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

Abnormal bleeding:

• Abnormal uterine bleeding (AUB).
  • Dysfunctional uterine bleeding, abbreviated DUB, is diagnosed if other causes of bleeding are excluded.
  • DUB may get a D&C if they fail medical management.
  • Post-menopausal bleeding.

Other indications:

• Products of conception - dealt with in a separate article.
• Dating of endometrium - infertility work-up.

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.

Glandular telescoping

AKA gland-within-a-gland.

AKA gland intussusception.

AKA telescoping.

• Considered an artifact of tissue processing, i.e. normal.

Image:

• Telescoping (bmjjournals.com).

Endometrial gland compression artifact

AKA compression artifact.

• Gland moulding.
• Tearing of tissue around the compressed glands - key feature.
• Usually at the edge of a tissue fragment.

DDx:

• Focal complex endometrial hyperplasia.

Image:

• Gland compression (bmjjournals.com).

Micro

An increased gland density is seen focally, at the edge of one tissue fragment, in association with tearing of the stroma (compression artifact).

Endocervical epithelium versus endometrial epithelium

Table

Feature	Endometrial	Endocervical	Tubal metaplasia
Cytoplasmic staining	usu. hyperchromatic +/-vacuoles	clear or light eosinophilic	hyperchromatic
Nuclear-to-cytoplasm ratio	moderate to high (1:2)	low (often 1:3)	high (1:1)
Surface features			villi
Associated stroma	cellular, hyperchromatic	inflamed, less cellular	variable

List

Endocervical:

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

Endometrial:

• More hyperchromatic.
• Nuclei columnar.

Images

• 

  Endocervical and endometrial epithelium - low mag. (WC)

• 

  Endocervical and endometrial epithelium - high mag. (WC)

Metaplasias of the endometrium

The big table of metaplasias - adapted from Nicolae et al.:

Metaplasia	Subtypes	Microscopic	Notes	Risk of malignancy
Morules	-			nearly always
Ciliary	-	ciliated cells	usu. lumped together with tubal, unopposed estrogen, endometriosis	frequent - endometrial hyperplasia (complex and simple), adenocarcinoma
Tubal	complex, simple	ciliated cells, secretory cell, intercallary cells	usu. lumped together with ciliary, unopposed estrogen, seen in endometriosis	frequent (complex only) - endometrial hyperplasia (complex and simple), adenocarcinoma
Mucinous	complex, simple			frequent (complex only)
Squamous	-			rare
Papillary syncytial change (surface)	-			rare
Eosinophilic, oxyphilic, oncocytic				not known
Clear cell (secretory)	-			not reported
Stromal metaplasia	osseous, cartilaginous, adipose, smooth muscle, myoid, sex-cord like			not reported

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.
• Ideally, the biopsy should have some endometrial stroma.
  • Without stroma it is not possible to assess the gland-to-stroma ratio.

Sign out

No stroma

ENDOMETRIUM, BIOPSY:
- VERY SCANT STRIPPED NON-PROLIFERATIVE COLUMNAR EPITHELIUM, PROBABLY FROM THE LOWER UTERINE SEGMENT.
- NO DEFINITE ENDOMETRIAL STROMA, SEE COMMENT.
- STRIPPED ENDOCERVICAL EPITHELIUM AND ENODOCERVICAL MUCOSA WITHIN NORMAL LIMITS.
- MUCOUS.

COMMENT:
A re-biopsy should be considered within the clinical context.

ENDOMETRIUM, BIOPSY:
- VERY SCANT STRIPPED EPITHELIUM PROBABLY FROM THE LOWER UTERINE SEGMENT.
- NO DEFINITE ENDOMETRIAL STROMA.
- SCANT STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
- SMALL FRAGMENTS OF DETACHED BENIGN SQUAMOUS EPITHELIUM.

COMMENT:
A re-biopsy should be considered within the clinical context.

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

ENDOMETRIUM, BIOPSY:
- ENDOMETRIUM: STRIPS OF EPITHELIUM, NON-PROLIFERATIVE. 
- ENDOCERVIX: SCANT BENIGN EPITHELIUM.
- EXOCERVIX: SCANT BENIGN EPITHELIUM.
- OTHER: TUBAL METAPLASIA.

ENDOMETRIUM, BIOPSY:
- STRIPS OF NON-PROLIFERATIVE ENDOMETRIUM. 
- SCANT BENIGN ENDOCERVICAL EPITHELIUM.
- SCANT BENIGN SQUAMOUS EPITHELIUM.
- TUBAL METAPLASIA.

ENDOMETRIUM, BIOPSY:
- STRIPS OF BENIGN ENDOMETRIAL EPITHELIUM/TUBAL METAPLASIA, NON-PROLIFERATIVE. 
- SCANT BENIGN ENDOCERVICAL EPITHELIUM.
- RARE SQUAMOUS METAPLASTIC CELLS.

Proliferative without definite stroma

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

No endometrium

ENDOMETRIUM, BIOPSY:
- SPECIMEN INADEQUATE; NO ENDOMETRIUM IDENTIFIED.
- ONE VERY TINY FRAGMENT OF ENDOCERVICAL MUCOSA WITHOUT APPARENT PATHOLOGY.

ENDOMETRIUM, BIOPSY:
- ENDOCERVICAL MUCOSA AND STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
- MICROGLANDULAR HYPERPLASIA AND FOCAL SQUAMOUS METAPLASIA.
- NO DEFINITE ENDOMETRIUM IDENTIFIED, SUGGEST RE-BIOPSY.

No tissue

ENDOMETRIUM, BIOPSY:
- NO TISSUE IDENTIFIED ON MICROSCOPY.

Overview

A simple approach

Low power

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

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.

Tabular summary

Diagnosis	Key feature (low power)	Additional features	DDx	Other	Image
Proliferative phase endometrium	round spaced pseudostratified glands	mitoses in glands and stroma	disordered proliferative phase, simple endometrial hyperplasia, complex endometrial hyperplasia, early secretory phase endometrium	normal	Proliferative endometrium. (WC)
Secretory phase endometrium	irregular glands with secretions or simple glands with vacuoles	decidual changes (nucleus central, eosinophilic cytoplasm, well-defined cell borders)	endometrial hyperplasia with secretory changes, late proliferative phase endometrium	normal	Secretory phase endometrium. (WC)
Menstrual endometrium	stromal condensation	nonproliferative glands, stromal/epithelial neutrophils, glandular cell apoptosis	disordered proliferative phase	normal	Image
Benign endometrial polyp	fibrous stroma, muscular blood vessels	polypoid shape (epithelium on 3 sides), +/-gland dilation	disordered proliferative phase, simple endometrial hyperplasia	Other	Image
Endometrium with changes due to exogenous hormones	decidualized stroma (nucleus central, eosinophilic cytoplasm, well-defined cell borders)	inactive glands (round/ovoid glands, simple cuboidal epithelium, no mitoses)	secretory phase endometrium, endometrial hyperplasia with secretory changes	Other	Endometrium with OCP changes. (WC)

Normal endometrium

Proliferative phase endometrium

Main article: Proliferative phase endometrium

Secretory phase endometrium

Main article: Secretory phase endometrium

Menstrual endometrium

General

• Technically part of the proliferative phase or follicular phase.

Microscopic

Features:

• Proliferative endometrium (mitoses).
• Apoptotic cells common.
• Tightly packed cellular balls of stromal cells with nuclear moulding.
  • Known as "blue balls".
  • Tightly packed cellular stromal cells known as "stromal condensation".
• Inflammation, especially abundant neutrophils.

DDx:

• Small cell carcinoma.
• Anovulatory endometrium - less neutrophils.

Images

• 

  Endometrial stromal condensation - high mag. (WC/Nephron)

www:

• Menstrual endometrium - several images (gfmer.ch).
• Menstrual phase endometrium (stonybrook.edu).

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ENDOMETRIUM, BIOPSY:
- CONSISTENT WITH MENSTRUAL ENDOMETRIUM:
-- STRIPPED WEAKLY PROLIFERATIVE ENDOMETRIAL GLANDS.
-- BALLS OF CONDENSED ENDOMETRIAL STROMA.
-- ABUNDANT NEUTROPHILS AND BLOOD.

ENDOMETRIUM, BIOPSY:
- CONSISTENT WITH MENSTRUAL PHASE ENDOMETRIUM:
-- WEAKLY PROLIFERATIVE ENDOMETRIAL GLANDS WITH NEUTROPHILS AND APOPTOSIS.
-- BALLS OF CONDENSED ENDOMETRIAL STROMA.
-- BLOOD.

ENDOMETRIUM, BIOPSY:
- VERY WEAKLY PROLIFERATIVE ENDOMETRIAL GLANDS WITH NEUTROPHILS AND APOPTOSIS.
- BALLS OF CONDENSED ENDOMETRIAL STROMA AND BLOOD.
- NEGATIVE FOR HYPERPLASIA AND NEGATIVE FOR MALIGNANCY.

Late menses

ENDOMETRIUM, ASPIRATION:
- ENDOMETRIAL GLANDS WITH APOPTOTIC CELLS, INFILTRATING NEUTROPHILS,
  AND GLANDULAR PROLIFERATIVE ACTIVITY.
- BALLS OF CONDENSED ENDOMETRIAL STROMA.
- SCANT STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
- NEGATIVE FOR HYPERPLASIA.

COMMENT:
The findings are most in keeping with late menstrual 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 - usually marked.
  • May form lymphoid aggregates - low power finding.
• +/-Eosinophils - presence should prompt a search for plasma cells.

Other findings:

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

Notes:

• One plasma cell is not enough to call it.

DDx:

• Mentrual endometrium - endometrial stromal condensation.

Images

• 

  Endometritis - high mag. (WC/Nephron)

• 

  Endometritis - very high mag. (WC/Nephron)

www:

• Chronic endometritis (webpathology.com).
• Chronic endometritis (webpathology.com).
• Tuberculous endometritis (webpathology.com).

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ENDOMETRIUM, BIOPSY:
- CHRONIC ENDOMETRITIS.

Not definite endometritis

ENDOMETRIUM, ASPIRATION:
- PROLIFERATIVE PHASE ENDOMETRIUM WITH A MILD LYMPHOCYTIC INFILTRATE AND VERY RARE
  PLASMA CELLS, SEE COMMENT.
- NEGATIVE FOR HYPERPLASIA.

COMMENT:
The lymphocytic infiltrate and plasma cells raise the possibility of a mild chronic
endometritis; clinical correlation is suggested.

Nonspecific lymphocytic infiltrate

If not more than one plasma cell is apparent after searching.

ENDOMETRIUM, ASPIRATION:
- PROLIFERATIVE PHASE ENDOMETRIUM WITH A MILD LYMPHOCYTIC INFILTRATE.
- SMALL FRAGMENT OF ENDOCERVICAL MUCOSA WITHIN NORMAL LIMITS.
- NEGATIVE FOR HYPERPLASIA.

Micro

The section show proliferative endometrium with a normal gland-to-stroma ratio. Mitotic activity is seen in the glands and stroma. No cytologic atypia is apparent. A mild nonspecific lymphocytic infiltrate is present.

No lymphoid aggregates are apparent. No eosinophils are apparent. No significant number of plasma cells is apparent.

Benign endometrial polyp

Main article: Benign endometrial polyp

Anovulatory endometrium

General

• May be used as a synonym for disordered proliferative phase.

Microscopic

Features:

• Shedding:
  • Stromal condensation.
  • Apoptotic endometrial epithelium.
• Nonproliferative glands.

DDx:

• Disordered proliferative phase.
• Simple endometrial hyperplasia.
• Menstrual endometrium - should have mitoses, abundant PMNs.

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ENDOMETRIUM, CURETTAGE:
- NON-PROLIFERATIVE ENDOMETRIUM WITH SMALL ROUND GLANDS AND SHEDDING, SEE COMMENT.
- BENIGN ENDOCERVICAL MUCOSA.
- NEGATIVE FOR HYPERPLASIA.
- NEGATIVE FOR MALIGNANCY.

COMMENT:
The changes are suggestive of anovulatory bleeding.

ENDOMETRIUM, BIOPSY:
- BENIGN ENDOCERVICAL POLYP WITH ACUTE AND CHRONIC INFLAMMATION, AND EVIDENCE
  SUGGESTIVE OF EROSIONS (SIDEROPHAGES, INCREASED BLOOD VESSEL DENSITY).
- SMALL NONPROLIFERATIVE ENDOMETRIAL GLANDS WITH RARE NEUTROPHILS AND RARE
  APOPTOTIC CELLS, WITH BALLS OF CONDENSED ENDOMETRIAL STROMA, SEE COMMENT.
- NEGATIVE FOR ENDOMETRIAL HYPERPLASIA AND NEGATIVE FOR DYSPLASIA.

COMMENT:
The changes are suggestive of anovulatory bleeding.

Disordered proliferative endometrium

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

General

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

Treatment:

• Progesterone versus observation.

Image:

• Treatment algorithim based on endometrial biopsy results (jabfm.org).

Microscopic

Features:

• Proliferative type endometrium with:
  • Cystic dilation of glands focally that do not have (glandular) secretions - key feature.
    • Glands >2x normal size - usually 3-4x normal.
    • Irregular shape, e.g. gland contour has inflection points.
    • Greater than fours glands involved (dilated).
• +/-Stromal condensation -- balls of stromal tissue, aka "blue balls" (due to breakdown of endometrium).

Notes:

• Dilated glands often have tubal metaplasia.^{[citation needed]}
• Eosinophilic syncytial metaplasia - common.
  • Features: abundant eosinophilic cytoplasm, mild nuclear atypia +/-loss of nuclear stratification, no mitoses).

DDx:

• 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.
• Simple endometrial hyperplasia without atypia - architectural atypia diffuse.
• Benign endometrial polyp.

Images

www:

• DPE (sciencedirect.com).
• DPE (sciencedirect.com).
• DPE (glowm.com).
• DPE (stonybrook.edu).

• 

  Endometrial stromal condensation - high mag. (WC/Nephron)

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ENDOMETRIUM, BIOPSY:
- DISORDERED PROLIFERATIVE ENDOMETRIUM.

With endocervix

ENDOMETRIUM, BIOPSY:
- DISORDERED PROLIFERATIVE ENDOMETRIUM.
- BENIGN ENDOCERVICAL MUCOSA.

Waffle a bit

ENDOMETRIUM, BIOPSY:
- COMPATIBLE WITH DISORDERED PROLIFERATIVE ENDOMETRIUM (FRAGMENTS OF PROLIFERATIVE
  ENDOMETRIUM WITH EVIDENCE OF SHEDDING AND VERY RARE GLAND DILATION).
- VERY SCANT STRIPPED ENDOCERVICAL EPITHELIUM WITHOUT APPARENT PATHOLOGY.
- NEGATIVE FOR ENDOMETRIAL HYPERPLASIA.
- NEGATIVE FOR MALIGNANCY.

Micro

The sections show a well-sampled endometrium. Mitotic figures are identified within the glands and stroma. Irregular, moderately enlarged glands are seen (only) in one of several fragments; most of the endometrial glands are round, regular and small.

No stromal condensation is apparent. No secretions are in the glands.

There are no back-to-back glands. No nuclear atypia is apparent. No thick-walled blood vessels are apparent.

Endometrium with changes due to exogenous hormones

Main article: Endometrium with changes due to exogenous hormones

Atrophic endometrium

Inactive endometrium redirect here.

• AKA atrophy of the endometrium.
• AKA endometrial atrophy.

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.

Gross

• Thin endometrium.

Microscopic

Features:

• Glands - small columnar cells:
  • Moderate quantity of eosinophilic cytoplasm.
  • Ovoid (palisaded) nuclei +/- nuclear pseudostratification.
  • Eosinophilic cytoplasm.
  • No mitoses.
• Architecture:
  • +/-Cystic dilation.

Notes:

• If a woman is truly postmenopausal, mitoses in the glandular epithelium is pathologic until demonstrated otherwise.
  • The exceptions are benign endometrial polyp, uterine prolapse, and possibly inflammation (e.g. the person has had several biopsy attempts and was seeded with pathogens).

DDx:

• Proliferative phase endometrium - esp. if there is pseudostratification.
• Serous carcinoma of the endometrium.

Images:

• Atrophic endometrium (nih.gov).

Sign out

ENDOMETRIUM, BIOPSY:
- NON-PROLIFERATIVE ENDOMETRIUM.
- BENIGN SQUAMOUS EPITHELIUM WITH METAPLASTIC CHANGE.
- SCANT ENDOCERVICAL MUCOSA WITH REACTIVE CHANGES.

ENDOMETRIUM, BIOPSY:
- NON-PROLIFERATIVE ENDOMETRIUM.
- BENIGN STRIPPED ENDOCERVICAL EPITHELIUM.
- NEGATIVE FOR HYPERPLASIA AND NEGATIVE FOR MALIGNANCY.

Micro

The sections show small fragments of endometrium. The gland-to-stroma ratio is normal. The glands are small and round, and have a pseudostratified epithelium.

Mitotic figures are not identified within the glands or stroma. No stromal condensation is apparent. No secretions are in the glands. No nuclear atypia is apparent.

Scant benign endocervical tissue (stripped epithelium and mucosa) is present.

Limited stroma

ENDOMETRIUM, BIOPSY:
- STRIPPED NONPROLIFERATIVE ENDOMETRIAL EPITHELIUM; NO APPRECIABLE STROMA PRESENT.
- SCANT ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
- MINUTE FRAGMENTS OF SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.

ENDOMETRIUM, BIOPSY:
- SCANT STRIPPED NON-PROLIFERATIVE ENDOMETRIAL EPITHELIUM.
- VERY SMALL FRAGMENT OF ENDOMETRIAL STROMA.
- TUBAL METAPLASTIC EPITHELIUM.

ENDOMETRIUM, ASPIRATION:
- SMALL FRAGMENTS OF NONPROLIFERATIVE ENDOMETRIAL EPITHELIUM ATTACHED TO
  A VERY SMALL AMOUNT OF STROMA.
- MINUTE BENIGN FRAGMENT OF SQUAMOUS EPITHELIUM.
- MUCOUS AND INFLAMMATORY CELLS.

COMMENT:
The sample is scant given the history of 'thickened endometrium'.

Micro

The sections show stripped endometrial epithelium and stripped tubal-type epithelium. No mitotic activity is identified. No nuclear atypia is apparent. A small fragment of definite endometrial stroma is present. The gland-to-stroma ratio cannot be assessed due to the limited stroma.

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.