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Uterus

Non tumor

Dating of endometrium


Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 15 March 2012, last major update September 2011
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

General
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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, and may not have accuracy to diagnose luteal phase deficiency or to guide clinical management of women with reproductive failure (Fertil Steril 2004;81:1333)
● Difficult to date endometrium of patients with IUD or on hormones or if endometrium is non-uniform

Phases
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Diagrams


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 and large nuclei

   
Early proliferative endometrium

   
Left: small, round and regular glands are widely separated by a stroma without edema, which contains small, regularly distributed blood vessels; right: (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


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


Mid proliferative endometrium and Ki-67 staining


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


Day 10-12 endometrium shows glands that are more tortuous and crowded. Intraglandular nuclear pseudostratification and mitotic activity are more prominent (see inset) and the stroma is edematous and mitotically active


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 activity 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
● Clinically, secretory endometrium is lush and polypoid with no necrosis; may be hemorrhagic if close to day 28

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

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

       
Day 17 endometrium, with reduced Ki-67 staining


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


The glands of this day 17 endometrium contain prominent subnuclear glycogen vacuoles underlying a single row of nuclei in the endometrial glands


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

Day 19: intraluminal secretion begins

Days 20-21: maximal secretion


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


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 and endothelial proliferation)

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


In this day 23-24 endometrium, 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


Day 25: predecidualization below surface endometrium


The glands of this day 25 endometrium are markedly regressed, and the superficial compacta has a diffusely predecidualized stroma


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


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

Day 27: prominent stromal granulocytes; focal necrosis and hemorrhage

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



Typical fragmentation, stromal collapse and bloody necrotic background of a menstrual specimen.


Balls of endometrial stroma that, taken out of context, are occasionally mistaken for endometrial carcinoma or sarcoma


Menstrual endometrium


● Note: don’t confuse shedding (nuclear crowding, squamoid appearance and 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
References: The Global Library of Women's Medicine

End of Uterus > Non tumor > Dating of endometrium


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