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]].


=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 carcinoma:<ref>LAE Jan 2009.</ref>
Approximate risk of progression to [[endometrial carcinoma]] - Latta rule of 3s:<ref>Latta, E. January 2009.</ref>
{| class="wikitable"
{| class="wikitable"
| || '''Simple''' || '''Complex'''
| || '''Simple''' || '''Complex'''
Line 39: Line 48:
| Without atypia || 1% || 3%
| Without atypia || 1% || 3%
|-
|-
| With atypia || 9% || 27%
| With atypia || 9% † || 27% ‡
|-
|-
|}
|}


=WHO system=
Notes:
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.
* † 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/>


==Simple endometrial hyperplasia==
===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.


===General===
===Simple endometrial hyperplasia===
*More common than simple endometrial hyperplasia with atypia.
*[[AKA]] ''simple hyperplasia''.
{{Main|Simple endometrial hyperplasia}}


===Microscopic===
===Simple endometrial hyperplasia with atypia===
Features:<ref name=Ref_GP236>{{Ref GP|236}}</ref>
{{Main|Simple endometrial hyperplasia}}
*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:
===Complex endometrial hyperplasia===
*[[Disordered proliferative phase]].
*Abbreviated ''CEH''.
{{Main|Complex endometrial hyperplasia}}


Images:
===Complex endometrial hyperplasia with atypia===
*[http://commons.wikimedia.org/wiki/File:Simple_endometrial_hyperplasia_-_low_mag.jpg Simple endometrial hyperplasia - low mag. (WC)].
*[[AKA]] ''complex atypical hyperplasia''.
*[http://commons.wikimedia.org/wiki/File:Simple_endometrial_hyperplasia_-_high_mag.jpg Simple endometrial hyperplasia - high mag. (WC)].
{{Main|Complex endometrial hyperplasia}}


==Simple endometrial hyperplasia with atypia==
=Other=
==Endometrial hyperplasia with secretory changes==
===General===
===General===
*Uncommon.
*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===
===Microscopic===
Features:<ref name=Ref_GP236>{{Ref GP|236}}</ref>
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>
*Irregular dilated glands (with large lumens) - '''important feature'''.
*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>
**Glands described as "animal shapes".  
*#Stromal decidualization.
*Variation of gland size.
*#Cytoplasmic vacuolization.
*No nuclear atypia.
*#Intraluminal secretions.
**Uniform columnar nuclei.
*Proliferative-type epithelium. †
*Normal gland density (gland area in plane of section/total area ~= 1/3).
**Mitoses.
*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>
**Nuclear atypia.
**Loss of basal nuclear stratification.
**Pseudostratified epithelium.
**Nuclear size variation.  
**Nuclear rounding.  
***Nuclei lacking atypical = uniform columnar nuclei.
**Nucleoli.
**Hyperchromasia or vesicular nuclei.


Notes:
Notes:
*There are no clear criteria for atypia. Different sources list different features.
* † 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).
*VL criteria for atypia (all should be present):
**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.
*#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==
 
===Microscopic===
Features:
*Increase in size & number of glands + irregular shape.
*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:
DDx:
*[[Complex endometrial hyperplasia with atypia]].
*[[Secretory phase endometrium]].
*[[Endometrioid endometrial carcinoma]] - see ''[[endometrial carcinoma versus complex endometrial hyperplasia]]''.
*[[Endometrium with hormonal changes]].


Image:
Images:
*[http://www.webpathology.com/image.asp?n=1&Case=568 Endometrial hyperplasia (webpathology.com)].
*[http://www.cap.org/apps/docs/cap_today/0612/0612a_qa.pdf Endometrial hyperplasia with secretory changes (cap.org)].
 
====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:<ref name=Ref_GP239>{{Ref GP|239}}</ref><ref name=pmid7074572>{{Cite journal  | last1 = Kurman | first1 = RJ. | last2 = Norris | first2 = HJ. | title = Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma. | journal = Cancer | volume = 49 | issue = 12 | pages = 2547-59 | month = Jun | year = 1982 | doi =  | PMID = 7074572 }}</ref><ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Endometrium_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Endometrium_11protocol.pdf]. Accessed on: 12 January 2012.</ref>
#Desmoplastic stromal response.
#Confluent cribriform growth. †
#Extensive papillary growth. †
#Severe cytologic atypia. †
 
Note:
* † There is a size cut-off for criteria 2, 3 and 4: > 2.1 mm.<ref name=pmid7074572/>
How to remember '''ABCDE''':
*'''A'''typia '''B'''ad.
*'''C'''onfluent cribriform growth.
*'''D'''esmoplasia.
*'''E'''xtensive papillary growth.
 
==Complex endometrial hyperplasia with atypia==
===General===
*High risk of transformation to endometrial carcinoma.
 
===Microscopic===
Features:
*Increase in size & number of glands + irreg. shape.
**Need cribriform architecture.
**Two "touching" glands are likely one gland in section.
*Cell stratification.
*Nuclear enlargement.
*Mitoses common.
*Nuclear atypia present.
 
DDx:
*[[Complex endometrial hyperplasia]].
*[[Endometrioid endometrial carcinoma]] - see ''[[endometrial carcinoma versus complex endometrial hyperplasia]]''.
 
Image:
*[http://www.webpathology.com/image.asp?n=2&Case=568 Complex endometrial hyperplasia with atypia (webpathology.com)].


=See also=
=See also=

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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