Endometrium

The endometrium is typically biopsied because of abnormal bleeding. Endometrial hyperplasia and endometrial carcinoma are dealt with in separate articles. An overview of gynecologic pathology is in the gynecologic pathology article.

Indications for endometrial biopsy

Biopsies done for bleeding:

• Too much bleeding (if premenopausal) - AUB = abnormal uterine bleeding.
• Post-menopausal bleeding.
• Dysfunctional uterine bleeding AKA DUB - may get D&C if they fail medical management.
  • DUB is diagnosed if other causes of bleeding are excluded.

Normal microscopic findings

Endometrium - consists of:

1. Epithelium (endometrial glands).
2. Stroma (endometrial stroma).

In endometrial biopsies:

• Endocervical glands are commonly seen, as is endocervical mucous.
  • This is 'cause the gynecologist scrapes some off on the way in or out.

Endocervical glands vs. Endometrial glands

Endocervical

• Less hyperchromatic.
• Nuclei round & small.
• Cell borders usually well-defined.

Endometrial

• More hyperchromatic.
• Nuclei columnar.

Tamoxifen effects

• Endometrial hyperplasia.
• Endometrial cancer.
• Endometrial polyps.
• Atrophy.

Inadequate endometrial biopsy

• Endometrial biopsies often have scant tissue.
  • This is normal in post-menopausal women.
• To be adequate the biopsy must have some endometrial stroma, as it is otherwise not possible to assess the gland-to-stroma ratio.

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ENDOMETRIUM, BIOPSY: 
	- FRAGMENTS OF DETACHED SQUAMOUS EPITHELIUM, ENDOCERVICAL EPITHELIUM AND FOCALLY PROLIFERATIVE ENDOMETRIAL GLANDS.  
	- ASSESSMENT LIMITED AS NO DEFINITE ENDOMETRIAL STROMA IS PRESENT.

ENDOMETRIUM, BIOPSY: 
	- FRAGMENTS OF DETACHED SQUAMOUS EPITHELIUM AND DETACHED NON-PROLIFERATIVE ENDOMETRIAL GLANDS. 
	- ASSESSMENT LIMITED AS VERY SCANT ENDOMETRIAL STROMA IS PRESENT.

A simple approach

Low power

1. Decide whether you're look at endometrium.
2. Gland-to-stroma ratio normal?
   • 1:3 is normal.
   • If gland-to-stroma ratio is increased... think endometrial hyperplasia.
   • If glands are fused to one another or cribriform... think endometrial carcinoma.
3. Glands round?
   • Round is normal.
   • Irregular - may be seen in menses, endometrial hyperplasia, disordered proliferative endometrium.
4. Glands pseudostratified?
   • Pseudostratified glands are normal in the proliferative phase, hyperplasias, malignancy.
5. Balls of cells?
   • Blue - likely menstrual (stromal condensation).
   • Pink - consider leiomyoma, squamous morules (associated with endometrial hyperplasia).

High power

1. Mitoses present in the glands?
   • Present in the proliferative phase, hyperplasias, malignancies.
2. Mitoses present in the stroma?
   • Present in the proliferative phase, hyperplasias, malignancies.
3. Mucous present in the glands?
   • Present in the secretory phase.
4. Inflammatory cells present?
   • Some are normal during menses.

Normal endometrium

Proliferative phase endometrium

General

• Day 1-13 in the protypical menstrual cycle of 28 days.
  • May be day 5-13 - if the menstruation is not included.
  • "Exodus" pattern is a term used to describe exfoliation of endometrial cells during the proliferative phase.
    • On pap tests this is associated with the classic double contoured balls of endometrial epithelium and stroma.

Microscopic

Features:

• Glands:
  • Straight, tubular, composed of tall pseudostratified columnar cells - key feature.
  • Mitotic figures - key feature.
  • NO vacuolation.
  • NO mucus secretion.
• Stroma:
  • Cellular stroma (spindle cells).
  • Mitoses.
    • Usually harder to find than in the glands.

Note:

• Proliferative phase = follicular phase.
  • Gynecologists prefer the ovarian descriptor, i.e. follicular phase; pathologists go by what they see, i.e. proliferative endometrium.
• When the patient is >40 years, some advocate the use of the term proliferative type endometrium (instead of the term proliferative endometrium).

DDx:

• Endometrial polyp.
• Endometrial hyperplasia.

Image:

• Proliferative phase endometrium (utah.edu).

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ENDOMETRIUM, BIOPSY: 
- PROLIFERATIVE PHASE ENDOMETRIUM.

Not quite normal

ENDOMETRIUM, BIOPSY:
- EARLY SECRETORY PHASE ENDOMETRIUM.
- FOCUS OF CROWDED PROLIFERATIVE GLANDS, SEE COMMENT.

COMMENT:  
There is a small focus of crowded and irregular proliferative glands
without cytologic atypia.  The possibility of a polyp is considered but the vessels and
polyp-type stroma are lacking.  Suggest clincal follow up with a consideration of a repeat
biopsy in 3 to 6 months to rule out a hyperplastic lesion.

Secretory phase endometrium

• Abbreviated SPE.

Microscopic

• Early secretory phase - post-ovulatory day 1-5:
  • Glands: secretory vacuoles.
    • First basal to the epithelial nuclei (infranuclear vacuoles).
    • Then apical to the epithelial nuclei (supranuclear vacuoles).

• Mid secretory phase - post-ovulatory day 6-8:
  • Glands: Mucus in glands.
  • Stroma: Edema (empty space around the glands).

• Late secretory phase (beginning) - post-ovulatory day 9-12:
  • Stroma:
    • Spiral arterioles.
    • Predecidual changes -- mnemonic NEW:
      1. Nucleus central.
      2. Eosinophilic cytoplasm key feature (may be subtle to the novice).
      3. Well-defined cell borders.

• Premenstrual:
  • Stroma: neutrophils, scattered lymphocytes, stromal balls ("blue balls"); "stromal condensation" (Image: Endometrial stromal condensation (WC)).
  • Glands: apoptosis at the base of the gland.

General refs.:

Notes:

• Secretory phase = luteal phase.
  • Gynecologists prefer the ovarian descriptor, i.e. luteal phase; pathologists go by what they see, i.e. Secretions in the (endometrial) glands.
• Stromal condensation (stromal balls) - premenstrual - stromal cells tightly packed together; nuclei molded together like in small cell tumours.

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ENDOMETRIUM, BIOPSY: 
- SECRETORY PHASE ENDOMETRIUM.

Specific entities/abnormalities

Arias-Stella reaction

Main article: Arias-Stella reaction

• Benign atypical endometrial changes associated with chorionic tissue -- may be seen in a completely normal pregnancy and misdiagnosed as a malignancy.

Endometritis

General

• Usually post-delivery or post-instrumentation, e.g. previous biopsy.
• May be spontaneous, e.g. tuberculous endometritis.

Microscopic

Acute endometritis

Features:

• Neutrophils clusters (>5 PMNs) in the:
  • Endometrial stroma.
  • Within uterine glands.

Notes:

• Neutrophils are normal in the context of menses.

Image:

• Acute endometritis (stonybrook.edu).

Chronic endometritis

Features:

• Plasma cells with in the endometrial stroma - key feature.
  • Usually superficial/close to the luminal aspect.
• Lymphocytic infiltrate - usu. marked.
  • May form lymphoid aggregates - low power finding.

Other findings:

• +/-Necrosis.
• Edema - common.
• Hemorrhage.

Notes:

• One plasma cell is not enough to call it.

DDx:

• Endometrial stromal condensation.

Images:

• WC:
  • Endometritis - high mag. (WC).
  • Endometritis - very high mag. (WC).
• www:
  • Chronic endometritis (webpathology.com).
  • Chronic endometritis (webpathology.com).
  • Tuberculous endometritis (webpathology.com).

Benign endometrial polyp

• AKA endometrial polyp.

General

• Very common.
• May be a cause of menorrhagia (heavy & long menses).

Microscopic

Features:

1. Large blood vessels (muscular) - key feature.
2. Fibrotic stroma - key feature.
3. Polypoid shape - epithelium on three sides.
   • May not be seen... as polyp is fragmented on removal.

Notes:

1. Apparently benign polyps should be examined closely at the surface for in situ & invasive malignancies.
2. Endometrial glands may be out of phase with surrounding endometrium.
   • Often proliferative.
3. +/-Cystic dilation of glands.
4. Cellular stroma.

Other considerations - DDx:

• Adenofibroma.
• Cervical polyp.
• Pedunculated leiomyoma.
• Secretory phase endometrium.

Disordered proliferative endometrium

• Abbreviated DPE.
• AKA endometrium with disordered proliferative phase.
• AKA disordered proliferative phase.

General

• Association: anovulation.
• Benign - can be grouped with normal.

Microscopic

Features:

• Proliferative type endometrium with:
  • Cystic dilation of glands without secretions.
• +/-Stromal condensation -- balls of stromal tissue, aka "blue balls" (due to breakdown of endometrium).

DDx:

• Simple endometrial hyperplasia without atypia - architectural atypia diffuse.

Notes:

• Proliferative phase endometrium:
  • Glands: straight, tubular, tall pseudostratified columnar cells, mitotic figures, NO vacuolation, NO mucus secretion, abundant mitoses.
  • Stroma: cellular, stroma (spindle cells), mitoses.
• Eosinophilic syncytial metaplasia - common.
  • Features: abundant eosinophilic cytoplasm, mild nuclear atypia +/-loss of nuclear stratification, no mitoses).

Image:

• Endometrial stromal condensation - high mag. (WC).

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ENDOMETRIUM, BIOPSY:
- DISORDERED PROLIFERATIVE ENDOMETRIUM.

Endometrial changes of oral contraception

Main article: Oral contraceptive pill

• AKA oral contraceptive effect.

General

• Very common.
• Most pills a mix of progesterone and estrogen.
  • The progesterone is what generates the characteristic appearance -- that is similar to pregnancy.

Microscopic

Features:

• Inactive glands (round/ovoid glands, simple cuboidal epithelium, no mitoses).
• Stroma decidualized -- mnemonic NEW:
  • Nucleus central.
  • Eosinophilic cytoplasm.
  • Well-defined cell borders.

Image:

• Endometrium of woman on an OCP (WC).

Atrophic endometrium

General

• Endometrium of normal postmenopausal women.
  • Menopause typically happens at around 50 years old.
• Very common diagnosis.
  • Atrophy may be associated with bleeding and therefore biopsied to rule-out hyperplasia and malignancy.

Microscopic

Features:

• Glands:
  • No mitoses/very few mitoses.
  • +/-Nuclear pseudostratification.
  • Cystic dilation.
• Thin endometrium.

Notes:

• If a woman is truly postmenopausal, mitoses in the glandular epithelium is pretty much always pathologic.
  • Exception is inflammation... e.g. the person has had several biopsy attempts and was seeded with pathogens.

Endometrial hyperplasia

Main article: Endometrial hyperplasia

Can be thought of as a precursor lesion for endometrial carcinoma.

It comes in two main flavours:

1. Simple.
2. Complex.

Each flavour may or may not have nuclear atypia.

Endometrial carcinoma

Main article: Endometrial carcinoma

Endometrial cancer is the most common gynecologic malignancy (in the USA).

See also

• Uterine tumours.
• Gynecologic pathology.