Non tumor
Dating of endometrium

Topic Completed: 1 September 2011

Revised: 8 October 2019

Copyright: 2002-2019, PathologyOutlines.com, Inc.

PubMed search: endometrial dating uterus

Nat Pernick, M.D.
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Cite this page: Pernick N. Dating of endometrium. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/uterusdating.html. Accessed October 22nd, 2019.
Definition / general
  • 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 nonuniform
Diagrams / tables

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  • 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

AFIP images

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

AFIP images

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)

Contributed by Andrey Bychkov, M.D., Ph.D.

Subnuclear vacuoles

Piano key

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

Images hosted on PathOut server:

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

AFIP images

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

Images hosted on PathOut server:

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

Images hosted on PathOut server:

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: 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
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