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

Biopsies done for bleeding:

  • Too much bleeding (if premenopausal) - AUB = abnormal uterine bleeding.
  • Post-menopausal bleeding.

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.[2]

Image:

Endocervical glands vs. Endometrial glands

Endocervical

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

Endometrial

  • More hyperchromatic.
  • Nuclei columnar.

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.

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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, 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.

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.

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.

Normal endometrium

Proliferative phase endometrium

  • Abbreviated PPE.

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.

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).[3]

Microscopic

Features:[2]

  • Glands:
    • Straight, tubular, composed of tall pseudostratified columnar cells - key feature.
    • Mitotic figures - key feature. †
  • Stroma:
    • Cellular stroma (spindle cells).
    • Mitoses.
      • Usually harder to find than in the glands.

Notes:

  • † McCluggage says one shouldn't call PPE without mitoses, as some pseudostratification can be seen in atrophic endometrium.[2]
    • There is no guidance on how hard one should look. VL suggests searching ~ 10 mm^2 with the 20x objective. This represents approximately ~ 10 fields of view with a microscope that has a 22 mm eye piece.
  • Significant negatives:
    • No vacuolation.
    • No mucus secretion.
  • Inflammation (neutrophils, rare plasma cell) & stromal breakdown common early in the proliferative phase.[4]

DDx:

Images:

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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.

General

  • 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.

Microscopic

Early secretory phase

Features - post-ovulatory day 1-5:[6]

  • Glands: secretory vacuoles.
    • First basal to the epithelial nuclei (infranuclear vacuoles).
    • Then apical to the epithelial nuclei (supranuclear vacuoles).
  • Mitoses may be present - common when vacuoles are subnuclear.

Mid secretory phase

Features - post-ovulatory day 6-8:[6]

  • Glands: Mucus in glands.
  • Stroma: Edema (empty space around the glands).

Late secretory phase

Features - post-ovulatory day 9-12:[6]

  • 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:

Notes:

  • Stromal condensation (stromal balls) - premenstrual - stromal cells tightly packed together; nuclei molded together like in small cell tumours.[8]
  • Gland-to-stroma ratio is increased in late secretory phase and menstruation.[9]

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ENDOMETRIUM, BIOPSY: 
- SECRETORY PHASE ENDOMETRIUM.

ENDOMETRIUM, BIOPSY:
- SECRETORY PHASE ENDOMETRIUM.
- BENIGN SUPERFICIAL EXOCERVICAL EPITHELIUM.
- SCANT BENIGN ENDOCERVICAL EPITHELIUM.

Menstrual endometrium

General

  • Technically part of the proliferative phase or follicular phase.

Microscopic

Features:

  • Non-proliferative endometrium.
  • Tightly packed cellular balls of stromal cells with nuclear moulding.
    • Known as "blue balls".
    • Tightly packed cellular stromal cells known as "stromal condensation".
  • Inflammation, esp. neutrophils.

DDx:

Image:

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

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.[10]

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:

Chronic endometritis

Features:[11]

  • 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:[11]

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

Notes:

DDx:

  • Mentrual endometrium - endometrial stromal condensation.

Images:

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ENDOMETRIUM, BIOPSY:
- CHRONIC ENDOMETRITIS.

Benign endometrial polyp

  • Abbreviated BEP.
  • AKA endometrial polyp.

General

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

Gross

  • Polypoid mass in the endometrial cavity.

Gross DDx:

Microscopic

Features - diagnostic criteria:[2]

  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.

Glandular changes common:[2]

  • Endometrial glands may be out of phase with surrounding endometrium.
    • Often proliferative.
  • +/-Cystic dilation of glands/unusual shapes
  • +/-Focal gland crowding.

Notes:

  1. Apparently benign polyps should be examined closely at the surface for in situ & invasive malignancies.
  2. Stroma often cellular.

DDx:

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Non-proliferative

ENDOMETRIUM, CURETTAGE:
- BENIGN ENDOMETRIAL POLYP.

Proliferative

ENDOMETRIUM, CURETTAGE:
- BENIGN ENDOMETRIAL POLYP WITH PROLIFERATIVE ACTIVITY.

Note:

  • It is useful to comment on whether non-polypoid endometrium is proliferative (if present), esp. in menopausal women.[2]

Polyp with disordered proliferative phase in the background

ENDOMETRIUM, BIOPSY:
- BENIGN ENDOMETRIAL POLYP WITH PROLIFERATIVE GLANDS AND FOCAL GLAND DILATION.
- SUSPICIOUS FOR A BACKGROUND OF DISORDERED PROLIFERATIVE
  PHASE ENDOMETRIUM, SEE COMMENT.
- STRIPPED BENIGN ENDOCERVICAL EPITHELIUM.

COMMENT:
The endometrium sampled is proliferative with focal gland dilation throughout. The
features of a polyp (large muscular blood vessels, fibrous stroma and polypoid fragments of
endometrium) are only focally present, suggesting there is a background of disordered
proliferative phase endometrium.  Clinical correlation is suggested.

Disordered proliferative endometrium

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

General

  • Association: anovulation.
  • Benign - can be grouped with normal.[12]

Microscopic

Features:[13]

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

DDx:

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).

Images:

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ENDOMETRIUM, BIOPSY:
- DISORDERED PROLIFERATIVE ENDOMETRIUM.

Micro

The sections show endometrium with glands that have pseudostratified columnar cells. The glands are lined by endometrial epithelium. Tubal-type epithelium is seen focally. Mitotic figures are identified within the glands. The gland-to-stroma ratio is slightly increased. Dilated glands are seen only focally; most glands are round and regular. Apoptotic cells are seen in the glands focally.

Benign stripped endocervical epithelium is present. No squamous epithelium is apparent.

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

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:[15]

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

Image:

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ENDOMETRIUM, BIOPSY:
- NON-PROLIFERATIVE ENDOMETRIAL GLANDS WITH STROMAL DECIDUALIZATION, CONSISTENT 
  WITH 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.[2]
    • Eosinophilic cytoplasm.
    • No mitoses.
  • Architecture:
    • +/-Cystic dilation.

Notes:

  • If a woman is truly postmenopausal, mitoses in the glandular epithelium is pathologic until demonstrated otherwise.

DDx:

Images:

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

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).[16]

See also

References

  1. ↑ URL: http://emedicine.medscape.com/article/257007-treatment. Accessed on: 15 July 2010.
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 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. Cite error: Invalid <ref> tag; name "pmid16873562" defined multiple times with different content Cite error: Invalid <ref> tag; name "pmid16873562" defined multiple times with different content Cite error: Invalid <ref> tag; name "pmid16873562" defined multiple times with different content
  3. ↑ GAG. January 2009.
  4. ↑ Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 197. ISBN 978-0443069208.
  5. ↑ URL: http://www.cytochemistry.net/microanatomy/medical_lectures/oviduct_and_uterus.htm. Accessed on: 23 October 2012.
  6. ↑ 6.0 6.1 6.2 Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 237. ISBN 978-0470519035.
  7. ↑ TC. 22 June 2009.
  8. ↑ GAG. 6 Oct 2009.
  9. ↑ URL: http://www.pathologyoutlines.com/topic/uteruspatternapproach.html. Accessed on: 6 December 2012.
  10. ↑ Arias-Stella, J. (Jan 2002). "The Arias-Stella reaction: facts and fancies four decades after.". Adv Anat Pathol 9 (1): 12-23. PMID 11756756.
  11. ↑ 11.0 11.1 Tawfik, O.; Venuti, S.; Brown, S.; Collins, J. (1996). "Immunohistochemical characterization of leukocytic subpopulations in chronic endometritis.". Infect Dis Obstet Gynecol 4 (5): 287-93. doi:10.1155/S1064744996000555. PMC 2364507. PMID 18476109. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364507/.
  12. ↑ Sherman, ME.; Ronnett, BM.; Ioffe, OB.; Richesson, DA.; Rush, BB.; Glass, AG.; Chatterjee, N.; Duggan, MA. et al. (Jul 2008). "Reproducibility of biopsy diagnoses of endometrial hyperplasia: evidence supporting a simplified classification.". Int J Gynecol Pathol 27 (3): 318-25. doi:10.1097/PGP.0b013e3181659167. PMID 18580308.
  13. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1080 and 1082. ISBN 0-7216-0187-1.
  14. ↑ URL: http://www.glowm.com/index.html?p=glowm.cml/section_view&articleid=235. Accessed on: 11 December 2012.
  15. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1082. ISBN 0-7216-0187-1.
  16. ↑ 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.
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