Difference between revisions of "Colon"

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The '''colon''' smell like poo... 'cause that's where poo comes from.  This article also covers the '''rectum''' and '''cecum''' as both have a similar mucosa.   
[[Image:Blausen_0603_LargeIntestine_Anatomy.png|thumb|right|Anatomy of the colon and rectum. (WC)]]
The '''colon''' is section of the large bowel.  This article also covers the '''rectum''' and '''cecum''' as both have a similar mucosa.   


It commonly comes to pathologists because there is a suspicion of [[colorectal cancer]] or a known history of [[inflammatory bowel disease]] (IBD).  
It commonly comes to pathologists because there is a suspicion of [[colorectal cancer]] or a known history of [[inflammatory bowel disease]] (IBD).


An introduction to gastrointestinal pathology is found in the ''[[gastrointestinal pathology]]'' article.  The ''[[anus]]'' is dealt with in a separate article.
An introduction to gastrointestinal pathology is found in the ''[[gastrointestinal pathology]]'' article.  The ''[[anus]]'' and ''[[ileocecal valve]]'' are dealt with in separate articles.


Technically, the rectum and cecum are ''not'' part of the colon.  Thus, inflammation of the rectum should be ''proctitis'' and inflammation of the cecum should be ''cecitis''.
Technically, the rectum and cecum are ''not'' part of the colon.  Thus, inflammation of the rectum should be ''proctitis'' and inflammation of the cecum should be ''cecitis''.
=Anatomy=
*The [[rectum]] has several definition. These are discussed in the ''[[rectum]]'' article.
*The large bowel may be submitted with segment names or with the distance to the anal verge.
A conversion between named segments and distance - as per NCI of the United States:<ref>URL: [https://training.seer.cancer.gov/colorectal/anatomy/figure/figure1.html]https://training.seer.cancer.gov/colorectal/anatomy/figure/figure1.html]. Accessed on: 8 February 2018.</ref>
{| class="wikitable sortable"
!Named segment
!Distance to anal verge (cm)
|-
|Anus
|0-4
|-
|[[Rectum]]
|4-16
|-
|Rectosigmoid
|15-17
|-
|Sigmoid
|17-57
|-
|Descending
|57-82
|-
|Transverse
|82-132
|-
|Ascending
|132-147
|-
|Cecum
|150
|}


=Common clinical problems=
=Common clinical problems=
Line 16: Line 51:
===Bleeding===
===Bleeding===
Mnemonic ''CHAND'':<ref>TN 2007 G29.</ref>
Mnemonic ''CHAND'':<ref>TN 2007 G29.</ref>
*Colitis (radiation, infectious, ischemic, IBD (UC >CD), iatrogenic (anticoagulants)).  
*Colitis ([[radiation colitis|radiation]], [[infectious colitis|infectious]], [[ischemic colitis|ischemic]], [[IBD]] (UC >CD), iatrogenic (anticoagulants)).  
*[[Hemorrhoids]].
*[[Hemorrhoids]].
*[[Angiodysplasia]].  
*[[Angiodysplasia]].  
Line 28: Line 63:
*Shigella.
*Shigella.


Infectious colitis in the immunosuppressed:
[[Infectious colitis]] in the immunosuppressed:
*[[Cytomegalovirus]] (CMV).<ref name=pmid7934809>{{cite journal |author=Golden MP, Hammer SM, Wanke CA, Albrecht MA |title=Cytomegalovirus vasculitis. Case reports and review of the literature |journal=Medicine (Baltimore) |volume=73 |issue=5 |pages=246–55 |year=1994 |month=September |pmid=7934809 |doi= |url=}}</ref>
*[[Cytomegalovirus]] (CMV).<ref name=pmid7934809>{{cite journal |author=Golden MP, Hammer SM, Wanke CA, Albrecht MA |title=Cytomegalovirus vasculitis. Case reports and review of the literature |journal=Medicine (Baltimore) |volume=73 |issue=5 |pages=246–55 |year=1994 |month=September |pmid=7934809 |doi= |url=}}</ref>
**May afflict patients with IBD and lead to colectomy... as IBD patients are put on immunosuppression.<ref name=pmid17026558>{{cite journal |author=Kandiel A, Lashner B |title=Cytomegalovirus colitis complicating inflammatory bowel disease |journal=Am. J. Gastroenterol. |volume=101 |issue=12 |pages=2857–65 |year=2006 |month=December |pmid=17026558 |doi=10.1111/j.1572-0241.2006.00869.x |url=}}</ref>
**May afflict patients with IBD and lead to colectomy... as IBD patients are put on immunosuppression.<ref name=pmid17026558>{{cite journal |author=Kandiel A, Lashner B |title=Cytomegalovirus colitis complicating inflammatory bowel disease |journal=Am. J. Gastroenterol. |volume=101 |issue=12 |pages=2857–65 |year=2006 |month=December |pmid=17026558 |doi=10.1111/j.1572-0241.2006.00869.x |url=}}</ref>
**Organ transplant recipients.
**Organ transplant recipients.
**[[HIV|HIV/AIDS]].
**[[HIV|HIV/AIDS]].
***Images:
 
****[http://commons.wikimedia.org/w/index.php?title=File:CMV_colitis_-_high_mag_-_cropped.jpg CMV colitis - high. mag. (WC)].
Images:
****[http://commons.wikimedia.org/w/index.php?title=File:CMV_colitis_-_intermed_mag.jpg CMV colitis - intermed. mag. (WC)].
<gallery>
Image:CMV_colitis_-_high_mag_-_cropped.jpg | CMV colitis - high. mag. (WC/Nephron)
Image:CMV_colitis_-_intermed_mag.jpg | CMV colitis - intermed. mag. (WC/Nephron)
</gallery>


=Grossing=
=Grossing=
Line 44: Line 82:
# Subtotal colectomy - part of colon removed --or-- some of the rectum remains.
# Subtotal colectomy - part of colon removed --or-- some of the rectum remains.
# Right hemicolectomy - right colon + distal ileum.
# Right hemicolectomy - right colon + distal ileum.
# Lower anterior resection (LAR) - proximal rectum +/- sigmoid (for proximal rectal malignancies).
# [[Lower anterior resection]] (LAR) - proximal rectum +/- sigmoid (for proximal rectal malignancies).
#* Specimens have should have intact mesorectum - ''total mesorectal excision'' (TME) - reduces local recurrence.<ref name=pmid8665198>{{Cite journal  | last1 = Arbman | first1 = G. | last2 = Nilsson | first2 = E. | last3 = Hallböök | first3 = O. | last4 = Sjödahl | first4 = R. | title = Local recurrence following total mesorectal excision for rectal cancer. | journal = Br J Surg | volume = 83 | issue = 3 | pages = 375-9 | month = Mar | year = 1996 | doi =  | PMID = 8665198 }}</ref>  
#* Specimens have should have intact mesorectum - ''[[total mesorectal excision]]'' (TME) - reduces local recurrence.<ref name=pmid8665198>{{Cite journal  | last1 = Arbman | first1 = G. | last2 = Nilsson | first2 = E. | last3 = Hallböök | first3 = O. | last4 = Sjödahl | first4 = R. | title = Local recurrence following total mesorectal excision for rectal cancer. | journal = Br J Surg | volume = 83 | issue = 3 | pages = 375-9 | month = Mar | year = 1996 | doi =  | PMID = 8665198 }}</ref>  
# Abdominoperineal resection (APR) - anus + rectum - results in a permanent stoma (for distal rectal malignancies).
# [[Abdominoperineal resection]] (APR) - anus + rectum - results in a permanent [[stoma]] (for distal rectal malignancies).
# [[Stoma]] - these are often done emergently and then get cut-out after the patient's condition has settled.
# [[Stoma]] - these are often done emergently and then get cut-out after the patient's condition has settled.
#[[Doughnuts]] (also ''donuts'') from an end-to-end anastomosis stapler.
#*Often accompany lower anterior resections.


Images:
===Images===
*[http://pathinfo.wikia.com/wiki/File:Rectum_anterior_view.jpg Rectal specimen - anterior (wikia.com)].<ref>URL: [http://pathinfo.wikia.com/wiki/Rectum http://pathinfo.wikia.com/wiki/Rectum]. Accessed on: 17 September 2012.</ref>
<gallery>
*[http://pathinfo.wikia.com/wiki/File:Rectum_lateral_view.jpg Rectal specimen - lateral (wikia.com)].
Image:Rectum - anterior view.jpg | APR specimen - anterior (WC)
*[http://pathinfo.wikia.com/wiki/File:Rectum_inking.jpg Rectal specimen - inked (wikia.com)].
Image: Rectum - lateral view.jpg | APR specimen - lateral (WC)
Image: Rectum - anterior and lateral - inked.jpg | APR specimen - inked (WC)
</gallery>


==Identifying the specimen==
==Identifying the specimen==
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**Anatomists define it in relation to the third sacral vertebra.<ref>URL: [http://www.bartleby.com/107/249.html http://www.bartleby.com/107/249.html]. Accessed on: 19 October 2012.</ref>
**Anatomists define it in relation to the third sacral vertebra.<ref>URL: [http://www.bartleby.com/107/249.html http://www.bartleby.com/107/249.html]. Accessed on: 19 October 2012.</ref>


Image:
===Images===
*[http://pathinfo.wikia.com/wiki/File:Rectum_lateral_view.jpg Rectum and sigmoid colon (wikia.com)].
<gallery>
Image: Rectum - lateral view.jpg | Sigmoid and rectum. APR specimen. (WC)
</gallery>


==Lymph nodes==
==Lymph nodes==
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==Standard method==
==Standard method==
*Bowel is prep'ed by opening it along the antimesenteric side.
*Bowel is prep'ed by [[opening]] it along the antimesenteric side.
*Dimensions - length, circumference at both [[margins]].
*Dimensions - length, circumference at both [[margins]].
*Radial margin/circumferential margin - should be painted.
*Radial margin/circumferential margin - should be painted.
**Rectum starts/sigmoid ends @ place where serosa ends on the posterior aspect of the bowel.
**Rectum starts/sigmoid ends @ place where serosa ends on the posterior aspect of the bowel.
***The proximal, anterior aspect of the rectum has serosa, i.e. it is not painted.
***The proximal, anterior aspect of the rectum has serosa, i.e. it is not painted.
Note:
*There are several definitions for the rectum.<ref name=pmid24130630>{{Cite journal  | last1 = Kenig | first1 = J. | last2 = Richter | first2 = P. | title = Definition of the rectum and level of the peritoneal reflection - still a matter of debate? | journal = Wideochir Inne Tech Maloinwazyjne | volume = 8 | issue = 3 | pages = 183-6 | month = Sep | year = 2013 | doi = 10.5114/wiitm.2011.34205 | PMID = 24130630 }}</ref>
**In a survey of surgeons:
**67% defined it by an anatomical landmark
***35% of all respondants considered the peritoneal reflection the proximal boundary of the rectum.
**30% defined the proximal boundary as a distance from the anal verge.


=Common non-neoplastic disease=
=Common non-neoplastic disease=
Line 90: Line 141:


Most common (images):
Most common (images):
*[http://commons.wikimedia.org/wiki/File:Hyperplastic_polyp1.jpg Hyperplastic polyp image - intermed. mag. (WC)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:Hyperplastic_polyp2.jpg Hyperplastic polyp image - low mag. (WC)].
Image:Hyperplastic_polyp1.jpg | Hyperplastic polyp image - intermed. mag. (WC/Nephron)
 
Image:Hyperplastic_polyp2.jpg | Hyperplastic polyp image - low mag. (WC/Nephron)
</gallery>
==Ischemic colitis==
==Ischemic colitis==
*[[AKA]] ''colonic ischemia''.
*[[AKA]] ''colonic ischemia''.
*[[AKA]] ''ischemia of the colon''.
*[[AKA]] ''ischemia of the colon''.
===General===
{{Main|Ischemic colitis}}
*May occur together with ''[[ischemic enteritis]]'', in which case it is known as ''ischemic enterocolitis''.
 
Etiology - anything that leads to vascular occlusion:
*[[Atherosclerosis]].
*[[Vasculitis]].
*Embolization, e.g. thrombotic, foreign body.
 
Possible associated pathology:
*[[Necrotizing enteritis]] - necrosis of the small bowel only.
*[[Necrotizing enterocolitis]] - necrosis of the small and large bowel.
 
Closely related:
*Radiation colitis.
*Infective colitis.
 
Note:
*Ischemia = compromised blood supply.
 
===Gross===
Features - location:<ref name=Ref_PBoD852>{{Ref PBoD|852}}</ref>
*Luminal part (mucosa & submucosa) affected - edema.
*Splenic flexture of colon commonly affected (vascular watershed).
 
Note:
*May have pseudomembranes (classically assoc. with ''C. difficile'' colitis), i.e. mimics an infectious process.
*DDx for pseudomembranes:<ref name=Ref_PBoD837-8>{{Ref PBoD|837-8}}</ref>
**[[C. difficile]] induced pseudomembranous colitis.
**Ischemic colitis.
**Volvulus.
**Necrotizing infections.
**... anything that causes severe mucosal injury.
*Radiologic correlate = bowel wall thickening.
 
===Microscopic===
Features:
*Crypt loss/drop-out.
**Less intestinal crypts present.
*Withering crypts.
**Colonic epithelium has decreased cytoplasm - NC ratio increased.
*Lamina propria hyalinization.
**Dense pink material replaces loose connective tissue.
*Submucosa hyalinization.
*+/-Pseudomembranes (microscopic):<ref name=Ref_PBoD837-8>{{Ref PBoD|837-8}}</ref>
**Loss of surface epithelium.
**[[PMN]]s in lamina propria.
**+/-Capillary fibrin thrombi.
 
Note:
*Pseudomembranes arise from the crypts - considered ''acute''.
 
DDx:
*[[Inflammatory bowel disease]].
*Radiation.
*Toxins/drugs.
*Infection.
 
Images:
*WC:
**[http://commons.wikimedia.org/wiki/File:Ischemic_colitis_-_low_mag.jpg Ischemic colitis - low mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Ischemic_colitis_-_high_mag.jpg Ischemic colitis - high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Ischemic_colitis_-_very_high_mag.jpg Ischemic colitis - very high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Colonic_pseudomembranes_low_mag.jpg Colonic pseudomembranes - low mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Colonic_pseudomembranes_intermed_mag.jpg Colonic pseudomembranes - intermed. mag. (WC)].
*www:
**[http://www.flickr.com/photos/euthman/3385570758/ Ischemic colitis (flickr.com/euthman)].
**[http://radiology.uchc.edu/eAtlas/GI/1019.htm Ischemic colitis (uchc.edu)].
 
===Sign out===
<pre>
LEFT COLON AND SIGMOID COLON, RESECTION:
- PSEUDOMEMBRANOUS COLITIS, SEE COMMENT.
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
 
COMMENT:
Pseudomembrane formation is a non-specific finding.  It is consistent with ischemia;
however, it may be seen in other contexts, including infection. Clinical correlation is
required.
</pre>


==Diverticular disease==
==Diverticular disease==
*[[AKA]] ''diverticulosis''.
{{Main|Diverticular disease}}
===General===
*Very common.
 
Complications:
*Diverticulitis.
*Diverticular-associated colitis<ref>{{Cite journal  | last1 = Mulhall | first1 = AM. | last2 = Mahid | first2 = SS. | last3 = Petras | first3 = RE. | last4 = Galandiuk | first4 = S. | title = Diverticular disease associated with inflammatory bowel disease-like colitis: a systematic review. | journal = Dis Colon Rectum | volume = 52 | issue = 6 | pages = 1072-9 | month = Jun | year = 2009 | doi = 10.1007/DCR.0b013e31819ef79a | PMID = 19581849 }}</ref> - rare.
**Rectal biopsy to differentiate from [[ulcerative colitis]].
 
===Gross===
*Corrugated - like cardboard.
*Wall thickening (reactive).<ref name=pmid21359889>{{Cite journal  | last1 = Nicholson | first1 = BD. | last2 = Hyland | first2 = R. | last3 = Rembacken | first3 = BJ. | last4 = Denyer | first4 = M. | last5 = Hull | first5 = MA. | last6 = Tolan | first6 = DJ. | title = Colonoscopy for colonic wall thickening at computed tomography: a worthwhile pursuit? | journal = Surg Endosc | volume = 25 | issue = 8 | pages = 2586-91 | month = Aug | year = 2011 | doi = 10.1007/s00464-011-1591-7 | PMID = 21359889 }}</ref>
 
Endoscopic image: [http://commons.wikimedia.org/wiki/File:Diverticulosis_2.jpg DD (WC)].
===Microscopic===
Features:
*Mucosa/submucosa invagination into the musuclaris propria (MP).
**At the site the blood vessels supplying the mucosa and submucosa penetrate the MP.<ref name=pmid18936652>{{Cite journal  | last1 = West | first1 = AB. | title = The pathology of diverticulitis. | journal = J Clin Gastroenterol | volume = 42 | issue = 10 | pages = 1137-8 | month =  | year =  | doi = 10.1097/MCG.0b013e3181862a9f | PMID = 18936652 }}</ref>
 
Image:
*[http://histology-group28.wikispaces.com/file/view/divertic.jpg/60992930/divertic.jpg DD (wikispaces.com)].<ref>URL: [http://histology-group28.wikispaces.com/DigestiveSystemProject http://histology-group28.wikispaces.com/DigestiveSystemProject]. Accessed on: 23 August 2011.</ref>
 
===Sign out===
<pre>
RECTO-SIGMOID, LARGE BOWEL RESECTION:
- PERFORATED DIVERTICULITIS WITH SEROSITIS AND ABSCESS FORMATION.
- SUBMUCOSAL FIBROSIS.
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).
- NEGATIVE FOR MALIGNANCY.
</pre>


==Pseudomembranous colitis==
==Pseudomembranous colitis==
===General===
{{Main|Pseudomembranous colitis}}
*''Pseudomembranous colitis'' is a histomorphologic description which has a [[DDx]]. In other words, it can be caused by a number of things.
 
DDx of pseudomembranous colitis:<ref name=Ref_PBoD837-8>{{Ref PBoD|837-8}}</ref>
*[[C. difficile]].
**Known as ''C. difficile colitis''.
*[[Ischemic colitis]].
**Volvulus.
*Other infections.
 
Etiology:
*Anything that causes a severe mucosal injury.
 
===Gross===
Features:<ref>URL: [http://radiology.uchc.edu/eAtlas/GI/1749.htm http://radiology.uchc.edu/eAtlas/GI/1749.htm]. Accessed on: 22 May 2012.</ref>
*Pseudomembranes:
**Pale yellow (or white) irregular, raised mucosal lesions.
**Early lesions: typical <10 mm.
*Interlesional mucosa often near normal grossly.
 
Images:
*[http://en.wikipedia.org/wiki/File:PMC_1.jpg Pseudomembranous colitis - endoscopic image (WP/Samir)].
*[http://commons.wikimedia.org/wiki/File:Pseudomembranous_colitis.JPG Pseudomembranous colitis (WC)].
 
===Microscopic===
Features:<ref name=Ref_PBoD837-8>{{Ref PBoD|837-8}}</ref>
*Heaped necrotic surface epithelium.
**Described as "volanco lesions" - this is what is seen endoscopically.
*[[PMN]]s in lamina propria.
*+/-Capillary fibrin thrombi.
 
Note:
*Pseudomembranes arise from the crypts.
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Colonic_pseudomembranes_low_mag.jpg Micrograph of pseudomembranes - low mag. (wikimedia.org)].
**[http://commons.wikimedia.org/wiki/File:Colonic_pseudomembranes_intermed_mag.jpg Micrograph of pseudomembranes - intermed. mag. (wikimedia.org)].
*www:
**[http://path.upmc.edu/cases/case153.html Pseudomembranous colitis (upmc.edu)].


==Volvulus==
==Volvulus==
===General===
{{Main|Volvulus}}
*Uncommonly comes to pathology.
*It is essentially a radiologic diagnosis.
*In the context of [[autopsy]], it is a gross diagnosis.
 
===Gross===
*Intestine folded over itself - typically leads to ischemia.
 
Images:
*[http://library.med.utah.edu/WebPath/GIHTML/GI032.html Cecal volvulus (utah.edu)].
*[http://pathsrvr.rockford.uic.edu/inet/GI/Photo%202%20-%20Volvulus%20of%20small%20intestine_%20gross.gif Volvulus (uic.edu)].<ref>URL: [http://pathsrvr.rockford.uic.edu/inet/GI/GI%20Station%201.htm http://pathsrvr.rockford.uic.edu/inet/GI/GI%20Station%201.htm]. Accessed on: 9 April 2012.</ref>
 
===Microscopic===
Features:
*+/-Ischemic changes and/or [[necrosis]].
 
DDx - essentially anything that causes ischemia:
*Embolus.
*Thrombosis.
*[[Vasculitis]].


=Inflammatory diseases=
=Inflammatory diseases=
Line 283: Line 169:
*Basal, i.e. crypt base, plasmacytosis with severe chronic inflammation,
*Basal, i.e. crypt base, plasmacytosis with severe chronic inflammation,
*Crypt architectural abnormalities, and
*Crypt architectural abnormalities, and
*Distal Paneth cell metaplasia.
*Distal [[Paneth cell]] metaplasia.
**Paneth cells should ''not'' be in the left colon<ref name=pmid11851832>{{cite journal |author=Tanaka M, Saito H, Kusumi T, ''et al'' |title=Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease |journal=J. Gastroenterol. Hepatol. |volume=16 |issue=12 |pages=1353–9 |year=2001 |month=December |pmid=11851832 |doi= |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0815-9319&date=2001&volume=16&issue=12&spage=1353}}</ref> - if you see 'em think of IBD and other long-standing injurious processes.
**Paneth cells should ''not'' be in the left colon<ref name=pmid11851832>{{cite journal |author=Tanaka M, Saito H, Kusumi T, ''et al'' |title=Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease |journal=J. Gastroenterol. Hepatol. |volume=16 |issue=12 |pages=1353–9 |year=2001 |month=December |pmid=11851832 |doi= |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0815-9319&date=2001&volume=16&issue=12&spage=1353}}</ref> - if you see 'em think of IBD and other long-standing injurious processes.
**Some claim that (friendly right colonic) paneth cells and paneth cell metaplasia look quite different and can be distinguished.<ref name=pmid12655793>{{cite journal |author=Rubio CA, Nesi G |title=A simple method to demonstrate normal and metaplastic Paneth cells in tissue sections |journal=In Vivo |volume=17 |issue=1 |pages=67–71 |year=2003 |pmid=12655793 |doi= |url=}}</ref>
**Some claim that (friendly right colonic) paneth cells and paneth cell metaplasia look quite different and can be distinguished.<ref name=pmid12655793>{{cite journal |author=Rubio CA, Nesi G |title=A simple method to demonstrate normal and metaplastic Paneth cells in tissue sections |journal=In Vivo |volume=17 |issue=1 |pages=67–71 |year=2003 |pmid=12655793 |doi= |url=}}</ref>


==Microscopic colitis==
==Microscopic colitis==
===General===
:''Microscopic colitis'' may refer to a microscopic manifestation of an unspecified disease process that can be apparent macroscopically. This section links to a pair of diseases (''lymphocytic colitis'' and ''collagenous colitis'') that are considered to only have microscopic manifestations and characteristic clinical presentation.
Definition:
{{Main|Lymphocytic colitis}}
*As the name suggests, they are microscopic, i.e. endoscopic examination is normal.
{{Main|Collagenous colitis}}


Presentation:
==Diversion colitis==
*Chronic diarrhea, non-bloody.<ref name=medscape180664>URL: [http://emedicine.medscape.com/article/180664-overview http://emedicine.medscape.com/article/180664-overview]. Accessed on: 31 May 2010.</ref>
{{Main|Diversion colitis}}


Notes:
==Eosinophilic colitis==
*Clinical DDx includes [[irritable bowel syndrome]] - which has no or subtle histopathologic changes.
*Abbreviated ''EC''.
{{Main|Eosinophilic colitis}}


====Microscopic colitis - types====
=Infectious=
*Lymphocytic colitis (LC).
==Infectious colitis==
*Collagenous colitis (CC).
:This section covers non-specific colitides that appear to have an infective etiology.
===General===
*Common.
*Diarrhea - typical symptom.


Some believe that LC and CC are different time points in the same process-- but this is unproven.<ref name=medscape180664/>
===Gross===
 
*+/-Erythema on endoscopy.
====Epidemiology====
*Age: a disease of adults - usually 50s.
*Sex:
**LC males ~= females,<ref name=medscape180664/>
**CC females:males = 20:1.<ref name=medscape180664/>
*Drugs are associated with LC and CC.
**NSAIDs - posulated association/weak association,
**SSRIs (used primarily for depression) - moderate association, dependent on specific drug.
*Associated with autoimmune disorders - [[celiac disease]], [[diabetes mellitus]], [[thyroid]] disorders and [[arthritis]].<ref name=pmid19109861>{{cite journal |author=Tysk C, Bohr J, Nyhlin N, Wickbom A, Eriksson S |title=Diagnosis and management of microscopic colitis |journal=World J. Gastroenterol. |volume=14 |issue=48 |pages=7280-8 |year=2008 |month=December |pmid=19109861 |doi= |url=http://www.wjgnet.com/1007-9327/14/7280.asp}}</ref>
*No increased risk of colorectal carcinoma.<ref name=pmid19109861/>
 
====Treatment====
*Sometimes just follow-up.
*Steroids - budesonide -- short-term treatment.<ref name=pmid19109861/>


===Microscopic===
===Microscopic===
====Lymphocytic colitis====
Features:
Features:
*Lots of intraepithelial lymphocytes (>=20/100 lymphocytes/surface epithelial cells<ref name=pmid19109861>{{cite journal |author=Tysk C, Bohr J, Nyhlin N, Wickbom A, Eriksson S |title=Diagnosis and management of microscopic colitis |journal=World J. Gastroenterol. |volume=14 |issue=48 |pages=7280-8 |year=2008 |month=December |pmid=19109861 | PMC = 2778111 |doi= |url=http://www.wjgnet.com/1007-9327/14/7280.asp}}</ref>) and
*Neutrophils predominant - '''key feature'''.<ref name=Ref_GLP324>{{Ref GLP|324}}</ref>
*Lymphocytes in the lamina propria.
**The neutrophils are often superficial - they go to were the bad guys are.
*NEGATIVES:<ref name=hopkins_cc_lc>[http://hopkins-gi.nts.jhu.edu/pages/latin/templates/index.cfm?pg=disease1&disease=29&organ=6&lang_id=1 http://hopkins-gi.nts.jhu.edu/pages/latin/templates/index.cfm?pg=disease1&disease=29&organ=6&lang_id=1]</ref>
*No architectural distortion - if acute.
**No PMNs.
**No crypt distortion.


Image:
DDx:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778111/figure/F2/ LC (nih.gov)].<ref name=pmid19109861/>
*[[Inflammatory bowel disease]] - lymphoplasmacytic infiltrate predominant,<ref name=Ref_GLP324>{{Ref GLP|324}}</ref> usually has chronic changes.
*[[Ischemic colitis]].
*Medications - focal neutrophils.
*[[Lymphocytic colitis]] - lymphocytes with a squiggly nucleus, may be confused with neutrophils.
*Specific causes of infective colitis - with a distinctive morphology.
**[[CMV colitis]] - esp. in the immunodeficient.
**[[Pseudomembranous colitis]] - usu. due to ''C. difficle'', has characteristic gross & microscopic appearance.
**[[Intestinal spirochetes]].
**[[Amebiasis]].
**[[Strongyloidiasis]].
**[[Cryptosporidiosis]].


====Collagenous colitis====
===IHC===
Features:
Done if the patient is immunosuppressed, or there is clinical or morphological suspicion:
*Intraepithelial lymphocytes, and
*[[CMV]].
*lymphocytes in the lamina propria.
*HSV-1.
*Collagenous material in the lamina propria (pink on H&E) -- '''key feature'''.
*HSV-2.
**Can be demonstrated with a trichrome stain -- collagen = green on trichrome.
*[[EBV]] - may mimic IBD.<ref name=pmid21119609>{{Cite journal  | last1 = Karlitz | first1 = JJ. | last2 = Li | first2 = ST. | last3 = Holman | first3 = RP. | last4 = Rice | first4 = MC. | title = EBV-associated colitis mimicking IBD in an immunocompetent individual. | journal = Nat Rev Gastroenterol Hepatol | volume = 8 | issue = 1 | pages = 50-4 | month = Jan | year = 2011 | doi = 10.1038/nrgastro.2010.192 | PMID = 21119609 }}</ref>
**Subepithelial collagen needs to be >= 10 micrometres thick for Dx.<ref name=pmid19109861/>
***8 micrometres is the diameter of a RBC.
***The normal thickness of the subepithelial collagen is 3 micrometres.<ref name=pmid19109861/>
**Thickening "follows the crypts from the surface" - useful for differentiating from tangential sections of the basement membrane.<ref>BEC 4 Mar 2009</ref>
**Collagen may envelope capillaries - useful to discern from basement membrane.<ref>BEC 4 Mar 2009</ref>


Images:
===Sign out===
*[http://commons.wikimedia.org/wiki/File:Collagenous_colitis_-_intermed_mag.jpg Collagenous colitis - intermed mag. (WC)].
<pre>
*[http://commons.wikimedia.org/wiki/File:Collagenous_colitis_-_high_mag.jpg Collagenous colitis - high mag. (WC)].
ASCENDING COLON, BIOPSY:
- MILD ACTIVE COLITIS, SEE COMMENT.


Notes:  
COMMENT:
*CC is typically more prominent in the proximal colon - may reflect concentration gradient of offending causitive agents.<ref name=pmid19109861/>
There is are no granulomas. The crypt architecture is normal. A benign lymphoid nodule is
*Significant negative findings:<ref name=hopkins_cc_lc/>
present.
**No [[PMN]]s.
**No crypt distortion.
*Should not be diagnosed in the cecum - as it (normally) has a thickened subepithelial collagen band. (???)


==Diversion colitis==
The differential diagnosis includes infective etiologies, early inflammatory
===General===
bowel disease and ischemia.  The histomorphology is more in keeping with an infective
*Segment of de-functioned bowel due to surgical diversion, i.e. ileostomy or stoma.
etiology as neutrophils are a predominant feature; however, clinical correlation is
*[[Diagnosis]] dependent on history - '''key point'''.
required.
 
</pre>
===Microscopic===
Features:<ref name=pmid9934577>{{Cite journal  | last1 = Edwards | first1 = CM. | last2 = George | first2 = B. | last3 = Warren | first3 = B. | title = Diversion colitis--new light through old windows. | journal = Histopathology | volume = 34 | issue = 1 | pages = 1-5 | month = Jan | year = 1999 | doi = | PMID = 9934577 }}</ref>
*Lymphoid follicular hyperplasia.
*Lymphocytes.
*[[Plasma cell]]s.
 
Notes:
*May show IBD-like changes.<ref name=pmid16405661>{{Cite journal  | last1 = Yantiss | first1 = RK. | last2 = Odze | first2 = RD. | title = Diagnostic difficulties in inflammatory bowel disease pathology. | journal = Histopathology | volume = 48 | issue = 2 | pages = 116-32 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2559.2005.02248.x | PMID = 16405661 }}</ref>
**IBD should '''not''' be diagnosed on a diverted segment of bowel.


=Infectious=
==Cytomegalovirus colitis==
==Cytomegalovirus colitis==
{{Main|CMV}}
{{Main|CMV}}
*Abbreviated ''CMV colitis''.
*Abbreviated ''CMV colitis''.
===General===
{{Main|Cytomegalovirus colitis}}
*Uncommon.
*Immunosuppressed population at risk, e.g. transplant recipients, individuals with [[HIV]].
 
===Microscopic===
Features:
*Enlarged nucleus - classically in endothelial cells.
 
Images:
*[http://commons.wikimedia.org/wiki/File:CMV_colitis_-_intermed_mag.jpg CMV colitis - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:CMV_colitis_-_high_mag_-_cropped.jpg CMV colitis - high mag. (WC)].
 
===IHC===
*CMV +ve.
 
Others:
*HSV-1.
*HSV-2.
*VZV.
*[[EBV]].


==Intestinal spirochetosis==
==Intestinal spirochetosis==
*[[AKA]] ''intestinal spirochetes''; more specifically ''colonic spirochetes'', ''colonic spirochetosis''.
*[[AKA]] ''intestinal spirochetes''; more specifically ''colonic spirochetes'', ''colonic spirochetosis''.
 
{{Main|Intestinal spirochetosis}}
===General===
*Caused by spirochetes<ref name=pmid14718105>{{cite journal |author=Amat Villegas I, Borobio Aguilar E, Beloqui Perez R, de Llano Varela P, Oquiñena Legaz S, Martínez-Peñuela Virseda JM |title=[Colonic spirochetes: an infrequent cause of adult diarrhea] |language=Spanish; Castilian |journal=Gastroenterol Hepatol |volume=27 |issue=1 |pages=21–3 |year=2004 |month=January |pmid=14718105 |doi= |url=}}</ref><ref name=jhasim>URL: [http://www.jhasim.com/files/articlefiles/pdf/XASIM_Master_6_5_May_Vignette.pdf http://www.jhasim.com/files/articlefiles/pdf/XASIM_Master_6_5_May_Vignette.pdf]. Accessed on: 25 April 2011.</ref> - specifically ''Brachyspira piloicoli''<ref name=pmid19141744>{{Cite journal  | last1 = Margawani | first1 = KR. | last2 = Robertson | first2 = ID. | last3 = Hampson | first3 = DJ. | title = Isolation of the anaerobic intestinal spirochaete Brachyspira pilosicoli from long-term residents and Indonesian visitors to Perth, Western Australia. | journal = J Med Microbiol | volume = 58 | issue = Pt 2 | pages = 248-52 | month = Feb | year = 2009 | doi = 10.1099/jmm.0.004770-0 | PMID = 19141744 | url = http://ukpmc.ac.uk/abstract/MED/19141744/abstract/MED/19141744?ukpmc_extredirect=http://dx.doi.org/10.1099/jmm.0.004770-0 }}</ref> (previously ''Serpulina pilosicoli''<ref>URL: [http://www.cdc.gov/ncidod/eid/vol12no05/05-1180.htm http://www.cdc.gov/ncidod/eid/vol12no05/05-1180.htm]. Accessed on: 28 June 2011.</ref>) and ''Brachyspira aalborgi''.
*Very rare cause of diarrhea, associated with male homosexual behaviour.
 
Symptoms:<ref name=jhasim>URL: [http://www.jhasim.com/files/articlefiles/pdf/XASIM_Master_6_5_May_Vignette.pdf http://www.jhasim.com/files/articlefiles/pdf/XASIM_Master_6_5_May_Vignette.pdf]. Accessed on: 25 April 2011.</ref>
*Watery diarrhea, abdominal pain, +/-blood per rectum.
 
Treatment:<ref name=pmid17914949>{{cite journal |author=Calderaro A, Bommezzadri S, Gorrini C, ''et al.'' |title=Infective colitis associated with human intestinal spirochetosis |journal=J. Gastroenterol. Hepatol. |volume=22 |issue=11 |pages=1772–9 |year=2007 |month=November |pmid=17914949 |doi=10.1111/j.1440-1746.2006.04606.x |url=}}</ref>
*Metronidazole.
 
===Microscopic===
Features:
*Hyperchromatic fuzz on luminal aspect of epithelial cells; at brush border.
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Intestinal_spirochetosis_-_cropped_-_very_high_mag.jpg Intestinal spirochetes - cropped - very high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Intestinal_spirochetosis_-_very_high_mag.jpg Intestinal spirochetes - very high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Intestinal_spirochetosis_-_intermed_mag.jpg Intestinal spirochetes - intermed. mag. (WC)].
*www:
**[http://path.upmc.edu/cases/case391.html Intestinal spirochetosis & CMV colitis - several images (upmc.edu)].
===Special stains===
*Silver stains highlight 'em (e.g. Warthin-Starry stain).


==Amebiasis==
==Amebiasis==
*May also be spelling ''amoebiasis''.
*May also be spelled ''amoebiasis''.
===General===
{{Main|Amebiasis}}
*Infection with ''Entamoeba histolytica''.<ref>URL: [http://www.health.state.ny.us/diseases/communicable/amebiasis/fact_sheet.htm http://www.health.state.ny.us/diseases/communicable/amebiasis/fact_sheet.htm]. Accessed on: 17 June 2010.</ref>
*May mimic [[colon cancer]].<ref name=pmid19332922>{{Cite journal  | last1 = Fernandes | first1 = H. | last2 = D'Souza | first2 = CR. | last3 = Swethadri | first3 = GK. | last4 = Naik | first4 = CN. | title = Ameboma of the colon with amebic liver abscess mimicking metastatic colon cancer. | journal = Indian J Pathol Microbiol | volume = 52 | issue = 2 | pages = 228-30 | month =  | year =  | doi =  | PMID = 19332922 | url=http://www.ijpmonline.org/article.asp?issn=0377-4929;year=2009;volume=52;issue=2;spage=228;epage=230;aulast=Fernandes }}</ref>
 
May cause:<ref name=pmid20303955>{{Cite journal  | last1 = Mortimer | first1 = L. | last2 = Chadee | first2 = K. | title = The immunopathogenesis of Entamoeba histolytica. | journal = Exp Parasitol | volume =  | issue =  | pages =  | month = Mar | year = 2010 | doi = 10.1016/j.exppara.2010.03.005 | PMID = 20303955 }}</ref>
*Dysentery (diarrhea containing mucus and/or blood in the feces).
*Colitis.
*Liver abscess.
 
===Microscopic===
Features:
*Entamoeba histolytica are round/ovoid eosinophilic bodies ~ 40-60 micrometers in maximal dimension.
**Found in bowel lumen.
**Ingest [[RBC]]s.
 
Image:
*[http://commons.wikimedia.org/wiki/File:Amebiasis_-_very_high_mag.jpg Amebiasis - very high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Amoebic_dysentery_in_colon_biopsy_%281%29.jpg Amebiasis (WC)].


==Cryptosporidiosis==
==Cryptosporidiosis==
Line 455: Line 262:
==Solitary rectal ulcer==
==Solitary rectal ulcer==
*[[AKA]] ''solitary ulcer syndrome of the rectum'', abbreviated ''SUS''.
*[[AKA]] ''solitary ulcer syndrome of the rectum'', abbreviated ''SUS''.
===General===
*[[AKA]] ''solitary rectal ulcer syndrome''.
*Clinically may be suspected to a malignancy - biopsied routinuely.
*''[[Mucosal prolapse syndrome]]'' may be used as a synonym; however, it encompasses other entities.<ref name=pmid22697798>{{Cite journal  | last1 = Abid | first1 = S. | last2 = Khawaja | first2 = A. | last3 = Bhimani | first3 = SA. | last4 = Ahmad | first4 = Z. | last5 = Hamid | first5 = S. | last6 = Jafri | first6 = W. | title = The clinical, endoscopic and histological spectrum of the solitary rectal ulcer syndrome: a single-center experience of 116 cases. | journal = BMC Gastroenterol | volume = 12 | issue = | pages = 72 | month = | year = 2012 | doi = 10.1186/1471-230X-12-72 | PMID = 22697798 }}</ref>
*Mucosal ulceration.
{{Main|Solitary rectal ulcer}}
*"Three-lies disease":<ref name=pmid18271667>{{cite journal |author=Crespo Pérez L, Moreira Vicente V, Redondo Verge C, López San Román A, Milicua Salamero JM |title=["The three-lies disease": solitary rectal ulcer syndrome] |language=Spanish; Castilian |journal=Rev Esp Enferm Dig |volume=99 |issue=11 |pages=663–6 |year=2007 |month=November |pmid=18271667 |doi= |url=http://www.grupoaran.com/mrmUpdate/lecturaPDFfromXML.asp?IdArt=459864&TO=RVN&Eng=1}}</ref>
# May not be solitary.
# May not be rectal -- can be in left colon.
# May not be ulcerating -- non-ulcerated lesions: polypoid and/or erythematous.
 
Note: Each of the words in ''solitary rectal ulcer'' is a lie.
 
====Epidemiology====
*Typically younger patients - average age of presentation ~30 years in one study.<ref name=pmid17139403>{{cite journal |author=Chong VH, Jalihal A |title=Solitary rectal ulcer syndrome: characteristics, outcomes and predictive profiles for persistent bleeding per rectum |journal=Singapore Med J |volume=47 |issue=12 |pages=1063–8 |year=2006 |month=December |pmid=17139403 |doi= |url=http://www.sma.org.sg/smj/4712/4712a7.pdf}}</ref>
*Rare.
 
====Clinical presentation====
*Usually presents as BRBPR ~ 85% of cases.<ref name=pmid17139403/>
*Abdominal pain present in approx. 1/3.<ref name=pmid17139403/>
**May be very painful.
 
Treatment:
*Usually conservative, i.e. non-surgical.
*Resection - may be done for fear of malignancy.
 
===Gross===
*Classically, anterior or anterolateral wall of the rectum.<ref name=pmid18271667/>
 
===Microscopic===
Features:<ref name=pmid18271667/><ref name=pmid2091997>{{Cite journal  | last1 = Malik | first1 = AK. | last2 = Bhaskar | first2 = KV. | last3 = Kochhar | first3 = R. | last4 = Bhasin | first4 = DK. | last5 = Singh | first5 = K. | last6 = Mehta | first6 = SK. | last7 = Datta | first7 = BN. | title = Solitary ulcer syndrome of the rectum--a histopathologic characterisation of 33 biopsies. | journal = Indian J Pathol Microbiol | volume = 33 | issue = 3 | pages = 216-20 | month = Jul | year = 1990 | doi = | PMID = 2091997 }}</ref>
*Fibrosis of the lamina propria.
*Thickened muscularis mucosa with abnormal extension to the lumen.
*+/-Mucosa ulceration.
*+/-Submucosal fibrosis.
 
DDx:
*[[Inflammatory pseudopolyp]] (inflammatory polyp).
**Associated with [[inflammatory bowel disease]].
*Rectal prolapse.{{fact}}


==Rectal prolapse==
==Rectal prolapse==
===General===
{{Main|Rectal prolapse}}
*Usually close to the anal verge.
*Rare forms can occasionally be confused with [[colorectal carcinoma|cancer]].<ref name=pmid19861563>{{cite journal |author=Brosens LA, Montgomery EA, Bhagavan BS, Offerhaus GJ, Giardiello FM |title=Mucosal prolapse syndrome presenting as rectal polyposis |journal=J. Clin. Pathol. |volume=62 |issue=11 |pages=1034–6 |year=2009 |month=November |pmid=19861563 |pmc=2853932 |doi=10.1136/jcp.2009.067801 |url=}}</ref>
 
===Microscopic===
Features:<ref name=pmid3234303>{{cite journal |author=Schneider A, Fritze C, Bosseckert H, Machnik G |title=[Primary clinical, endoscopic and histologic findings in solitary rectal ulcer] |language=German |journal=Dtsch Z Verdau Stoffwechselkr |volume=48 |issue=3-4 |pages=183–9 |year=1988 |pmid=3234303 |doi= |url=}}</ref>
*"Fibromuscular hyperplasia" - '''key feature''':
**Fibrosis (submucosa, lamina propria).
**Muscularis mucosae is "too superficial" (muscle in the lamina propria).
*Surface ulceration + inflammation ([[neutrophil]]s).
*+/-Serration of epithelium at the surface.
 
Notes:
*'''Important negative''': no nuclear atypia.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Rectal_prolapse_-_low_mag.jpg Rectal prolapse - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Rectal_prolapse_-_intermed_mag.jpg Rectal prolapse - intermed. mag. (WC)].


=Neoplastic disease=
=Neoplastic disease=
Line 528: Line 284:


=Other=
=Other=
==Colonic pseudo-obstruction==
{{Main|Colonic pseudo-obstruction}}
==Pseudomelanosis coli==
==Pseudomelanosis coli==
*AKA ''melanosis coli''.<ref>URL: [http://www.medicinenet.com/melanosis_coli/article.htm http://www.medicinenet.com/melanosis_coli/article.htm]. Accessed on: 4 March 2011.</ref>
*[[AKA]] ''melanosis coli''.
===General===
{{Main|Pseudomelanosis coli}}
*''Not melanin'' as the name ''melanosis coli'' suggests; it is actually lipofuscin (in macrophages).<ref name=pmid18666316>{{cite journal |author=Freeman HJ |title="Melanosis" in the small and large intestine |journal=World J. Gastroenterol. |volume=14 |issue=27 |pages=4296-9 |year=2008 |month=July |pmid=18666316 |doi= |url=http://www.wjgnet.com/1007-9327/14/4296.asp}}</ref>
*Endoscopist may see brown pigmentation of mucosa and suspect the diagnosis.
*Presence may lead to endoscopic misinterpretation of colitis severity.<ref name=pmid21375218>{{Cite journal  | last1 = Zapatier | first1 = JA. | last2 = Schneider | first2 = A. | last3 = Parra | first3 = JL. | title = Overestimation of ulcerative colitis due to melanosis coli. | journal = Acta Gastroenterol Latinoam | volume = 40 | issue = 4 | pages = 351-3 | month = Dec | year = 2010 | doi =  | PMID = 21375218 }}</ref>
 
====Epidemiology====
*Classically associated with anthracene containing laxative (e.g. Senokot) use and herbal remedies.<ref name=pmid18666316/>
**May be seen in individuals not using laxatives.<ref name=pmid9600362/>
*Seen in (long-standing) [[inflammatory bowel disease]], especially [[ulcerative colitis]].<ref name=pmid9600362>{{Cite journal  | last1 = Pardi | first1 = DS. | last2 = Tremaine | first2 = WJ. | last3 = Rothenberg | first3 = HJ. | last4 = Batts | first4 = KP. | title = Melanosis coli in inflammatory bowel disease. | journal = J Clin Gastroenterol | volume = 26 | issue = 3 | pages = 167-70 | month = Apr | year = 1998 | doi =  | PMID = 9600362 }}</ref>
 
===Gross===
*Brown pigmentation of the mucosa, esp. cecum and proximal colon.
 
Image:
*[http://commons.wikimedia.org/wiki/File:Melanosis_coli.jpg Melanosis coli - endoscopic image (WC)].
===Microscopic===
Features:
*Brown granular pigment - in the lamina propria.
**Typically more prominent in the cecum and proximal colon.<ref name=pmid18666316/>
 
Images:
*[http://commons.wikimedia.org/wiki/File:Melanosis_coli_high_mag.jpg Melanosis coli - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Melanosis_coli_low_mag.jpg Melanosis coli - low mag. (WC)].
 
Notes:
*DDx of brown pigment:
**Lipofuscin - comes with age (can be demonstrated with a ''[[PAS stain]]''<ref name=pmid5463681 >{{cite journal |author=Kovi J, Leifer C |title=Lipofuscin pigment accumulation in spontaneous mammary carcinoma of A/Jax mouse |journal=J Natl Med Assoc |volume=62 |issue=4 |pages=287–90 |year=1970 |month=July |pmid=5463681 |pmc=2611776 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2611776/pdf/jnma00512-0077.pdf}}</ref> or ''[[Kluver-Barrera stain]]''<ref>URL: [http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exkluvbarr.htm http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exkluvbarr.htm]. Accessed on: 5 May 2010.</ref>).
***Melanosis coli.
**Old haemorrhage, i.e. hemosiderin-laden macrophages (may be demonstrated with ''[[Prussian blue stain]]''<ref>URL: [http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exprussb.htm http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exprussb.htm]. Accessed on: 5 May 2010.</ref>).
**Melanin (from melanocytes) - rare in colon (may be demonstrated with a ''[[Fontana-Masson stain]]''<ref>URL: [http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exfontana.htm http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exfontana.htm]. Accessed on: 5 May 2010.</ref> -- though not so useful in the GI tract).
**Foreign material (e.g. tattoo pigment) - not seen in GI tract.
 
===Stains===
*Can be demonstrated with a [[PAS stain]].<ref name=pmid9283862>{{cite journal |author=Benavides SH, Morgante PE, Monserrat AJ, Zárate J, Porta EA |title=The pigment of melanosis coli: a lectin histochemical study |journal=Gastrointest. Endosc. |volume=46 |issue=2 |pages=131–8 |year=1997 |month=August |pmid=9283862 |doi= |url=}}</ref>


==Angiodysplasia==
==Angiodysplasia==
===General===
{{Main|Angiodysplasia}}
*Causes (lower) GI haemorrhage.
*Generally, not a problem pathologists see.
*May be associated with [[aortic stenosis]]; known as ''Heyde syndrome''.<ref name=pmid19652242>{{cite journal |author=Hui YT, Lam WM, Fong NM, Yuen PK, Lam JT |title=Heyde's syndrome: diagnosis and management by the novel single-balloon enteroscopy |journal=Hong Kong Med J |volume=15 |issue=4 |pages=301–3 |year=2009 |month=August |pmid=19652242 |doi= |url=http://www.hkmj.org/abstracts/v15n4/301.htm}}</ref>
 
Epidemiology:
*Older people.
 
Etiology:
*Thought to be caused by the higher wall tension of cecum (due to larger diameter) and result from (intermittent) venous occlusion/focal dilation of vessels.<ref name=Ref_PBoD854>{{Ref PBoD|854}}</ref>
 
===Gross===
*Cecum - classic location.
 
Note:
*[[Crohn's disease]] - may mimic angiodysplasia radiographically.<ref name=pmid3054852/>
 
===Microscopic===
Features:<ref name=pmid3054852>{{Cite journal  | last1 = Hemingway | first1 = AP. | title = Angiodysplasia: current concepts. | journal = Postgrad Med J | volume = 64 | issue = 750 | pages = 259-63 | month = Apr | year = 1988 | doi =  | PMID = 3054852 }}</ref>
*Dilated vessels in mucosa and submucosa.


==Drugs==
==Drugs==
Line 599: Line 306:
*Can cause focal [[necrosis]].
*Can cause focal [[necrosis]].


Image:
=====Image=====
*[http://commons.wikimedia.org/wiki/File:Cecal_adenocarcinoma.jpg Sodium polystyrene crystals (WC)].
<gallery>
 
Image:Cecal_adenocarcinoma.jpg | Adenocarcinoma and sodium polystyrene crystals (WC/Nephron)
</gallery>
==Graft-versus host disease==
==Graft-versus host disease==
{{Main|Graft-versus-host disease}}
{{Main|Graft-versus-host disease}}
Line 611: Line 319:


==Chronic constipation==
==Chronic constipation==
This is occasionally an indication for colectomy.
:This section deals with ''chronic constipation'' that has no apparent cause.
===General===
*This is occasionally an indication for [[colectomy]].<ref name=pmid21382578>{{Cite journal  | last1 = Knowles | first1 = CH. | last2 = Farrugia | first2 = G. | title = Gastrointestinal neuromuscular pathology in chronic constipation. | journal = Best Pract Res Clin Gastroenterol | volume = 25 | issue = 1 | pages = 43-57 | month = Feb | year = 2011 | doi = 10.1016/j.bpg.2010.12.001 | PMID = 21382578 }}
</ref>


Causes:
General differential diagnosis for constipation:
*Tumour.
*Tumour.
*Adhesions - due to previous surgery.
*Adhesions - due to previous surgery.
*Neuropathy.
*Neuropathy.<ref name=pmid21382578/>
*Congenital defect (Hirschsprung's disease).
**[[Parkinson disease]].
*Congenital defect ([[Hirschsprung's disease]]).
*Myopathy.<ref name=pmid21382578/>
*Medications/substance use.
*Medications/substance use.
*Idiopathic.
*Idiopathic.


Work-up if no tumour is identified:<ref>IAV. 15 December 2009.</ref>
===Gross===
*No changes.
 
===Microscopic===
Features:
*Colon within normal limits.
**Look for the Ganglion cells (submucosal plexus, myenteric plexus).
**Look for interstitial cells of Cajal (with CD117) - typically most common around the myenteric plexus.<ref name=pmid17222246>{{Cite journal  | last1 = Streutker | first1 = CJ. | last2 = Huizinga | first2 = JD. | last3 = Driman | first3 = DK. | last4 = Riddell | first4 = RH. | title = Interstitial cells of Cajal in health and disease. Part I: normal ICC structure and function with associated motility disorders. | journal = Histopathology | volume = 50 | issue = 2 | pages = 176-89 | month = Jan | year = 2007 | doi = 10.1111/j.1365-2559.2006.02493.x | PMID = 17222246 | url = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2559.2006.02493.x/pdf }}</ref>
 
Negatives:
*No significant vascular disease.
*No fibrosis.
*No loss of muscle.
 
===Stains & IHC===
Work-up if no tumour is identified:<ref>IAV. 15 December 2009.</ref><ref name=pmid19360428/>
*Routine H&E.
*Routine H&E.
*Pan-actin.
*Smooth muscle actin - confirm myocyte loss.
*Gomori trichrome.
*Gomori trichrome - examine connective tissue.
*CD117 - to look for the ''interstitial cells of Cajal''.
*CD117 - to look for the ''interstitial cells of Cajal''.
**<50% the expected = abnormal.<ref name=pmid19360428/>
***Normal numbers not defined.
*HU - neuronal marker.<ref name=pmid8586967>{{cite journal |author=Barami K, Iversen K, Furneaux H, Goldman SA |title=Hu protein as an early marker of neuronal phenotypic differentiation by subependymal zone cells of the adult songbird forebrain |journal=J. Neurobiol. |volume=28 |issue=1 |pages=82–101 |year=1995 |month=September |pmid=8586967 |doi=10.1002/neu.480280108 |url=}}</ref>
*HU - neuronal marker.<ref name=pmid8586967>{{cite journal |author=Barami K, Iversen K, Furneaux H, Goldman SA |title=Hu protein as an early marker of neuronal phenotypic differentiation by subependymal zone cells of the adult songbird forebrain |journal=J. Neurobiol. |volume=28 |issue=1 |pages=82–101 |year=1995 |month=September |pmid=8586967 |doi=10.1002/neu.480280108 |url=}}</ref>
===Sign out===
*A long list of things to report is contained the recommendation of a working group.<ref name=pmid19360428>{{Cite journal  | last1 = Knowles | first1 = CH. | last2 = De Giorgio | first2 = R. | last3 = Kapur | first3 = RP. | last4 = Bruder | first4 = E. | last5 = Farrugia | first5 = G. | last6 = Geboes | first6 = K. | last7 = Gershon | first7 = MD. | last8 = Hutson | first8 = J. | last9 = Lindberg | first9 = G. | title = Gastrointestinal neuromuscular pathology: guidelines for histological techniques and reporting on behalf of the Gastro 2009 International Working Group. | journal = Acta Neuropathol | volume = 118 | issue = 2 | pages = 271-301 | month = Aug | year = 2009 | doi = 10.1007/s00401-009-0527-y | PMID = 19360428 }}</ref>
**Most pathology practises do not report much.
<pre>
TERMINAL ILEUM, CECUM, COLON (ASCENDING, TRANSVERSE AND SIGMOID), COLECTOMY:
- SMALL BOWEL, CECUM, AND COLON WITHIN NORMAL LIMITS.
- FOUR LYMPH NODES NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 4 ).
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
COMMENT:
Several stains were done:
CD117: interstitial cells of Cajal present, no apparent decrease.
SMA: no significant myocyte loss.
Gomori trichrome: no abnormal fibrosis apparent.
Tau: no abnormalities apparent.
</pre>


=See also=
=See also=
Line 633: Line 381:
*[[Intestinal polyps]].
*[[Intestinal polyps]].
*[[Small bowel]].
*[[Small bowel]].
*[[Doughnuts]].


=References=
=References=
Line 638: Line 387:


[[Category:Gastrointestinal pathology]]
[[Category:Gastrointestinal pathology]]
[[Category:Colon|Colon]]

Latest revision as of 14:46, 5 October 2023

Anatomy of the colon and rectum. (WC)

The colon is section of the large bowel. This article also covers the rectum and cecum as both have a similar mucosa.

It commonly comes to pathologists because there is a suspicion of colorectal cancer or a known history of inflammatory bowel disease (IBD).

An introduction to gastrointestinal pathology is found in the gastrointestinal pathology article. The anus and ileocecal valve are dealt with in separate articles.

Technically, the rectum and cecum are not part of the colon. Thus, inflammation of the rectum should be proctitis and inflammation of the cecum should be cecitis.

Anatomy

  • The rectum has several definition. These are discussed in the rectum article.
  • The large bowel may be submitted with segment names or with the distance to the anal verge.

A conversion between named segments and distance - as per NCI of the United States:[1]

Named segment Distance to anal verge (cm)
Anus 0-4
Rectum 4-16
Rectosigmoid 15-17
Sigmoid 17-57
Descending 57-82
Transverse 82-132
Ascending 132-147
Cecum 150

Common clinical problems

Obstruction

Top three (in adults):[2]

Bleeding

Mnemonic CHAND:[3]

Infectious colitis with bleeding - causes:

  • Enterohemorrhagic Escherichia coli (EHEC) -- commonly 0157:H7.
  • Campylobacter jejuni.
  • Clostridium difficile.
  • Shigella.

Infectious colitis in the immunosuppressed:

  • Cytomegalovirus (CMV).[4]
    • May afflict patients with IBD and lead to colectomy... as IBD patients are put on immunosuppression.[5]
    • Organ transplant recipients.
    • HIV/AIDS.

Images:

  • CMV colitis - high. mag. (WC/Nephron)

  • CMV colitis - intermed. mag. (WC/Nephron)

Grossing

Types of specimens

Introduction to colorectal surgery:

  1. Colonic resection - remove a piece of large bowel.
  2. Total colectomy - leaves rectum and anus.[6]
  3. Subtotal colectomy - part of colon removed --or-- some of the rectum remains.
  4. Right hemicolectomy - right colon + distal ileum.
  5. Lower anterior resection (LAR) - proximal rectum +/- sigmoid (for proximal rectal malignancies).
  6. Abdominoperineal resection (APR) - anus + rectum - results in a permanent stoma (for distal rectal malignancies).
  7. Stoma - these are often done emergently and then get cut-out after the patient's condition has settled.
  8. Doughnuts (also donuts) from an end-to-end anastomosis stapler.
    • Often accompany lower anterior resections.

Images

  • APR specimen - anterior (WC)

  • APR specimen - lateral (WC)

  • APR specimen - inked (WC)

Identifying the specimen

  • Transverse colon - has omentum.
  • Ascending colon - usu. comes with ileocecal valve and a bit of ileum.
  • Descending colon - has a bare area.
  • Rectum - has adventitia.
    • Pathologists define it as starting where the adventitia starts/the serosal surface no longer completely surrounds the large intestine.[8]
    • Anatomists define it in relation to the third sacral vertebra.[9]

Images

  • Sigmoid and rectum. APR specimen. (WC)

Lymph nodes

Quirke method

  • Bowel is not opened - it is fixed... then sliced.[11][12]

Standard method

  • Bowel is prep'ed by opening it along the antimesenteric side.
  • Dimensions - length, circumference at both margins.
  • Radial margin/circumferential margin - should be painted.
    • Rectum starts/sigmoid ends @ place where serosa ends on the posterior aspect of the bowel.
      • The proximal, anterior aspect of the rectum has serosa, i.e. it is not painted.

Note:

  • There are several definitions for the rectum.[13]
    • In a survey of surgeons:
    • 67% defined it by an anatomical landmark
      • 35% of all respondants considered the peritoneal reflection the proximal boundary of the rectum.
    • 30% defined the proximal boundary as a distance from the anal verge.

Common non-neoplastic disease

Colorectal polyps

Main article: Intestinal polyps

Polyps are the bread & butter of GI pathology. They are very common.

Main types:

  • Hyperplastic - most common, benign.
  • Adenomatous - quite common, pre-malignant.
  • Hamartomatous - rare, weird & wonderful.
  • Inflammatory, AKA inflammatory pseudopolyps - associated with IBD.

Most common (images):

  • Hyperplastic polyp image - intermed. mag. (WC/Nephron)

  • Hyperplastic polyp image - low mag. (WC/Nephron)

Ischemic colitis

  • AKA colonic ischemia.
  • AKA ischemia of the colon.
Main article: Ischemic colitis

Diverticular disease

Main article: Diverticular disease

Pseudomembranous colitis

Main article: Pseudomembranous colitis

Volvulus

Main article: Volvulus

Inflammatory diseases

Inflammatory bowel disease

Main article: Inflammatory bowel disease

The bread 'n butter of gastroenterology. A detailed discussion of IBD is in the inflammatory bowel disease article. It comes in two main flavours (Crohn's disease, ulcerative colitis).

Microscopic

Features helpful for the diagnosis of IBD - as based on a study:[14]

  • Basal, i.e. crypt base, plasmacytosis with severe chronic inflammation,
  • Crypt architectural abnormalities, and
  • Distal Paneth cell metaplasia.
    • Paneth cells should not be in the left colon[15] - if you see 'em think of IBD and other long-standing injurious processes.
    • Some claim that (friendly right colonic) paneth cells and paneth cell metaplasia look quite different and can be distinguished.[16]

Microscopic colitis

Microscopic colitis may refer to a microscopic manifestation of an unspecified disease process that can be apparent macroscopically. This section links to a pair of diseases (lymphocytic colitis and collagenous colitis) that are considered to only have microscopic manifestations and characteristic clinical presentation.
Main article: Lymphocytic colitis
Main article: Collagenous colitis

Diversion colitis

Main article: Diversion colitis

Eosinophilic colitis

  • Abbreviated EC.
Main article: Eosinophilic colitis

Infectious

Infectious colitis

This section covers non-specific colitides that appear to have an infective etiology.

General

  • Common.
  • Diarrhea - typical symptom.

Gross

  • +/-Erythema on endoscopy.

Microscopic

Features:

  • Neutrophils predominant - key feature.[17]
    • The neutrophils are often superficial - they go to were the bad guys are.
  • No architectural distortion - if acute.

DDx:

IHC

Done if the patient is immunosuppressed, or there is clinical or morphological suspicion:

Sign out

ASCENDING COLON, BIOPSY:
- MILD ACTIVE COLITIS, SEE COMMENT.

COMMENT:
There is are no granulomas.  The crypt architecture is normal.  A benign lymphoid nodule is
present.

The differential diagnosis includes infective etiologies, early inflammatory
bowel disease and ischemia.  The histomorphology is more in keeping with an infective
etiology as neutrophils are a predominant feature; however, clinical correlation is
required.

Cytomegalovirus colitis

Main article: CMV
  • Abbreviated CMV colitis.
Main article: Cytomegalovirus colitis

Intestinal spirochetosis

  • AKA intestinal spirochetes; more specifically colonic spirochetes, colonic spirochetosis.
Main article: Intestinal spirochetosis

Amebiasis

  • May also be spelled amoebiasis.
Main article: Amebiasis

Cryptosporidiosis

Main article: Cryptosporidiosis

General

  • Usually in immune incompetent individuals, e.g. HIV/AIDS.

Microscopic

Features:

  • Uniform spherical nodules 2-4 micrometres in diameter, typical location - GI tract brush border.
    • Bluish staining of brush border key feature - low power.

Rectal pathology

Solitary rectal ulcer

  • AKA solitary ulcer syndrome of the rectum, abbreviated SUS.
  • AKA solitary rectal ulcer syndrome.
  • Mucosal prolapse syndrome may be used as a synonym; however, it encompasses other entities.[19]
Main article: Solitary rectal ulcer

Rectal prolapse

Main article: Rectal prolapse

Neoplastic disease

Colorectal Tumours

Main article: Colorectal tumours

These are very common. The are covered in a separate article entitled colorectal tumours.

Neuroendocrine tumour

Main article: Neuroendocrine neoplasms#GI tract

Goblet cell carcinoid

Described in detail in the appendix article.
  • AKA crypt cell carcinoma.
  • Biphasic tumour; features of carcinoid tumour and adenocarcinoma.

Other

Colonic pseudo-obstruction

Main article: Colonic pseudo-obstruction

Pseudomelanosis coli

  • AKA melanosis coli.
Main article: Pseudomelanosis coli

Angiodysplasia

Main article: Angiodysplasia

Drugs

Main article: Drug toxicity

Sodium polystyrene sulfonate

  • AKA Kayexalate.

General

  • Used to treat hyperkalemia - as may be seen in renal failure.

Microscopic

Features:[20]

Image

  • Adenocarcinoma and sodium polystyrene crystals (WC/Nephron)

Graft-versus host disease

Main article: Graft-versus-host disease
  • Abbreviated as GVHD.
  • Seen in the context of bone marrow transplants.

Bowel transplant

The histology of bowel transplant rejection is identical to GVHD - see GVHD.

Chronic constipation

This section deals with chronic constipation that has no apparent cause.

General

General differential diagnosis for constipation:

Gross

  • No changes.

Microscopic

Features:

  • Colon within normal limits.
    • Look for the Ganglion cells (submucosal plexus, myenteric plexus).
    • Look for interstitial cells of Cajal (with CD117) - typically most common around the myenteric plexus.[22]

Negatives:

  • No significant vascular disease.
  • No fibrosis.
  • No loss of muscle.

Stains & IHC

Work-up if no tumour is identified:[23][24]

  • Routine H&E.
  • Smooth muscle actin - confirm myocyte loss.
  • Gomori trichrome - examine connective tissue.
  • CD117 - to look for the interstitial cells of Cajal.
    • <50% the expected = abnormal.[24]
      • Normal numbers not defined.
  • HU - neuronal marker.[25]

Sign out

  • A long list of things to report is contained the recommendation of a working group.[24]
    • Most pathology practises do not report much.
TERMINAL ILEUM, CECUM, COLON (ASCENDING, TRANSVERSE AND SIGMOID), COLECTOMY:
- SMALL BOWEL, CECUM, AND COLON WITHIN NORMAL LIMITS.
- FOUR LYMPH NODES NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 4 ).
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

COMMENT:
Several stains were done:
 CD117: interstitial cells of Cajal present, no apparent decrease.
 SMA: no significant myocyte loss.
 Gomori trichrome: no abnormal fibrosis apparent.
 Tau: no abnormalities apparent.

See also

References

  1. ↑ URL: [1]https://training.seer.cancer.gov/colorectal/anatomy/figure/figure1.html]. Accessed on: 8 February 2018.
  2. ↑ URL: http://www.emedicine.com/EMERG/topic65.htm. Accessed on: 28 June 2011.
  3. ↑ TN 2007 G29.
  4. ↑ Golden MP, Hammer SM, Wanke CA, Albrecht MA (September 1994). "Cytomegalovirus vasculitis. Case reports and review of the literature". Medicine (Baltimore) 73 (5): 246–55. PMID 7934809.
  5. ↑ Kandiel A, Lashner B (December 2006). "Cytomegalovirus colitis complicating inflammatory bowel disease". Am. J. Gastroenterol. 101 (12): 2857–65. doi:10.1111/j.1572-0241.2006.00869.x. PMID 17026558.
  6. ↑ http://www.allaboutbowelsurgery.com/shared/stoma_care/stoma_surgery/procedures/surgery_colon/subtotal.htm
  7. ↑ Arbman, G.; Nilsson, E.; Hallböök, O.; Sjödahl, R. (Mar 1996). "Local recurrence following total mesorectal excision for rectal cancer.". Br J Surg 83 (3): 375-9. PMID 8665198.
  8. ↑ Lester, Susan Carole (2010). Manual of Surgical Pathology (3rd ed.). Saunders. pp. 339. ISBN 978-0-323-06516-0.
  9. ↑ URL: http://www.bartleby.com/107/249.html. Accessed on: 19 October 2012.
  10. ↑ Bilimoria KY, Bentrem DJ, Stewart AK, et al. (September 2008). "Lymph node evaluation as a colon cancer quality measure: a national hospital report card". J. Natl. Cancer Inst. 100 (18): 1310–7. doi:10.1093/jnci/djn293. PMID 18780863. http://www.medscape.com/viewarticle/581463.
  11. ↑ West NP, Morris EJ, Rotimi O, Cairns A, Finan PJ, Quirke P (September 2008). "Pathology grading of colon cancer surgical resection and its association with survival: a retrospective observational study". Lancet Oncol. 9 (9): 857–65. doi:10.1016/S1470-2045(08)70181-5. PMID 18667357.
  12. ↑ West NP, Finan PJ, Anderin C, Lindholm J, Holm T, Quirke P (July 2008). "Evidence of the oncologic superiority of cylindrical abdominoperineal excision for low rectal cancer". J. Clin. Oncol. 26 (21): 3517–22. doi:10.1200/JCO.2007.14.5961. PMID 18541901.
  13. ↑ Kenig, J.; Richter, P. (Sep 2013). "Definition of the rectum and level of the peritoneal reflection - still a matter of debate?". Wideochir Inne Tech Maloinwazyjne 8 (3): 183-6. doi:10.5114/wiitm.2011.34205. PMID 24130630.
  14. ↑ Tanaka M, Riddell RH, Saito H, Soma Y, Hidaka H, Kudo H (January 1999). "Morphologic criteria applicable to biopsy specimens for effective distinction of inflammatory bowel disease from other forms of colitis and of Crohn's disease from ulcerative colitis". Scand. J. Gastroenterol. 34 (1): 55–67. PMID 10048734.
  15. ↑ Tanaka M, Saito H, Kusumi T, et al (December 2001). "Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease". J. Gastroenterol. Hepatol. 16 (12): 1353–9. PMID 11851832. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0815-9319&date=2001&volume=16&issue=12&spage=1353.
  16. ↑ Rubio CA, Nesi G (2003). "A simple method to demonstrate normal and metaplastic Paneth cells in tissue sections". In Vivo 17 (1): 67–71. PMID 12655793.
  17. ↑ 17.0 17.1 Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 324. ISBN 978-0443066573.
  18. ↑ Karlitz, JJ.; Li, ST.; Holman, RP.; Rice, MC. (Jan 2011). "EBV-associated colitis mimicking IBD in an immunocompetent individual.". Nat Rev Gastroenterol Hepatol 8 (1): 50-4. doi:10.1038/nrgastro.2010.192. PMID 21119609.
  19. ↑ Abid, S.; Khawaja, A.; Bhimani, SA.; Ahmad, Z.; Hamid, S.; Jafri, W. (2012). "The clinical, endoscopic and histological spectrum of the solitary rectal ulcer syndrome: a single-center experience of 116 cases.". BMC Gastroenterol 12: 72. doi:10.1186/1471-230X-12-72. PMID 22697798.
  20. ↑ Abraham SC, Bhagavan BS, Lee LA, Rashid A, Wu TT (May 2001). "Upper gastrointestinal tract injury in patients receiving kayexalate (sodium polystyrene sulfonate) in sorbitol: clinical, endoscopic, and histopathologic findings". Am. J. Surg. Pathol. 25 (5): 637-44. PMID 11342776. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0147-5185&volume=25&issue=5&spage=637.
  21. ↑ 21.0 21.1 21.2 Knowles, CH.; Farrugia, G. (Feb 2011). "Gastrointestinal neuromuscular pathology in chronic constipation.". Best Pract Res Clin Gastroenterol 25 (1): 43-57. doi:10.1016/j.bpg.2010.12.001. PMID 21382578.
  22. ↑ Streutker, CJ.; Huizinga, JD.; Driman, DK.; Riddell, RH. (Jan 2007). "Interstitial cells of Cajal in health and disease. Part I: normal ICC structure and function with associated motility disorders.". Histopathology 50 (2): 176-89. doi:10.1111/j.1365-2559.2006.02493.x. PMID 17222246. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2559.2006.02493.x/pdf.
  23. ↑ IAV. 15 December 2009.
  24. ↑ 24.0 24.1 24.2 Knowles, CH.; De Giorgio, R.; Kapur, RP.; Bruder, E.; Farrugia, G.; Geboes, K.; Gershon, MD.; Hutson, J. et al. (Aug 2009). "Gastrointestinal neuromuscular pathology: guidelines for histological techniques and reporting on behalf of the Gastro 2009 International Working Group.". Acta Neuropathol 118 (2): 271-301. doi:10.1007/s00401-009-0527-y. PMID 19360428.
  25. ↑ Barami K, Iversen K, Furneaux H, Goldman SA (September 1995). "Hu protein as an early marker of neuronal phenotypic differentiation by subependymal zone cells of the adult songbird forebrain". J. Neurobiol. 28 (1): 82–101. doi:10.1002/neu.480280108. PMID 8586967.
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