Endometrial hyperplasia

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See Endometrium for dating and benign pathologies.

Endometrial hyperplasia, abbreviated EH, is a precursor to endometrial carcinoma.

Overview

The most widely used system is from the World Health Organization (WHO). The WHO system is based on determining:

  1. Gland density (normal = simple hyperplasia, high density = complex hyperplasia), and
  2. Presence of atypia.

An alternative grading system from Harvard exists. It is not widely used. It defines a term called endometrial intraepithelial neoplasia (EIN).

WHO system

Management of endometrial hyperplasia

  • Endometrial hyperplasia with atypia is usually treated with hysterectomy.[1]
    • In women who want to maintain fertility it may be treated with progestin + short interval re-biopsies (q3 months).[2]
  • Endometrial hyperplasia without atypia is treated by:
    • Progestins + close follow-up OR hysterectomy.

Risk of progression to carcinoma

Approximate risk of progression to carcinoma:[3]

Simple Complex
Without atypia 1% 3%
With atypia 9% 27%

WHO system

Simple endometrial hyperplasia

General

  • More common than simple endometrial hyperplasia with atypia.

Microscopic

Features:[4]

  • Irregular dilated glands (with large lumens) - key feature.
    • Glands described as "animal shapes".
  • Variation of gland size.
  • No nuclear atypia.
    • Uniform columnar nuclei.
  • Normal gland density (gland area in plane of section/total area ~= 1/3).

DDx:

Images:

Simple endometrial hyperplasia with atypia

General

  • Uncommon.

Microscopic

Features:[4]

  • Irregular dilated glands (with large lumens) - important feature.
    • Glands described as "animal shapes".
  • Variation of gland size.
  • No nuclear atypia.
    • Uniform columnar nuclei.
  • Normal gland density (gland area in plane of section/total area ~= 1/3).
  • Nuclear atypia:[5]
    • Loss of basal nuclear stratification.
    • Nuclear size variation.
    • Nuclear rounding.
      • Nuclei lacking atypical = uniform columnar nuclei.
    • Nucleoli.
    • Hyperchromasia or vesicular nuclei.

Notes:

  • There are no clear criteria for atypia. Different sources list different features.
  • VL criteria for atypia (all should be present):
    1. Increased NC ratio.
      • Atypical: ~ 1:2
      • Not atypical: ~1:3.
    2. Oval nuclei with small major axis to minor axis ratio.
      • Atypical: major axis:minor axis = <=2:1.
      • Not atypical: major axis:minor axis = >=3:1
        • NB: round nuclei: major axis:minor axis = 1:1.
    3. Small nucleoli (~1/5 the size of the nucleus).

Complex endometrial hyperplasia

Microscopic

Features:

  • Increase in size & number of glands + irreg. shape.
    • Need cribriform architecture.
    • Two "touching" glands are likely one gland in section.
  • Cell stratification.
  • Nuclear enlargement.
  • Mitoses common.
  • No nuclear atypia.

Notes:

  • Normal gland-to-stroma ratio is 1:3.

Image:

Endometrial carcinoma vs. complex endometrial hyperplasia:

  • Complex endometrial hyperplasia: non-confluent (glands distinct from one another).
  • Diagnosis of complex EH is based on histology (cytologic features).

Complex endometrial hyperplasia with atypia

Microscopic

Features:

  • Increase in size & number of glands + irreg. shape.
    • Need cribriform architecture.
    • Two "touching" glands are likely one gland in section.
  • Cell stratification.
  • Nuclear enlargement.
  • Mitoses common.
  • Nuclear atypia present.

Image:

See also

References

  1. http://www.aafp.org/afp/990600ap/3069.html
  2. http://www.aafp.org/afp/20060801/practice.html
  3. LAE Jan 2009.
  4. 4.0 4.1 Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 236. ISBN 978-0443069208.
  5. Silverberg, SG. (Mar 2000). "Problems in the differential diagnosis of endometrial hyperplasia and carcinoma.". Mod Pathol 13 (3): 309-27. doi:10.1038/modpathol.3880053. PMID 10757341.