Endometrial hyperplasia

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

Risk of progression to carcinoma

Approximate risk of progression to carcinoma:

	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:

• 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:

• Disordered proliferative phase.

Images:

• Simple endometrial hyperplasia - low mag. (WC).
• Simple endometrial hyperplasia - high mag. (WC).

Simple endometrial hyperplasia with atypia

General

• Very uncommon.

Microscopic

Features:

• 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:
  • 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:

• Complex endometrial hyperplasia with atypia.
• Endometrioid endometrial carcinoma - see endometrial carcinoma versus complex endometrial hyperplasia.

Image:

• Endometrial hyperplasia (webpathology.com).

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:

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.

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:

• Complex endometrial hyperplasia.
• Endometrioid endometrial carcinoma - see endometrial carcinoma versus complex endometrial hyperplasia.

Image:

• Complex endometrial hyperplasia with atypia (webpathology.com).

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Insufficient confluence for carcinoma

ENDOMETRIUM, BIOPSY: 
- COMPLEX ENDOMETRIAL HYPERPLASIA WITH ATYPIA, SEE COMMENT. 

COMMENT: 
The sections show architecturally complex crowded glands with focal 
morular squamous metaplasia and focal cribriforming.  Desmoplasia is not identified. The degree of gland confluence is not considered sufficient for the diagnosis of endometrial carcinoma. Nuclear atypia is present focally.

Insufficient extent for carcinoma

ENDOMETRIUM, BIOPSY: 
- COMPLEX ENDOMETRIAL HYPERPLASIA WITH ATYPIA, SEE COMMENT. 

COMMENT: 
The sections show architecturally complex back-to-back glands with focal 
morular squamous metaplasia and cribriforming. Desmoplasia is not present. 
The extent, i.e. the size of the abnormality, is not considered sufficient 
for the diagnosis of endometrial carcinoma.

See also

• Endometrium.
• Endometrial carcinoma.
• Gynecologic pathology.