Difference between revisions of "Inflammatory bowel disease"

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*Biopsies for diagnosis should specify the (anatomical) site:
*Biopsies for diagnosis should specify the (anatomical) site:
**Slight gradients exist in the large bowel that can be exploited for diagnostic purposes if the site information is known, for example:
**Slight gradients exist in the large bowel that can be exploited for diagnostic purposes if the site information is known, for example:
***Paneth cell distal to the splenic flexure are abnormal.
***[[Paneth cell]]s distal to the splenic flexure are abnormal.
***Ulcerative colitis is often more severe distally - even in a pancolitis, as the disease starts in the rectum and progresses toward the cecum.
***Ulcerative colitis is often more severe distally - even in a pancolitis, as the disease starts in the rectum and progresses toward the cecum.
*Surveillance biopsies should specify the (anatomical) site - so, it possible to find any site of interest on a follow-up colonoscopy.<ref name=pmid16609751>{{Cite journal  | last1 = Panaccione | first1 = R. | title = The approach to dysplasia surveillance in inflammatory bowel disease. | journal = Can J Gastroenterol | volume = 20 | issue = 4 | pages = 251-3 | month = Apr | year = 2006 | doi =  | PMID = 16609751 | PMC = 2659899}}</ref>
*Surveillance biopsies should specify the (anatomical) site - so, it possible to find any site of interest on a follow-up colonoscopy.<ref name=pmid16609751>{{Cite journal  | last1 = Panaccione | first1 = R. | title = The approach to dysplasia surveillance in inflammatory bowel disease. | journal = Can J Gastroenterol | volume = 20 | issue = 4 | pages = 251-3 | month = Apr | year = 2006 | doi =  | PMID = 16609751 | PMC = 2659899}}</ref>


===Spanking the clinician for submitting it all in one bottle===
===Biopsies all submitted in one bottle===
<pre>
<pre>
COLON (SITE NOT FURTHER SPECIFIED), BIOPSIES:
COLON (SITE NOT FURTHER SPECIFIED), BIOPSIES:
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#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>
#*Paneth cells have basal nuclei and coarse luminal granules.<ref name=Ref_H4P3_631>{{Ref H4P3|631}}</ref>   
#*Paneth cells have basal nuclei and coarse luminal granules.<ref name=Ref_H4P3_631>{{Ref H4P3|631}}</ref>   
#**They should '''not''' be confused with endocrine cells -- these have apical nuclei and fine granules.
#**They should '''not''' be confused with endocrine cells -- these have apical nuclei and fine granules.
#**They should '''not''' be confused with intraepithelial eosinophils -- have smaller (~1/2) more intensely red granules.
#**They should '''not''' be confused with intraepithelial [[eosinophil]]s -- have smaller (~1/2) more intensely red granules.
Notes:  
Notes:  
# Microscopic features can be remembered by [[mnemonic]] ''CPP'': Crypts (abnormal), Plasmacytosis, Paneth cells where they don't belong.
# Microscopic features can be remembered by [[mnemonic]] ''CPP'': Crypts (abnormal), Plasmacytosis, Paneth cells where they don't belong.
# If you see architectural distortion (e.g. crypt branching) in the left colon, look for Paneth cells.
# If you see architectural distortion (e.g. crypt branching) in the left colon, look for Paneth cells.
# The hepatic flexure is considered the divider for normal paneth cells and abnormal paneth cells, i.e. paneth cells proximal to the hepatic flexure are normal; paneth cells distal to the hepatic flexure are abnormal.<ref>STC. 14 December 2009.</ref>
# The hepatic flexure is considered the divider for normal paneth cells and abnormal paneth cells, i.e. paneth cells proximal to the hepatic flexure are normal; paneth cells distal to the hepatic flexure are abnormal.<ref>STC. 14 December 2009.</ref>
# Stretching of tissue may mimic atrophy; tip-off it is artefact: thinning of mucosa.<ref name=Kirsch>Kirsch, R. 13 December 2010.</ref>
# Stretching of tissue may mimic atrophy; tip-off it is artifact: thinning of mucosa.<ref name=Kirsch>Kirsch, R. 13 December 2010.</ref>


Images:
====Images====
*[http://commons.wikimedia.org/w/index.php?title=File:Crohn%27s_disease_-_colon_-_high_mag.jpg Crohn's disease - beautiful granulomas in the colon - high mag. (WC)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:Crohn%27s_disease_-_duodenum_-_intermed_mag.jpg Crohn's disease - duodenum - intermed. mag. (WC)].
Image:Crohn%27s_disease_-_colon_-_high_mag.jpg | Crohn's disease - very well-formed granulomas in the [[colon]] - high mag. (WC)
*[http://commons.wikimedia.org/wiki/File:Cryptitis_high_mag.jpg Cryptitis - high mag. (WC)].
Image:Crohn%27s_disease_-_duodenum_-_intermed_mag.jpg | Crohn's disease - duodenum - intermed. mag. (WC)
*[http://commons.wikimedia.org/wiki/File:Crypt_branching_high_mag.jpg Crypt branching (WC)].
Image: Cryptitis_-_alt_--_very_high_mag.jpg | Cryptitis. (WC)
Image:Crypt_branching_high_mag.jpg | Crypt branching. (WC)
</gallery>


===Grading===
===Grading===
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| "A grading scheme"<ref name=Kirsch>Kirsch, R. 13 December 2010.</ref>
| "A grading scheme"<ref name=Kirsch>Kirsch, R. 13 December 2010.</ref>
| -
| -
| cryptitis
| [[cryptitis]]
| PMN abscesses
| [[crypt abscesses]]
| erosions
| erosions
|-
|-
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|-
|-
|}
|}
=====Images=====
<gallery>
Image: Cryptitis_--_very_high_mag.jpg | [[Cryptitis]]. (WC)
Image: Crypt_abscess_--_very_high_mag.jpg | [[Crypt abscess]]. (WC)
</gallery>


==Crohn's disease versus ulcerative colitis==
==Crohn's disease versus ulcerative colitis==
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**~ 10% of UC patients.  
**~ 10% of UC patients.  
**~ 40% of UC + colectomy + [[pouchitis]].  
**~ 40% of UC + colectomy + [[pouchitis]].  
Another study compares UC, CD and control individuals:<ref name=pmid20848539>{{Cite journal  | last1 = Sonnenberg | first1 = A. | last2 = Melton | first2 = SD. | last3 = Genta | first3 = RM. | title = Frequent occurrence of gastritis and duodenitis in patients with inflammatory bowel disease. | journal = Inflamm Bowel Dis | volume = 17 | issue = 1 | pages = 39-44 | month = Jan | year = 2011 | doi = 10.1002/ibd.21356 | PMID = 20848539 }}</ref>
*Gastritis:
**UC: 19%.
**CD: 33%
**Controls: 13%.
*Duodenitis:
**UC: 3%.
**CD: 26%.
**Controls: 1%.
Note:
*Younger individuals (<18 years old) have significantly more gastritis and duodenitis.<ref name=pmid20848539/>


====A tabular comparison====
====A tabular comparison====
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=Sign out=
=Sign out=
==Quiescent inflammatory bowel disease==
===Quiescent inflammatory bowel disease===
Used when:
*No accepted formal definition.
 
May be used when:
#Non-specific "minimal abnormalities" are present.
#Non-specific "minimal abnormalities" are present.
#There is a history of inflammatory bowel disease.
#There is a history of inflammatory bowel disease.
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*Macrophages in the lamina propria.
*Macrophages in the lamina propria.
*Lymphoid nodules.
*Lymphoid nodules.
*Abundant plasma cells in the lamina propria.
*"Abundant" plasma cells in the lamina propria.
**''Abundant'' is subjective.


<pre>
<pre>
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</pre>
</pre>


==Mild inflammation==
===Mild inflammation===
<pre>
<pre>
SIGMOID COLON, BIOPSY:
SIGMOID COLON, BIOPSY:
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</pre>
</pre>


=Specific diagnoses=
===Mild-to-moderate inflammation===
==Ulcerative colitis==
*Often abbreviated as ''UC''.
===General===
*May be associated with ''toxic megacolon''.
 
Epidemiology:
*Associated with ''[[primary sclerosing cholangitis]]''.
*[[Appendicitis]] is considered protective against UC.<ref name=pmid19685454>{{Cite journal  | last1 = Beaugerie | first1 = L. | last2 = Sokol | first2 = H. | title = Appendicitis, not appendectomy, is protective against ulcerative colitis, both in the general population and first-degree relatives of patients with IBD. | journal = Inflamm Bowel Dis | volume =  | issue =  | pages =  | month = Aug | year = 2009 | doi = 10.1002/ibd.21064 | PMID = 19685454 }}</ref><ref name=pmid19273505>{{Cite journal  | last1 = Timmer | first1 = A. | last2 = Obermeier | first2 = F. | title = Reduced risk of ulcerative colitis after appendicectomy. | journal = BMJ | volume = 338 | issue =  | pages = b225 | month =  | year = 2009 | doi =  | PMID = 19273505 }}</ref>
*[[Smoking]] is protective; the opposite is true for [[Crohn's disease]].<ref name=pmid19273505/>
 
===Gross===
*Conventionally considered to be contiguous, i.e. no "skip lesions", with rectal involvement being most severe.
*Dependent on the study one reads... rectal sparing may be seen in 15% of UC patients.<ref>{{cite journal |author=Bernstein CN, Shanahan F, Anton PA, Weinstein WM |title=Patchiness of mucosal inflammation in treated ulcerative colitis: a prospective study |journal=Gastrointest. Endosc. |volume=42 |issue=3 |pages=232-7 |year=1995 |month=September |pmid=7498688 |doi= |url=}}</ref>
 
===Microscopic===
Features:
*Inflammation:
**Active:
***Neutrophils:
****Intraepithelial (cryptitis).†
****Clusters in crypts (crypt abscesses).
****Erosions.
**Chronic:
***Architectural distortion.
***Basal plasmacytosis.
***Foveolar metaplasia.
***Paneth cell metaplasia (distal).
**Lack of [[granulomas]].
 
Notes:
*†Neutrophils are usually numerous in the lamina propria in minimal/mild active inflammation.
*No full wall-thickness inflammation.
*Epithelial apoptosis correlated with inflammation.<ref name=pmid19958058>{{Cite journal  | last1 = Seidelin | first1 = JB. | last2 = Nielsen | first2 = OH. | title = Epithelial apoptosis: cause or consequence of ulcerative colitis? | journal = Scand J Gastroenterol | volume = 44 | issue = 12 | pages = 1429-34 | month =  | year = 2009 | doi = 10.3109/00365520903301212 | PMID = 19958058 }}</ref>
 
DDx:
*[[Crohn's disease]].
*[[Infectious colitis]].
*[[Ischemic colitis]].
*[[Diversion colitis]].
 
===Sign out===
<pre>
SIGMOID COLON, BIOPSY:
- MODERATE ACTIVE COLITIS WITH CHRONIC CHANGES, SEE COMMENT.
- NEGATIVE FOR DYSPLASIA.
 
COMMENT:
No granulomata are identified. The sampled mucosa is diffusely inflamed. Crypt drop-out and
architectural distortion are present.
 
The findings are consistent with inflammatory bowel disease; however, an infectious etiology
should be considered as a possibility.
</pre>
 
<pre>
<pre>
SIGMOID COLON, BIOPSY:
COLON, LEFT, BIOPSY:
- MILD ACTIVE COLITIS, SEE COMMENT.
- MILD-TO-MODERATE ACTIVE COLITIS WITH CHRONIC CHANGES.
- NEGATIVE FOR DYSPLASIA.
- NEGATIVE FOR DYSPLASIA.


COMMENT:
COMMENT:
No granulomata are identified.
No definite granulomata are identified. Mild architectural changes are present.
</pre>
Cryptitis is seen in several crypts. Rare crypt abscesses are present. Lamina propria
plasma cells are abundant throughout the biopsy.


<pre>
The findings are compatible with inflammatory bowel disease or an infectious
A. RIGHT COLON, BIOPSY:
etiology. Clinical correlation is required.
- MODERATE ACTIVE COLITIS, SEE COMMENT.
- NEGATIVE FOR DYSPLASIA.
 
B. LEFT COLON, BIOPSY:
- MODERATE-TO-SEVERE CHRONIC ACTIVE COLITIS, SEE COMMENT.
- NEGATIVE FOR DYSPLASIA.
 
COMMENT:
No granulomata are identified. The mucosa is diffusely inflamed. Architectural distortion
is present in the left colon.  The findings are consistent with ulcerative colitis;
however, an infectious etiology should be considered as a possibility.
</pre>
</pre>


===Moderate inflammation===
<pre>
<pre>
RECTUM, BIOPSY:
RECTUM, BIOPSY:
- MODERATE DIFFUSE CHRONIC ACTIVE PROCTITIS.
- RECTAL MUCOSA WITH MODERATE ACTIVE INFLAMMATION AND CHRONIC CHANGES.
- NEGATIVE FOR DYSPLASIA.
- NEGATIVE FOR DYSPLASIA.
- SEE COMMENT.


COMMENT:
COMMENT:
No definite granulomata are identified. Crypt drop-out is present.
No definite granulomata are identified. Architectural changes, including crypt drop out,
Within the proper clinical context, these are findings of  
are present. Lamina propria plasma cells are abundant throughout the biopsy and eosinophil
inflammatory bowel disease.
numbers are mildly increased. Lymphoid aggregates with germinal centre formation are  
</pre>
present. All fragments of tissue are affected.


====Inactive disease====
The findings are compatible with inflammatory bowel disease or an infectious
<pre>
etiology. Clinical correlation is required.
SIGMOID COLON, BIOPSY:
- CHRONIC COLITIS, SEE COMMENT.
- NEGATIVE FOR ACTIVE COLITIS.
- NEGATIVE FOR DYSPLASIA.
 
COMMENT:
The sections show chronic changes (basal plasmacytosis, marked crypt architectural
distortion, crypt branching); however, no active colitis is present. Also, lamina propria
neutrophils, which are often easy to identify in an active colitis, are not apparent.
Appreciable numbers of lamina propria eosinophils are present and focally intraepithelial.
No granulomas are identified. Clinical correlation is required.
</pre>
</pre>


====Surveillance====
=Specific diagnoses=
<pre>
==Ulcerative colitis==
A. ASCENDING COLON, BIOPSY:
*Often abbreviated as ''UC''.
- COLONIC MUCOSA WITHOUT APPARENT PATHOLOGY.
{{Main|Ulcerative colitis}}
- NEGATIVE FOR ACTIVE COLITIS.
- NEGATIVE FOR DYSPLASIA.
 
B. TRANSVERSE COLON, BIOPSY:
- COLONIC MUCOSA WITHOUT APPARENT PATHOLOGY.
- NEGATIVE FOR ACTIVE COLITIS.
- NEGATIVE FOR DYSPLASIA.
 
C. DESCENDING COLON, BIOPSY:
- COLONIC MUCOSA WITHOUT APPARENT PATHOLOGY.
- NEGATIVE FOR ACTIVE COLITIS.
- NEGATIVE FOR DYSPLASIA.
 
D. SIGMOID COLON, BIOPSY:
- COLONIC MUCOSA WITHOUT APPARENT PATHOLOGY.
- NEGATIVE FOR ACTIVE COLITIS.
- NEGATIVE FOR DYSPLASIA.
 
E. RECTUM, BIOPSY:
- RECTAL MUCOSA WITHOUT APPARENT PATHOLOGY.
- NEGATIVE FOR ACTIVE COLITIS.
- NEGATIVE FOR DYSPLASIA.
 
COMMENT:
Morphologically benign lymphoid aggregates are found focally. No granulomas are
identified. Minimal architectural changes are seen focally.
</pre>
 
<pre>
A. CECUM, BIOPSY:
- QUIESCENT INFLAMMATORY BOWEL DISEASE.
- NEGATIVE FOR DYSPLASIA.
 
B. ASCENDING COLON, BIOPSY:
- QUIESCENT INFLAMMATORY BOWEL DISEASE.
- NEGATIVE FOR DYSPLASIA.
 
C. COLON, HEPATIC FLEXURE, BIOPSY,
- QUIESCENT INFLAMMATORY BOWEL DISEASE.
- NEGATIVE FOR DYSPLASIA.
 
D. TRANSVERSE COLON, BIOPSY:
- QUIESCENT INFLAMMATORY BOWEL DISEASE.
- NEGATIVE FOR DYSPLASIA.
 
E. COLON, SPLENIC FLEXURE, BIOPSY:
- QUIESCENT INFLAMMATORY BOWEL DISEASE.
- NEGATIVE FOR DYSPLASIA.
 
F. DESCENDING COLON, BIOPSY:
- QUIESCENT INFLAMMATORY BOWEL DISEASE.
- NEGATIVE FOR DYSPLASIA.
 
G. SIGMOID COLON, BIOPSY:
- QUIESCENT INFLAMMATORY BOWEL DISEASE.
- NEGATIVE FOR DYSPLASIA.
 
H. RECTUM, BIOPSY
- QUIESCENT INFLAMMATORY BOWEL DISEASE.
- NEGATIVE FOR DYSPLASIA.
 
COMMENT:
No granulomas are identified. Mild architectural distortion is present. No active
inflammation is identified. Scattered mucosal lymphoid nodules with germinal center
formation are present.
</pre>
 
====Granulomas and inflamed crypts - clinically UC====
<pre>
A. CECUM, BIOPSY:
- ACTIVE CECITIS, MILD.
- SMALL MUCOSAL GRANULOMAS, SUPERFICIAL, SEE COMMENT.
- NEGATIVE FOR DYSPLASIA.
 
...
 
COMMENT - PART A:
The small granulomas are mucosal and near, but not all adjacent to, inflamed crypts; this
finding raises the possibility of Crohn's disease. It should be noted that mucosal
granulomas may be seen in ulcerative colitis beside inflamed crypts.
 
COMMENT - GENERAL:
The inflammation is diffuse and chronic changes are seen throughout. Distal paneth cell
metaplasia is present. The diffuse nature of the inflammation would be more in keeping with
ulcerative colitis. Clinical correlation is required.
</pre>
 
====Micro====
The sections show focal intraepithelial neutrophils (cryptitis).  No crypt abscesses are identified. Granulation tissue is present. There is focal Paneth cell metaplasia and foveolar metaplasia. No granulomata are identified.


==Crohn's disease==
==Crohn's disease==
*Often abbreviated as ''CD''.
*Abbreviated ''CD''.
===General===
{{Main|Crohn's disease}}
*Autoimmune disease.
*Increased risk for cancer - usu. rectal cancer; classically [[colorectal adenocarcinoma|mucinous adenocarcinoma]].
 
Associations:<ref name=pmid20074146>{{Cite journal  | last1 = Gearry | first1 = RB. | last2 = Richardson | first2 = AK. | last3 = Frampton | first3 = CM. | last4 = Dodgshun | first4 = AJ. | last5 = Barclay | first5 = ML. | title = Population-based cases control study of inflammatory bowel disease risk factors. | journal = J Gastroenterol Hepatol | volume = 25 | issue = 2 | pages = 325-33 | month = Feb | year = 2010 | doi = 10.1111/j.1440-1746.2009.06140.x | PMID = 20074146 }}
</ref>
*High socioeconomic status.
*Family history of [[IBD]].
*City dwellers.
*Not breastfed.
 
Treatment:
*Immune suppression.
*Surgery considered treatment of last resort.
 
===Gross===
*Aphthous ulcer - first gross finding of IBD.
*Transmural inflammation, i.e. full thickness of bowel wall.
*[[Creeping fat]] (also "fat wrapping" and "fat hypertrophy"<ref name=pmid15888774>{{Cite journal  | last1 = Schäffler | first1 = A. | last2 = Herfarth | first2 = H. | title = Creeping fat in Crohn's disease: travelling in a creeper lane of research? | journal = Gut | volume = 54 | issue = 6 | pages = 742-4 | month = Jun | year = 2005 | doi = 10.1136/gut.2004.061531 | PMID = 15888774 }}</ref>) - abundant fat, fat on anti-mesenteric side of the bowel.<ref>{{Cite journal  | last1 = Schäffler | first1 = A. | last2 = Herfarth | first2 = H. | title = Creeping fat in Crohn's disease: travelling in a creeper lane of research? | journal = Gut | volume = 54 | issue = 6 | pages = 742-4 | month = Jun | year = 2005 | doi = 10.1136/gut.2004.061531 | PMID = 15888774 }}
</ref>
**Definition: fat on more than 50% of the intestinal surface.<ref name=pmid15888774/>
***''[[onlinepathology|OP]]'' understands this as ''fat on 50% of the circumference''.
**DDx of creeping fat: [[ulcerative colitis]], sclerosing mesenteritis, mesenteric panniculitis, epiploic appendagitis, omental infarction, gastrointestinal complication a renal transplant, idiopathic segmental ureteritis.<ref name=pmid18815796/>
**Can be seen radiologically.
*Cobblestone appearance -- may be described as such on endoscopy; due to edema.
*Serpiginous ulcers.
** Image: [http://en.wikipedia.org/wiki/File:CD_serpiginous_ulcer.jpg Serpiginous ulcer (endoscopy) - wikipedia.org].
 
Notes:
*Grossly, the [[margins]] should be clear of disease; the [[surgical clearance]] and microscopic involvement are not considered important.<ref name=pmid6348672>{{Cite journal  | last1 = Hamilton | first1 = SR. | title = Pathologic features of Crohn's disease associated with recrudescence after resection. | journal = Pathol Annu | volume = 18 Pt 1 | issue =  | pages = 191-203 | month =  | year = 1983 | doi =  | PMID = 6348672 }}</ref>
*The term ''creeping fat'' may be used in the context of a [[vasculitis]] outside of the abdominal cavity.<ref name=pmid18815796>{{Cite journal  | last1 = Golder | first1 = WA. | title = The "creeping fat sign"-really diagnostic for Crohn's disease? | journal = Int J Colorectal Dis | volume = 24 | issue = 1 | pages = 1-4 | month = Jan | year = 2009 | doi = 10.1007/s00384-008-0585-y | PMID = 18815796 }}</ref>
 
===Microscopic===
Features:<ref name=pmid10048734/>
*Segmental crypt architectural abnormalities.
*Mucin depletion -- less goblet cells. (???)<ref name=pmid2318990>{{cite journal |author=McCormick DA, Horton LW, Mee AS |title=Mucin depletion in inflammatory bowel disease |journal=J. Clin. Pathol. |volume=43 |issue=2 |pages=143–6 |year=1990 |month=February |pmid=2318990 |pmc=502296 |doi= |url=}}</ref>
*Mucin preservation at the active sites.
*Focal chronic inflammation without crypt atrophy.
*Pseudopyloric mucous glands ([[AKA]] pyloric gland metaplasia).<ref name=medunigraz>URL: [http://www.medunigraz.at/22698 http://www.medunigraz.at/22698]. Accessed on: 6 August 2013.</ref>
**Round glands with abundant pale cytoplasm - stubby champagne flute.
**Usually in the deep aspect of the mucosa.
***Look somewhat similar to Brunner's glands.
*Granulomas - esp. deep (non-mucosal).
**Superficial [[granulomas]] in the mucosa are non-specific (especially if they are beside an inflamed crypt); they may be present in ulcerative colitis.<ref name=pmid12147095>{{Cite journal  | last1 = Shepherd | first1 = NA. | title = Granulomas in the diagnosis of intestinal Crohn's disease: a myth exploded? | journal = Histopathology | volume = 41 | issue = 2 | pages = 166-8 | month = Aug | year = 2002 | doi =  | PMID = 12147095 }}</ref><ref name=pmid12121237>{{Cite journal  | last1 = Mahadeva | first1 = U. | last2 = Martin | first2 = JP. | last3 = Patel | first3 = NK. | last4 = Price | first4 = AB. | title = Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis. | journal = Histopathology | volume = 41 | issue = 1 | pages = 50-5 | month = Jul | year = 2002 | doi =  | PMID = 12121237 }}</ref>
 
DDx:
*Infectious colitis:
**[[Amebiasis]].
**[[EBV]]-associated colitis.<ref>{{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>
*[[Ulcerative colitis]].
*NSAID-induced small bowel injury.<ref name=pmid19148795>{{Cite journal  | last1 = Hayashi | first1 = Y. | last2 = Yamamoto | first2 = H. | last3 = Taguchi | first3 = H. | last4 = Sunada | first4 = K. | last5 = Miyata | first5 = T. | last6 = Yano | first6 = T. | last7 = Arashiro | first7 = M. | last8 = Sugano | first8 = K. | title = Nonsteroidal anti-inflammatory drug-induced small-bowel lesions identified by double-balloon endoscopy: endoscopic features of the lesions and endoscopic treatments for diaphragm disease. | journal = J Gastroenterol | volume = 44 Suppl 19 | issue =  | pages = 57-63 | month =  | year = 2009 | doi = 10.1007/s00535-008-2277-3 | PMID = 19148795 }}</ref>
*Others - a long DDx is [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2914216/table/T1/ here].<ref name=pmid20532706>{{Cite journal  | last1 = Dilauro | first1 = S. | last2 = Crum-Cianflone | first2 = NF. | title = Ileitis: when it is not Crohn's disease. | journal = Curr Gastroenterol Rep | volume = 12 | issue = 4 | pages = 249-58 | month = Aug | year = 2010 | doi = 10.1007/s11894-010-0112-5 | PMID = 20532706 }}</ref>
====Images====
www:
*[http://www.medunigraz.at/images/content/image/presse/patho-netzwerk/1012_06.jpg Crohn's disease - pyloric gland metaplasia (medunigraz.at)].<ref name=medunigraz>URL: [http://www.medunigraz.at/22698 http://www.medunigraz.at/22698]. Accessed on: 6 August 2013.</ref>
*[http://www.medunigraz.at/images/content/image/presse/patho-netzwerk/1012_07.jpg Crohn's disease - pyloric gland metaplasia (medunigraz.at)].<ref name=medunigraz/>
 
===Sign-out===
====Biopsies====
<pre>
TERMINAL ILEUM, BIOPSY
- PATCHY MILD ACTIVE ILEITIS.
 
COMMENT:
No granulomas are identified. An infective etiology should be considered, as
it cannot be excluded on pathologic grounds. 
</pre>
=====Classic=====
<pre>
A. TERMINAL ILEUM, BIOPSY
- MODERATE GRANULOMATOUS ILEITIS.
 
B. CECUM, BIOPSY:
- MILD PATCHY ACTIVE CECITIS.
 
C. SIGMOID COLON, BIOPSY:
- CHRONIC INFLAMMATORY CHANGES. NO ACTIVE COLITIS.
 
COMMENT:
The histomorphological findings (patchy inflammation, granulomas, ileitis, paneth cell
metaplasia, crypt loss and crypt elongation) are suggestive of Crohn's disease. An infective
etiology should be considered, as it cannot be excluded on pathologic grounds.
</pre>
=====Quiescent Crohn's disease=====
<pre>
DESCENDING COLON, BIOPSY:
- COLONIC MUCOSA WITH PROMINENT LAMINA PROPRIA PLASMA CELLS.
- NEGATIVE FOR ACTIVE COLITIS.
 
COMMENT:
Minimal architectural changes consistent with chronic inflammation are present. There are
no granulomas. No dysplasia is identified. The findings are compatible with quiescent
Crohn's disease.
</pre>
 
====Resection====
<pre>
TERMINAL ILEUM, CECUM, AND APPENDIX, CECUM-ILEUM RESECTION:
- CHRONIC ACTIVE GRANULOMATOUS ILEITIS -- INCLUDING:
-- MURAL MICROABSCESS FORMATION.
-- SEROSITIS.
-- A STRICTURE.
-- DEEP ULCERATION (AT LEAST THROUGH THE MUSCULARIS PROPRIA).
- PERIAPPENDICITIS, NEGATIVE FOR APPENDICITIS.
- CECUM WITHIN NORMAL LIMITS.
- TEN LYMPH NODES NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 10 ).
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
 
COMMENT:
The sections show patchy transmural inflammation and skip lesions.
The findings are consistent with Crohn's disease.
</pre>
 
<pre>
TERMINAL ILEUM, CECUM, APPENDIX, AND ASCENDING COLON, RIGHT HEMICOLECTOMY:
- CHRONIC ACTIVE ILEITIS -- INCLUDING:
-- INFLAMMATORY PSEUDOPOLYP.
-- STRICTURE ASSOCIATED WITH LARGE LYMPHOID AGGREGATE.
- THIRTEEN LYMPH NODES NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 13 ).
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
 
COMMENT:
The sections show patchy transmural inflammation and skip lesions. Submucosal fibrosis is
present. Focal ulceration and abscess formation is identified. No granulomas are identified.
 
The findings are consistent with Crohn's disease.
</pre>
 
<pre>
ILEUM, COLON, ILEO-COLIC RESECTION:
- SEVERE FOCAL ILEITIS WITH ULCERATION AND TRANSMURAL INFLAMMATION.
- BENIGN STRICTURE ASSOCIATED WITH A LARGE LYMPHOID AGGREGATE.
- FIBROUS ADHESION.
- COLON WITHIN NORMAL LIMITS.
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
 
COMMENT:
The findings are consistent with chronic, active Crohn's disease.
</pre>


=="Indeterminate colitis"==
=="Indeterminate colitis"==
Line 590: Line 311:
#CUTE = Colitis of uncertain type or etiology.
#CUTE = Colitis of uncertain type or etiology.
#*Should be reserved for resection specimens only.
#*Should be reserved for resection specimens only.


==Dysplasia in inflammatory bowel disease==
==Dysplasia in inflammatory bowel disease==
Line 597: Line 316:
Classified as per Riddell ''et al.'':<ref name=pmid6629368>{{Cite journal  | last1 = Riddell | first1 = RH. | last2 = Goldman | first2 = H. | last3 = Ransohoff | first3 = DF. | last4 = Appelman | first4 = HD. | last5 = Fenoglio | first5 = CM. | last6 = Haggitt | first6 = RC. | last7 = Ahren | first7 = C. | last8 = Correa | first8 = P. | last9 = Hamilton | first9 = SR. | title = Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. | journal = Hum Pathol | volume = 14 | issue = 11 | pages = 931-68 | month = Nov | year = 1983 | doi =  | PMID = 6629368 }}</ref><ref name=pmid11400142>{{Cite journal  | last1 = Eaden | first1 = J. | last2 = Abrams | first2 = K. | last3 = McKay | first3 = H. | last4 = Denley | first4 = H. | last5 = Mayberry | first5 = J. | title = Inter-observer variation between general and specialist gastrointestinal pathologists when grading dysplasia in ulcerative colitis. | journal = J Pathol | volume = 194 | issue = 2 | pages = 152-7 | month = Jun | year = 2001 | doi = 10.1002/path.876 | PMID = 11400142 }}</ref><ref name=pmid11936264>{{Cite journal  | last1 = Greenson | first1 = JK. | title = Dysplasia in inflammatory bowel disease. | journal = Semin Diagn Pathol | volume = 19 | issue = 1 | pages = 31-7 | month = Feb | year = 2002 | doi =  | PMID = 11936264 }}</ref>
Classified as per Riddell ''et al.'':<ref name=pmid6629368>{{Cite journal  | last1 = Riddell | first1 = RH. | last2 = Goldman | first2 = H. | last3 = Ransohoff | first3 = DF. | last4 = Appelman | first4 = HD. | last5 = Fenoglio | first5 = CM. | last6 = Haggitt | first6 = RC. | last7 = Ahren | first7 = C. | last8 = Correa | first8 = P. | last9 = Hamilton | first9 = SR. | title = Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. | journal = Hum Pathol | volume = 14 | issue = 11 | pages = 931-68 | month = Nov | year = 1983 | doi =  | PMID = 6629368 }}</ref><ref name=pmid11400142>{{Cite journal  | last1 = Eaden | first1 = J. | last2 = Abrams | first2 = K. | last3 = McKay | first3 = H. | last4 = Denley | first4 = H. | last5 = Mayberry | first5 = J. | title = Inter-observer variation between general and specialist gastrointestinal pathologists when grading dysplasia in ulcerative colitis. | journal = J Pathol | volume = 194 | issue = 2 | pages = 152-7 | month = Jun | year = 2001 | doi = 10.1002/path.876 | PMID = 11400142 }}</ref><ref name=pmid11936264>{{Cite journal  | last1 = Greenson | first1 = JK. | title = Dysplasia in inflammatory bowel disease. | journal = Semin Diagn Pathol | volume = 19 | issue = 1 | pages = 31-7 | month = Feb | year = 2002 | doi =  | PMID = 11936264 }}</ref>
*Negative for dysplasia.
*Negative for dysplasia.
*Indefinite for dysplasia.
*[[Indefinite for dysplasia]].
*Low grade dysplasia.
*Low grade dysplasia.
*High grade dysplasia.
*High grade dysplasia.


Notes:
Notes:
*GI experts and generalists have similar rates agreement.<ref name=pmid11400142>{{Cite journal  | last1 = Eaden | first1 = J. | last2 = Abrams | first2 = K. | last3 = McKay | first3 = H. | last4 = Denley | first4 = H. | last5 = Mayberry | first5 = J. | title = Inter-observer variation between general and specialist gastrointestinal pathologists when grading dysplasia in ulcerative colitis. | journal = J Pathol | volume = 194 | issue = 2 | pages = 152-7 | month = Jun | year = 2001 | doi = 10.1002/path.876 | PMID = 11400142 }}</ref>
*GI experts and generalists have similar rates of agreement.<ref name=pmid11400142>{{Cite journal  | last1 = Eaden | first1 = J. | last2 = Abrams | first2 = K. | last3 = McKay | first3 = H. | last4 = Denley | first4 = H. | last5 = Mayberry | first5 = J. | title = Inter-observer variation between general and specialist gastrointestinal pathologists when grading dysplasia in ulcerative colitis. | journal = J Pathol | volume = 194 | issue = 2 | pages = 152-7 | month = Jun | year = 2001 | doi = 10.1002/path.876 | PMID = 11400142 }}</ref>


===Microscopic===
===Microscopic===
Line 612: Line 331:
==Dysplasia-associated lesion or mass==
==Dysplasia-associated lesion or mass==
*Abbreviated ''DALM''.
*Abbreviated ''DALM''.
===General===
{{Main|Dysplasia-associated lesion or mass}}
*Proving invasive malignancy (on histopathologic grounds alone) in the setting of chronic inflammation is difficult.<ref name=pmid7450425>{{Cite journal  | last1 = Blackstone | first1 = MO. | last2 = Riddell | first2 = RH. | last3 = Rogers | first3 = BH. | last4 = Levin | first4 = B. | title = Dysplasia-associated lesion or mass (DALM) detected by colonoscopy in long-standing ulcerative colitis: an indication for colectomy. | journal = Gastroenterology | volume = 80 | issue = 2 | pages = 366-74 | month = Feb | year = 1981 | doi =  | PMID = 7450425 }}</ref>
*This diagnosis depends on correlation of endoscopy and histopathology - '''important'''.<ref name=pmid21912466>{{Cite journal  | last1 = Neumann | first1 = H. | last2 = Vieth | first2 = M. | last3 = Langner | first3 = C. | last4 = Neurath | first4 = MF. | last5 = Mudter | first5 = J. | title = Cancer risk in IBD: how to diagnose and how to manage DALM and ALM. | journal = World J Gastroenterol | volume = 17 | issue = 27 | pages = 3184-91 | month = Jul | year = 2011 | doi = 10.3748/wjg.v17.i27.3184 | PMID = 21912466 }}</ref>
**Biopsies are usually taken of the lesion and around the base.
*This diagnosis usually leads to a [[colectomy]].
 
===Gross===
*Endoscopically "suspicious", i.e. endoscopist thinks this is a DALM - '''essential feature'''.
**Usually have a positive lifting sign.
===Microscopic===
Features:
*Cytologic dysplasia - as in [[adenomatous polyps]] - '''key feature'''.
*Flat or polypoid.<ref name=pmid7450425/>
 
DDx:
*Sporadic [[adenomatous polyp]] -- favouring sporadic:
**Sharp transition between lesion and the surrounding tissue.<ref name=pmid21912466/>
**Polyps not at site of active disease.<ref name=pmid10746669>{{Cite journal  | last1 = Fogt | first1 = F. | last2 = Urbanski | first2 = SJ. | last3 = Sanders | first3 = ME. | last4 = Furth | first4 = EE. | last5 = Zimmerman | first5 = RL. | last6 = Deren | first6 = JJ. | last7 = Noffsinger | first7 = AE. | last8 = Vortmeyer | first8 = AO. | last9 = Hartmann | first9 = CJ. | title = Distinction between dysplasia-associated lesion or mass (DALM) and adenoma in patients with ulcerative colitis. | journal = Hum Pathol | volume = 31 | issue = 3 | pages = 288-91 | month = Mar | year = 2000 | doi =  | PMID = 10746669 }}</ref>
 
Image:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158393/figure/F7/ DALM (nlm.nih.gov)].<ref name=pmid21912466/>


==Pouchitis==
==Pouchitis==
Line 640: Line 338:
**Generally, pouches are ''not'' used in Crohn's disease.
**Generally, pouches are ''not'' used in Crohn's disease.
*Chronic pouchitis seen in approximately 15% of patients.<ref name=pmid12617884 >{{Cite journal  | last1 = Gionchetti | first1 = P. | last2 = Amadini | first2 = C. | last3 = Rizzello | first3 = F. | last4 = Venturi | first4 = A. | last5 = Poggioli | first5 = G. | last6 = Campieri | first6 = M. | title = Diagnosis and treatment of pouchitis. | journal = Best Pract Res Clin Gastroenterol | volume = 17 | issue = 1 | pages = 75-87 | month = Feb | year = 2003 | doi =  | PMID = 12617884 }}</ref>
*Chronic pouchitis seen in approximately 15% of patients.<ref name=pmid12617884 >{{Cite journal  | last1 = Gionchetti | first1 = P. | last2 = Amadini | first2 = C. | last3 = Rizzello | first3 = F. | last4 = Venturi | first4 = A. | last5 = Poggioli | first5 = G. | last6 = Campieri | first6 = M. | title = Diagnosis and treatment of pouchitis. | journal = Best Pract Res Clin Gastroenterol | volume = 17 | issue = 1 | pages = 75-87 | month = Feb | year = 2003 | doi =  | PMID = 12617884 }}</ref>
*May be assessed by fecal calprotectin.<ref name=pmid18301296>{{Cite journal  | last1 = Johnson | first1 = MW. | last2 = Maestranzi | first2 = S. | last3 = Duffy | first3 = AM. | last4 = Dewar | first4 = DH. | last5 = Forbes | first5 = A. | last6 = Bjarnason | first6 = I. | last7 = Sherwood | first7 = RA. | last8 = Ciclitira | first8 = P. | last9 = Nicholls | first9 = JR. | title = Faecal calprotectin: a noninvasive diagnostic tool and marker of severity in pouchitis. | journal = Eur J Gastroenterol Hepatol | volume = 20 | issue = 3 | pages = 174-9 | month = Mar | year = 2008 | doi = 10.1097/MEG.0b013e3282f1c9a7 | PMID = 18301296 }}</ref>
*May be assessed by [[fecal calprotectin]].<ref name=pmid18301296>{{Cite journal  | last1 = Johnson | first1 = MW. | last2 = Maestranzi | first2 = S. | last3 = Duffy | first3 = AM. | last4 = Dewar | first4 = DH. | last5 = Forbes | first5 = A. | last6 = Bjarnason | first6 = I. | last7 = Sherwood | first7 = RA. | last8 = Ciclitira | first8 = P. | last9 = Nicholls | first9 = JR. | title = Faecal calprotectin: a noninvasive diagnostic tool and marker of severity in pouchitis. | journal = Eur J Gastroenterol Hepatol | volume = 20 | issue = 3 | pages = 174-9 | month = Mar | year = 2008 | doi = 10.1097/MEG.0b013e3282f1c9a7 | PMID = 18301296 }}</ref>
*Considered a clinico-pathologic diagnosis.<ref name=pmid20958905>{{Cite journal  | last1 = Royston | first1 = DJ. | last2 = Warren | first2 = BF. | title = Are we reporting ileal pouch biopsies correctly? | journal = Colorectal Dis | volume = 13 | issue = 11 | pages = 1285-9 | month = Nov | year = 2011 | doi = 10.1111/j.1463-1318.2010.02452.x | PMID = 20958905 }}</ref><ref name=pmid12617884 >{{Cite journal  | last1 = Gionchetti | first1 = P. | last2 = Amadini | first2 = C. | last3 = Rizzello | first3 = F. | last4 = Venturi | first4 = A. | last5 = Poggioli | first5 = G. | last6 = Campieri | first6 = M. | title = Diagnosis and treatment of pouchitis. | journal = Best Pract Res Clin Gastroenterol | volume = 17 | issue = 1 | pages = 75-87 | month = Feb | year = 2003 | doi =  | PMID = 12617884 }}</ref>
*Considered a clinico-pathologic diagnosis.<ref name=pmid20958905>{{Cite journal  | last1 = Royston | first1 = DJ. | last2 = Warren | first2 = BF. | title = Are we reporting ileal pouch biopsies correctly? | journal = Colorectal Dis | volume = 13 | issue = 11 | pages = 1285-9 | month = Nov | year = 2011 | doi = 10.1111/j.1463-1318.2010.02452.x | PMID = 20958905 }}</ref><ref name=pmid12617884 >{{Cite journal  | last1 = Gionchetti | first1 = P. | last2 = Amadini | first2 = C. | last3 = Rizzello | first3 = F. | last4 = Venturi | first4 = A. | last5 = Poggioli | first5 = G. | last6 = Campieri | first6 = M. | title = Diagnosis and treatment of pouchitis. | journal = Best Pract Res Clin Gastroenterol | volume = 17 | issue = 1 | pages = 75-87 | month = Feb | year = 2003 | doi =  | PMID = 12617884 }}</ref>
===Microscopic===
===Microscopic===
Features:<ref name=pmid12794576>{{Cite journal  | last1 = Shen | first1 = B. | last2 = Achkar | first2 = JP. | last3 = Connor | first3 = JT. | last4 = Ormsby | first4 = AH. | last5 = Remzi | first5 = FH. | last6 = Bevins | first6 = CL. | last7 = Brzezinski | first7 = A. | last8 = Bambrick | first8 = ML. | last9 = Fazio | first9 = VW. | title = Modified pouchitis disease activity index: a simplified approach to the diagnosis of pouchitis. | journal = Dis Colon Rectum | volume = 46 | issue = 6 | pages = 748-53 | month = Jun | year = 2003 | doi = 10.1097/01.DCR.0000070528.00563.D9 | PMID = 12794576 | URL = http://www.lri.ccf.org/pathobio/achkar/documents/Shen2003DisColonRectum.pdf }}</ref>
Features:<ref name=pmid12794576>{{Cite journal  | last1 = Shen | first1 = B. | last2 = Achkar | first2 = JP. | last3 = Connor | first3 = JT. | last4 = Ormsby | first4 = AH. | last5 = Remzi | first5 = FH. | last6 = Bevins | first6 = CL. | last7 = Brzezinski | first7 = A. | last8 = Bambrick | first8 = ML. | last9 = Fazio | first9 = VW. | title = Modified pouchitis disease activity index: a simplified approach to the diagnosis of pouchitis. | journal = Dis Colon Rectum | volume = 46 | issue = 6 | pages = 748-53 | month = Jun | year = 2003 | doi = 10.1097/01.DCR.0000070528.00563.D9 | PMID = 12794576 | URL = http://www.lri.ccf.org/pathobio/achkar/documents/Shen2003DisColonRectum.pdf }}</ref>
*[[Neutrophil]]s - intraepithelial (cryptitis).
*[[Neutrophil]]s - intraepithelial ([[cryptitis]]).
*+/-Crypt abscess (cluster of neutrophils in a gland) - indicator of moderate or severe.
*+/-[[Crypt abscess]] (cluster of neutrophils in a gland) - indicator of moderate or severe.
*Ulceration.
*Ulceration.


Line 652: Line 350:


DDx:
DDx:
*[[Crohn's disease]] - pyloric gland metaplasia (PGM) suggestive but not diagnostic.<ref name=pmid23543088>{{Cite journal  | last1 = Agarwal | first1 = S. | last2 = Stucchi | first2 = AF. | last3 = Dendrinos | first3 = K. | last4 = Cerda | first4 = S. | last5 = O'Brien | first5 = MJ. | last6 = Becker | first6 = JM. | last7 = Heeren | first7 = T. | last8 = Farraye | first8 = FA. | title = Is pyloric gland metaplasia in ileal pouch biopsies a marker for Crohn's disease? | journal = Dig Dis Sci | volume = 58 | issue = 10 | pages = 2918-25 | month = Oct | year = 2013 | doi = 10.1007/s10620-013-2655-4 | PMID = 23543088 }}</ref>
*[[Crohn's disease]] - [[pyloric gland metaplasia]] (PGM) suggestive but not diagnostic.<ref name=pmid23543088>{{Cite journal  | last1 = Agarwal | first1 = S. | last2 = Stucchi | first2 = AF. | last3 = Dendrinos | first3 = K. | last4 = Cerda | first4 = S. | last5 = O'Brien | first5 = MJ. | last6 = Becker | first6 = JM. | last7 = Heeren | first7 = T. | last8 = Farraye | first8 = FA. | title = Is pyloric gland metaplasia in ileal pouch biopsies a marker for Crohn's disease? | journal = Dig Dis Sci | volume = 58 | issue = 10 | pages = 2918-25 | month = Oct | year = 2013 | doi = 10.1007/s10620-013-2655-4 | PMID = 23543088 }}</ref>
**PGM = glands with tall columnar cells with pale pink cytoplasm and a small basal nuclei - typically in the deep mucosa.<ref name=pmid23925821>{{Cite journal  | last1 = Weber | first1 = CR. | last2 = Rubin | first2 = DT. | title = Chronic pouchitis versus recurrent Crohn's disease: a diagnostic challenge. | journal = Dig Dis Sci | volume = 58 | issue = 10 | pages = 2748-50 | month = Oct | year = 2013 | doi = 10.1007/s10620-013-2816-5 | PMID = 23925821 }}</ref>
**PGM = glands with tall columnar cells with pale pink cytoplasm and a small basal nuclei - typically in the deep mucosa.<ref name=pmid23925821>{{Cite journal  | last1 = Weber | first1 = CR. | last2 = Rubin | first2 = DT. | title = Chronic pouchitis versus recurrent Crohn's disease: a diagnostic challenge. | journal = Dig Dis Sci | volume = 58 | issue = 10 | pages = 2748-50 | month = Oct | year = 2013 | doi = 10.1007/s10620-013-2816-5 | PMID = 23925821 }}</ref>
*Irritable pouch disease<ref name=pmid15073663>{{Cite journal  | last1 = Beart | first1 = RW. | title = Is pouchitis a clinical, endoscopic, or histologic problem? | journal = Dis Colon Rectum | volume = 47 | issue = 6 | pages = 949; author reply 949-50 | month = Jun | year = 2004 | doi = 10.1007/s10350-004-0516-0 | PMID = 15073663 }}</ref><ref name=pmid18702649>{{Cite journal  | last1 = Shen | first1 = B. | last2 = Liu | first2 = W. | last3 = Remzi | first3 = FH. | last4 = Shao | first4 = Z. | last5 = Lu | first5 = H. | last6 = DeLaMotte | first6 = C. | last7 = Hammel | first7 = J. | last8 = Queener | first8 = E. | last9 = Bambrick | first9 = ML. | title = Enterochromaffin cell hyperplasia in irritable pouch syndrome. | journal = Am J Gastroenterol | volume = 103 | issue = 9 | pages = 2293-300 | month = Sep | year = 2008 | doi = 10.1111/j.1572-0241.2008.01990.x | PMID = 18702649 }}</ref> - functional disease similar to [[irritable bowel syndrome]].  
*Irritable pouch disease<ref name=pmid15073663>{{Cite journal  | last1 = Beart | first1 = RW. | title = Is pouchitis a clinical, endoscopic, or histologic problem? | journal = Dis Colon Rectum | volume = 47 | issue = 6 | pages = 949; author reply 949-50 | month = Jun | year = 2004 | doi = 10.1007/s10350-004-0516-0 | PMID = 15073663 }}</ref><ref name=pmid18702649>{{Cite journal  | last1 = Shen | first1 = B. | last2 = Liu | first2 = W. | last3 = Remzi | first3 = FH. | last4 = Shao | first4 = Z. | last5 = Lu | first5 = H. | last6 = DeLaMotte | first6 = C. | last7 = Hammel | first7 = J. | last8 = Queener | first8 = E. | last9 = Bambrick | first9 = ML. | title = Enterochromaffin cell hyperplasia in irritable pouch syndrome. | journal = Am J Gastroenterol | volume = 103 | issue = 9 | pages = 2293-300 | month = Sep | year = 2008 | doi = 10.1111/j.1572-0241.2008.01990.x | PMID = 18702649 }}</ref> - functional disease similar to [[irritable bowel syndrome]].  
Line 676: Line 374:


===Sign out===
===Sign out===
Note:
*Dr. Robert Riddell is of the opinion: "Do '''not''' call any pouch inflammation as consistent with Crohn's disease."
<pre>
<pre>
SMALL BOWEL POUCH, BIOPSY:
SMALL BOWEL POUCH, BIOPSY:
Line 708: Line 409:
*[[Gastrointestinal pathology]].
*[[Gastrointestinal pathology]].
*[[Intestinal polyps]].
*[[Intestinal polyps]].
*[[Diverticular disease-associated colitis]].
*[[Pseudopyloric mucous glands]].


=References=
=References=

Latest revision as of 17:09, 16 February 2019

Inflammatory bowel disease, abbreviated IBD, is the bread 'n butter of gastroenterology, and a significant number of gastrointestinal pathology specimens.

It exists in two main flavours:

  • Crohn's disease (CD).
  • Ulcerative colitis (UC).

Both are associated with an increased risk of colorectal carcinoma.[1]

Clinical

  • It is important to differentiate UC and CD as the management is different.
  • UC patients get pouches... CD patients do not.
    • It is said that: There 's nothing like a pouch to bring out Crohn's disease.[2]
  • People with long standing IBD have an increased risk for:

Extra-intestinal manifestations of inflammatory bowel disease

Mnemonic (family-rated version) excellent cardiac surgery is pleasant and appreciated:

Molecular

  • NOD2[5] (AKA CARD15) variants are associated with stricturing CD, early need for surgery and recurrence.[6]

General clinical differential diagnosis

  • Crohn's disease.
  • Ulcerative colitis.
  • Infective colitis/enteritis.
  • Ischemic colitis/enteritis.
  • Radiation colitis.

Others:

Specimens

  • Biopsies for diagnosis.
  • Surveillance biopsies - to rule-out dysplasia.
  • Resections for disease that has failed medical management.
  • Resections for dysplasia associated with inflammatory bowel disease.

Notes:

  • Biopsies for diagnosis should specify the (anatomical) site:
    • Slight gradients exist in the large bowel that can be exploited for diagnostic purposes if the site information is known, for example:
      • Paneth cells distal to the splenic flexure are abnormal.
      • Ulcerative colitis is often more severe distally - even in a pancolitis, as the disease starts in the rectum and progresses toward the cecum.
  • Surveillance biopsies should specify the (anatomical) site - so, it possible to find any site of interest on a follow-up colonoscopy.[7]

Biopsies all submitted in one bottle

COLON (SITE NOT FURTHER SPECIFIED), BIOPSIES:
- MODERATE CHRONIC ACTIVE COLITIS.
- NEGATIVE FOR DYSPLASIA.
- PLEASE SEE COMMENT.

COMMENT:
The sections show colorectal-type mucosa with focal cryptitis and rare neutrophilic crypt
abscesses.  

Mild architectural changes, suggestive of a chronic colitis, are present. No granulomas are
identified. Lymphoid aggregates with germinal centre formation are present in multiple
fragments.  The lamina propria has abundant plasma cells throughout the fragments; no 
fragments have apparent relative sparing. 

Paneth cells are present focally; however, the significance of the paneth cells cannot 
determined as the biopsy sites are not known. 

The findings are compatible with inflammatory bowel disease and chronic active infectious
colitides. Clinical correlation is suggested.

Microscopic

Features helpful for the diagnosis of IBD - as based on a study:[8]

  1. Basal inflammation, i.e. crypt base, plasmacytosis with severe chronic inflammation.
    • Basal cell plasmacytosis makes an infectious etiology less likely.[9]
    • "Basal plasmacytosis" = plasma cells in the lamina propria between the crypts and muscularis mucosae.[10]
  2. Crypt architectural abnormalities.
    • Atrophy = less glands ~ 3-4 glands/mm (normal = 7-8 glands/mm).
    • Branching = common (normal = very rare branching).
    • Distortion = bent glands, marked size variation[11] (normal = "rack of test tubes").
  3. Distal Paneth cell metaplasia.
    • Paneth cells should not be in the left colon[12] - if you see 'em think of IBD and other long-standing injurious processes.
    • Paneth cells have basal nuclei and coarse luminal granules.[13]
      • They should not be confused with endocrine cells -- these have apical nuclei and fine granules.
      • They should not be confused with intraepithelial eosinophils -- have smaller (~1/2) more intensely red granules.

Notes:

  1. Microscopic features can be remembered by mnemonic CPP: Crypts (abnormal), Plasmacytosis, Paneth cells where they don't belong.
  2. If you see architectural distortion (e.g. crypt branching) in the left colon, look for Paneth cells.
  3. The hepatic flexure is considered the divider for normal paneth cells and abnormal paneth cells, i.e. paneth cells proximal to the hepatic flexure are normal; paneth cells distal to the hepatic flexure are abnormal.[14]
  4. Stretching of tissue may mimic atrophy; tip-off it is artifact: thinning of mucosa.[9]

Images

  • Crohn's disease - very well-formed granulomas in the colon - high mag. (WC)

  • Crohn's disease - duodenum - intermed. mag. (WC)

  • Cryptitis. (WC)

  • Crypt branching. (WC)

Grading

  • Several systems exists.[9]
  • One that is often cited is by Gupta et al.[15]

Grading schemes for IBD in a table

Nil Mild Moderate Severe
"A grading scheme"[9] - cryptitis crypt abscesses erosions
Gupta[15] "0" (nil) "1" (<50% of crypts
have PMNs) 		"2" (>50% of crypts
have PMNs) 		"3" (presence of
ulcers or erosions)
Images

Crohn's disease versus ulcerative colitis

Robbins

UC features:[16]

  • Mucosal involvement -- sometimes submucosa.
  • No skip lesions.
  • Colon/rectum only.
    • UC may have 'ileal backwash' -- mild ileal inflammation due to backwash of inflammatory soup from colon.
  • "No granulomas".
    • Superficial granulomas in the mucosa are non-specific, especially if they are beside an inflamed crypt, i.e. they may be present in UC.[17][18]
      • Deep granulomas are specific for Crohn's disease.

Example of a superficial granuloma that is non-specific, i.e. this could be UC or CD:

Kirsch

Features of UC[9] - memory device DDDR:

  • Diffuse inflammation.
  • Diffuse arch. changes.
  • Diffuse atrophy.
  • Rectal involvement.

Words of caution

The following may be present in UC:[9]

  • Cecal patch (cecal involvement without pancolitis).
  • Patchy involvement
    • Esp. in Tx'ed patients.
    • Esp. in children.
  • Ileitis - esp. in the context of severe pancolitis; known as backwash ileitis.
  • Deep inflammation (in a fissure).
  • Upper GI tract involvement -- see below.

Upper gastrointestinal tract involvement

  • The old dogma was upper GI tract = Crohn's disease.

Characteristics of upper GI tract UC:[19]

  • Most common:
    1. Focal gastritis.
    2. Mixed basal inflammation and superficial plasmacytosis in the stomach.
  • Unique:
    • Diffuse chronic duodenitis.
    • ~ 10% of UC patients.
    • ~ 40% of UC + colectomy + pouchitis.

Another study compares UC, CD and control individuals:[20]

  • Gastritis:
    • UC: 19%.
    • CD: 33%
    • Controls: 13%.
  • Duodenitis:
    • UC: 3%.
    • CD: 26%.
    • Controls: 1%.

Note:

  • Younger individuals (<18 years old) have significantly more gastritis and duodenitis.[20]

A tabular comparison

Gross pathology:

Feature Crohn's disease Ulcerative colitis
Lesion distribution patchy diffuse
Strictures maybe no
Perianal disease yes/no no
Rectal involvement no yes
Ileal involvement yes, classic usu. no; seen in pancolitis
Upper GI tract involvement yes yes (gaining acceptance)
Associated with PSC not classically yes

Sign out

Quiescent inflammatory bowel disease

  • No accepted formal definition.

May be used when:

  1. Non-specific "minimal abnormalities" are present.
  2. There is a history of inflammatory bowel disease.

"Minimal abnormalities" - features:

  • Apoptosis.
  • Macrophages in the lamina propria.
  • Lymphoid nodules.
  • "Abundant" plasma cells in the lamina propria.
    • Abundant is subjective.
COLON, BIOPSIES:
- QUIESCENT INFLAMMATORY BOWEL DISEASE.
- NEGATIVE FOR DYSPLASIA.

Mild inflammation

SIGMOID COLON, BIOPSY:
- MILD ACTIVE COLITIS WITH CHRONIC CHANGES, SEE COMMENT.
- NEGATIVE FOR DYSPLASIA.

COMMENT:
No granulomata are identified.  Mild architectural changes are present.

The findings are compatible with inflammatory bowel disease or an infectious
etiology. Clinical correlation is required.

Mild-to-moderate inflammation

COLON, LEFT, BIOPSY:
- MILD-TO-MODERATE ACTIVE COLITIS WITH CHRONIC CHANGES.
- NEGATIVE FOR DYSPLASIA.

COMMENT:
No definite granulomata are identified.  Mild architectural changes are present.
Cryptitis is seen in several crypts. Rare crypt abscesses are present. Lamina propria
plasma cells are abundant throughout the biopsy.

The findings are compatible with inflammatory bowel disease or an infectious
etiology. Clinical correlation is required.

Moderate inflammation

RECTUM, BIOPSY:
- RECTAL MUCOSA WITH MODERATE ACTIVE INFLAMMATION AND CHRONIC CHANGES.
- NEGATIVE FOR DYSPLASIA.
- SEE COMMENT.

COMMENT:
No definite granulomata are identified. Architectural changes, including crypt drop out,
are present. Lamina propria plasma cells are abundant throughout the biopsy and eosinophil 
numbers are mildly increased. Lymphoid aggregates with germinal centre formation are 
present. All fragments of tissue are affected.

The findings are compatible with inflammatory bowel disease or an infectious
etiology. Clinical correlation is required.

Specific diagnoses

Ulcerative colitis

  • Often abbreviated as UC.
Main article: Ulcerative colitis

Crohn's disease

  • Abbreviated CD.
Main article: Crohn's disease

"Indeterminate colitis"

  • "Indeterminate colitis" is a confusing term and should be avoided.[21]

Suggested terminology

  1. IBDU = IBD unclassified.
  2. CUTE = Colitis of uncertain type or etiology.
    • Should be reserved for resection specimens only.

Dysplasia in inflammatory bowel disease

General

Classified as per Riddell et al.:[22][23][24]

Notes:

  • GI experts and generalists have similar rates of agreement.[23]

Microscopic

Features:[25]

  • Nuclear changes at the surface - key feature.
    • Nuclear hyperchromasia.
    • Nuclear enlargement - ellipsoid or spherical.

Dysplasia-associated lesion or mass

  • Abbreviated DALM.
Main article: Dysplasia-associated lesion or mass

Pouchitis

General

  • Inflammation of an ileal pouch; pouches are a treatment for ulcerative colitis.
    • Generally, pouches are not used in Crohn's disease.
  • Chronic pouchitis seen in approximately 15% of patients.[26]
  • May be assessed by fecal calprotectin.[27]
  • Considered a clinico-pathologic diagnosis.[28][26]

Microscopic

Features:[29]

Note:

  • Absence of Paneth cells and villi = colonic metaplasia,[30] associated with inflammation.[31]

DDx:

Images:

Scoring system

Pouchitis disease activity index (PDAI) - based on clinical and pathologic factors:

  • Active pouchitis >= 7.
  • Remission < 7.

The histologic component of the PDAI:[29]

  • Neutrophils.
    • Mild.
    • Moderate - crypt abscesses.
    • Severe - crypt abscesses.
  • Ulceration per LPF (mean).
    • <25%.
    • 25-50%.
    • >50.

Sign out

Note:

  • Dr. Robert Riddell is of the opinion: "Do not call any pouch inflammation as consistent with Crohn's disease."
SMALL BOWEL POUCH, BIOPSY:
- SMALL BOWEL MUCOSA WITH CHRONIC ACTIVE INFLAMMATION WITH ULCERATION, EARLY
  CRYPT ABSCESS FORMATION, CRYPTITIS, AND LOSS OF THE VILLOUS ARCHITECTURE.
- NEGATIVE FOR GRANULOMAS AND NEGATIVE FOR PYLORIC GLAND METAPLASIA.
- NEGATIVE FOR DYSPLASIA.

COMMENT:
The findings are consistent with pouchitis.

Pyloric gland metaplasia present

SMALL BOWEL POUCH, BIOPSY:
- SMALL BOWEL MUCOSA WITH CHRONIC ACTIVE INFLAMMATION WITH ULCERATION, EARLY
  CRYPT ABSCESS FORMATION, CRYPTITIS, AND LOSS OF THE VILLOUS ARCHITECTURE.
- PYLORIC GLAND METAPLASIA, FOCAL, SEE COMMENT.
- NEGATIVE FOR GRANULOMAS.
- NEGATIVE FOR DYSPLASIA.

COMMENT:
The presence of pyloric gland metaplasia raises the possibility of Crohn's disease;
however, in the context of previous biopsies with inflammation, the concurrent
negative ileal biopsy and lack of granulomas, this individual is favoured to have 
pouchitis.

See also

References

  1. ↑ Schmidt C, Bielecki C, Felber J, Stallmach A (June 2010). "Surveillance strategies in inflammatory bowel disease". Minerva Gastroenterol Dietol 56 (2): 189–201. PMID 20485256.
  2. ↑ URL: http://www.gihealthfoundation.org/library/ppts/postcolectomypatient.pdf. 3 March 2011.
  3. ↑ 3.0 3.1 Claessen, MM.; Siersema, PD.; Vleggaar, FP. (Apr 2011). "IBD-related carcinoma.". Best Pract Res Clin Gastroenterol 25 Suppl 1: S27-38. doi:10.1016/S1521-6918(11)70007-5. PMID 21640928.
  4. ↑ Vos, AC.; Bakkal, N.; Minnee, RC.; Casparie, MK.; de Jong, DJ.; Dijkstra, G.; Stokkers, P.; van Bodegraven, AA. et al. (Sep 2011). "Risk of malignant lymphoma in patients with inflammatory bowel diseases: A Dutch nationwide study.". Inflamm Bowel Dis 17 (9): 1837-1845. doi:10.1002/ibd.21582. PMID 21830262.
  5. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 605956
  6. ↑ Alvarez-Lobos M, Arostegui JI, Sans M, et al. (November 2005). "Crohn's disease patients carrying Nod2/CARD15 gene variants have an increased and early need for first surgery due to stricturing disease and higher rate of surgical recurrence". Ann. Surg. 242 (5): 693–700. PMC 1409853. PMID 16244543. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1409853/.
  7. ↑ Panaccione, R. (Apr 2006). "The approach to dysplasia surveillance in inflammatory bowel disease.". Can J Gastroenterol 20 (4): 251-3. PMC 2659899. PMID 16609751. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659899/.
  8. ↑ 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.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 Kirsch, R. 13 December 2010.
  10. ↑ "Pathology of ulcerative colitis". http://www.histopathology-india.net/UlCol.htm. Retrieved 17 January 2011.
  11. ↑ URL: http://www.histopath.com.au/assets/documents/Inflammatory%20bowel%20disease.pdf. Accessed on: 25 October 2013.
  12. ↑ 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.
  13. ↑ Mills, Stacey E. (2006). Histology for Pathologists (3rd ed.). Lippincott Williams & Wilkins. pp. 631. ISBN 9780781762410.
  14. ↑ STC. 14 December 2009.
  15. ↑ 15.0 15.1 Gupta RB, Harpaz N, Itzkowitz S, et al. (October 2007). "Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study". Gastroenterology 133 (4): 1099–105; quiz 1340–1. doi:10.1053/j.gastro.2007.08.001. PMC 2175077. PMID 17919486. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2175077/.
  16. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 850. ISBN 0-7216-0187-1.
  17. ↑ Shepherd, NA. (Aug 2002). "Granulomas in the diagnosis of intestinal Crohn's disease: a myth exploded?". Histopathology 41 (2): 166-8. PMID 12147095.
  18. ↑ Mahadeva, U.; Martin, JP.; Patel, NK.; Price, AB. (Jul 2002). "Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis.". Histopathology 41 (1): 50-5. PMID 12121237.
  19. ↑ Lin J, McKenna BJ, Appelman HD (November 2010). "Morphologic findings in upper gastrointestinal biopsies of patients with ulcerative colitis: a controlled study". Am. J. Surg. Pathol. 34 (11): 1672–7. doi:10.1097/PAS.0b013e3181f3de93. PMID 20962621.
  20. ↑ 20.0 20.1 Sonnenberg, A.; Melton, SD.; Genta, RM. (Jan 2011). "Frequent occurrence of gastritis and duodenitis in patients with inflammatory bowel disease.". Inflamm Bowel Dis 17 (1): 39-44. doi:10.1002/ibd.21356. PMID 20848539.
  21. ↑ Geboes K, Colombel JF, Greenstein A, et al. (June 2008). "Indeterminate colitis: a review of the concept--what's in a name?". Inflamm. Bowel Dis. 14 (6): 850–7. doi:10.1002/ibd.20361. PMID 18213696.
  22. ↑ Riddell, RH.; Goldman, H.; Ransohoff, DF.; Appelman, HD.; Fenoglio, CM.; Haggitt, RC.; Ahren, C.; Correa, P. et al. (Nov 1983). "Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications.". Hum Pathol 14 (11): 931-68. PMID 6629368.
  23. ↑ 23.0 23.1 Eaden, J.; Abrams, K.; McKay, H.; Denley, H.; Mayberry, J. (Jun 2001). "Inter-observer variation between general and specialist gastrointestinal pathologists when grading dysplasia in ulcerative colitis.". J Pathol 194 (2): 152-7. doi:10.1002/path.876. PMID 11400142.
  24. ↑ Greenson, JK. (Feb 2002). "Dysplasia in inflammatory bowel disease.". Semin Diagn Pathol 19 (1): 31-7. PMID 11936264.
  25. ↑ URL: http://surgpathcriteria.stanford.edu/gi/ulcerative-colitis/printable.html. Accessed on: 12 March 2013.
  26. ↑ 26.0 26.1 Gionchetti, P.; Amadini, C.; Rizzello, F.; Venturi, A.; Poggioli, G.; Campieri, M. (Feb 2003). "Diagnosis and treatment of pouchitis.". Best Pract Res Clin Gastroenterol 17 (1): 75-87. PMID 12617884.
  27. ↑ Johnson, MW.; Maestranzi, S.; Duffy, AM.; Dewar, DH.; Forbes, A.; Bjarnason, I.; Sherwood, RA.; Ciclitira, P. et al. (Mar 2008). "Faecal calprotectin: a noninvasive diagnostic tool and marker of severity in pouchitis.". Eur J Gastroenterol Hepatol 20 (3): 174-9. doi:10.1097/MEG.0b013e3282f1c9a7. PMID 18301296.
  28. ↑ Royston, DJ.; Warren, BF. (Nov 2011). "Are we reporting ileal pouch biopsies correctly?". Colorectal Dis 13 (11): 1285-9. doi:10.1111/j.1463-1318.2010.02452.x. PMID 20958905.
  29. ↑ 29.0 29.1 Shen, B.; Achkar, JP.; Connor, JT.; Ormsby, AH.; Remzi, FH.; Bevins, CL.; Brzezinski, A.; Bambrick, ML. et al. (Jun 2003). "Modified pouchitis disease activity index: a simplified approach to the diagnosis of pouchitis.". Dis Colon Rectum 46 (6): 748-53. doi:10.1097/01.DCR.0000070528.00563.D9. PMID 12794576.
  30. ↑ 30.0 30.1 30.2 Arashiro, RT.; Teixeira, MG.; Rawet, V.; Quintanilha, AG.; Paula, HM.; Silva, AZ.; Nahas, SC.; Cecconello, I. (Jul 2012). "Histopathological evaluation and risk factors related to the development of pouchitis in patients with ileal pouches for ulcerative colitis.". Clinics (Sao Paulo) 67 (7): 705-10. PMC 3400158. PMID 22892912. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400158/.
  31. ↑ Fruin, AB.; El-Zammer, O.; Stucchi, AF.; O'Brien, M.; Becker, JM. (Feb 2003). "Colonic metaplasia in the ileal pouch is associated with inflammation and is not the result of long-term adaptation.". J Gastrointest Surg 7 (2): 246-53; discussion 253-4. PMID 12600449.
  32. ↑ Agarwal, S.; Stucchi, AF.; Dendrinos, K.; Cerda, S.; O'Brien, MJ.; Becker, JM.; Heeren, T.; Farraye, FA. (Oct 2013). "Is pyloric gland metaplasia in ileal pouch biopsies a marker for Crohn's disease?". Dig Dis Sci 58 (10): 2918-25. doi:10.1007/s10620-013-2655-4. PMID 23543088.
  33. ↑ Weber, CR.; Rubin, DT. (Oct 2013). "Chronic pouchitis versus recurrent Crohn's disease: a diagnostic challenge.". Dig Dis Sci 58 (10): 2748-50. doi:10.1007/s10620-013-2816-5. PMID 23925821.
  34. ↑ Beart, RW. (Jun 2004). "Is pouchitis a clinical, endoscopic, or histologic problem?". Dis Colon Rectum 47 (6): 949; author reply 949-50. doi:10.1007/s10350-004-0516-0. PMID 15073663.
  35. ↑ Shen, B.; Liu, W.; Remzi, FH.; Shao, Z.; Lu, H.; DeLaMotte, C.; Hammel, J.; Queener, E. et al. (Sep 2008). "Enterochromaffin cell hyperplasia in irritable pouch syndrome.". Am J Gastroenterol 103 (9): 2293-300. doi:10.1111/j.1572-0241.2008.01990.x. PMID 18702649.

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