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Diagrams

Phases
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

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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

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Early proliferative endometrium

Mid proliferative (days 8 - 10): columnar surface epithelium; longer curving glands, variable stromal edema and numerous mitotic figures
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Mid proliferative
endometrium and
Ki67 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

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Day 10 - 12 endometrium shows glands that are more


tortuous and crowded; intraglandular nuclear pseudo-
stratification 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)

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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 glyco-
gen vacuoles underlying a single row
of nuclei in the endometrial glands

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Day 17 endometrium, with reduced Ki67 staining

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

Day 19: intraluminal secretion begins

Days 20 - 21: maximal secretion

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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 predecidualization (stromal cell hypertrophy with accumulation of cytoplasmic eosinophilia); serrated / tortuous glands

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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

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The glands of this day 25 endo-


metrium 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
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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 endo-
metrial carcinoma or sarcoma

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Menstrual endometrium

Note: dont 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

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