Endometrium

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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:

Other indications:[2]

Endometrial thickness on ultrasound

  • A thin endometrium on ultrasound has a very low risk of malignancy.[3]

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.[4]

Image:

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:

Image

Micro

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

See also

Endocervical epithelium versus endometrial epithelium

Table

Feature Endometrial Endocervical Tubal metaplasia
Cytoplasmic staining usu. hyperchromatic +/-vacuoles clear or light eosinophilic hyperchromatic
Nucleus-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

Metaplasias of the endometrium

The big table of metaplasias - adapted from Nicolae et al.:[5]

Metaplasia Subtypes Microscopic Notes Risk of malignancy Image
Morules - nearly always SM. (WC)
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

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.

Possible endometrium - insufficient

ENDOMETRIUM, ASPIRATION:
- ONE MINUTE STRIP OF POSSIBLE NONPROLIFERATIVE ENDOMETRIAL EPITHELIUM, INSUFFICIENT
  FOR ADEQUATE DIAGNOSTIC ASSESSMENT.
- VERY SCANT BENIGN STRIPPED ENDOCERVICAL EPITHELIUM.
- VERY SCANT METAPLASTIC SQUAMOUS EPITHELIUM.

COMMENT:
Re-biopsy is advised.
ENDOMETRIUM, BIOPSY:
- BENIGN STRIPPED ENDOCERVICAL EPITHELIUM AND BENIGN INFLAMED ENDOCERVICAL MUCOSA.
- NO DEFINITE ENDOMETRIUM WITH STROMA, INADEQUATE SPECIMEN.

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?
  3. Glands round?
  4. Glands pseudostratified?
  5. Balls of cells?

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 endometrium (DPE), simple endometrial hyperplasia (SEH) DPE and SEH do not occur in polyps
Benign endometrial polyp. (WC)
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 variant of normal
Endometrium with changes due to exogenous hormones. (WC)
Atrophic endometrium nonproliferative glands no nuclear atypia, often without appreciable stroma serous endometrial carcinoma normal postmenopausal finding
Inactive endometrium. (WC)
Disordered proliferative endometrium proliferative focally dilated & irregular glands (usu. with tubal metaplasia) no nuclear atypia, +/-evidence of shedding (stromal condensation) simple endometrial hyperplasia, proliferative phase endometrium can be thought of a waffle diagnosis
Disordered proliferative endometrium. (WC)

Normal endometrium

Proliferative phase endometrium

Secretory phase endometrium

Menstrual endometrium

General

  • Technically part of the proliferative phase or follicular phase.

Microscopic

Features:

  • Proliferative endometrium (mitoses).[6]
  • Apoptotic cells common.[7]
  • 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:

Images

www:

Sign out

Endometrium, Biopsy:
- Consistent with menstrual endometrium.
-- Weakly proliferative endometrial glands with apoptosis, fragmented.
-- Abundant balls of condensed non-proliferative endometrial stroma and blood.

Block letters

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.

Consistent with menstrual endometrium

ENDOMETRIUM, ASPIRATION:
- CONSISTENT WITH MENSTRUAL ENDOMETRIUM (FRAGMENTED ENDOMETRIUM WITH PSEUDOSTRATIFIED
  GLANDS WITH APOPTOTIC CELLS, ABUNDANT NEUTROPHILS, CONDENSED ENDOMETRIAL STROMA
  AND BLOOD).
- NEGATIVE FOR HYPERPLASIA AND NEGATIVE FOR MALIGNANCY.
ENDOMETRIUM, ASPIRATION:
- CONSISTENT WITH MENSTRUAL ENDOMETRIUM (FRAGMENTED ENDOMETRIUM WITH SIMPLE
  GLANDS WITH APOPTOTIC CELLS, ABUNDANT NEUTROPHILS, CONDENSED ENDOMETRIAL STROMA
  (FOCAL) 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

Adipose tissue on endometrial biopsy

  • AKA fat on endometrial biopsy.

General

  • Benign.
  • Raises the possibility of perforation - should prompt a phone call to the clinician.

Microscopic

Features:

  • Adipose tissue, benign - key finding.
  • Definite endometrium.

DDx:

Images

Sign out

ENDOMETRIUM, BIOPSY:
- BENIGN ADIPOSE TISSUE, SEE COMMENT.
- PROLIFERATIVE PHASE ENDOMETRIUM.

COMMENT:
The presence of adipose tissue raises the possibility of perforation.

The findings were briefly discussed with Dr. Brown on November 6, 2009.

Arias-Stella reaction

  • Benign atypical endometrial changes associated with chorionic tissue -- may be seen in a completely normal pregnancy and misdiagnosed as a malignancy.[8]

Endometritis

Benign endometrial polyp

Anovulatory endometrium

Disordered proliferative endometrium

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

Endometrium with changes due to exogenous hormones

Atrophic endometrium

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

Ablated endometrium

Endometrium with squamous morules

Endometrium with psammoma bodies

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

Endometrial cancer is the most common gynecologic malignancy (in the USA).[9]

See also

References

  1. URL: http://emedicine.medscape.com/article/257007-treatment. Accessed on: 15 July 2010.
  2. Mazur, Michael T.; Kurman, Robert J. (2005). Diagnosis of Endometrial Biopsies and Curettings: A Practical Approach (2nd ed.). Springer. pp. 1. ISBN 978-0387986159.
  3. Gambacciani, M.; Monteleone, P.; Ciaponi, M.; Sacco, A.; Genazzani, AR. (Aug 2004). "Clinical usefulness of endometrial screening by ultrasound in asymptomatic postmenopausal women.". Maturitas 48 (4): 421-4. doi:10.1016/j.maturitas.2003.10.006. PMID 15283934.
  4. 4.0 4.1 4.2 McCluggage, WG. (Aug 2006). "My approach to the interpretation of endometrial biopsies and curettings.". J Clin Pathol 59 (8): 801-12. doi:10.1136/jcp.2005.029702. PMID 16873562.
  5. Nicolae, A.; Preda, O.; Nogales, FF. (Feb 2011). "Endometrial metaplasias and reactive changes: a spectrum of altered differentiation.". J Clin Pathol 64 (2): 97-106. doi:10.1136/jcp.2010.085555. PMID 21126963.
  6. Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 237. ISBN 978-0470519035.
  7. Spencer, SJ.; Cataldo, NA.; Jaffe, RB. (May 1996). "Apoptosis in the human female reproductive tract.". Obstet Gynecol Surv 51 (5): 314-23. PMID 8744416.
  8. Arias-Stella, J. (Jan 2002). "The Arias-Stella reaction: facts and fancies four decades after.". Adv Anat Pathol 9 (1): 12-23. PMID 11756756.
  9. Lu KH (April 2009). "Management of early-stage endometrial cancer". Semin. Oncol. 36 (2): 137–44. doi:10.1053/j.seminoncol.2008.12.005. PMID 19332248.