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=
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:<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]].
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)].
==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:
Notes:
*There are no clear criteria for atypia. Different sources list different features.
* † 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>
*VL criteria for atypia (all should be present):
* ‡ 29% is the true number.<ref name=pmid4005805/>
*#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==
===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>
===Microscopic===
{| class="wikitable sortable"
Features:
! Diagnosis
*Increase in size & number of glands + irregular shape - '''key feature'''.
! Percent positive
*Cell stratification.
|-
*Nuclear enlargement.
| [[Secretory phase endometrium]]
*Mitoses common.
| <center>15%</center>
*No nuclear atypia.
|-
 
| [[Proliferative phase endometrium]]
Notes:
| <center>42%</center>
*Normal "gland-to-stroma ratio" is 1:3.
|-
*Two "touching" glands may be one gland in section.
| [[Simple endometrial hyperplasia|Simple hyperplasia]]
 
| <center>26%</center>
DDx:
|-
*[[Complex endometrial hyperplasia with atypia]].
| [[Simple endometrial hyperplasia with atypia|Simple hyperplasia with atypia]]
*[[Endometrioid endometrial carcinoma]] - see ''[[endometrial carcinoma versus complex endometrial hyperplasia]]''.
| <center>23%</center>
|-
| [[Complex endometrial hyperplasia|Complex hyperplasia]]
| <center>16%</center>
|-
| [[Complex endometrial hyperplasia with atypia|Complex hyperplasia with atypia]]
| <center>42%</center>
|}


Image:
==WHO system of 1994 - detail articles==
*[http://www.webpathology.com/image.asp?n=1&Case=568 Endometrial hyperplasia (webpathology.com)].
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.


====Endometrial carcinoma versus complex endometrial hyperplasia====
===Simple endometrial hyperplasia===
Complex endometrial hyperplasia:
*[[AKA]] ''simple hyperplasia''.
*Non-confluent - glands distinct from one another.
{{Main|Simple endometrial hyperplasia}}


=====Classic criteria for endometrial carcinoma=====
===Simple endometrial hyperplasia with atypia===
This is pimping material that shows up on exams.
{{Main|Simple endometrial hyperplasia}}


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>
===Complex endometrial hyperplasia===
#Desmoplastic stromal response.
*Abbreviated ''CEH''.
#Confluent cribriform growth. †
{{Main|Complex endometrial hyperplasia}}
#Extensive papillary growth. †
#Severe cytologic atypia. †


Note:
===Complex endometrial hyperplasia with atypia===
* † There is a size cut-off for criteria 2, 3 and 4: > 2.1 mm.<ref name=pmid7074572/>
*[[AKA]] ''complex atypical hyperplasia''.
{{Main|Complex endometrial hyperplasia}}
How to remember '''ABCDE''':
*'''A'''typia '''B'''ad.
*'''C'''onfluent cribriform growth.
*'''D'''esmoplasia.
*'''E'''xtensive papillary growth.


==Complex endometrial hyperplasia with atypia==
=Other=
==Endometrial hyperplasia with secretory changes==
===General===
===General===
*High risk of transformation to endometrial carcinoma.
*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:
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>
*Increase in size & number of glands + irregular shape - '''key 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>
*Cell stratification.
*#Stromal decidualization.
*Nuclear enlargement.
*#Cytoplasmic vacuolization.
*Nuclear atypia:
*#Intraluminal secretions.
**Round nuclei ~ 2-3x the size of a lymphocyte.
*Proliferative-type epithelium. †
**Grey/translucent chromatin.
**Mitoses.
**Nucleoli.
**Nuclear atypia.
*Mitoses common.
**Pseudostratified epithelium.


Note:
Notes:
*Atypical nuclei often hide between non-typical nuclei, like peg cells in the [[fallopian tube]].
* † 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:
DDx:
*[[Complex endometrial hyperplasia]].
*[[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=2&Case=568 Complex endometrial hyperplasia with atypia (webpathology.com)].
*[http://www.cap.org/apps/docs/cap_today/0612/0612a_qa.pdf Endometrial hyperplasia with secretory changes (cap.org)].
 
===Sign out===
====Insufficient confluence for carcinoma====
<pre>
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.
</pre>
 
====Insufficient extent for carcinoma====
<pre>
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.
</pre>


=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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