Difference between revisions of "Colon"

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The '''colon''' smells 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]]'' and ''[[ileocecal valve]]'' are dealt with in separate articles.
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=
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# 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===
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**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=
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==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)].
<gallery>
Image:Pseudomembranous_colitis.JPG | Pseudomembranous colitis. (WC)
</gallery>
 
===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.
 
Notes:
*Pseudomembranes arise from the crypts.
*Rarely have (benign) [[signet ring cell]]-like cells.<ref name=pmid12684766>{{Cite journal  | last1 = Abdulkader | first1 = I. | last2 = Cameselle-Teijeiro | first2 = J. | last3 = Forteza | first3 = J. | title = Signet-ring cells associated with pseudomembranous colitis. | journal = Virchows Arch | volume = 442 | issue = 4 | pages = 412-4 | month = Apr | year = 2003 | doi = 10.1007/s00428-003-0779-1 | PMID = 12684766 }}</ref>
 
DDx:
*[[Cap polyposis]] - very rare.
 
====Images====
<gallery>
Image:Colonic_pseudomembranes_low_mag.jpg | Pseudomembranes - low mag. (WC/Nephron)
Image:Colonic_pseudomembranes_intermed_mag.jpg | Pseudomembranes - intermed. mag. (WC/Nephron)
</gallery>
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]].
 
===Sign out===
<pre>
RECTOSIGMOID, RESECTION:
- MURAL ISCHEMIA WITH PERFORATION, SEROSITIS, MICROABSCESS FORMATION AND POORLY FORMED PSEUDOMEMBRANES.
- SUBMUCOSAL FIBROSIS.
- NEGATIVE FOR MALIGNANCY.
 
COMMENT:
The findings are consistent with volvulus and the submucosal fibrosis suggests this may have been recurrent.
</pre>


=Inflammatory diseases=
=Inflammatory diseases=
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*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>
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==Eosinophilic colitis==
==Eosinophilic colitis==
===General===
*Abbreviated ''EC''.
*Rare.
{{Main|Eosinophilic colitis}}
*May be a component of ''[[eosinophilic gastroenteritis]]''.<ref name=pmid22012125/>
 
Clinical features:<ref name=pmid22012125/>
*Abdominal pain
*Diarrhea +/-blood.
*+/-Weight loss.
 
===Gross===
Features - endoscopic:<ref name=pmid22012125>{{Cite journal  | last1 = Alfadda | first1 = AA. | last2 = Storr | first2 = MA. | last3 = Shaffer | first3 = EA. | title = Eosinophilic colitis: an update on pathophysiology and treatment. | journal = Br Med Bull | volume = 100 | issue =  | pages = 59-72 | month =  | year = 2011 | doi = 10.1093/bmb/ldr045 | PMID = 22012125 | PMC = 3165205 }}</ref>
*Edema.
*Granular appearance.
 
===Microscopic===
Features:<ref name=pmid22012125/>
*Abundant eosinophils - no agreed upon number.
**"Most use 20/[[HPF]]" <ref name=pmid19554649>{{Cite journal  | last1 = Okpara | first1 = N. | last2 = Aswad | first2 = B. | last3 = Baffy | first3 = G. | title = Eosinophilic colitis. | journal = World J Gastroenterol | volume = 15 | issue = 24 | pages = 2975-9 |  month = Jun | year = 2009 | doi =  | PMID = 19554649 | PMC = 2702104 }}</ref> - a definition that suffers from [[HPFitis]].
***There is variation along the large bowel - normal in rectum <10/HPF, normal in cecum <30/HPF (???).<ref name=pmid19554649/>
 
DDx:<ref name=pmid22012125/>
*[[Inflammatory bowel disease]]:
**[[Crohn's disease]].
**[[Ulcerative colitis]].
*Infection:
**[[Pinworm]].
**[[Strongyloidiasis]].
*Autoimmune disease:
**[[Scleroderma]].
**[[Churg-Strauss syndrome]].
**[[Celiac disease]].
*[[Drug reaction]]s.
 
Image:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702104/figure/F1/ EC (nih.gov)].<ref name=pmid19554649>{{Cite journal  | last1 = Okpara | first1 = N. | last2 = Aswad | first2 = B. | last3 = Baffy | first3 = G. | title = Eosinophilic colitis. | journal = World J Gastroenterol | volume = 15 | issue = 24 | pages = 2975-9 | month = Jun | year = 2009 | doi =  | PMID = 19554649 | PMC = 2702104 }}</ref>
 
===Sign out===
<pre>
DESCENDING COLON, BIOPSY:
- COLONIC MUCOSA WITH MILD EOSINOPHILIA, SEE COMMENT.
- NEGATIVE FOR DYSPLASIA.
 
COMMENT:
Focally, there are up to 40 eosinophils / 0.2376 mm*mm (approx. field area at 400X). This
is a non-specific finding. No eosinophilic crypt abscesses are seen. No (neutrophilic)
cryptitis is present. Clinical correlation is suggested.
</pre>
 
<pre>
DESCENDING COLON, BIOPSY:
- COLONIC MUCOSA WITH MILD EOSINOPHILIA, SEE COMMENT.
- NEGATIVE FOR ACTIVE COLITIS.
- NEGATIVE FOR DYSPLASIA.
 
COMMENT:
There are up to 40 eosinophils / 0.2376 mm*mm (field area at 400X). This is a
non-specific finding.  The differential diagnosis includes inflammatory bowel
disease, infection (especially helminths), a drug reaction, and autoimmune
disorders (e.g. Churg-Strauss syndrome, celiac disease, scleroderma). Clinical
correlation is required.
</pre>


=Infectious=
=Infectious=
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{{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.
 
DDx:
*[[Infectious colitis]] without a distinctive morphology.
*CMV colitis superimposed on [[inflammatory bowel disease]].
 
====Images====
<gallery>
Image:CMV_colitis_-_intermed_mag.jpg | CMV colitis - intermed. mag. (WC/Nephron)
Image:CMV_colitis_-_high_mag_-_cropped.jpg | CMV colitis - high mag. (WC/Nephron)
</gallery>
www:
*[http://www.flickr.com/photos/lunarcaustic/4615988256/ CMV colitis (flickr.com/lunar caustic)].
*[http://www.flickr.com/photos/lunarcaustic/4615988164/ CMV colitis (flickr.com/lunar caustic)]
===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.
 
DDx:
*Normal colon.
*[[Infectious colitis]] without a distinctive morphology.
 
====Images====
<gallery>
Image:Intestinal_spirochetosis_-_cropped_-_very_high_mag.jpg | Intestinal spirochetes - cropped - very high mag. (WC/Nephron)
Image:Intestinal_spirochetosis_-_very_high_mag.jpg | Intestinal spirochetes - very high mag. (WC/Nephron)
Image:Intestinal_spirochetosis_-_intermed_mag.jpg | Intestinal spirochetes - intermed. mag. (WC/Nephron)
</gallery>
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 spelled ''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====
<gallery>
Image:Amebiasis_-_very_high_mag.jpg | Amebiasis - very high mag. (WC/Nephron)
Image:Amoebic_dysentery_in_colon_biopsy_%281%29.jpg | Amebiasis (WC)
</gallery>


==Cryptosporidiosis==
==Cryptosporidiosis==
Line 429: Line 264:
*[[AKA]] ''solitary rectal ulcer syndrome''.
*[[AKA]] ''solitary rectal ulcer syndrome''.
*''[[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 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>
===General===
{{Main|Solitary rectal ulcer}}
*Clinically may be suspected to a malignancy - biopsied routinely.
*Mucosal ulceration.
*"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]].
*Well-differentiated [[colonic adenocarcinoma|adenocarcinoma]].
 
===IHC===
*p53 -ve.
**May be used to help exclude adenocarcinoma.


==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>
 
Epidemiology:
*~90% women, postmenopausal and multiparous.<ref name=pmid22413077>{{Cite journal  | last1 = Lee | first1 = S. | last2 = Kye | first2 = BH. | last3 = Kim | first3 = HJ. | last4 = Cho | first4 = HM. | last5 = Kim | first5 = JG. | title = Delorme's Procedure for Complete Rectal Prolapse: Does It Still Have It's Own Role? | journal = J Korean Soc Coloproctol | volume = 28 | issue = 1 | pages = 13-8 | month = Feb | year = 2012 | doi = 10.3393/jksc.2012.28.1.13 | PMID = 22413077 }}</ref>
 
Treatment:
*Surgical:
**Delorme procedure = mucosa stripped.
 
===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====
<gallery>
Image:Rectal_prolapse_-_low_mag.jpg | Rectal prolapse - low mag. (WC/Nephon)
Image:Rectal_prolapse_-_intermed_mag.jpg | Rectal prolapse - intermed. mag. (WC/Nephron)
</gallery>
 
===Sign out===
<pre>
RECTAL MUCOSA, DELORME PROCEDURE:
- SUPERFICIAL RECTAL WALL WITH FIBROMUSCULAR HYPERPLASIA AND EDEMA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
</pre>
 
====Micro====
The sections show rectal mucosa, submucosa and a small amount of muscularis propria.  The mucosa shows fibromuscular hyperplasia with thickening of the muscularis mucosae and mild lamina propria fibrosis. The submucosa is edematous. The small amount of muscularis propria is unremarkable. The epithelium matures normally to the surface. No significant nuclear atypia is identified.


=Neoplastic disease=
=Neoplastic disease=
Line 534: Line 292:


==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 642: Line 381:
*[[Intestinal polyps]].
*[[Intestinal polyps]].
*[[Small bowel]].
*[[Small bowel]].
*[[Doughnuts]].


=References=
=References=

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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