Difference between revisions of "Endometrial hyperplasia"

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=Overview=
=Overview=
The most widely used system is from the World Health Organization (WHO).  
===WHO endometrial hyperplasia classification of 2014===
The 2014 WHO system has two categories:<ref name=pmid25797956 >{{Cite journal  | last1 = Emons | first1 = G. | last2 = Beckmann | first2 = MW. | last3 = Schmidt | first3 = D. | last4 = Mallmann | first4 = P. | title = New WHO Classification of Endometrial Hyperplasias. | journal = Geburtshilfe Frauenheilkd | volume = 75 | issue = 2 | pages = 135-136 | month = Feb | year = 2015 | doi = 10.1055/s-0034-1396256 | PMID = 25797956 }}</ref>
*Hyperplasia without atypia.
*Atypical hyperplasia/endometrioid intraepithelial neoplasia.


===WHO classification - overview===
===WHO endometrial hyperplasia classification of 1994===
The WHO system is based on determining:
The 1994 WHO system is based on determining:<ref name=pmid25797956>{{Cite journal  | last1 = Emons | first1 = G. | last2 = Beckmann | first2 = MW. | last3 = Schmidt | first3 = D. | last4 = Mallmann | first4 = P. | title = New WHO Classification of Endometrial Hyperplasias. | journal = Geburtshilfe Frauenheilkd | volume = 75 | issue = 2 | pages = 135-136 | month = Feb | year = 2015 | doi = 10.1055/s-0034-1396256 | PMID = 25797956 }}</ref>
# Gland density (normal = ''simple hyperplasia'', high density = ''complex hyperplasia'').
# Gland density (normal/low = ''simple hyperplasia'', high density = ''complex hyperplasia'').
# Presence/absence of nuclear atypia.  
# Presence/absence of nuclear atypia.  
It consists of four categories:
*[[Simple endometrial hyperplasia]].
*[[Simple endometrial hyperplasia with atypia]].
*[[Complex endometrial hyperplasia]].
*[[Complex endometrial hyperplasia with atypia]].


===Alternate classifications - overview===
===Alternate classifications - overview===
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#Endometrial intraepithelial neoplasia (EIN).
#Endometrial intraepithelial neoplasia (EIN).


==WHO classification==
==WHO classification of 1994==
===Management of endometrial hyperplasia===
===Management of endometrial hyperplasia===
*Endometrial hyperplasia with atypia is usually treated with hysterectomy.<ref>URL: [http://www.aafp.org/afp/990600ap/3069.html http://www.aafp.org/afp/990600ap/3069.html].</ref>
*Endometrial hyperplasia with atypia is usually treated with hysterectomy.<ref>URL: [http://www.aafp.org/afp/990600ap/3069.html http://www.aafp.org/afp/990600ap/3069.html].</ref>
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**Progestins + close follow-up ''OR'' hysterectomy.
**Progestins + close follow-up ''OR'' hysterectomy.


===Risk of progression to carcinoma===
===Risk of progression to carcinoma as per 1994 system===
Approximate risk of progression to [[endometrial carcinoma]] - Latta rule of 3s:<ref>Latta, E. January 2009.</ref>
Approximate risk of progression to [[endometrial carcinoma]] - Latta rule of 3s:<ref>Latta, E. January 2009.</ref>
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=WHO system=
==WHO system of 1994 - detail articles==
Almost all hyperplasia is seen in the context of proliferative-type endometrium. [[Endometrial hyperplasia with secretory changes|Hyperplasia in the secretory-type endometrium]] is extremely rare and something diagnosed by or in consultation with an expert in gynecologic pathology.
Almost all hyperplasia is seen in the context of proliferative-type endometrium. [[Endometrial hyperplasia with secretory changes|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==
===Simple endometrial hyperplasia===
*[[AKA]] ''simple hyperplasia''.
*[[AKA]] ''simple hyperplasia''.
===General===
{{Main|Simple endometrial hyperplasia}}
*More common than simple endometrial hyperplasia with atypia.
*Very low risk for progressing to [[endometrioid endometrial carcinoma]].
 
===Microscopic===
Features:<ref name=Ref_GP236>{{Ref GP|236}}</ref>
*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.
*[[Atrophic endometrium|Cystic atrophy of the endometrium]] - does not have proliferative activity.<ref name=pmid16873562>{{Cite journal  | last1 = McCluggage | first1 = WG. | title = My approach to the interpretation of endometrial biopsies and curettings. | journal = J Clin Pathol | volume = 59 | issue = 8 | pages = 801-12 | month = Aug | year = 2006 | doi = 10.1136/jcp.2005.029702 | PMID = 16873562 | PMC = 1860448 }}</ref>
*[[Benign endometrial polyp]] - has thick-walled blood vessels; simple endometrial hyperplasia should not be diagnosed in a polyp.<ref name=pmid16873562/>


Images:
===Simple endometrial hyperplasia with atypia===
*[http://commons.wikimedia.org/wiki/File:Simple_endometrial_hyperplasia_-_low_mag.jpg Simple endometrial hyperplasia - low mag. (WC)].
{{Main|Simple endometrial hyperplasia}}
*[http://commons.wikimedia.org/wiki/File:Simple_endometrial_hyperplasia_-_high_mag.jpg Simple endometrial hyperplasia - high mag. (WC)].
 
==Simple endometrial hyperplasia with atypia==
===General===
*Very uncommon.
 
===Microscopic===
Features:<ref name=Ref_GP236>{{Ref GP|236}}</ref>
*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:<ref>{{Cite journal  | last1 = Silverberg | first1 = SG. | title = Problems in the differential diagnosis of endometrial hyperplasia and carcinoma. | journal = Mod Pathol | volume = 13 | issue = 3 | pages = 309-27 | month = Mar | year = 2000 | doi = 10.1038/modpathol.3880053 | PMID = 10757341 }}</ref>
**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):
*#Increased NC ratio.
*#*Atypical: ~ 1:2
*#*Not atypical: ~1:3.
*#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.
*#Small nucleoli (~1/5 the size of the nucleus).


==Complex endometrial hyperplasia==
===Complex endometrial hyperplasia===
*Abbreviated ''CEH''.
*Abbreviated ''CEH''.
{{Main|Complex endometrial hyperplasia}}
{{Main|Complex endometrial hyperplasia}}


==Complex endometrial hyperplasia with atypia==
===Complex endometrial hyperplasia with atypia===
*[[AKA]] ''complex atypical hyperplasia''.
*[[AKA]] ''complex atypical hyperplasia''.
{{Main|Complex endometrial hyperplasia}}
{{Main|Complex endometrial hyperplasia}}

Latest revision as of 15:42, 27 June 2016

See Endometrium for an introduction to the topic.

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

Overview

WHO endometrial hyperplasia classification of 2014

The 2014 WHO system has two categories:[1]

  • Hyperplasia without atypia.
  • Atypical hyperplasia/endometrioid intraepithelial neoplasia.

WHO endometrial hyperplasia classification of 1994

The 1994 WHO system is based on determining:[1]

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

It consists of four categories:

Alternate classifications - overview

Two alternative grading systems exist, that are (currently) not widely used:[2]

  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 of 1994

Management of endometrial hyperplasia

  • Endometrial hyperplasia with atypia is usually treated with hysterectomy.[3]
    • In women who want to maintain fertility it may be treated with progestin + short interval re-biopsies (q3 months).[4]
  • Endometrial hyperplasia without atypia is treated by:
    • Progestins + close follow-up OR hysterectomy.

Risk of progression to carcinoma as per 1994 system

Approximate risk of progression to endometrial carcinoma - Latta rule of 3s:[5]

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

Notes:

  • † 8% is the true number.[6]
  • ‡ 29% is the true number.[6]

Ki-67

There is one paper that looks at Ki-67:[7]

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 of 1994 - detail articles

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.

Simple endometrial hyperplasia with atypia

Complex endometrial hyperplasia

  • Abbreviated CEH.

Complex endometrial hyperplasia with atypia

  • AKA complex atypical hyperplasia.

Other

Endometrial hyperplasia with secretory changes

General

  • Rare.
  • Secretory changes seen in 1-2% of endometrial hyperplasias/endometrial carcinomas.[8]

Microscopic

Features:[9]

  • Secretory changes - includes at least one of three following:[10]
    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[11] mention (mitoses, nuclear atypia, pseudostratified epithelium).
    • Bell and Ostrezega[11] 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:

Images:

See also

References

  1. 1.0 1.1 Emons, G.; Beckmann, MW.; Schmidt, D.; Mallmann, P. (Feb 2015). "New WHO Classification of Endometrial Hyperplasias.". Geburtshilfe Frauenheilkd 75 (2): 135-136. doi:10.1055/s-0034-1396256. PMID 25797956.
  2. Dietel, M. (Nov 2001). "The histological diagnosis of endometrial hyperplasia. Is there a need to simplify?". Virchows Arch 439 (5): 604-8. PMID 11764378.
  3. URL: http://www.aafp.org/afp/990600ap/3069.html.
  4. URL: http://www.aafp.org/afp/20060801/practice.html.
  5. Latta, E. January 2009.
  6. 6.0 6.1 Kurman, RJ.; Kaminski, PF.; Norris, HJ. (Jul 1985). "The behavior of endometrial hyperplasia. A long-term study of untreated hyperplasia in 170 patients.". Cancer 56 (2): 403-12. PMID 4005805.
  7. Abike, F.; Tapisiz, OL.; Zergeroglu, S.; Dunder, I.; Temizkan, O.; Temizkan, I.; Payasli, A. (2011). "PCNA and Ki-67 in endometrial hyperplasias and evaluation of the potential of malignancy.". Eur J Gynaecol Oncol 32 (1): 77-80. PMID 21446331.
  8. Simon RA, Hansen K, Xiong JJ, et al. PTEN status and frequency of endometrial carcinoma and its precursors arising in functional secretory endometrium; an immunohistochemical study of 29 cases. Mod Pathol. 2012;25(Suppl 2): 1248A.
  9. Simon RA. CAP Today. June 2012. Accessed on: 24 April 2013.
  10. Tresserra, F.; Lopez-Yarto, M.; Grases, PJ.; Ubeda, A.; Pascual, MA.; Labastida, R. (Mar 2003). "Endometrial hyperplasia with secretory changes.". Gynecol Oncol 88 (3): 386-93. PMID 12648591.
  11. 11.0 11.1 Bell, CD.; Ostrezega, E. (Aug 1987). "The significance of secretory features and coincident hyperplastic changes in endometrial biopsy specimens.". Hum Pathol 18 (8): 830-8. PMID 3610133.