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'''Endometriosis''' causes significant morbidity and is associated with increased risk of certain malignancies.
{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Image      = Endometriosis_of_the_ovary.jpg
| Width      =
| Caption    = Endometriosis of the ovary. [[H&E stain]].
| Micro      = at least 2 of 3: (1) endometrial glands, (2) endometrial stroma, (3) hemosiderin-laden macrophages
| Subtypes  =
| LMDDx      = [[adenocarcinoma]], [[endosalpingiosis]]
| Stains    =
| IHC        = CK7 +ve, ER +ve, [[CD10]] +ve (stroma), CK20 -ve, CDX2 -ve
| EM        =
| Molecular  =
| IF        =
| Gross      = chocolate cyst
| Grossing  =
| Site      = [[ovary]], uterine ligaments, cul-de-sac, [[peritoneum]], [[cervix]], [[vagina]], [[fallopian tubes]], surgical [[scar]]s, [[gastrointestinal tract]]
| Assdx      = infertility, [[endometrioid adenocarcinoma of the ovary]], [[clear cell adenocarcinoma of the ovary]], [[seromucinous borderline tumour]]
| Syndromes  =
| Clinicalhx =
| Signs      =
| Symptoms  = +/-pelvic pain, +/-deep dyspareunia
| Prevalence = common
| Bloodwork  = [[CA-125]] mildly elevated
| Rads      =
| Endoscopy  =
| Prognosis  = benign
| Other      =
| ClinDDx    =
}}
'''Endometriosis''' causes significant morbidity and is associated with increased risk of [[Endometriosis#Tumours associated with endometriosis|certain malignancies]].


==Clinical==
==General==
*A cause of infertility.
===Pathophysiology===
*A cause of pelvic pain.
There are several theories for endometriosis, i.e. how it is that endometrial tissue gets found outside of the uterus:
*Retrograde menstruation - probably the most common.<ref name=pmid3945444/>
*Ectopic endometrial tissue.<ref name=pmid19358700>{{Cite journal  | last1 = Signorile | first1 = PG. | last2 = Baldi | first2 = F. | last3 = Bussani | first3 = R. | last4 = D'Armiento | first4 = M. | last5 = De Falco | first5 = M. | last6 = Baldi | first6 = A. | title = Ectopic endometrium in human foetuses is a common event and sustains the theory of müllerianosis in the pathogenesis of endometriosis, a disease that predisposes to cancer. | journal = J Exp Clin Cancer Res | volume = 28 | issue =  | pages = 49 | month =  | year = 2009 | doi = 10.1186/1756-9966-28-49 | PMID = 19358700 }}</ref>
*Coelomic metaplasia.
*Hematogenous spread or lymphatic spread.
 
===Clinical===
*Associated with infertility.
*Pelvic pain.
*Deep dyspareunia.
*Affects approximately 10% of women of child bearing age.
*Affects approximately 10% of women of child bearing age.
*Associated with moderate elevation of (serum) CA-125.
*Associated with moderate elevation of (serum) CA-125.


==Diagnosis==  
===Tumours associated with endometriosis===
Endometriosis is associated with gynecologic tumours:
#[[Endometrioid adenocarcinoma of the ovary]].<ref name=pmid18707869>{{cite journal |author=Nagle CM, Olsen CM, Webb PM, Jordan SJ, Whiteman DC, Green AC |title=Endometrioid and clear cell ovarian cancers: a comparative analysis of risk factors |journal=Eur. J. Cancer |volume=44 |issue=16 |pages=2477-84 |year=2008 |month=November |pmid=18707869 |doi=10.1016/j.ejca.2008.07.009 |url=}}</ref>
#[[Clear cell carcinoma of the ovary]].<ref name=pmid18834345>{{cite journal |author=Kawaguchi R, Tsuji Y, Haruta S, ''et al.'' |title=Clinicopathologic features of ovarian cancer in patients with ovarian endometrioma |journal=J. Obstet. Gynaecol. Res. |volume=34 |issue=5 |pages=872–7 |year=2008 |month=October |pmid=18834345 |doi=10.1111/j.1447-0756.2008.00849.x |url=}}</ref>
#Endocervical-like mucinous borderline tumour (EMBT).<ref name=pmid16228656>{{cite journal |author=Moriya T, Mikami Y, Sakamoto K, ''et al.'' |title=Endocervical-like mucinous borderline tumors of the ovary: clinicopathological features and electron microscopic findings |journal=Med Electron Microsc |volume=36 |issue=4 |pages=240–6 |year=2003 |month=December |pmid=16228656 |doi=10.1007/s00795-003-0221-4 |url=}}</ref>
#*Mixture of EMBT and serous borderline tumor = [[seromucinous borderline tumour]].
 
Other tumours & decreased risk:<ref>URL: [http://www.medicalnewstoday.com/articles/3890.php http://www.medicalnewstoday.com/articles/3890.php]. Accessed on: 26 September 2011.</ref>
*Increased: endocrine tumours, [[non-Hodgkin's lymphoma]], [[brain tumours]].
*Decreased: [[cervical cancer]].
 
Rare stuff:
*There are case reports of endometriosis in men on estrogen therapy for [[prostate cancer]].<ref name=pmid22104297>{{Cite journal  | last1 = Fukunaga | first1 = M. | title = Paratesticular endometriosis in a man with a prolonged hormonal therapy for prostatic carcinoma. | journal = Pathol Res Pract | volume = 208 | issue = 1 | pages = 59-61 | month = Jan | year = 2012 | doi = 10.1016/j.prp.2011.10.007 | PMID = 22104297 }}</ref><ref name=pmid2418693>{{Cite journal  | last1 = Beckman | first1 = EN. | last2 = Pintado | first2 = SO. | last3 = Leonard | first3 = GL. | last4 = Sternberg | first4 = WH. | title = Endometriosis of the prostate. | journal = Am J Surg Pathol | volume = 9 | issue = 5 | pages = 374-9 | month = May | year = 1985 | doi =  | PMID = 2418693 }}</ref>
 
==Gross==
Appearance:
*''Chocolate cyst'' = cyst containing light brown material.
 
Classic locations:
*Ovary - most common location according to Jenkins ''et al''.<ref name=pmid3945444>{{Cite journal  | last1 = Jenkins | first1 = S. | last2 = Olive | first2 = DL. | last3 = Haney | first3 = AF. | title = Endometriosis: pathogenetic implications of the anatomic distribution. | journal = Obstet Gynecol | volume = 67 | issue = 3 | pages = 335-8 | month = Mar | year = 1986 | doi =  | PMID = 3945444 }}</ref>
*Utero-sacral ligament.<ref name=pmid17662280>{{Cite journal  | last1 = Stegmann | first1 = BJ. | last2 = Sinaii | first2 = N. | last3 = Liu | first3 = S. | last4 = Segars | first4 = J. | last5 = Merino | first5 = M. | last6 = Nieman | first6 = LK. | last7 = Stratton | first7 = P. | title = Using location, color, size, and depth to characterize and identify endometriosis lesions in a cohort of 133 women. | journal = Fertil Steril | volume = 89 | issue = 6 | pages = 1632-6 | month = Jun | year = 2008 | doi = 10.1016/j.fertnstert.2007.05.042 | PMID = 17662280 }}</ref>
*Cul-de-sac.<ref name=pmid17662280/>
*Broad ligament.
 
Note:
*The hierarchy of the most common sites, i.e. what is most common and what is the second most common etc., depends on the paper one reads, e.g. compare Jenkins ''et al''<ref name=pmid3945444/> with Stegmann ''et al''.<ref name=pmid17662280/>
**''Robbins'' gives the order as: ovaries, uterine ligaments, rectovaginal septum, cul-de-sac, pelvic periteoneum, [[gastrointestinal tract]], [[cervix]], [[vagina]], [[fallopian tubes]], laparotomy scars.<ref name=Ref_PCPBoD8_524>{{Ref PCPBoD8|524}}</ref>
*Endometriosis can appear almost any where.
**A well-reported uncommon location is the abdominal wall post-caesarian section.<ref name=pmid22381104>{{Cite journal  | last1 = Ozel | first1 = L. | last2 = Sagiroglu | first2 = J. | last3 = Unal | first3 = A. | last4 = Unal | first4 = E. | last5 = Gunes | first5 = P. | last6 = Baskent | first6 = E. | last7 = Aka | first7 = N. | last8 = Titiz | first8 = MI. | last9 = Tufekci | first9 = EC. | title = Abdominal wall endometriosis in the cesarean section surgical scar: a potential diagnostic pitfall. | journal = J Obstet Gynaecol Res | volume = 38 | issue = 3 | pages = 526-30 | month = Mar | year = 2012 | doi = 10.1111/j.1447-0756.2011.01739.x | PMID = 22381104 }}</ref>
*Intraluminal endometriosis in the Fallopian tube - is relatively common,<ref>{{cite journal |authors=Hill CJ, Fakhreldin M, Maclean A, Dobson L, Nancarrow L, Bradfield A, Choi F, Daley D, Tempest N, Hapangama DK |title=Endometriosis and the Fallopian Tubes: Theories of Origin and Clinical Implications |journal=J Clin Med |volume=9 |issue=6 |pages= |date=June 2020 |pmid=32570847 |pmc=7355596 |doi=10.3390/jcm9061905 |url=}}</ref> it may be less obvious to the surgeon.
 
===Images===
<gallery>
Image: Endometriosis,_abdominal_wall.jpg |Endometriosis in C-section scar at cut-up. (Ed Uthman/WC)
</gallery>
 
==Microscopic==  
Criteria - need at least 2 / 3 for the diagnosis:<ref name=Ref_DCHH239>{{Ref DCHH|239}}</ref>
Criteria - need at least 2 / 3 for the diagnosis:<ref name=Ref_DCHH239>{{Ref DCHH|239}}</ref>
#Endometrial glands - endometrial glands are classically: circular, with nuclei that are hyperchromatic & cigar-shaped.
#Endometrial glands - endometrial glands are classically: circular, with nuclei that are hyperchromatic & cigar-shaped.
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*Epithelial component may have tubal metaplasia.<ref name=pmid17592255>{{cite journal |author=Clement PB |title=The pathology of endometriosis: a survey of the many faces of a common disease emphasizing diagnostic pitfalls and unusual and newly appreciated aspects |journal=Adv Anat Pathol |volume=14 |issue=4 |pages=241–60 |year=2007 |month=July |pmid=17592255 |doi=10.1097/PAP.0b013e3180ca7d7b |url=}}</ref>
*Epithelial component may have tubal metaplasia.<ref name=pmid17592255>{{cite journal |author=Clement PB |title=The pathology of endometriosis: a survey of the many faces of a common disease emphasizing diagnostic pitfalls and unusual and newly appreciated aspects |journal=Adv Anat Pathol |volume=14 |issue=4 |pages=241–60 |year=2007 |month=July |pmid=17592255 |doi=10.1097/PAP.0b013e3180ca7d7b |url=}}</ref>
*Endometriosis may mimic [[cancer]]<ref name=pmid20631604>{{Cite journal  | last1 = Corben | first1 = AD. | last2 = Nehhozina | first2 = T. | last3 = Garg | first3 = K. | last4 = Vallejo | first4 = CE. | last5 = Brogi | first5 = E. | title = Endosalpingiosis in axillary lymph nodes: a possible pitfall in the staging of patients with breast carcinoma. | journal = Am J Surg Pathol | volume = 34 | issue = 8 | pages = 1211-6 | month = Aug | year = 2010 | doi = 10.1097/PAS.0b013e3181e5e03e | PMID = 20631604 }}</ref> - see images below.
*Endometriosis may mimic [[cancer]]<ref name=pmid20631604>{{Cite journal  | last1 = Corben | first1 = AD. | last2 = Nehhozina | first2 = T. | last3 = Garg | first3 = K. | last4 = Vallejo | first4 = CE. | last5 = Brogi | first5 = E. | title = Endosalpingiosis in axillary lymph nodes: a possible pitfall in the staging of patients with breast carcinoma. | journal = Am J Surg Pathol | volume = 34 | issue = 8 | pages = 1211-6 | month = Aug | year = 2010 | doi = 10.1097/PAS.0b013e3181e5e03e | PMID = 20631604 }}</ref> - see images below.
*If it is just endometrial type glands... it is probably [[endosalpingiosis]].  
*If it is just endometrial type glands - the stroma is missing... it is probably [[endosalpingiosis]].
 
DDx:
*[[Adenocarcinoma]] - especially colorectal adenocarcinoma.
*[[Endosalpingiosis]] - does not have stromal component.
**In the GI tract, it classically expands the muscularis propria.


===Images===
===Images===
*[http://commons.wikimedia.org/wiki/File:Endometriosis_of_the_ovary.jpg Endometriosis - ovary (WC)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:Endometrioma1.jpg Endometriosis - low mag. (WC)].
Image:Endometriosis_of_the_ovary.jpg | Endometriosis - ovary. (WC/Nephron)
*[http://commons.wikimedia.org/wiki/File:Endometrioma3.jpg Endometriosis - high mag. (WC)].
Image:Endometrioma1.jpg | Endometriosis - low mag. (WC/Nephron)
Image:Endometrioma3.jpg | Endometriosis - high mag. (WC/Nephron)
</gallery>


Mimicking cancer:
Mimicking cancer:
*[http://commons.wikimedia.org/wiki/File:Intestine_with_endometriosis_-_low_mag.jpg Endometriosis in the small intestine - low mag. (WC)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:Endometriosis_lymph_node_-_2_-_intermed_mag.jpg Endometriosis in a lymph node - intermed. mag. (WC)].
Image:Intestine_with_endometriosis_-_low_mag.jpg | Endometriosis in the small intestine - low mag. (WC/Nephron)
Image:Endometriosis_lymph_node_-_2_-_intermed_mag.jpg | Endometriosis in a lymph node - intermed. mag. (WC/Nephron)
</gallery>
www:
*[http://path.upmc.edu/cases/case375.html Endometriosis - several images (upmc.edu)].


==Associations==
==Immunohistochemical stains==
Endometriosis is associated with gynecologic tumours:
Features:<ref>{{cite journal |authors=Jiang W, Roma AA, Lai K, Carver P, Xiao SY, Liu X |title=Endometriosis involving the mucosa of the intestinal tract: a clinicopathologic study of 15 cases |journal=Mod Pathol |volume=26 |issue=9 |pages=1270–8 |date=September 2013 |pmid=23579618 |doi=10.1038/modpathol.2013.51 |url=}}</ref>
#Endometrioid adenocarcinoma of the [[ovarian tumours|ovary]]<ref>{{cite journal |author=Nagle CM, Olsen CM, Webb PM, Jordan SJ, Whiteman DC, Green AC |title=Endometrioid and clear cell ovarian cancers: a comparative analysis of risk factors |journal=Eur. J. Cancer |volume=44 |issue=16 |pages=2477-84 |year=2008 |month=November |pmid=18707869 |doi=10.1016/j.ejca.2008.07.009 |url=}}</ref>
*ER +ve
#Clear cell carcinoma of the ovary.<ref name=pmid18834345>{{cite journal |author=Kawaguchi R, Tsuji Y, Haruta S, ''et al.'' |title=Clinicopathologic features of ovarian cancer in patients with ovarian endometrioma |journal=J. Obstet. Gynaecol. Res. |volume=34 |issue=5 |pages=872–7 |year=2008 |month=October |pmid=18834345 |doi=10.1111/j.1447-0756.2008.00849.x |url=}}</ref>
**Stains the epithelium.
#Endocervical-like mucinous borderline tumour (EMBT).<ref name=pmid16228656>{{cite journal |author=Moriya T, Mikami Y, Sakamoto K, ''et al.'' |title=Endocervical-like mucinous borderline tumors of the ovary: clinicopathological features and electron microscopic findings |journal=Med Electron Microsc |volume=36 |issue=4 |pages=240–6 |year=2003 |month=December |pmid=16228656 |doi=10.1007/s00795-003-0221-4 |url=}}</ref>
*[[CK7]] +ve
#*Mixture of EMBT and serous borderline tumor = seromucinous borderline tumour.
**Stains the epithelium.
*[[CK20]] -ve
**Used to exclude [[colorectal adenocarcinoma]].
*CDX2 -ve.
**Used to exclude [[colorectal adenocarcinoma]].
*[[CD10]] +ve
**Marks the stromal cells.<ref name=Ref_DCHH236>{{Ref DCHH|236}}</ref>
 
==Sign out==
===Biopsy===
<pre>
OVARIAN FOSSA, RIGHT, BIOPSY:
- ENDOMETRIOSIS.
- FIBROADIPOSE TISSUE PARTIALLY COVERED BY MESOTHELIUM.  
</pre>
 
<pre>
CYST WALL, OVARY LEFT, CYSTECTOMY:
- ENDOMETRIOSIS.
</pre>
 
<pre>
CUL-DE-SAC, BIOPSY:
- ENDOMETRIOSIS.
 
COMMENT:
A CD10 immunostain marks the endometrial-type stroma and confirms the presence of
endometriosis.
</pre>
 
===Ovary and tube===
<pre>
OVARY AND FALLOPIAN TUBE, LEFT, SALPINO-OOPHORECTOMY:
- OVARY WITH ENDOMETRIOSIS.
- FALLOPIAN TUBE WITHIN NORMAL LIMITS.
- NEGATIVE FOR MALIGNANCY.
</pre>
 
===TAH-USO===
<pre>
UTERUS, UTERINE TUBES, LEFT OVARY, TOTAL HYSTERECTOMY, BILATERAL SALPINGECTOMY
AND LEFT OOPHRECTOMY:
- LEIOMYOMATA WITH HYALINE CHANGE.
- NONPROLIFERATIVE ENDOMETRIAL GLANDS WITH STROMAL DECIDUALIZATION, AND GLANDULAR
  DILATION.
- LEFT OVARY WITH ENDOMETRIOSIS, SEE COMMENT.
- LEFT UTERINE TUBE WITH ENDOMETRIOSIS, SEE COMMENT.
- RIGHT UTERINE TUBE WITHIN NORMAL LIMITS.
- UTERINE CERVIX WITHIN NORMAL LIMITS.
- NEGATIVE FOR MALIGNANCY.
 
COMMENT:
The presence of endometrial stroma was demonstrated with CD10 immunostaining, thus
confirming the presence of endometriosis.
</pre>
 
===TAH-BSO===
<pre>
UTERINE CERVIX, UTERUS, UTERINE TUBES AND OVARIES, TOTAL HYSTERECTOMY AND BILATERAL SALPINGOOPHERECTOMY:
- UTERINE CERVIX WITHIN NORMAL LIMITS.
- PROLIFERATIVE PHASE ENDOMETRIUM.
- UTERUS WITH FIBROUS SEROSAL ADHESIONS.
- LEFT UTERINE TUBE WITH ENDOMETRIOSIS.
- RIGHT UTERINE TUBE WITHIN NORMAL LIMITS.
- RIGHT AND LEFT OVARIES WITH ENDOMETRIOSIS.
</pre>
 
===Soft tissue abdominal wall mass===
<pre>
MASS, RIGHT LOWER ABDOMEN, EXCISION:
- ENDOMETRIOMA.
- SCAR.


Other tumours & decreased risk:<ref>URL: [http://www.medicalnewstoday.com/articles/3890.php http://www.medicalnewstoday.com/articles/3890.php]. Accessed on: 26 September 2011.</ref>
COMMENT:
*Increased: endocrine tumours, [[non-Hodgkin's lymphoma]], [[brain tumours]].
Immunostains confirm the presence of endometriosis (glandular component ER positive,
*Decreased: [[cervical cancer]].
endometrial-like stroma CD10 positive).
</pre>


==Immunohistochemical stains==
===Micro===
*CD10 [[stains]] the stromal cells<ref name=Ref_DCHH236>{{Ref DCHH|236}}</ref> - used to look for endometriosis.
The sections show soft tissue with endometrial-type glands surrounded by endometrial-type
stroma. Siderophages are present. No nuclear atypia is identified. Mitotic activity is not
apparent.


==See also==
==See also==
Michael
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