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).

WHO classification - overview

The WHO system is based on determining:

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

Alternate classifications - overview

Two alternative grading systems exist, that are (currently) not widely used:[1]

  1. European group of experts (1999).
  2. Endometrial collaborative group/Harvard (2000).

Both consist of two categories, as opposed to four found in the WHO classification.

European group of experts classification

  1. Endometrial hyperplasia.
  2. Endometrioid neoplasia.

Endometrial collaborative group/Harvard classification

  1. Endometrial hyperplasia.
  2. Endometrial intraepithelial neoplasia (EIN).

WHO classification

Management of endometrial hyperplasia

  • Endometrial hyperplasia with atypia is usually treated with hysterectomy.[2]
    • In women who want to maintain fertility it may be treated with progestin + short interval re-biopsies (q3 months).[3]
  • Endometrial hyperplasia without atypia is treated by:
    • Progestins + close follow-up OR hysterectomy.

Risk of progression to carcinoma

Approximate risk of progression to carcinoma:[4]

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

WHO system

Almost all hyperplasia is seen in the context of proliferative-type glands. Hyperplasia in the secretory phase is extremely rare and something diagnosed by or in consultation with an expert in gynecologic pathology.

Simple endometrial hyperplasia

General

  • More common than simple endometrial hyperplasia with atypia.

Microscopic

Features:[5]

  • 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

  • Very uncommon.

Microscopic

Features:[5]

  • 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:[6]
    • 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 + irregular shape - key feature.
  • Cell stratification.
  • Nuclear enlargement.
  • Mitoses common.
  • No nuclear atypia.

Notes:

  • Normal "gland-to-stroma ratio" is 1:3.
  • Two "touching" glands may be one gland in section.

DDx:

Image:

Endometrial carcinoma versus complex endometrial hyperplasia

Complex endometrial hyperplasia:

  • Non-confluent - glands distinct from one another.
Classic criteria for endometrial carcinoma

This is pimping material that shows up on exams.

Endometrial carcinoma has one of the following:[7][8][9]

  1. Desmoplastic stromal response.
  2. Confluent cribriform growth. †
  3. Extensive papillary growth. †
  4. Severe cytologic atypia. †

Note:

  • † There is a size cut-off for criteria 2, 3 and 4: > 2.1 mm.[8]

How to remember ABCDE:

  • Atypia Bad.
  • Confluent cribriform growth.
  • Desmoplasia.
  • Extensive papillary growth.

Complex endometrial hyperplasia with atypia

General

  • High risk of transformation to endometrial carcinoma.

Microscopic

Features:

  • Increase in size & number of glands + irregular shape - key feature.
  • Cell stratification.
  • Nuclear enlargement.
  • Nuclear atypia:
    • Round nuclei ~ 2-3x the size of a lymphocyte.
    • Grey/translucent chromatin.
    • Nucleoli.
  • Mitoses common.

Note:

  • Atypical nuclei often hide between non-typical nuclei, like peg cells in the fallopian tube.

DDx:

Image:

See also

References

  1. ↑ Dietel, M. (Nov 2001). "The histological diagnosis of endometrial hyperplasia. Is there a need to simplify?". Virchows Arch 439 (5): 604-8. PMID 11764378.
  2. ↑ URL: http://www.aafp.org/afp/990600ap/3069.html.
  3. ↑ URL: http://www.aafp.org/afp/20060801/practice.html.
  4. ↑ LAE Jan 2009.
  5. ↑ 5.0 5.1 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.
  6. ↑ 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.
  7. ↑ Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 239. ISBN 978-0443069208.
  8. ↑ 8.0 8.1 Kurman, RJ.; Norris, HJ. (Jun 1982). "Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma.". Cancer 49 (12): 2547-59. PMID 7074572.
  9. ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Endometrium_11protocol.pdf. Accessed on: 12 January 2012.
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