidualized stroma.

ENDOMETRIUM, LATE SECRETORY PHASE
This high-power photomicrograph of a day-25 endometrium shows a spiral arteriole cut in multiple profiles and surrounded by predecidual stroma. Note the admixture in the stroma of large decidualized cells and smaller endometrial granulocytes.

MENSTRUAL ENDOMETRIUM
This low-power photomicrograph shows the typical fragmentation, stromal collapse, and the bloody necrotic background of a menstrual specimen.

MENSTRUAL ENDOMETRIUM
This photomicrograph shows the balls of endometrial stroma that, taken out of context, are occasionally mistaken for endometrial carcinoma or sarcoma.

LYMPHOID AGGREGATE IN PROLIFERATIVE ENDOMETRIUM

This is a normal finding and should not be interpreted as evidence of endometritis.

PROLIFERATIVE ENDOMETRIUM
This is an example of a proliferative endometrium with artifactual changes secondary to curettage, which was misinterpreted as endometrial hyperplasia. The glands in this field are neither architecturally irregular nor cystically dilated. The ratio of glands to stroma is about normal for a midproliferative endometrium, and a general orientation of the glands from upper left to lower right is noteworthy.

Persistent mullerian duct syndrome – Uterus chapter

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Rare form of male pseudohermaphroditism caused by lack of regression of Mullerian ducts in phenotypically and genotypically male individuals

Mullerian ducts normally regress in male fetus at 8 weeks due to anti-Mullerian hormone (AMH), which binds to anti-Mullerian type 2 receptor, causing disappearance of Mullerian ducts at 10 weeks of fetal age; mutations of either AMH or receptor block duct regression

<200 cases described in English literature

Usually associated with unilateral cryptorchidism and contralateral hernia

Rarely is bilateral cryptorchidism, pelvic uterus, 2 testes embedded in broad ligament

Associated with testicular germ cell tumors

Case report: clear cell adenocarcinoma of remnant uterus in clinically normal 67 year old man, AJSP 2002;26:1231

Dating of endometrium – Uterus chapter

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To date endometrium, should see surface endometrium, but date based on most advanced area

Must biopsy uterine corpus above the level of the isthmus; must also biopsy functionalis as basalis layer does not respond to progesterone

Dating has low interobserver agreement

Difficult to date in patient with IUD or on hormones or if endometrium is non-uniform

Proliferative phase

Length varies from 10-20 days, “ideal” is 14 days; during this phase, glands become more tortuous due to epithelial proliferation, in response to estrogen production and estrogen receptors on epithelium

Early proliferative (days 4-7): thin surface epithelium, straight short glands, compact stroma, minimal mitotic activity, large nuclei

Micro image: image1

Mid proliferative (days 8-10): columnar surface epithelium; longer curving glands, variable stromal edema, numerous mitotic figures

Late proliferative (days 11-14): undulant surface epithelium, tortuous glands with prominent mitotic activity and pseudostratification; dense stroma, subnuclear vacuoles in less than 50% of glands

Ovulation: presence of subnuclear vacuoles in 50% of glands is evidence of ovulation; must biopsy functionalis layer, not basal layer

To rule out anovulatory cycles, should biopsy 2 days before menstruation

Secretory/luteal phase

Traditionally assumed to be 14 days, but may vary

Progesterone secretion inhibits endometrial proliferative active and induces secretory activity

Note: secretory material in glands is NOT specific for secretory epithelium; seen also in disordered proliferative and hyperplastic endometrium and carcinoma

Gross: lush, polypoid, no necrosis; may be hemorrhagic if close to day 28

Day 15: no changes from late proliferative; aka interval endometrium; presence of scattered nuclear vacuoles is NOT specific for ovulation (must be 50% or mor)

Days 16-17 - “piano key” appearance; subnuclear vacuoles (day 16), vacuoles at level of nuclei (day 17)

Micro image: image1

Day 18: luminal vacuoles, smaller size, nuclei approach base of cell

Day 19: intraluminal secretion begins

Days 20-21: maximal secretion

Micro image: image1

Day 22: maximal stromal edema in luteal phase; best time for implantation (“day 22, I'm ready for you”)

Day 23: prominent spiral arterioles (thickened walls, coiling, endothelial proliferation)

Day 24: perivascular pre-decidualization (stromal cell hypertrophy with accumulation of cytoplasmic eosinophilia); serrated / tortuous glands

Day 25: predecidualization below surface endometrium

Day 26: confluence of predecidual tissue; stromal granulocytes (probably lymphocytes) appear

Day 27: prominent stromal granulocytes; focal necrosis and hemorrhage

Day 28: prominent necrosis and hemorrhage, aka shedding (glandular and stromal breakdown); predecidual stroma and glandular exhaustion; nuclear dust at base of glandular epithelium; condensed stroma with overlying papillary-syncytial change; intravascular fibrin thrombi; stromal granulocytes

Note: don’t confuse shedding (nuclear crowding, squamoid appearance, focal cytoplasmic acidophilia) with malignancy

Note: shedding in perimenopausal women with bloody background is consistent with anovulatory cycle

Note: endometrial tissue within vessels does not imply malignancy

Dyssynchronous endometrium

Glands and stroma out of synchronization by at least 2 to 3 days

Luteal phase defect – Uterus chapter

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Due to inadequate progesterone production

Associated with infertility and spontaneous abortions

Lag of histologic endometrial date of 3+ days from actual post-ovulatory date (some say 2+ days)

Must be found in 2 consecutive cycles to be clinically significant

Meaning of this diagnosis has been questioned due to substantial variability present in late luteal phase of menstrual cycle, the usual time to obtain an endometrial biopsy

Micro: either immature endometrium or persistence of proliferative changes; may see dyssynchronous endometrium (dissociation between endometrial glands and stroma)

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Similar changes seen with intrauterine pregnancy, ectopic pregnancy, progesterone therapy

Arias-Stella reaction – Uterus chapter

Exaggerated gestational hyperplasia; endometrial glands are enlarged with abundant clear or eosinophilic cytoplasm and marked nuclear changes (large, hyperchromatic, pleomorphic, smudged) with rare mitotic figures; decidualized stroma; changes usually focal, may occur in cervix, endocervical polyps, adenomyosis, endometriosis, post- abortion curettings (20-70%), pregnancies, moles, choriocarcinoma (endometrial nuclei may be gigantic in moles and choriocarcinoma)

DD: clear cell carcinoma (post-menopausal so not pregnant, mitotic figures, coarsely granular chromatin, no decidual reaction unless patient on progesterone), in situ endometrial carcinoma

Decidua – Uterus chapter

Bland nuclei, minimal atypia, abundant cytoplasm

Gestational hyperplasia – Uterus chapter

Gross: lush decidua; placental fragments; gestational sac

Micro: early - prominent glandular secretion, stromal edema and predecidual reaction, all simultaneous; implies fertilized ovum has implanted

later - glands are tubular, not coiled; glandular cells have inclusion-like cleared chromatin resembling HSV infection (see below); may see intermediate trophoblasts or villi

DD: late secretory changes in cycling endometrium

Placental site nodules – Uterus chapter

Aka implantation site reaction

Usually regresses after delivery or abortion

Micro: numerous extravillous (intermediate) trophoblasts, with large, atypical nuclei arranged in a syncytium, often with mitotic figures, that may invade blood vessels (to keep them patent during pregnancy); also cytotrophoblasts and syncytiotrophoblasts; chronic inflammatory cells

Positive stains: hPL (intermediate trophoblasts), hCG (syncytiotrophoblasts, cytotrophoblasts)

DD: leiomyosarcoma, placental site trophoblastic tumor (large masses of intermediate trophoblasts, no villi), choriocarcinoma (laminar pattern of syncytiotrophoblasts and cytotrophoblasts with extensive hemorrhagic necrosis, no villi)

Viral-like inclusions – Uterus chapter

Optically clear nuclei, resembling viral inclusions, present during pregnancy

Due to replacement of chromatin by fine filamentous network that is biotin immunoreactive

Fetus 10th week of pregnancy

Fetus within uterus.

Gestational endometrium

Stark glands increased with hoses star Lumina.

Gland-like buds with Epithelaussprossungen. The cells bear round basalständige nuclei. In the apical cytoplasm Sekretvakuolen. The stromal-left corner of the picture are dezidualisiert.

Gland-like buds with Epithelaussprossungen. The cells bear round basalständige nuclei. In the apical cytoplasm Sekretvakuolen. The stromal-left corner of the picture are dezidualisiert with abundant cytoplasm and sharp cell borders.

Endometrial curettage and biopsy – Uterus chapter

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D & C (dilatation and curettage) and endometrial biopsy are methods of choice for sampling localized lesions

Fractional curettage: separate sampling from endometrial and endocervical cavities during same procedure; do endocervix first to minimize contamination

Note: report endocervical extension of a tumor only if normal endocervical glands and carcinoma are present in the SAME fragment

Asherman’s syndrome: intrauterine adhesions after D & C, causing amenorrhea; usually postpartum or post-termination, may be due to subclinical uterine infection

Endometrial biopsy: to evaluate infertile or dysmenorrheic patients; sensitive if done properly

Helpful clinical information: patient’s age, date and characteristics of last and current menstrual period, use of hormones/steroids, chief complaint, physical findings