Difference between revisions of "Endometrium"

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The '''endometrium''' is typically biopsied because of abnormal bleeding.
The '''endometrium''' is typically biopsied because of abnormal bleeding.  [[Endometrial hyperplasia]] and [[endometrial carcinoma]] are dealt with in separate articles.  An overview of gynecologic pathology is in the ''[[gynecologic pathology]]'' article.


==Indications for endometrial biopsy==
==Indications for endometrial biopsy==
Biopsies done for bleeding:  
Abnormal bleeding:  
*Too much bleeding (if premenopausal) - ''AUB'' = abnormal uterine bleeding.
*[[Abnormal uterine bleeding]] (AUB).
*Post-menopausal bleeding.
**[[Dysfunctional uterine bleeding]], abbreviated ''DUB'', is diagnosed if other causes of bleeding are excluded.
*Dysfunctional uterine bleeding [[AKA]] ''DUB'' - may get D&C if they fail medical management.<ref>URL: [http://emedicine.medscape.com/article/257007-treatment http://emedicine.medscape.com/article/257007-treatment]. Accessed on: 15 July 2010.</ref>
**''DUB'' may get a D&C if they fail medical management.<ref>URL: [http://emedicine.medscape.com/article/257007-treatment http://emedicine.medscape.com/article/257007-treatment]. Accessed on: 15 July 2010.</ref>
**DUB is diagnosed if other causes of bleeding are excluded.
**Post-menopausal bleeding.
 
Other indications:<ref>{{Ref EMB|1}}</ref>
*[[Products of conception]] - dealt with in a separate article.
*Dating of endometrium - infertility work-up.
 
===Endometrial thickness on ultrasound===
*A thin endometrium on ultrasound has a very low risk of malignancy.<ref name=pmid15283934>{{Cite journal  | last1 = Gambacciani | first1 = M. | last2 = Monteleone | first2 = P. | last3 = Ciaponi | first3 = M. | last4 = Sacco | first4 = A. | last5 = Genazzani | first5 = AR. | title = Clinical usefulness of endometrial screening by ultrasound in asymptomatic postmenopausal women. | journal = Maturitas | volume = 48 | issue = 4 | pages = 421-4 | month = Aug | year = 2004 | doi = 10.1016/j.maturitas.2003.10.006 | PMID = 15283934 }}</ref>


=Normal microscopic findings=
=Normal microscopic findings=
==General==
Endometrium - consists of:
#Epithelium (endometrial glands).
#Stroma (endometrial stroma).
 
In endometrial biopsies:
*Endocervical glands are commonly seen, as is endocervical mucous.
*Endocervical glands are commonly seen, as is endocervical mucous.
**This is 'cause the gynecologist scrapes some off on the way in or out.
**This is 'cause the gynecologist scrapes some off on the way in or out.


==Endocervical glands vs. Endometrial glands==
==Glandular telescoping==
===Endocervical===
:[[AKA]] ''gland-within-a-gland''.
:[[AKA]] ''gland intussusception''.
:[[AKA]] ''telescoping''.
*Considered an artifact of tissue processing, i.e. normal.<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 }}</ref>
 
Image:
*[http://jcp.bmjjournals.com/content/59/8/801/F3.large.jpg Telescoping (bmjjournals.com)].<ref name=pmid16873562/>
 
==Endometrial gland compression artifact==
:[[AKA]] ''compression artifact''.
*Gland moulding.
*Tearing of tissue around the compressed glands - '''key feature'''.
*Usually at the edge of a tissue fragment.
 
DDx:
*Focal [[complex endometrial hyperplasia]].
 
===Image===
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860448/figure/fig4/ Gland compression (bmjjournals.com)].<ref name=pmid16873562/>
 
===Micro===
An increased gland density is seen focally, at the edge of one tissue fragment, in association with tearing of the stroma (compression artifact).
 
===See also===
*[[Endometrial gland coiling]].
 
==Endocervical epithelium versus endometrial epithelium==
===Table===
{| class="wikitable sortable"
! Feature
! Endometrial
! Endocervical
! Tubal metaplasia
|-
| Cytoplasmic staining
| usu. hyperchromatic +/-vacuoles
| clear or light eosinophilic
| hyperchromatic
|-
| [[Nucleus-to-cytoplasm ratio]]
| moderate to high (1:2)
| low (often 1:3)
| high (1:1)
|-
| Surface features
|
|
| villi
|-
| Associated stroma
| cellular, hyperchromatic
| inflamed, less cellular
| variable
|}
 
===List===
Endocervical:
*Less hyperchromatic.
*Less hyperchromatic.
*Nuclei round & small.
*Nuclei round & small.
*Cell borders usually well-defined.
*Cell borders usually well-defined.
===Endometrial===
 
Endometrial:
*More hyperchromatic.
*More hyperchromatic.
*Nuclei columnar.
*Nuclei columnar.


=A simple approach=
===Images===
==Low power==
<gallery>
#Decide whether you're look at endometrium.
Image:Endometrial and endocervical epithelium - low mag.jpg | Endocervical and endometrial epithelium - low mag. (WC)
#Gland-to-stroma ratio normal?
Image:Endometrial and endocervical epithelium - high mag.jpg | Endocervical and endometrial epithelium - high mag. (WC)
</gallery>
 
==Metaplasias of the endometrium==
The big table of metaplasias - adapted from Nicolae ''et al.'':<ref name=pmid21126963>{{Cite journal  | last1 = Nicolae | first1 = A. | last2 = Preda | first2 = O. | last3 = Nogales | first3 = FF. | title = Endometrial metaplasias and reactive changes: a spectrum of altered differentiation. | journal = J Clin Pathol | volume = 64 | issue = 2 | pages = 97-106 | month = Feb | year = 2011 | doi = 10.1136/jcp.2010.085555 | PMID = 21126963 }}</ref>
{| class="wikitable sortable"
! Metaplasia
! Subtypes
! Microscopic
! Notes
! Risk of malignancy
! Image
|-
| [[Endometrium with squamous morules|Morules]]
| -
|
|
| nearly always
| [[Image:Squamous morule 2 - endometrium -- very high mag.jpg|150px|SM. (WC)]]
|-
| Ciliary
| -
| ciliated cells
| usu. lumped together with ''tubal'', unopposed estrogen, [[endometriosis]]
| frequent - [[endometrial hyperplasia]] (complex and simple), adenocarcinoma
|
|-
| Tubal
| complex, simple
| ciliated cells, secretory cell, intercallary cells
| usu. lumped together with ''ciliary'', unopposed estrogen, seen in [[endometriosis]]
| frequent (complex only) - [[endometrial hyperplasia]] (complex and simple), adenocarcinoma
|
|-
| Mucinous
| complex, simple
|
|
| frequent (complex only)
|
|-
| Squamous
| -
|
|
| rare
|
|-
| Papillary syncytial change (surface)
| -
|
|
| rare
|
|-
| Eosinophilic, oxyphilic, oncocytic
|
|
|
| not known
|
|-
| Clear cell (secretory)
| -
|
|
| not reported
|
|-
| Stromal metaplasia
| osseous, cartilaginous, adipose, smooth muscle, myoid, sex-cord like
|
|
| not reported
|
|}
 
=Tamoxifen effects=
*[[Endometrial hyperplasia]].
*[[Endometrial cancer]].
*[[Endometrial polyps]].
*[[Endometrial atrophy|Atrophy]].
 
=Inadequate endometrial biopsy=
*Endometrial biopsies often have scant tissue. 
**This is normal in post-menopausal women.
*Ideally, the biopsy should have some endometrial stroma.
**Without stroma it is ''not'' possible to assess the gland-to-stroma ratio.
 
==Sign out==
===No stroma===
<pre>
ENDOMETRIUM, BIOPSY:
- VERY SCANT STRIPPED NON-PROLIFERATIVE COLUMNAR EPITHELIUM, PROBABLY FROM THE LOWER UTERINE SEGMENT.
- NO DEFINITE ENDOMETRIAL STROMA, SEE COMMENT.
- STRIPPED ENDOCERVICAL EPITHELIUM AND ENODOCERVICAL MUCOSA WITHIN NORMAL LIMITS.
- MUCOUS.
 
COMMENT:
A re-biopsy should be considered within the clinical context.
</pre>
 
<pre>
ENDOMETRIUM, BIOPSY:
- VERY SCANT STRIPPED EPITHELIUM PROBABLY FROM THE LOWER UTERINE SEGMENT.
- NO DEFINITE ENDOMETRIAL STROMA.
- SCANT STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
- SMALL FRAGMENTS OF DETACHED BENIGN SQUAMOUS EPITHELIUM.
 
COMMENT:
A re-biopsy should be considered within the clinical context.
</pre>
 
<pre>
ENDOMETRIUM, BIOPSY:
- FRAGMENTS OF DETACHED SQUAMOUS EPITHELIUM AND DETACHED NON-PROLIFERATIVE ENDOMETRIAL GLANDS.
- ASSESSMENT LIMITED AS VERY SCANT ENDOMETRIAL STROMA IS PRESENT.
</pre>
 
<pre>
ENDOMETRIUM, BIOPSY:
- ENDOMETRIUM: STRIPS OF EPITHELIUM, NON-PROLIFERATIVE.
- ENDOCERVIX: SCANT BENIGN EPITHELIUM.
- EXOCERVIX: SCANT BENIGN EPITHELIUM.
- OTHER: TUBAL METAPLASIA.
</pre>
 
<pre>
ENDOMETRIUM, BIOPSY:
- STRIPS OF NON-PROLIFERATIVE ENDOMETRIUM.
- SCANT BENIGN ENDOCERVICAL EPITHELIUM.
- SCANT BENIGN SQUAMOUS EPITHELIUM.
- TUBAL METAPLASIA.
</pre>
 
<pre>
ENDOMETRIUM, BIOPSY:
- STRIPS OF BENIGN ENDOMETRIAL EPITHELIUM/TUBAL METAPLASIA, NON-PROLIFERATIVE.
- SCANT BENIGN ENDOCERVICAL EPITHELIUM.
- RARE SQUAMOUS METAPLASTIC CELLS.
</pre>
 
===Proliferative without definite stroma===
<pre>
ENDOMETRIUM, BIOPSY:
- FRAGMENTS OF DETACHED SQUAMOUS EPITHELIUM, ENDOCERVICAL EPITHELIUM AND FOCALLY PROLIFERATIVE ENDOMETRIAL GLANDS. 
- ASSESSMENT LIMITED AS NO DEFINITE ENDOMETRIAL STROMA IS PRESENT.
</pre>
 
===Possible endometrium - insufficient===
<pre>
ENDOMETRIUM, ASPIRATION:
- ONE MINUTE STRIP OF POSSIBLE NONPROLIFERATIVE ENDOMETRIAL EPITHELIUM, INSUFFICIENT
  FOR ADEQUATE DIAGNOSTIC ASSESSMENT.
- VERY SCANT BENIGN STRIPPED ENDOCERVICAL EPITHELIUM.
- VERY SCANT METAPLASTIC SQUAMOUS EPITHELIUM.
 
COMMENT:
Re-biopsy is advised.
</pre>
 
<pre>
ENDOMETRIUM, BIOPSY:
- BENIGN STRIPPED ENDOCERVICAL EPITHELIUM AND BENIGN INFLAMED ENDOCERVICAL MUCOSA.
- NO DEFINITE ENDOMETRIUM WITH STROMA, INADEQUATE SPECIMEN.
</pre>
 
===No endometrium===
<pre>
ENDOMETRIUM, BIOPSY:
- SPECIMEN INADEQUATE; NO ENDOMETRIUM IDENTIFIED.
- ONE VERY TINY FRAGMENT OF ENDOCERVICAL MUCOSA WITHOUT APPARENT PATHOLOGY.
</pre>
 
<pre>
ENDOMETRIUM, BIOPSY:
- ENDOCERVICAL MUCOSA AND STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
- MICROGLANDULAR HYPERPLASIA AND FOCAL SQUAMOUS METAPLASIA.
- NO DEFINITE ENDOMETRIUM IDENTIFIED, SUGGEST RE-BIOPSY.
</pre>
 
===No tissue===
<pre>
ENDOMETRIUM, BIOPSY:
- NO TISSUE IDENTIFIED ON MICROSCOPY.
</pre>
 
=Overview=
==A simple approach==
===Low power===
#Decide whether you are looking at endometrium.
#Is the gland-to-stroma ratio normal?
#*1:3 is normal.
#*1:3 is normal.
#*If gland-to-stroma ratio is increased... think ''[[endometrial hyperplasia]]''.
#*If the gland-to-stroma ratio is increased... think ''[[complex endometrial hyperplasia]]''.
#*If glands are fused to one another or [[cribriform]]... think ''[[endometrial carcinoma]]''.
#*If the glands are fused to one another or [[cribriform]]... think ''[[endometrial carcinoma]]''.
#Glands round?
#Glands round?
#*Round is normal.
#*Round is normal.
#*Irregular - may be seen in menses, endometrial hyperplasia, disordered proliferative endometrium.
#*Irregular - may be seen in [[secretory phase endometrium]], menses, [[disordered proliferative endometrium]] (focal), [[simple endometrial hyperplasia]] (diffuse).
#Glands pseudostratified?
#Glands pseudostratified?
#*Pseudostratified glands are normal in the proliferative phase, hyperplasias, malignancy.
#*Pseudostratified glands are normal in the [[proliferative phase endometrium]], hyperplasias, malignancy.
#Balls of cells?
#Balls of cells?
#*Blue - likely menstrual (stromal condensation).
#*Blue - likely menstrual (stromal condensation).
#*Pink - consider leiomyoma, squamous morules (associated with endometrial hyperplasia).
#*Pink - consider [[uterine leiomyoma|leiomyoma]], squamous morules (associated with [[endometrial hyperplasia]], [[endometrioid endometrial carcinoma]], may be benign).


==High power==
===High power===
#Mitoses present in the glands?
#Mitoses present in the glands?
#*Present in the proliferative phase, hyperplasias, malignancies.
#*Present in the proliferative phase, hyperplasias, malignancies.
Line 48: Line 307:
#*Some are normal during menses.
#*Some are normal during menses.


=Dating endometrium=
==Tabular summary==
==Proliferative phase==
{| class="wikitable sortable"
*Glands: straight, tubular, tall pseudostratified columnar cells, mitotic figures, NO vacuolation, NO mucus secretion.
! Diagnosis
**Key features: pseudostratification, mitoses.
! Key feature (low power)
*Stroma: cellular stroma (spindle cells), mitoses.
! Additional features
! DDx
! Other
! Image
|-
| [[Proliferative phase endometrium]]
| round spaced pseudostratified glands
| mitoses in glands and stroma
| [[disordered proliferative phase]], [[simple endometrial hyperplasia]], [[complex endometrial hyperplasia]], early [[secretory phase endometrium]]
| normal
| [[Image:Proliferative endometrium - very high mag.jpg|thumb|150px|center|Proliferative endometrium. (WC)]]
|-
| [[Secretory phase endometrium]]
| irregular glands with secretions ''or'' simple glands with vacuoles
| decidual changes (nucleus central, eosinophilic cytoplasm, well-defined cell borders)
| [[endometrial hyperplasia with secretory changes]], late [[proliferative phase endometrium]]
| normal
| [[Image:Secretory phase endometrium -- high mag.jpg|thumb|120px|center|Secretory phase endometrium. (WC)]]
|-
| [[Menstrual endometrium]]
| stromal condensation
| nonproliferative glands, stromal/epithelial neutrophils, glandular cell apoptosis
| [[disordered proliferative phase]]
| normal
| Image
|-
| [[Benign endometrial polyp]]
| fibrous stroma, muscular blood vessels
| polypoid shape (epithelium on 3 sides), +/-gland dilation
| [[disordered proliferative endometrium]] (DPE), [[simple endometrial hyperplasia]] (SEH)
| DPE and SEH do ''not'' occur in polyps
| [[Image:Benign endometrial polyp -- low mag.jpg|thumb|150px|center|Benign endometrial polyp. (WC)]]
|-
| [[Endometrium with changes due to exogenous hormones]]
| decidualized stroma (nucleus central, eosinophilic cytoplasm, well-defined cell borders)
| inactive glands (round/ovoid glands, simple cuboidal epithelium, no mitoses)
| [[secretory phase endometrium]], [[endometrial hyperplasia with secretory changes]]
| variant of normal
| [[Image:Endometrium with hormone effect -- high mag.jpg|thumb|150px|center|Endometrium with changes due to exogenous hormones. (WC)]]
|-
| [[Atrophic endometrium]]
| nonproliferative glands
| no nuclear atypia, often without appreciable stroma
| [[serous endometrial carcinoma]]
| normal postmenopausal finding
| [[Image:Nonproliferative endometrial epithelium - alt -- high mag.jpg|thumb|150px|center|Inactive endometrium. (WC)]]
|-
| [[Disordered proliferative endometrium]]
| proliferative focally dilated & irregular glands (usu. with tubal metaplasia)
| no nuclear atypia, +/-evidence of shedding (stromal condensation)
| [[simple endometrial hyperplasia]], [[proliferative phase endometrium]]
| can be thought of a [[waffle diagnosis]]
| [[Image:Disordered proliferative endometrium -- low mag.jpg|thumb|150px|center|Disordered proliferative endometrium. (WC)]]
|- <!--
|  Diagnosis
| Key feature
| Additional features
| DDx
| Other
| Image -->
|}
 
=Normal endometrium=
==Proliferative phase endometrium==
{{Main|Proliferative phase endometrium}}
 
==Secretory phase endometrium==
{{Main|Secretory phase endometrium}}


Note:
==Menstrual endometrium==
*Proliferative phase = folicular phase.
===General===
**Gynecologists prefer the ovarian descriptor, i.e. ''follicular phase''; pathologists go by what they see, i.e. ''proliferative'' endometrium.
*Technically part of the ''proliferative phase'' or ''follicular phase''.


==Secretory phase==
===Microscopic===
*Early secretory phase - post-ovulatory day 1-5:
Features:
**Glands: secretory vacuoles.
*Proliferative endometrium (mitoses).<ref name=Ref_DCHH237>{{Ref DCHH|237}}</ref>
***First basal to the epithelial nuclei (infranuclear vacuoles).
*Apoptotic cells common.<ref name=pmid8744416>{{Cite journal  | last1 = Spencer | first1 = SJ. | last2 = Cataldo | first2 = NA. | last3 = Jaffe | first3 = RB. | title = Apoptosis in the human female reproductive tract. | journal = Obstet Gynecol Surv | volume = 51 | issue = 5 | pages = 314-23 | month = May | year = 1996 | doi =  | PMID = 8744416 }}</ref>
***Then apical to the epithelial nuclei (supranuclear vacuoles).
*Tightly packed cellular balls of stromal cells with nuclear moulding.
**Known as "blue balls".
**Tightly packed cellular stromal cells known as "stromal condensation".
*Inflammation, especially abundant [[neutrophil]]s.


*Mid secretory phase - post-ovulatory day 6-8:
DDx:
**Glands: Mucus in glands.
*[[Small cell carcinoma]] - proliferative activity in the moulded (stromal condensation-like) cells.
**Stroma: Edema (empty space around the glands).
*[[Anovulatory endometrium]] - less neutrophils.


*Late secretory phase (beginning) - post-ovulatory day 9-12:
====Images====
**Stroma:  
<gallery>
***Spiral arterioles.
Image:Endometrial_stromal_condensation_high_mag.jpg | Endometrial stromal condensation - high mag. (WC/Nephron)
***Predecidual changes -- mnemonic ''NEW'':
</gallery>
***#Nucleus central.
www:
***#Eosinophilic cytoplasm '''key feature''' (may be subtle to the novice).
*[http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=5&cat2=26&cat3=0&cat4=3&stype=n Menstrual endometrium - several images (gfmer.ch)].
***#Well-defined cell borders.
*[http://www.hsc.stonybrook.edu/gyn-atlas/UT3415B.htm Menstrual phase endometrium (stonybrook.edu)].


*Premenstrual
===Sign out===
**Stroma: Neutrophils, scattered lymphocytes, stromal balls ("blue balls"); "stromal condensation" (Image: [http://commons.wikimedia.org/wiki/File:Endometrial_stromal_condensation_high_mag.jpg Endometrial stromal condensation (WC)]).
<pre>
**Glands: apoptosis at the base of the gland.<ref>TC. 22 June 2009.</ref>
Endometrium, Biopsy:
- Consistent with menstrual endometrium.
-- Weakly proliferative endometrial glands with apoptosis, fragmented.
-- Abundant balls of condensed non-proliferative endometrial stroma and blood.
</pre>


General refs.: <ref>{{Ref PBoD|1081}}</ref><ref>{{Ref DCHH|237}}</ref>
====Block letters====
<pre>
ENDOMETRIUM, BIOPSY:
- CONSISTENT WITH MENSTRUAL ENDOMETRIUM:
-- STRIPPED WEAKLY PROLIFERATIVE ENDOMETRIAL GLANDS.
-- BALLS OF CONDENSED ENDOMETRIAL STROMA.
-- ABUNDANT NEUTROPHILS AND BLOOD.
</pre>


Notes:  
<pre>
*Secretory phase = luteal phase.
ENDOMETRIUM, BIOPSY:
**Gynecologists prefer the ovarian descriptor, i.e. ''luteal phase''; pathologists go by what they see, i.e. ''Secretions'' in the (endometrial) glands.
- CONSISTENT WITH MENSTRUAL PHASE ENDOMETRIUM:
*When the patient is >40 years, some advocate the use of the term ''proliferative type endometrium'' (instead of the term ''proliferative endometrium'').<ref>GAG. Jan 2009</ref>
-- WEAKLY PROLIFERATIVE ENDOMETRIAL GLANDS WITH NEUTROPHILS AND APOPTOSIS.
*Stromal condensation (stromal balls) - premenstrual - stromal cells tightly packed together; nuclei molded together like in small cell tumours.<ref>GAG. 6 Oct 2009.</ref>
-- BALLS OF CONDENSED ENDOMETRIAL STROMA.
-- BLOOD.
</pre>


=Specific entities/abnormalities=
<pre>
==Arias-Stella reaction==
ENDOMETRIUM, BIOPSY:
{{Main|Arias-Stella reaction}}
- VERY WEAKLY PROLIFERATIVE ENDOMETRIAL GLANDS WITH NEUTROPHILS AND APOPTOSIS.
*Benign atypical endometrial changes associated with chorionic tissue -- may be seen in a completely normal pregnancy and misdiagnosed as a malignancy.<ref name=pmid11756756>{{Cite journal  | last1 = Arias-Stella | first1 = J. | title = The Arias-Stella reaction: facts and fancies four decades after. | journal = Adv Anat Pathol | volume = 9 | issue = 1 | pages = 12-23 | month = Jan | year = 2002 | doi =  | PMID = 11756756 }}</ref>
- BALLS OF CONDENSED ENDOMETRIAL STROMA AND BLOOD.
- NEGATIVE FOR HYPERPLASIA AND NEGATIVE FOR MALIGNANCY.
</pre>


==Endometritis==
====Consistent with menstrual endometrium====
===General===
<pre>
*Post-delivery.
ENDOMETRIUM, ASPIRATION:
*Post-instrumentation, e.g. previous biopsy.
- CONSISTENT WITH MENSTRUAL ENDOMETRIUM (FRAGMENTED ENDOMETRIUM WITH PSEUDOSTRATIFIED
  GLANDS WITH APOPTOTIC CELLS, ABUNDANT NEUTROPHILS, CONDENSED ENDOMETRIAL STROMA
  AND BLOOD).
- NEGATIVE FOR HYPERPLASIA AND NEGATIVE FOR MALIGNANCY.
</pre>
<pre>
ENDOMETRIUM, ASPIRATION:
- CONSISTENT WITH MENSTRUAL ENDOMETRIUM (FRAGMENTED ENDOMETRIUM WITH SIMPLE
  GLANDS WITH APOPTOTIC CELLS, ABUNDANT NEUTROPHILS, CONDENSED ENDOMETRIAL STROMA
  (FOCAL) AND BLOOD).
- NEGATIVE FOR HYPERPLASIA AND NEGATIVE FOR MALIGNANCY.


===Microscopic===
</pre>
====Acute endometritis====
Features:
*Neutrophils clusters (>5 PMNs) in the:
**Endometrial stroma.
**Within uterine glands.


Notes:
====Late menses====
*Neutrophils are normal in the context of menses.
<pre>
ENDOMETRIUM, ASPIRATION:
- ENDOMETRIAL GLANDS WITH APOPTOTIC CELLS, INFILTRATING NEUTROPHILS,
  AND GLANDULAR PROLIFERATIVE ACTIVITY.
- BALLS OF CONDENSED ENDOMETRIAL STROMA.
- SCANT STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
- NEGATIVE FOR HYPERPLASIA.


Image:
COMMENT:
*[http://www.hsc.stonybrook.edu/gyn-atlas/UT53.10.1.htm Acute endometritis (stonybrook.edu)].
The findings are most in keeping with late menstrual endometrium.
</pre>


====Chronic endometritis====
=Specific entities/abnormalities=
==Adipose tissue on endometrial biopsy==
*[[AKA]] ''fat on endometrial biopsy''.
===General===
*Benign.
*Raises the possibility of perforation - should prompt a phone call to the clinician.
===Microscopic===
Features:
Features:
*Plasma cells with in the endometrial stroma - '''key feature'''.
*Adipose tissue, benign - '''key finding'''.
*Definite endometrium.


Notes:
DDx:
*One plasma cell is not enough to call it.
*Extraneous tissue.
**[[Tissue floater]].
**Pick-up.


Images:
====Images====
*[http://www.webpathology.com/image.asp?n=2&Case=565 ]Chronic endometritis (webpathology.com)].
<gallery>
*[http://www.webpathology.com/image.asp?n=3&Case=565 Chronic endometritis (webpathology.com)].
Image: Endometrium and adipose tissue - alt -- intermed mag.jpg | EMB with fat - intermed. mag.
Image: Endometrium and adipose tissue -- intermed mag.jpg | EMB with fat - intermed. mag.
Image: Endometrium and adipose tissue -- high mag.jpg | EMB with fat - high mag.
</gallery>


==Endometrial polyp==
===Sign out===
===General===
<pre>
*Very common.
ENDOMETRIUM, BIOPSY:
*May be a cause of menorrhagia (heavy & long menses).
- BENIGN ADIPOSE TISSUE, SEE COMMENT.
- PROLIFERATIVE PHASE ENDOMETRIUM.


===Microscopic===
COMMENT:
Features:<ref>URL: [http://www.pathologyoutlines.com/uterus.html#endopolyp http://www.pathologyoutlines.com/uterus.html#endopolyp].</ref>
The presence of adipose tissue raises the possibility of perforation.
*Large blood vessels (muscular) - '''key feature'''.
*Fibrotic stroma - '''key feature'''.
*Polypoid shape - epithelium on three sides.
**May not be seen... as polyp is fragmented on removal.


Notes:
The findings were briefly discussed with Dr. Brown on November 6, 2009.
*Endometrial glands may be out of phase with surrounding endometrium.
</pre>
**Often proliferative.
*+/-Cystic dilation of glands.
*Cellular stroma.


==Disordered proliferative phase==
==Arias-Stella reaction==
===General===
{{Main|Arias-Stella reaction}}
*Association: anovulation.
*Benign atypical endometrial changes associated with chorionic tissue -- may be seen in a completely normal pregnancy and misdiagnosed as a malignancy.<ref name=pmid11756756>{{Cite journal  | last1 = Arias-Stella | first1 = J. | title = The Arias-Stella reaction: facts and fancies four decades after. | journal = Adv Anat Pathol | volume = 9 | issue = 1 | pages = 12-23 | month = Jan | year = 2002 | doi = | PMID = 11756756 }}</ref>


===Microscopic===
==Endometritis==
Features:<ref name=Ref_PBoD1080>{{Ref PBoD|1080 and 1082}}</ref>
{{Main|Endometritis}}
*Proliferative type endometrium with:
**Cystic dilation of glands without secretions.
*+/-Stromal condensation -- balls of stromal tissue, aka "blue balls" (due to breakdown of endometrium).


Notes:
==Benign endometrial polyp==
*Proliferative phase endometrium:
{{Main|Benign endometrial polyp}}
**Glands: straight, tubular, tall pseudostratified columnar cells, mitotic figures, NO vacuolation, NO mucus secretion, abundant mitoses.
**Stroma: cellular, stroma (spindle cells), mitoses.


Image: [http://upload.wikimedia.org/wikipedia/commons/a/ab/Endometrial_stromal_condensation_high_mag.jpg Endometrial stromal condensation - high mag. (WC)].
==Anovulatory endometrium==
{{Main|Anovulatory endometrium}}


==Oral contraceptive effect==
==Disordered proliferative endometrium==
===General===
*Abbreviated ''DPE''.
*Very common.
*[[AKA]] ''endometrium with disordered proliferative phase''.
*Most pills a mix of progesterone and estrogen.
*[[AKA]] ''disordered proliferative phase''.
**The progesterone is what generates the characteristic appearance -- that is similar to pregnancy.
{{Main|Disordered proliferative endometrium}}


===Microscopic===
==Endometrium with changes due to exogenous hormones==
Features:<ref name=Ref_PBoD1082>{{Ref PBoD|1082}}</ref>
{{Main|Endometrium with changes due to exogenous hormones}}
*Inactive glands (round/ovoid glands, simple cuboidal epithelium, no mitoses).
*Stroma decidualized -- mnemonic ''NEW'':
**Nucleus central.
**Eosinophilic cytoplasm.
**Well-defined cell borders.


Image: [http://commons.wikimedia.org/wiki/File:Endometrium_ocp_use3.jpg Endometrium of woman on an OCP (WC)].
==Atrophic endometrium==
*[[AKA]] ''atrophy of the endometrium''.
*[[AKA]] ''endometrial atrophy''.
{{Main|Inactive endometrium}}


==Postmenopausal women==
==Ablated endometrium==
===General===
{{Main|Ablated endometrium}}
*Menopause happens at around 50 years old.


===Microscopic===
==Endometrium with squamous morules==
Features:
{{Main|Endometrium with squamous morules}}
*Atrophy glands.
*Thin endometrium.


Notes:
==Endometrium with psammoma bodies==
*If a woman is truly postmenopausal, mitoses in the glandular epithelium is pretty much always pathologic.
{{Main|Endometrium with psammoma bodies}}
**Exception is inflammation... e.g. the person has had several biopsy attempts and was seeded with pathogens.


==Endometrial hyperplasia==
==Endometrial hyperplasia==
Line 203: Line 555:
*[[Uterine tumours]].
*[[Uterine tumours]].
*[[Gynecologic pathology]].
*[[Gynecologic pathology]].
*[[Psammoma bodies]].


=References=
=References=
Line 208: Line 561:


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

Latest revision as of 14:37, 2 March 2017

The endometrium is typically biopsied because of abnormal bleeding. Endometrial hyperplasia and endometrial carcinoma are dealt with in separate articles. An overview of gynecologic pathology is in the gynecologic pathology article.

Indications for endometrial biopsy

Abnormal bleeding:

Other indications:[2]

Endometrial thickness on ultrasound

  • A thin endometrium on ultrasound has a very low risk of malignancy.[3]

Normal microscopic findings

Endometrium - consists of:

  1. Epithelium (endometrial glands).
  2. Stroma (endometrial stroma).

In endometrial biopsies:

  • Endocervical glands are commonly seen, as is endocervical mucous.
    • This is 'cause the gynecologist scrapes some off on the way in or out.

Glandular telescoping

AKA gland-within-a-gland.
AKA gland intussusception.
AKA telescoping.
  • Considered an artifact of tissue processing, i.e. normal.[4]

Image:

Endometrial gland compression artifact

AKA compression artifact.
  • Gland moulding.
  • Tearing of tissue around the compressed glands - key feature.
  • Usually at the edge of a tissue fragment.

DDx:

Image

Micro

An increased gland density is seen focally, at the edge of one tissue fragment, in association with tearing of the stroma (compression artifact).

See also

Endocervical epithelium versus endometrial epithelium

Table

Feature Endometrial Endocervical Tubal metaplasia
Cytoplasmic staining usu. hyperchromatic +/-vacuoles clear or light eosinophilic hyperchromatic
Nucleus-to-cytoplasm ratio moderate to high (1:2) low (often 1:3) high (1:1)
Surface features villi
Associated stroma cellular, hyperchromatic inflamed, less cellular variable

List

Endocervical:

  • Less hyperchromatic.
  • Nuclei round & small.
  • Cell borders usually well-defined.

Endometrial:

  • More hyperchromatic.
  • Nuclei columnar.

Images

  • Endocervical and endometrial epithelium - low mag. (WC)

  • Endocervical and endometrial epithelium - high mag. (WC)

Metaplasias of the endometrium

The big table of metaplasias - adapted from Nicolae et al.:[5]

Metaplasia Subtypes Microscopic Notes Risk of malignancy Image
Morules - nearly always SM. (WC)
Ciliary - ciliated cells usu. lumped together with tubal, unopposed estrogen, endometriosis frequent - endometrial hyperplasia (complex and simple), adenocarcinoma
Tubal complex, simple ciliated cells, secretory cell, intercallary cells usu. lumped together with ciliary, unopposed estrogen, seen in endometriosis frequent (complex only) - endometrial hyperplasia (complex and simple), adenocarcinoma
Mucinous complex, simple frequent (complex only)
Squamous - rare
Papillary syncytial change (surface) - rare
Eosinophilic, oxyphilic, oncocytic not known
Clear cell (secretory) - not reported
Stromal metaplasia osseous, cartilaginous, adipose, smooth muscle, myoid, sex-cord like not reported

Tamoxifen effects

Inadequate endometrial biopsy

  • Endometrial biopsies often have scant tissue.
    • This is normal in post-menopausal women.
  • Ideally, the biopsy should have some endometrial stroma.
    • Without stroma it is not possible to assess the gland-to-stroma ratio.

Sign out

No stroma

ENDOMETRIUM, BIOPSY:
- VERY SCANT STRIPPED NON-PROLIFERATIVE COLUMNAR EPITHELIUM, PROBABLY FROM THE LOWER UTERINE SEGMENT.
- NO DEFINITE ENDOMETRIAL STROMA, SEE COMMENT.
- STRIPPED ENDOCERVICAL EPITHELIUM AND ENODOCERVICAL MUCOSA WITHIN NORMAL LIMITS.
- MUCOUS.

COMMENT:
A re-biopsy should be considered within the clinical context.

ENDOMETRIUM, BIOPSY:
- VERY SCANT STRIPPED EPITHELIUM PROBABLY FROM THE LOWER UTERINE SEGMENT.
- NO DEFINITE ENDOMETRIAL STROMA.
- SCANT STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
- SMALL FRAGMENTS OF DETACHED BENIGN SQUAMOUS EPITHELIUM.

COMMENT:
A re-biopsy should be considered within the clinical context.

ENDOMETRIUM, BIOPSY: 
- FRAGMENTS OF DETACHED SQUAMOUS EPITHELIUM AND DETACHED NON-PROLIFERATIVE ENDOMETRIAL GLANDS. 
- ASSESSMENT LIMITED AS VERY SCANT ENDOMETRIAL STROMA IS PRESENT.

ENDOMETRIUM, BIOPSY:
- ENDOMETRIUM: STRIPS OF EPITHELIUM, NON-PROLIFERATIVE. 
- ENDOCERVIX: SCANT BENIGN EPITHELIUM.
- EXOCERVIX: SCANT BENIGN EPITHELIUM.
- OTHER: TUBAL METAPLASIA.

ENDOMETRIUM, BIOPSY:
- STRIPS OF NON-PROLIFERATIVE ENDOMETRIUM. 
- SCANT BENIGN ENDOCERVICAL EPITHELIUM.
- SCANT BENIGN SQUAMOUS EPITHELIUM.
- TUBAL METAPLASIA.

ENDOMETRIUM, BIOPSY:
- STRIPS OF BENIGN ENDOMETRIAL EPITHELIUM/TUBAL METAPLASIA, NON-PROLIFERATIVE. 
- SCANT BENIGN ENDOCERVICAL EPITHELIUM.
- RARE SQUAMOUS METAPLASTIC CELLS.

Proliferative without definite stroma

ENDOMETRIUM, BIOPSY: 
- FRAGMENTS OF DETACHED SQUAMOUS EPITHELIUM, ENDOCERVICAL EPITHELIUM AND FOCALLY PROLIFERATIVE ENDOMETRIAL GLANDS.  
- ASSESSMENT LIMITED AS NO DEFINITE ENDOMETRIAL STROMA IS PRESENT.

Possible endometrium - insufficient

ENDOMETRIUM, ASPIRATION:
- ONE MINUTE STRIP OF POSSIBLE NONPROLIFERATIVE ENDOMETRIAL EPITHELIUM, INSUFFICIENT
  FOR ADEQUATE DIAGNOSTIC ASSESSMENT.
- VERY SCANT BENIGN STRIPPED ENDOCERVICAL EPITHELIUM.
- VERY SCANT METAPLASTIC SQUAMOUS EPITHELIUM.

COMMENT:
Re-biopsy is advised.

ENDOMETRIUM, BIOPSY:
- BENIGN STRIPPED ENDOCERVICAL EPITHELIUM AND BENIGN INFLAMED ENDOCERVICAL MUCOSA.
- NO DEFINITE ENDOMETRIUM WITH STROMA, INADEQUATE SPECIMEN.

No endometrium

ENDOMETRIUM, BIOPSY:
- SPECIMEN INADEQUATE; NO ENDOMETRIUM IDENTIFIED.
- ONE VERY TINY FRAGMENT OF ENDOCERVICAL MUCOSA WITHOUT APPARENT PATHOLOGY.

ENDOMETRIUM, BIOPSY:
- ENDOCERVICAL MUCOSA AND STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
- MICROGLANDULAR HYPERPLASIA AND FOCAL SQUAMOUS METAPLASIA.
- NO DEFINITE ENDOMETRIUM IDENTIFIED, SUGGEST RE-BIOPSY.

No tissue

ENDOMETRIUM, BIOPSY:
- NO TISSUE IDENTIFIED ON MICROSCOPY.

Overview

A simple approach

Low power

  1. Decide whether you are looking at endometrium.
  2. Is the gland-to-stroma ratio normal?
  3. Glands round?
  4. Glands pseudostratified?
  5. Balls of cells?

High power

  1. Mitoses present in the glands?
    • Present in the proliferative phase, hyperplasias, malignancies.
  2. Mitoses present in the stroma?
    • Present in the proliferative phase, hyperplasias, malignancies.
  3. Mucous present in the glands?
    • Present in the secretory phase.
  4. Inflammatory cells present?
    • Some are normal during menses.

Tabular summary

Diagnosis Key feature (low power) Additional features DDx Other Image
Proliferative phase endometrium round spaced pseudostratified glands mitoses in glands and stroma disordered proliferative phase, simple endometrial hyperplasia, complex endometrial hyperplasia, early secretory phase endometrium normal
Proliferative endometrium. (WC)
Secretory phase endometrium irregular glands with secretions or simple glands with vacuoles decidual changes (nucleus central, eosinophilic cytoplasm, well-defined cell borders) endometrial hyperplasia with secretory changes, late proliferative phase endometrium normal
Secretory phase endometrium. (WC)
Menstrual endometrium stromal condensation nonproliferative glands, stromal/epithelial neutrophils, glandular cell apoptosis disordered proliferative phase normal Image
Benign endometrial polyp fibrous stroma, muscular blood vessels polypoid shape (epithelium on 3 sides), +/-gland dilation disordered proliferative endometrium (DPE), simple endometrial hyperplasia (SEH) DPE and SEH do not occur in polyps
Benign endometrial polyp. (WC)
Endometrium with changes due to exogenous hormones decidualized stroma (nucleus central, eosinophilic cytoplasm, well-defined cell borders) inactive glands (round/ovoid glands, simple cuboidal epithelium, no mitoses) secretory phase endometrium, endometrial hyperplasia with secretory changes variant of normal
Endometrium with changes due to exogenous hormones. (WC)
Atrophic endometrium nonproliferative glands no nuclear atypia, often without appreciable stroma serous endometrial carcinoma normal postmenopausal finding
Inactive endometrium. (WC)
Disordered proliferative endometrium proliferative focally dilated & irregular glands (usu. with tubal metaplasia) no nuclear atypia, +/-evidence of shedding (stromal condensation) simple endometrial hyperplasia, proliferative phase endometrium can be thought of a waffle diagnosis
Disordered proliferative endometrium. (WC)

Normal endometrium

Proliferative phase endometrium

Main article: Proliferative phase endometrium

Secretory phase endometrium

Main article: Secretory phase endometrium

Menstrual endometrium

General

  • Technically part of the proliferative phase or follicular phase.

Microscopic

Features:

  • Proliferative endometrium (mitoses).[6]
  • Apoptotic cells common.[7]
  • Tightly packed cellular balls of stromal cells with nuclear moulding.
    • Known as "blue balls".
    • Tightly packed cellular stromal cells known as "stromal condensation".
  • Inflammation, especially abundant neutrophils.

DDx:

Images

  • Endometrial stromal condensation - high mag. (WC/Nephron)

www:

Sign out

Endometrium, Biopsy:
- Consistent with menstrual endometrium.
-- Weakly proliferative endometrial glands with apoptosis, fragmented.
-- Abundant balls of condensed non-proliferative endometrial stroma and blood.

Block letters

ENDOMETRIUM, BIOPSY:
- CONSISTENT WITH MENSTRUAL ENDOMETRIUM:
-- STRIPPED WEAKLY PROLIFERATIVE ENDOMETRIAL GLANDS.
-- BALLS OF CONDENSED ENDOMETRIAL STROMA.
-- ABUNDANT NEUTROPHILS AND BLOOD.

ENDOMETRIUM, BIOPSY:
- CONSISTENT WITH MENSTRUAL PHASE ENDOMETRIUM:
-- WEAKLY PROLIFERATIVE ENDOMETRIAL GLANDS WITH NEUTROPHILS AND APOPTOSIS.
-- BALLS OF CONDENSED ENDOMETRIAL STROMA.
-- BLOOD.

ENDOMETRIUM, BIOPSY:
- VERY WEAKLY PROLIFERATIVE ENDOMETRIAL GLANDS WITH NEUTROPHILS AND APOPTOSIS.
- BALLS OF CONDENSED ENDOMETRIAL STROMA AND BLOOD.
- NEGATIVE FOR HYPERPLASIA AND NEGATIVE FOR MALIGNANCY.

Consistent with menstrual endometrium

ENDOMETRIUM, ASPIRATION:
- CONSISTENT WITH MENSTRUAL ENDOMETRIUM (FRAGMENTED ENDOMETRIUM WITH PSEUDOSTRATIFIED
  GLANDS WITH APOPTOTIC CELLS, ABUNDANT NEUTROPHILS, CONDENSED ENDOMETRIAL STROMA
  AND BLOOD).
- NEGATIVE FOR HYPERPLASIA AND NEGATIVE FOR MALIGNANCY.

ENDOMETRIUM, ASPIRATION:
- CONSISTENT WITH MENSTRUAL ENDOMETRIUM (FRAGMENTED ENDOMETRIUM WITH SIMPLE
  GLANDS WITH APOPTOTIC CELLS, ABUNDANT NEUTROPHILS, CONDENSED ENDOMETRIAL STROMA
  (FOCAL) AND BLOOD).
- NEGATIVE FOR HYPERPLASIA AND NEGATIVE FOR MALIGNANCY.

Late menses

ENDOMETRIUM, ASPIRATION:
- ENDOMETRIAL GLANDS WITH APOPTOTIC CELLS, INFILTRATING NEUTROPHILS,
  AND GLANDULAR PROLIFERATIVE ACTIVITY.
- BALLS OF CONDENSED ENDOMETRIAL STROMA.
- SCANT STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.
- NEGATIVE FOR HYPERPLASIA.

COMMENT:
The findings are most in keeping with late menstrual endometrium.

Specific entities/abnormalities

Adipose tissue on endometrial biopsy

  • AKA fat on endometrial biopsy.

General

  • Benign.
  • Raises the possibility of perforation - should prompt a phone call to the clinician.

Microscopic

Features:

  • Adipose tissue, benign - key finding.
  • Definite endometrium.

DDx:

Images

  • EMB with fat - intermed. mag.

  • EMB with fat - intermed. mag.

  • EMB with fat - high mag.

Sign out

ENDOMETRIUM, BIOPSY:
- BENIGN ADIPOSE TISSUE, SEE COMMENT.
- PROLIFERATIVE PHASE ENDOMETRIUM.

COMMENT:
The presence of adipose tissue raises the possibility of perforation.

The findings were briefly discussed with Dr. Brown on November 6, 2009.

Arias-Stella reaction

Main article: Arias-Stella reaction
  • Benign atypical endometrial changes associated with chorionic tissue -- may be seen in a completely normal pregnancy and misdiagnosed as a malignancy.[8]

Endometritis

Main article: Endometritis

Benign endometrial polyp

Main article: Benign endometrial polyp

Anovulatory endometrium

Main article: Anovulatory endometrium

Disordered proliferative endometrium

  • Abbreviated DPE.
  • AKA endometrium with disordered proliferative phase.
  • AKA disordered proliferative phase.
Main article: Disordered proliferative endometrium

Endometrium with changes due to exogenous hormones

Main article: Endometrium with changes due to exogenous hormones

Atrophic endometrium

  • AKA atrophy of the endometrium.
  • AKA endometrial atrophy.
Main article: Inactive endometrium

Ablated endometrium

Main article: Ablated endometrium

Endometrium with squamous morules

Main article: Endometrium with squamous morules

Endometrium with psammoma bodies

Main article: Endometrium with psammoma bodies

Endometrial hyperplasia

Main article: Endometrial hyperplasia

Can be thought of as a precursor lesion for endometrial carcinoma.

It comes in two main flavours:

  1. Simple.
  2. Complex.

Each flavour may or may not have nuclear atypia.

Endometrial carcinoma

Main article: Endometrial carcinoma

Endometrial cancer is the most common gynecologic malignancy (in the USA).[9]

See also

References

  1. ↑ URL: http://emedicine.medscape.com/article/257007-treatment. Accessed on: 15 July 2010.
  2. ↑ Mazur, Michael T.; Kurman, Robert J. (2005). Diagnosis of Endometrial Biopsies and Curettings: A Practical Approach (2nd ed.). Springer. pp. 1. ISBN 978-0387986159.
  3. ↑ Gambacciani, M.; Monteleone, P.; Ciaponi, M.; Sacco, A.; Genazzani, AR. (Aug 2004). "Clinical usefulness of endometrial screening by ultrasound in asymptomatic postmenopausal women.". Maturitas 48 (4): 421-4. doi:10.1016/j.maturitas.2003.10.006. PMID 15283934.
  4. ↑ 4.0 4.1 4.2 McCluggage, WG. (Aug 2006). "My approach to the interpretation of endometrial biopsies and curettings.". J Clin Pathol 59 (8): 801-12. doi:10.1136/jcp.2005.029702. PMID 16873562.
  5. ↑ Nicolae, A.; Preda, O.; Nogales, FF. (Feb 2011). "Endometrial metaplasias and reactive changes: a spectrum of altered differentiation.". J Clin Pathol 64 (2): 97-106. doi:10.1136/jcp.2010.085555. PMID 21126963.
  6. ↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 237. ISBN 978-0470519035.
  7. ↑ Spencer, SJ.; Cataldo, NA.; Jaffe, RB. (May 1996). "Apoptosis in the human female reproductive tract.". Obstet Gynecol Surv 51 (5): 314-23. PMID 8744416.
  8. ↑ Arias-Stella, J. (Jan 2002). "The Arias-Stella reaction: facts and fancies four decades after.". Adv Anat Pathol 9 (1): 12-23. PMID 11756756.
  9. ↑ Lu KH (April 2009). "Management of early-stage endometrial cancer". Semin. Oncol. 36 (2): 137–44. doi:10.1053/j.seminoncol.2008.12.005. PMID 19332248.
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