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{{Endometrial hyperplasia}}
{{Endometrial hyperplasia}}
{{CMG}}{{AE}}  {{Badria}} , {{STM}}
{{CMG}}{{AE}}  {{Swathi}}


==Overview==
==Overview==
[[Endometrial hyperplasia]] is a condition of excessive proliferation of the [[endometrial cells]] (inner lining of the [[uterus]]) associated with an increased gland to [[stroma]] ratio. The majority of cases of [[endometrial hyperplasia]] result from high concentrations of [[estrogen]] combined with insufficient concentration of the [[progesterone]]-like [[hormone]]s which normally counteract the proliferative effects of [[estrogen]] on the endometrial tissue.
[[Endometrial hyperplasia]] is a [[condition]] of excessive [[proliferation]] of the [[endometrial]] [[Cells (biology)|cells]] (inner [[lining]] of the [[uterus]]) associated with an increased [[gland]] to [[stroma]] [[ratio]]. The majority of cases of [[endometrial hyperplasia]] result from high [[concentrations]] of [[estrogen]] combined with insufficient [[concentration]] of the [[progesterone]]-like [[hormone]]s which [[Normal|normally]] counteract the [[Proliferation|proliferative]] effects of [[estrogen]] on the [[endometrial]] [[tissue]].
==Pathophysiology==
==Pathophysiology==
===Pathogenesis===
===Pathogenesis===
*[[Endometrial hyperplasia]] is a condition of excessive proliferation of the endometrial cells (inner lining of the uterus) associated with an increased gland to stroma ratio.
*[[Endometrial hyperplasia]] is a [[condition]] of excessive [[proliferation]] of the [[endometrial]] [[Cells (biology)|cells]] (inner lining of the [[uterus]]) associated with an increased [[gland]] to [[stroma]] [[ratio]].
*The majority of cases of endometrial hyperplasia result from high concentrations of [[estrogen]] combined with insufficient concentration of the [[progesterone]]-like hormones which normally counteract the proliferative effects of [[estrogen]] on the endometrial tissue.<ref name="wj">Endometrial hyperplasia. Wikipedia. https://en.wikipedia.org/wiki/Endometrial_hyperplasia Accessed on March 7, 2016.</ref>
*The majority of cases of [[endometrial]] [[hyperplasia]] result from high [[concentrations]] of [[estrogen]] combined with insufficient [[Concentrations|concentration]] of the [[progesterone]]-like [[hormones]] which [[Normal|normally]] counteract the [[Proliferate|proliferative]] effects of [[estrogen]] on the [[endometrial]] [[tissue]].<ref name="wj">Endometrial hyperplasia. Wikipedia. https://en.wikipedia.org/wiki/Endometrial_hyperplasia Accessed on March 7, 2016.</ref>
*Normal endometrial changes during menstrual cycle:<ref name="df">Menstrual cycle. Wikipedia. https://en.wikipedia.org/wiki/Menstrual_cycle Accessed on March 7, 2016</ref>  
*[[Normal]] [[endometrial]] changes during [[Menstrual cycle|menstrual]] [[Menstrual cycle|cycle]]:<ref name="df">Menstrual cycle. Wikipedia. https://en.wikipedia.org/wiki/Menstrual_cycle Accessed on March 7, 2016</ref>  
**The proliferative phase is the second phase in normal mentrual cycle when [[estrogen]] causes the lining of the uterus to proliferate. As the [[ovarian follicle]]s mature, they begin to secrete increasing amounts of [[estradiol]] and [[estrogen]]. The [[estrogen]]s initiate the formation of a new layer of [[endometrium]] in the [[uterus]], histologically identified as the proliferative endometrium.
**The [[Menstrual cycle|proliferative phase]] is the [[second]] phase in [[normal]] [[Menstrual cycle|mentrual cycle]] when [[estrogen]] [[causes]] the lining of the [[uterus]] to [[proliferate]]. As the [[ovarian follicle]]s mature, they begin to [[secrete]] increasing amounts of [[estradiol]] and [[estrogen]]. The [[estrogen]]s initiate the formation of a new layer of [[endometrium]] in the [[uterus]], [[histologically]] identified as the [[Proliferate|proliferative]] [[endometrium]].
**After [[ovulation]], the remains of the dominant follicle in the [[ovary]] become a [[corpus luteum]] which produces large amounts of [[progesterone]].
**After [[ovulation]], the remains of the [[dominant]] [[follicle]] in the [[ovary]] become a [[corpus luteum]] which produces large amounts of [[progesterone]].
**[[Anovulation]] results in the prolonged release of [[estrogen]] and the relative lack of [[progesterone]] resulting in excessive stimulation of the [[endometrium]].
**[[Anovulation]] results in the prolonged release of [[estrogen]] and the relative lack of [[progesterone]] [[Result|resulting]] in excessive stimulation of the [[endometrium]].
*Unopposed [[estrogen]] stimulation may be either from an endogenous or exogenous source.<ref name="pmid24678678">{{cite journal| author=Owings RA, Quick CM| title=Endometrial intraepithelial neoplasia. | journal=Arch Pathol Lab Med | year= 2014 | volume= 138 | issue= 4 | pages= 484-91 | pmid=24678678 | doi=10.5858/arpa.2012-0709-RA | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24678678  }} </ref><ref name="wj">Endometrial hyperplasia. Wikipedia. https://en.wikipedia.org/wiki/Endometrial_hyperplasia Accessed on March 7, 2016.</ref>  
*Unopposed [[estrogen]] stimulation may be either from an [[endogenous]] or [[exogenous]] source.<ref name="pmid24678678">{{cite journal| author=Owings RA, Quick CM| title=Endometrial intraepithelial neoplasia. | journal=Arch Pathol Lab Med | year= 2014 | volume= 138 | issue= 4 | pages= 484-91 | pmid=24678678 | doi=10.5858/arpa.2012-0709-RA | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24678678  }} </ref><ref name="wj">Endometrial hyperplasia. Wikipedia. https://en.wikipedia.org/wiki/Endometrial_hyperplasia Accessed on March 7, 2016.</ref>  
**Excessive endogenous [[estrogen]] in pre or [[perimenopausal]] women may result from chronic [[anovulation]] caused by [[obesity]], [[polycystic ovary disease]], and [[estrogen]] producing tumors (e.g. [[granulosa cell tumor]]).
**Excessive [[endogenous]] [[estrogen]] in pre or [[perimenopausal]] [[Female|women]] may result from [[Chronic (medical)|chronic]] [[anovulation]] caused by [[obesity]], [[polycystic ovary disease]], and [[estrogen]] producing [[tumors]] (e.g. [[granulosa cell tumor]]).
**Excessive exogenous [[estrogen]] may result from [[hormone replacement therapy]] or non-prescription herbal medications.
**Excessive [[exogenous]] [[estrogen]] may [[result]] from [[hormone replacement therapy]] or non-[[prescription]] [[Herbal medicine|herbal]] [[medications]].
*[[Tamoxifen]] therapy in [[breast cancer]] patients results in an endometrial lesion within 6-36 months of therapy.<ref name="mn">Tamoxifen associated endometrial changes. Radiopedia. http://radiopaedia.org/articles/tamoxifen-associated-endometrial-changes Accessed on March 10, 2016</ref>
*[[Tamoxifen]] [[therapy]] in [[breast cancer]] [[patients]] results in an [[endometrial]] [[lesion]] within 6-36 months of [[therapy]].<ref name="mn">Tamoxifen associated endometrial changes. Radiopedia. http://radiopaedia.org/articles/tamoxifen-associated-endometrial-changes Accessed on March 10, 2016</ref>
**[[Tamoxifen]] is a non-steroidal anti-estrogen that binds to the [[estrogen receptor]] and is used primarily for adjuvant therapy in [[breast cancer]]
**[[Tamoxifen]] is a non-[[steroidal]] anti-[[estrogen]] that binds to the [[estrogen receptor]] and is used primarily for [[adjuvant]] [[therapy]] in [[breast cancer]]
**Tamoxifen may also act as an [[estrogen]] agonist in a low [[estradiol]] environment
**[[Tamoxifen]] may also act as an [[estrogen]] [[agonist]] in a low [[estradiol]] environment
**Any patient who develops bleeding while on [[tamoxifen]] needs evaluation   
**Any [[patient]] who [[Development (biology)|develops]] [[bleeding]] while on [[tamoxifen]] needs evaluation   
*Endometrial hyperplasia may rarely result from the peripheral conversion of [[androgen]]s to [[estrogen]]s in androgen-secreting tumors of the [[adrenal cortex]].<ref>Endometrial hyperplasia. Wiley Online Library.http://onlinelibrary.wiley.com/doi/10.1576/toag.10.4.211.27436/full Accessed on March 7, 2016</ref><ref name="pmid12586588">{{cite journal |vauthors=Wang S, Pudney J, Song J, Mor G, Schwartz PE, Zheng W |title=Mechanisms involved in the evolution of progestin resistance in human endometrial hyperplasia--precursor of endometrial cancer |journal=Gynecol. Oncol. |volume=88 |issue=2 |pages=108–17 |date=February 2003 |pmid=12586588 |doi= |url=}}</ref>
*[[Endometrial]] [[hyperplasia]] may [[Rare|rarely]] result from the peripheral conversion of [[androgen]]s to [[estrogen]]s in [[androgen]]-[[Secrete|secreting]] [[tumors]] of the [[adrenal cortex]].<ref>Endometrial hyperplasia. Wiley Online Library.http://onlinelibrary.wiley.com/doi/10.1576/toag.10.4.211.27436/full Accessed on March 7, 2016</ref><ref name="pmid12586588">{{cite journal |vauthors=Wang S, Pudney J, Song J, Mor G, Schwartz PE, Zheng W |title=Mechanisms involved in the evolution of progestin resistance in human endometrial hyperplasia--precursor of endometrial cancer |journal=Gynecol. Oncol. |volume=88 |issue=2 |pages=108–17 |date=February 2003 |pmid=12586588 |doi= |url=}}</ref>


==Genetics==
==Genetics==
It is assumed that there is association between endometrial hyperplasia and DNA repair gene (XPD, XRCC4, and XRCC1) polymorphisms. After experiments, it became evident the DNA repair gene XPD and XRCC4 polymorphisms had a role in the pathophysiology of endometrial hyperplasia.<ref name="pmid30275440">{{cite journal |vauthors=Öztürk E, Pehlivan S, Balat O, Ugur MG, Ozcan HC, Erkılıç S |title=DNA Repair Gene (XPD, XRCC4, and XRCC1) Polymorphisms in Patients with Endometrial Hyperplasia: A Pilot Study |journal=Med Sci Monit Basic Res |volume=24 |issue= |pages=146–150 |date=October 2018 |pmid=30275440 |doi=10.12659/MSMBR.911041 |url=}}</ref>
It is assumed that there is association between [[Endometrium|endometrial]] [[hyperplasia]] and [[DNA]] repair [[gene]] (XPD, XRCC4, and XRCC1) [[polymorphisms]]. After [[experiments]], it became evident the [[DNA]] repair [[gene]] XPD and XRCC4 [[polymorphisms]] had a role in the [[pathophysiology]] of [[endometrial]] [[hyperplasia]].<ref name="pmid30275440">{{cite journal |vauthors=Öztürk E, Pehlivan S, Balat O, Ugur MG, Ozcan HC, Erkılıç S |title=DNA Repair Gene (XPD, XRCC4, and XRCC1) Polymorphisms in Patients with Endometrial Hyperplasia: A Pilot Study |journal=Med Sci Monit Basic Res |volume=24 |issue= |pages=146–150 |date=October 2018 |pmid=30275440 |doi=10.12659/MSMBR.911041 |url=}}</ref>


===Other Genes involved===
===Other Genes involved===
* Oncogene bcl-2 in complex hyperplasia<ref name="pmid1458483">{{cite journal |vauthors=McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C, Chung LW, Hsieh JT, Tu SM, Campbell ML |title=Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer |journal=Cancer Res. |volume=52 |issue=24 |pages=6940–4 |date=December 1992 |pmid=1458483 |doi= |url=}}</ref><ref>{{cite journal|doi=10.1002/1097-0142(19950501)75:9<2209}}</ref>
* [[Oncogene]] bcl-2 in [[Complex (chemistry)|complex]] [[hyperplasia]]<ref name="pmid1458483">{{cite journal |vauthors=McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C, Chung LW, Hsieh JT, Tu SM, Campbell ML |title=Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer |journal=Cancer Res. |volume=52 |issue=24 |pages=6940–4 |date=December 1992 |pmid=1458483 |doi= |url=}}</ref><ref>{{cite journal|doi=10.1002/1097-0142(19950501)75:9<2209}}</ref>


* Mutations in [[PTEN]] and [[KRAS]] [[PTEN]] [[tumor suppressor gene]] [[mutations]] have also been found<ref name="pmid8617450">{{cite journal |vauthors=Lu QL, Abel P, Foster CS, Lalani EN |title=bcl-2: role in epithelial differentiation and oncogenesis |journal=Hum. Pathol. |volume=27 |issue=2 |pages=102–10 |date=February 1996 |pmid=8617450 |doi= |url=}}</ref>  
* [[Mutations]] in [[PTEN]] and [[KRAS]] [[PTEN]] [[tumor suppressor gene]] [[mutations]] have also been found<ref name="pmid8617450">{{cite journal |vauthors=Lu QL, Abel P, Foster CS, Lalani EN |title=bcl-2: role in epithelial differentiation and oncogenesis |journal=Hum. Pathol. |volume=27 |issue=2 |pages=102–10 |date=February 1996 |pmid=8617450 |doi= |url=}}</ref>  


* [[Fas/FasL]] [[gene]] also has been investigated recently in the development of endometrial hyperplasia  
* [[Fas/FasL]] [[gene]] also has been investigated recently in the [[development]] of [[endometrial]] [[hyperplasia]]
===Mtor Signallin pathway===
===Mtor Signallin pathway===
* [[mTOR]] signaling is required for [[estrogen]]-mediated growth of [[endometrial cells]]
* [[mTOR]] [[Signal (biology)|signaling]] is required for [[estrogen]]-mediated [[growth]] of [[endometrial cells]]
* Dysregulated [[mTOR]] signaling leads to female [[infertility]] due to defects in [[ovarian]], oviductal, and [[endometrial]] functions .<ref name="pmid22128018">{{cite journal |vauthors=Tanaka Y, Park JH, Tanwar PS, Kaneko-Tarui T, Mittal S, Lee HJ, Teixeira JM |title=Deletion of tuberous sclerosis 1 in somatic cells of the murine reproductive tract causes female infertility |journal=Endocrinology |volume=153 |issue=1 |pages=404–16 |date=January 2012 |pmid=22128018 |pmc=3249683 |doi=10.1210/en.2011-1191 |url=}}</ref><ref name="pmid25733860">{{cite journal |vauthors=Wang Y, Zhu L, Kuokkanen S, Pollard JW |title=Activation of protein synthesis in mouse uterine epithelial cells by estradiol-17β is mediated by a PKC-ERK1/2-mTOR signaling pathway |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=112 |issue=11 |pages=E1382–91 |date=March 2015 |pmid=25733860 |pmc=4371960 |doi=10.1073/pnas.1418973112 |url=}}</ref><ref name="pmid20519781">{{cite journal |vauthors=Blagosklonny MV |title=Why men age faster but reproduce longer than women: mTOR and evolutionary perspectives |journal=Aging (Albany NY) |volume=2 |issue=5 |pages=265–73 |date=May 2010 |pmid=20519781 |pmc=2898017 |doi=10.18632/aging.100149 |url=}}</ref>
* Dysregulated [[mTOR]] [[Signal (biology)|signaling]] leads to [[female]] [[infertility]] due to defects in [[ovarian]], oviductal, and [[endometrial]] [[Function (biology)|functions]] .<ref name="pmid22128018">{{cite journal |vauthors=Tanaka Y, Park JH, Tanwar PS, Kaneko-Tarui T, Mittal S, Lee HJ, Teixeira JM |title=Deletion of tuberous sclerosis 1 in somatic cells of the murine reproductive tract causes female infertility |journal=Endocrinology |volume=153 |issue=1 |pages=404–16 |date=January 2012 |pmid=22128018 |pmc=3249683 |doi=10.1210/en.2011-1191 |url=}}</ref><ref name="pmid25733860">{{cite journal |vauthors=Wang Y, Zhu L, Kuokkanen S, Pollard JW |title=Activation of protein synthesis in mouse uterine epithelial cells by estradiol-17β is mediated by a PKC-ERK1/2-mTOR signaling pathway |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=112 |issue=11 |pages=E1382–91 |date=March 2015 |pmid=25733860 |pmc=4371960 |doi=10.1073/pnas.1418973112 |url=}}</ref><ref name="pmid20519781">{{cite journal |vauthors=Blagosklonny MV |title=Why men age faster but reproduce longer than women: mTOR and evolutionary perspectives |journal=Aging (Albany NY) |volume=2 |issue=5 |pages=265–73 |date=May 2010 |pmid=20519781 |pmc=2898017 |doi=10.18632/aging.100149 |url=}}</ref>


==Gross pathology==
==Gross pathology==
[[Endometrial]] [[hyperplasia]] typically represents as: <ref name="LaceyIoffe2007">{{cite journal|last1=Lacey|first1=J V|last2=Ioffe|first2=O B|last3=Ronnett|first3=B M|last4=Rush|first4=B B|last5=Richesson|first5=D A|last6=Chatterjee|first6=N|last7=Langholz|first7=B|last8=Glass|first8=A G|last9=Sherman|first9=M E|title=Endometrial carcinoma risk among women diagnosed with endometrial hyperplasia: the 34-year experience in a large health plan|journal=British Journal of Cancer|volume=98|issue=1|year=2007|pages=45–53|issn=0007-0920|doi=10.1038/sj.bjc.6604102}}</ref>
[[Endometrial]] [[hyperplasia]] typically represents as: <ref name="LaceyIoffe2007">{{cite journal|last1=Lacey|first1=J V|last2=Ioffe|first2=O B|last3=Ronnett|first3=B M|last4=Rush|first4=B B|last5=Richesson|first5=D A|last6=Chatterjee|first6=N|last7=Langholz|first7=B|last8=Glass|first8=A G|last9=Sherman|first9=M E|title=Endometrial carcinoma risk among women diagnosed with endometrial hyperplasia: the 34-year experience in a large health plan|journal=British Journal of Cancer|volume=98|issue=1|year=2007|pages=45–53|issn=0007-0920|doi=10.1038/sj.bjc.6604102}}</ref>
* A thickened [[endometrial]] stripe on [[transvaginal ultrasound]]
* A thickened [[endometrial]] stripe on [[transvaginal ultrasound]]
* Increased volume of [[endometrial]] tissue on [[hysteroscopy]] or curettage
* Increased [[volume]] of [[endometrial]] tissue on [[hysteroscopy]] or [[curettage]]
* [[Hyperplasia]] may be associated with abundant [[endometrial]] tissue  
* [[Hyperplasia]] may be associated with abundant [[endometrial]] [[Tissue (biology)|tissue]]
* In some cases, localized [[hyperplasia]] may mimic a [[polyp]], arise in a background of a [[polyp]], or involve [[adenomyosis]], including deep [[foci]]  
* In some cases, [[Localized disease|localized]] [[hyperplasia]] may mimic a [[polyp]], arise in a [[background]] of a [[polyp]], or involve [[adenomyosis]], including deep [[foci]]  


==Microscopic Pathology==
==Microscopic Pathology==
*Prolonged estrogenic stimulation results in larger, more complex, and proliferating endometrial glands.<ref name="pmid24678678">{{cite journal| author=Owings RA, Quick CM| title=Endometrial intraepithelial neoplasia. | journal=Arch Pathol Lab Med | year= 2014 | volume= 138 | issue= 4 | pages= 484-91 | pmid=24678678 | doi=10.5858/arpa.2012-0709-RA | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24678678  }} </ref>
*Prolonged [[estrogenic]] stimulation [[Result|results]] in larger, more [[Complex (chemistry)|complex]], and [[Proliferate|proliferating]] [[endometrial]] [[glands]].<ref name="pmid24678678">{{cite journal| author=Owings RA, Quick CM| title=Endometrial intraepithelial neoplasia. | journal=Arch Pathol Lab Med | year= 2014 | volume= 138 | issue= 4 | pages= 484-91 | pmid=24678678 | doi=10.5858/arpa.2012-0709-RA | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24678678  }} </ref>
*On microscopic histopathological analysis, the proliferating [[endometrium]] is characterized by the following:<ref name="pmid16873562">{{cite journal| author=McCluggage WG| title=My approach to the interpretation of endometrial biopsies and curettings. | journal=J Clin Pathol | year= 2006 | volume= 59 | issue= 8 | pages= 801-12 | pmid=16873562 | doi=10.1136/jcp.2005.029702 | pmc=PMC1860448 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16873562  }} </ref>
*On [[microscopic]] [[histopathological]] [[analysis]], the [[Proliferate|proliferating]] [[endometrium]] is characterized by the following:<ref name="pmid16873562">{{cite journal| author=McCluggage WG| title=My approach to the interpretation of endometrial biopsies and curettings. | journal=J Clin Pathol | year= 2006 | volume= 59 | issue= 8 | pages= 801-12 | pmid=16873562 | doi=10.1136/jcp.2005.029702 | pmc=PMC1860448 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16873562  }} </ref>


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* Endometrial hyperplasia is morphologically defined as proliferating endometrium with architectural abnormalities.
* [[Endometrial hyperplasia]] is [[Morphology (biology)|morphologically]] defined as [[Proliferation|proliferating]] [[endometrium]] with architectural [[abnormalities]].
* These architectural changes range as :  
* These architectural changes are :  
** Cystic dilatation  
** [[Cystic]] [[dilatation]]
** Budding and branching
** [[Budding]] and [[Branching process|branching]]
** Papillary infoldings
** [[Papillary]] infoldings
** Villous and villoglandular growths
** [[Villous folds|Villous]] and villoglandular [[Growth|growths]]
** Cribriform structures.
** [[Cribriform]] structures.
* In addition to abnormal architecture, a diagnosis of hyperplasia usually requires increased glandular density with a gland-to-stroma ratio of ∼3:1.  
* In addition to [[abnormal]] architecture, a [[diagnosis]] of [[hyperplasia]] usually requires increased [[glandular]] [[density]] with a [[gland]]-to-[[stroma]] [[ratio]] of ∼3:1.  
* Luminal spaces and villoglandular structures are also included in the glandular component for this calculation.
* [[Luminal]] spaces and villoglandular structures are also included in the [[glandular]] component for this calculation.
* If the gland-to-stroma ratio fails to meet the required cut-off, a lesion is probably best classified as disordered proliferative endometrium rather than hyperplasia.  
* If the [[gland]]-to-[[stroma]] ratio fails to meet the required cut-off, a lesion is classified as disordered proliferative [[endometrium]] rather than [[hyperplasia]].  
* Although hyperplastic endometrium might have cytologic atypia, this criterion is neither required nor sufficient for this diagnosis.
* Although [[Hyperplasia|hyperplastic]] [[endometrium]] might have [[Cytological|cytologic]] [[atypia]], this criterion is neither required nor sufficient for this diagnosis.
*  The assessment of cytologic atypia is poorly understood, but the various criteria include:  
*  The assessment of cytologic [[atypia]] is poorly understood, but the various criteria include:  
** Nuclear rounding and enlargement
** [[Nuclear]] rounding and enlargement
** Nuclear pleomorphism
** [[Nuclear]] [[pleomorphism]]
** Loss of polarity
** Loss of [[polarity]]
** Increased nuclear-to-cytoplasm ratio
** Increased [[nuclear]]-to-[[cytoplasm]] ratio
**  Prominent nucleoli
**  Prominent [[nucleoli]]
** Irregular nuclear borders
** Irregular [[nuclear]] borders
** Vesicular chromatin
** [[Vesicular]] [[chromatin]]
** Clumped chromatin
** Clumped [[chromatin]]
**  Atypical cells may show tufting and focal stratification
**  Atypical cells may show tufting and focal stratification
=== World Health Organization classification of endometrial hyperplasia===
** Simple hyperplasia without atypia
** Simple hyperplasia is characterized by:
*** Densely packed, cystically dilated, variable sized glands separated by normal intervening stroma ( Figure 10 ). Although
*** 3:1 gland-to-stroma ratio.
*** Ciliated cells
*** squamous morular metaplasia
** Complex hyperplasia without atypia
** Complex hyperplasia without atypia is defined as:
*** Glands with abnormal, irregular architecture set in a background of scant intervening stroma
*** Some stroma must be present,
*** Basement membrane lining individual glands and a rim of intervening endometrial-type stroma between them. In addition to back-to-back and cribriform-like arrangements, other glandular architectural abnormalities warranting designation of complex hyperplasia include
*** Outpouchings,
*** Infoldings, and budding
*** Squamous or morular metaplasia
*** Eosinophilic and ciliated cell changes 
** Simple hyperplasia with atypia
** Complex hyperplasia with atypia
*** Increased gland-to-stroma ratio (≥3:1)
*** Gland complexity—caused by:
**** Branching
**** Outward budding
**** Internal papillary infoldings
**** Internal bridge
===Gallery===
===Gallery===
<gallery>
<gallery>

Latest revision as of 15:00, 7 May 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Swathi Venkatesan, M.B.B.S.[2]

Overview

Endometrial hyperplasia is a condition of excessive proliferation of the endometrial cells (inner lining of the uterus) associated with an increased gland to stroma ratio. The majority of cases of endometrial hyperplasia result from high concentrations of estrogen combined with insufficient concentration of the progesterone-like hormones which normally counteract the proliferative effects of estrogen on the endometrial tissue.

Pathophysiology

Pathogenesis

Genetics

It is assumed that there is association between endometrial hyperplasia and DNA repair gene (XPD, XRCC4, and XRCC1) polymorphisms. After experiments, it became evident the DNA repair gene XPD and XRCC4 polymorphisms had a role in the pathophysiology of endometrial hyperplasia.[7]

Other Genes involved

Mtor Signallin pathway

Gross pathology

Endometrial hyperplasia typically represents as: [14]

Microscopic Pathology
Character Simple hyperplasia Complex hyperplasia

Gland to stroma ratio

  • Normal or slightly increased
  • Increased

Endometrium

  • Irregularly dilated cystic glands
  • Out‐pouching, infoldings, and budding of the glands may be present
  • Glandular crowding
  • Luminal outpouching of glands

Mitoses

  • May or may not be present
  • Typically present

Location

  • Generalized
  • Focal

Nuclear atypia

  • Not seen
  • Not seen

Gallery

  • Diagram illustrating how the uterus lining builds up and breaks down during the menstrual cycle[16]

    Diagram illustrating how the uterus lining builds up and breaks down during the menstrual cycle[16]

  • Low magnification micrograph of simple endometrial hyperplasia without nuclear atypia. Normal gland-to-stroma ratio (~1:3); proliferating pseudostratified glandular epithelium; irregular endometrial glands: dilated glands or glands with variable size; non-ovoid/non-circular glands[17]

    Low magnification micrograph of simple endometrial hyperplasia without nuclear atypia. Normal gland-to-stroma ratio (~1:3); proliferating pseudostratified glandular epithelium; irregular endometrial glands: dilated glands or glands with variable size; non-ovoid/non-circular glands[17]

References

  1. ↑ 1.0 1.1 Endometrial hyperplasia. Wikipedia. https://en.wikipedia.org/wiki/Endometrial_hyperplasia Accessed on March 7, 2016.
  2. ↑ Menstrual cycle. Wikipedia. https://en.wikipedia.org/wiki/Menstrual_cycle Accessed on March 7, 2016
  3. ↑ 3.0 3.1 Owings RA, Quick CM (2014). "Endometrial intraepithelial neoplasia". Arch Pathol Lab Med. 138 (4): 484–91. doi:10.5858/arpa.2012-0709-RA. PMID 24678678.
  4. ↑ Tamoxifen associated endometrial changes. Radiopedia. http://radiopaedia.org/articles/tamoxifen-associated-endometrial-changes Accessed on March 10, 2016
  5. ↑ Endometrial hyperplasia. Wiley Online Library.http://onlinelibrary.wiley.com/doi/10.1576/toag.10.4.211.27436/full Accessed on March 7, 2016
  6. ↑ Wang S, Pudney J, Song J, Mor G, Schwartz PE, Zheng W (February 2003). "Mechanisms involved in the evolution of progestin resistance in human endometrial hyperplasia--precursor of endometrial cancer". Gynecol. Oncol. 88 (2): 108–17. PMID 12586588.
  7. ↑ Öztürk E, Pehlivan S, Balat O, Ugur MG, Ozcan HC, Erkılıç S (October 2018). "DNA Repair Gene (XPD, XRCC4, and XRCC1) Polymorphisms in Patients with Endometrial Hyperplasia: A Pilot Study". Med Sci Monit Basic Res. 24: 146–150. doi:10.12659/MSMBR.911041. PMID 30275440.
  8. ↑ McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C, Chung LW, Hsieh JT, Tu SM, Campbell ML (December 1992). "Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer". Cancer Res. 52 (24): 6940–4. PMID 1458483.
  9. ↑ . doi:10.1002/1097-0142(19950501)75:9<2209. Missing or empty |title= (help)
  10. ↑ Lu QL, Abel P, Foster CS, Lalani EN (February 1996). "bcl-2: role in epithelial differentiation and oncogenesis". Hum. Pathol. 27 (2): 102–10. PMID 8617450.
  11. ↑ Tanaka Y, Park JH, Tanwar PS, Kaneko-Tarui T, Mittal S, Lee HJ, Teixeira JM (January 2012). "Deletion of tuberous sclerosis 1 in somatic cells of the murine reproductive tract causes female infertility". Endocrinology. 153 (1): 404–16. doi:10.1210/en.2011-1191. PMC 3249683. PMID 22128018.
  12. ↑ Wang Y, Zhu L, Kuokkanen S, Pollard JW (March 2015). "Activation of protein synthesis in mouse uterine epithelial cells by estradiol-17β is mediated by a PKC-ERK1/2-mTOR signaling pathway". Proc. Natl. Acad. Sci. U.S.A. 112 (11): E1382–91. doi:10.1073/pnas.1418973112. PMC 4371960. PMID 25733860.
  13. ↑ Blagosklonny MV (May 2010). "Why men age faster but reproduce longer than women: mTOR and evolutionary perspectives". Aging (Albany NY). 2 (5): 265–73. doi:10.18632/aging.100149. PMC 2898017. PMID 20519781.
  14. ↑ Lacey, J V; Ioffe, O B; Ronnett, B M; Rush, B B; Richesson, D A; Chatterjee, N; Langholz, B; Glass, A G; Sherman, M E (2007). "Endometrial carcinoma risk among women diagnosed with endometrial hyperplasia: the 34-year experience in a large health plan". British Journal of Cancer. 98 (1): 45–53. doi:10.1038/sj.bjc.6604102. ISSN 0007-0920.
  15. ↑ McCluggage WG (2006). "My approach to the interpretation of endometrial biopsies and curettings". J Clin Pathol. 59 (8): 801–12. doi:10.1136/jcp.2005.029702. PMC 1860448. PMID 16873562.
  16. ↑ Menstrual cycle. Wikipedia. https://en.wikipedia.org/wiki/Menstrual_cycle Accessed on March 7, 2016
  17. ↑ Endometrial hyperplasia. Wikipedia. https://en.wikipedia.org/wiki/Endometrial_hyperplasia#/media/File:Simple_endometrial_hyperplasia_-_low_mag.jpg Accessed on March 7, 2016

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