Endometrium

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The endometrium is typically biopsied because of abnormal bleeding.

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.[1]
    • 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

A simple approach

Low power

  1. Decide whether you're look at endometrium.
  2. Gland-to-stroma ratio normal?
  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 = folicular phase.
    • Gynecologists prefer the ovarian descriptor, i.e. follicular phase; pathologists go by what they see, i.e. proliferative endometrium.

Secretory phase endometrium

  • 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.

General refs.: [3][4]

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.
  • When the patient is >40 years, some advocate the use of the term proliferative type endometrium (instead of the term proliferative endometrium).[5]
  • Stromal condensation (stromal balls) - premenstrual - stromal cells tightly packed together; nuclei molded together like in small cell tumours.[6]

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.[7]

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:

  • Plasma cells with in the endometrial stroma - key feature.

Notes:

  • One plasma cell is not enough to call it.

Images:

Benign endometrial polyp

  • AKA endometrial polyp.

General

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

Microscopic

Features:[8]

  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:

Disordered proliferative phase

  • AKA endometrium with disordered proliferative phase.

General

  • Association: anovulation.

Microscopic

Features:[9]

  • 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:

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).

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:[10]

  • 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).[11]

See also

References

  1. ↑ URL: http://emedicine.medscape.com/article/257007-treatment. Accessed on: 15 July 2010.
  2. ↑ TC. 22 June 2009.
  3. ↑ 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. 1081. ISBN 0-7216-0187-1.
  4. ↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 237. ISBN 978-0470519035.
  5. ↑ GAG. Jan 2009
  6. ↑ GAG. 6 Oct 2009.
  7. ↑ Arias-Stella, J. (Jan 2002). "The Arias-Stella reaction: facts and fancies four decades after.". Adv Anat Pathol 9 (1): 12-23. PMID 11756756.
  8. ↑ URL: http://www.pathologyoutlines.com/uterus.html#endopolyp. Accessed on: 15 September 2011.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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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