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).

Sign out

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; however, 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 of gland confluence is not considered sufficient for the diagnosis 
of endometrial carcinoma.

See also

• Endometrium.
• Endometrial carcinoma.
• Gynecologic pathology.