Difference between revisions of "Endometrial hyperplasia"

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:''See [[Endometrium]] for dating and benign pathologies.''
:''See [[Endometrium]] for an introduction to the topic.''
'''Endometrial hyperplasia''', abbreviated '''EH''', is a precursor to [[endometrial carcinoma]].
'''Endometrial hyperplasia''', abbreviated '''EH''', is a precursor to [[endometrial carcinoma]].


The most widely used system is from the World Health Organization (WHO). The WHO system is based on determining:
=Overview=
# Gland density (normal = ''simple hyperplasia'', high density = ''complex hyperplasia''), and
===WHO endometrial hyperplasia classification of 2014===
# Presence of atypia.  
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 system==
===WHO endometrial hyperplasia classification of 1994===
===Simple endometrial hyperplasia===
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>
Features:
# Gland density (normal/low = ''simple hyperplasia'', high density = ''complex hyperplasia'').
*Irregular gland shape.
# Presence/absence of nuclear atypia.  
*Variation of gland size.
*With or without atypia.
**Most commonly seen without atypia.
 
DDx:
*[[Disorder proliferative phase]].
 
Images:
*[http://commons.wikimedia.org/wiki/File:Simple_endometrial_hyperplasia_-_low_mag.jpg Simple endometrial hyperplasia - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Simple_endometrial_hyperplasia_-_high_mag.jpg Simple endometrial hyperplasia - high mag. (WC)].


===Complex endometrial hyperplasia===
It consists of four categories:  
Features:
*[[Simple endometrial hyperplasia]].
*Increase in size & number of glands + irreg. shape.
*[[Simple endometrial hyperplasia with atypia]].
**Need cribriform architecture.
*[[Complex endometrial hyperplasia]].
**Two "touching" glands are likely one gland in section.
*[[Complex endometrial hyperplasia with atypia]].
*Cell stratification.
*Nuclear enlargement.
*Mitoses common.
*May occur with atypia.


Notes:  
===Alternate classifications - overview===
*Normal ''gland-to-stroma ratio'' is 1:3.
Two alternative grading systems exist, that are (currently) not widely used:<ref name=pmid11764378>{{Cite journal  | last1 = Dietel | first1 = M. | title = The histological diagnosis of endometrial hyperplasia. Is there a need to simplify? | journal = Virchows Arch | volume = 439 | issue = 5 | pages = 604-8 | month = Nov | year = 2001 | doi =  | PMID = 11764378 }}</ref>
#European group of experts (1999).
#Endometrial collaborative group/Harvard (2000).


Images:
Both consist of two categories, as opposed to four found in the WHO classification.
*[http://www.webpathology.com/image.asp?n=1&Case=568 Endometrial hyperplasia (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=2&Case=568 Complex endometrial hyperplasia with atypia (webpathology.com)].


==Endometrial cancer vs. complex endometrial hyperplasia==
====European group of experts classification====
*Complex endometrial hyperplasia: non-confluent (glands distinct from one another).
#Endometrial hyperplasia.
*Diagnosis of complex EH is based on histology (cytologic features).
#Endometrioid neoplasia.


Note: An alternative grading system from Harvard exists. It is not widely used. It defines a term called ''endometrial intraepithelial neoplasia'' (EIN).
====Endometrial collaborative group/Harvard classification====
#Endometrial hyperplasia.  
#Endometrial intraepithelial neoplasia (EIN).


==Management of endometrial hyperplasia==
==WHO classification of 1994==
*Endometrial hyperplasia with atypia is usually treated with hysterectomy.<ref>[http://www.aafp.org/afp/990600ap/3069.html http://www.aafp.org/afp/990600ap/3069.html]</ref>
===Management of endometrial hyperplasia===
**In women who want to maintain fertility it may be treated with progestin + short interval re-biopsies (q3 months).<ref>[http://www.aafp.org/afp/20060801/practice.html http://www.aafp.org/afp/20060801/practice.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>
**In women who want to maintain fertility it may be treated with progestin + short interval re-biopsies (q3 months).<ref>URL: [http://www.aafp.org/afp/20060801/practice.html http://www.aafp.org/afp/20060801/practice.html].</ref>
*Endometrial hyperplasia without atypia is treated by:
*Endometrial hyperplasia without atypia is treated by:
**Progestins + close follow-up ''OR'' hysterectomy.
**Progestins + close follow-up ''OR'' hysterectomy.


==Endometrial carcinoma==
===Risk of progression to carcinoma as per 1994 system===
{{main|Endometrial carcinoma}}
Approximate risk of progression to [[endometrial carcinoma]] - Latta rule of 3s:<ref>Latta, E. January 2009.</ref>
Endometrial hyperplasia (EH) is a risk for the development of ''endometrioid endometrial carcinoma''.
 
===Risk of progression to carcinoma===
Approximate risk of progression to carcinoma:<ref>LAE Jan 2009.</ref>
{| class="wikitable"
{| class="wikitable"
| || '''Simple''' || '''Complex'''
| || '''Simple''' || '''Complex'''
Line 61: Line 48:
| Without atypia || 1% || 3%
| Without atypia || 1% || 3%
|-
|-
| With atypia || 9% || 27%
| With atypia || 9% † || 27% ‡
|-
|-
|}
|}


==See also==
Notes:
* † 8% is the true number.<ref name=pmid4005805>{{Cite journal  | last1 = Kurman | first1 = RJ. | last2 = Kaminski | first2 = PF. | last3 = Norris | first3 = HJ. | title = The behavior of endometrial hyperplasia. A long-term study of untreated hyperplasia in 170 patients. | journal = Cancer | volume = 56 | issue = 2 | pages = 403-12 | month = Jul | year = 1985 | doi =  | PMID = 4005805 }}</ref>
* ‡ 29% is the true number.<ref name=pmid4005805/>
 
===Ki-67===
There is one paper that looks at Ki-67:<ref>{{Cite journal  | last1 = Abike | first1 = F. | last2 = Tapisiz | first2 = OL. | last3 = Zergeroglu | first3 = S. | last4 = Dunder | first4 = I. | last5 = Temizkan | first5 = O. | last6 = Temizkan | first6 = I. | last7 = Payasli | first7 = A. | title = PCNA and Ki-67 in endometrial hyperplasias and evaluation of the potential of malignancy. | journal = Eur J Gynaecol Oncol | volume = 32 | issue = 1 | pages = 77-80 | month =  | year = 2011 | doi =  | PMID = 21446331 }}</ref>
{| class="wikitable sortable"
! Diagnosis
! Percent positive
|-
| [[Secretory phase endometrium]]
| <center>15%</center>
|-
| [[Proliferative phase endometrium]]
| <center>42%</center>
|-
| [[Simple endometrial hyperplasia|Simple hyperplasia]]
| <center>26%</center>
|-
| [[Simple endometrial hyperplasia with atypia|Simple hyperplasia with atypia]]
| <center>23%</center>
|-
| [[Complex endometrial hyperplasia|Complex hyperplasia]]
| <center>16%</center>
|-
| [[Complex endometrial hyperplasia with atypia|Complex hyperplasia with atypia]]
| <center>42%</center>
|}
 
==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.
 
===Simple endometrial hyperplasia===
*[[AKA]] ''simple hyperplasia''.
{{Main|Simple endometrial hyperplasia}}
 
===Simple endometrial hyperplasia with atypia===
{{Main|Simple endometrial hyperplasia}}
 
===Complex endometrial hyperplasia===
*Abbreviated ''CEH''.
{{Main|Complex endometrial hyperplasia}}
 
===Complex endometrial hyperplasia with atypia===
*[[AKA]] ''complex atypical hyperplasia''.
{{Main|Complex endometrial hyperplasia}}
 
=Other=
==Endometrial hyperplasia with secretory changes==
===General===
*Rare.
*Secretory changes seen in 1-2% of endometrial hyperplasias/endometrial carcinomas.<ref>Simon RA, Hansen K, Xiong JJ, et al. [http://www.abstracts2view.com/uscap12/view.php?nu=USCAP12L_1248 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.</ref>
 
===Microscopic===
Features:<ref>Simon RA. [http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt%7BactionForm.contentReference%7D=cap_today%2F0612%2F0612_qa.html CAP Today]. June 2012. Accessed on: 24 April 2013.</ref>
*Secretory changes - includes at least one of three following:<ref name=pmid12648591>{{Cite journal  | last1 = Tresserra | first1 = F. | last2 = Lopez-Yarto | first2 = M. | last3 = Grases | first3 = PJ. | last4 = Ubeda | first4 = A. | last5 = Pascual | first5 = MA. | last6 = Labastida | first6 = R. | title = Endometrial hyperplasia with secretory changes. | journal = Gynecol Oncol | volume = 88 | issue = 3 | pages = 386-93 | month = Mar | year = 2003 | doi =  | PMID = 12648591 }}</ref>
*#Stromal decidualization.
*#Cytoplasmic vacuolization.
*#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<ref name=pmid3610133/> mention (mitoses, nuclear atypia, pseudostratified epithelium).
**Bell and Ostrezega<ref name=pmid3610133>{{Cite journal  | last1 = Bell | first1 = CD. | last2 = Ostrezega | first2 = E. | title = The significance of secretory features and coincident hyperplastic changes in endometrial biopsy specimens. | journal = Hum Pathol | volume = 18 | issue = 8 | pages = 830-8 | month = Aug | year = 1987 | doi =  | PMID = 3610133 }}</ref> 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:
*[http://www.cap.org/apps/docs/cap_today/0612/0612a_qa.pdf Endometrial hyperplasia with secretory changes (cap.org)].
 
=See also=
*[[Endometrium]].
*[[Endometrium]].
*[[Endometrial carcinoma]].
*[[Gynecologic pathology]].
*[[Gynecologic pathology]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}


[[Category:Gynecologic pathology]]
[[Category:Gynecologic pathology]]

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.
Main article: Simple endometrial hyperplasia

Simple endometrial hyperplasia with atypia

Main article: Simple endometrial hyperplasia

Complex endometrial hyperplasia

  • Abbreviated CEH.
Main article: Complex endometrial hyperplasia

Complex endometrial hyperplasia with atypia

  • AKA complex atypical hyperplasia.
Main article: Complex endometrial 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.
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