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 endometrial carcinoma - Latta rule of 3s:

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

Notes:

• † 8% is the true number.
• ‡ 29% is the true number.

Ki-67

There is one paper that looks at Ki-67:

Diagnosis	Percent positive
Secretory phase endometrium	15%
Proliferative phase endometrium	42%
Simple hyperplasia	26%
Simple hyperplasia with atypia	23%
Complex hyperplasia	16%
Complex hyperplasia with atypia	42%

WHO system

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

Simple endometrial hyperplasia

• AKA simple hyperplasia.

General

• More common than simple endometrial hyperplasia with atypia.
• Very low risk for progressing to endometrioid endometrial carcinoma.

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.
• Complex endometrial hyperplasia - has increased gland-to-stroma ratio.
• Cystic atrophy of the endometrium - does not have proliferative activity.
• Benign endometrial polyp - has thick-walled blood vessels; simple endometrial hyperplasia should not be diagnosed in a polyp.

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

Complex endometrial hyperplasia
External resources
EHVSC	10169

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.

Sign out

ENDOMETRIUM, BIOPSY: 
- COMPLEX ENDOMETRIAL HYPERPLASIA.
-- NEGATIVE FOR CYTOLOGIC ATYPIA. 

ENDOMETRIUM, BIOPSY:
- SMALL FOCUS OF COMPLEX ENDOMETRIAL HYPERPLASIA WITHOUT ATYPIA, WITH
  SQUAMOUS MORULES.
- ENDOMETRIAL POLYP WITH ONE ATYPICAL GLAND AND A SQUAMOUS MORULE.
- SCANT ENDOCERVICAL EPITHELIUM WITHOUT APPARENT PATHOLOGY.

Complex endometrial hyperplasia with atypia

Complex endometrial hyperplasia with atypia
External resources
EHVSC	10181

• AKA complex atypical hyperplasia.

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.  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.

Other

Endometrial hyperplasia with secretory changes

General

• Rare.
• Secretory changes seen in 1-2% of endometrial hyperplasias/endometrial carcinomas.

Microscopic

Features:

• Secretory changes - includes at least one of three following:
  1. Stromal decidualization.
  2. Cytoplasmic vacuolization.
  3. Intraluminal secretions.
• Proliferative-type epithelium. †
  • Mitoses.
  • Nuclear atypia.
  • Pseudostratified epithelium.

Notes:

• † This is not precisely defined. I suppose it is some of the things Bell and Ostrezega mention (mitoses, nuclear atypia, pseudostratified epithelium).
  • Bell and Ostrezega give a laundry list for differentiating benign secretory endometrium from hyperplasia with secretory changes: focal architectural abnormalities, metaplastic ciliated & "clear" cells, sharp luminal border, epithelial pseudopalisading, nuclear atypia, vesicular nuclei, mitoses.

DDx:

• Secretory phase endometrium.
• Endometrium with hormonal changes.

Images:

• Endometrial hyperplasia with secretory changes (cap.org).

See also

• Endometrium.
• Endometrial carcinoma.
• Gynecologic pathology.