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'''Celiac sprue''' is a common pathology that affects the [[duodenum]]. | {{ Infobox diagnosis | ||
| Name = {{PAGENAME}} | |||
| Image = Celiac disease - high mag.jpg | |||
| Width = | |||
| Caption = Celiac disease. [[H&E stain]]. | |||
| Synonyms = celiac disease | |||
| Micro = Intraepithelial lymphocytes +/- villous blunting | |||
| Subtypes = | |||
| LMDDx = [[Giardiasis]], [[Enteropathy-associated T-cell lymphoma]] ([[EATL]]), [[inflammatory bowel disease]], [[MALT lymphoma]], others | |||
| Stains = | |||
| IHC = | |||
| EM = | |||
| Molecular = | |||
| IF = | |||
| Gross = | |||
| Grossing = | |||
| Site = [[Duodenum]] | |||
| Assdx = [[dermatitis herpetiformis]], IgA deficiency, [[EATL]], [[duodenal adenocarcinoma]] | |||
| Syndromes = | |||
| Clinicalhx = improves with gluten free diet | |||
| Signs = diarrhea | |||
| Symptoms = | |||
| Prevalence = uncommon | |||
| Bloodwork = TTG elevated (>10 U/mL) | |||
| Rads = | |||
| Endoscopy = | |||
| Prognosis = | |||
| Other = | |||
| ClinDDx = [[normal duodenum]] | |||
| Tx = gluten free diet | |||
}} | |||
'''Celiac sprue''', also '''celiac disease''' (abbreviated '''CD'''), is a common pathology that affects the [[duodenum]]. | |||
It should not be confused with ''tropical sprue''. | |||
An introduction to gastrointestinal pathology is in the ''[[gastrointestinal pathology]]'' article. It covers basic gastrointestinal histology. | An introduction to gastrointestinal pathology is in the ''[[gastrointestinal pathology]]'' article. It covers basic gastrointestinal histology. | ||
== | ==General== | ||
* | *Considered an autoimmune disease. | ||
*The typical individual with celiac disease has a normal weight or is underweight. | |||
**[[Obese]] and overweight individuals can have celiac disease.<ref name=pmid26892766>{{Cite journal | last1 = Singh | first1 = I. | last2 = Agnihotri | first2 = A. | last3 = Sharma | first3 = A. | last4 = Verma | first4 = AK. | last5 = Das | first5 = P. | last6 = Thakur | first6 = B. | last7 = Sreenivas | first7 = V. | last8 = Gupta | first8 = SD. | last9 = Ahuja | first9 = V. | title = Patients with celiac disease may have normal weight or may even be overweight. | journal = Indian J Gastroenterol | volume = | issue = | pages = | month = Feb | year = 2016 | doi = 10.1007/s12664-016-0620-9 | PMID = 26892766 }}</ref> | |||
==Epidemiology== | ===Epidemiology=== | ||
Associated with: | |||
* | *[[Dermatitis herpetiformis]] - skin condition.<ref name=Ref_TN2007_D22>{{Ref TN2007| D22}}</ref> | ||
**Tx: dapsone. | |||
*IgA deficiency - 10-15X more common in celiac disease vs. healthy controls.<ref name=pmid12414763>{{Cite journal | last1 = Kumar | first1 = V. | last2 = Jarzabek-Chorzelska | first2 = M. | last3 = Sulej | first3 = J. | last4 = Karnewska | first4 = K. | last5 = Farrell | first5 = T. | last6 = Jablonska | first6 = S. | title = Celiac disease and immunoglobulin a deficiency: how effective are the serological methods of diagnosis? | journal = Clin Diagn Lab Immunol | volume = 9 | issue = 6 | pages = 1295-300 | month = Nov | year = 2002 | doi = | PMID = 12414763 }}</ref> | |||
*Risk factor for ''gastrointestinal T cell lymphoma'' - known as: ''[[enteropathy-associated T cell lymphoma]]'' (EATL). | |||
*[[IgA nephropathy]] is associated with an increased frequency of [[celiac disease]].<ref name=pmid19332868>{{Cite journal | last1 = Smerud | first1 = HK. | last2 = Fellström | first2 = B. | last3 = Hällgren | first3 = R. | last4 = Osagie | first4 = S. | last5 = Venge | first5 = P. | last6 = Kristjánsson | first6 = G. | title = Gluten sensitivity in patients with IgA nephropathy. | journal = Nephrol Dial Transplant | volume = 24 | issue = 8 | pages = 2476-81 | month = Aug | year = 2009 | doi = 10.1093/ndt/gfp133 | PMID = 19332868 }}</ref> | |||
*Esophageal [[squamous cell carcinoma]] - increased risk.<ref name=pmid11355914>{{Cite journal | last1 = Messmann | first1 = H. | title = Squamous cell cancer of the oesophagus. | journal = Best Pract Res Clin Gastroenterol | volume = 15 | issue = 2 | pages = 249-65 | month = Apr | year = 2001 | doi = 10.1053/bega.2000.0172 | PMID = 11355914 }}</ref> | |||
*Small bowel adenocarcinoma - increased risk.<ref name=pmid1060711>{{Cite journal | last1 = West | first1 = RA. | last2 = McNeill | first2 = RW. | title = Maxillary alveolar hyperplasia, diagnosis and treatment planning. | journal = J Maxillofac Surg | volume = 3 | issue = 4 | pages = 239-50 | month = Dec | year = 1975 | doi = | PMID = 1060711 }}</ref><ref name=pmid12940435>{{Cite journal | last1 = Rampertab | first1 = SD. | last2 = Fleischauer | first2 = A. | last3 = Neugut | first3 = AI. | last4 = Green | first4 = PH. | title = Risk of duodenal adenoma in celiac disease. | journal = Scand J Gastroenterol | volume = 38 | issue = 8 | pages = 831-3 | month = Aug | year = 2003 | doi = | PMID = 12940435 }}</ref> | |||
*Thought to be related to the very rare [[collagenous sprue]] - controversial.<ref name=pmid21631278>{{Cite journal | last1 = Zhao | first1 = X. | last2 = Johnson | first2 = RL. | title = Collagenous sprue: a rare, severe small-bowel malabsorptive disorder. | journal = Arch Pathol Lab Med | volume = 135 | issue = 6 | pages = 803-9 | month = Jun | year = 2011 | doi = 10.1043/2010-0028-RS.1 | PMID = 21631278 }}</ref><ref name=pmid23735026>{{Cite journal | last1 = Busto-Bea | first1 = V. | last2 = Crespo-Pérez | first2 = L. | last3 = García-Miralles | first3 = N. | last4 = Ruiz-Del-Árbol-Olmos | first4 = L. | last5 = Cano-Ruiz | first5 = A. | title = Collagenous sprue: Don´t forget connective tissue in chronic diarrhea evaluation. | journal = Rev Esp Enferm Dig | volume = 105 | issue = 3 | pages = 171-174 | month = May | year = 2013 | doi = | PMID = 23735026 }}</ref> | |||
*[[Lymphocytic gastritis]] - seen in ~10% of individuals with celiac disease.<ref name=pmid9659261>{{Cite journal | last1 = Feeley | first1 = KM. | last2 = Heneghan | first2 = MA. | last3 = Stevens | first3 = FM. | last4 = McCarthy | first4 = CF. | title = Lymphocytic gastritis and coeliac disease: evidence of a positive association. | journal = J Clin Pathol | volume = 51 | issue = 3 | pages = 207-10 | month = Mar | year = 1998 | doi = | PMID = 9659261 }}</ref> | |||
==Variants of celiac sprue== | ==Variants of celiac sprue== | ||
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#*NO villous arch. change. | #*NO villous arch. change. | ||
#Refractory celiac sprue. | #Refractory celiac sprue. | ||
#*Subclassified - see ''microscopic''. | |||
#Collagenous sprue. | #Collagenous sprue. | ||
#*Abundant mucosal collagen | #*Abundant mucosal collagen - see ''microscopic''. | ||
==Clinical== | ==Clinical== | ||
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===Serologic testing=== | ===Serologic testing=== | ||
*Anti-transglutaminase antibody. | *Anti-tissue transglutaminase (TTG) antibody -- >10 U/mL considered positive.<ref>URL: [http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/82587 http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/82587]. Accessed on: 13 August 2012.</ref> | ||
**Alternative test: anti-endomysial antibody. | **Alternative test: anti-endomysial antibody. | ||
* | *Anti-gliadin antibodies.<ref name=pmid19629760>{{Cite journal | last1 = Matthias | first1 = T. | last2 = Pfeiffer | first2 = S. | last3 = Selmi | first3 = C. | last4 = Eric Gershwin | first4 = M. | title = Diagnostic challenges in celiac disease and the role of the tissue transglutaminase-neo-epitope. | journal = Clin Rev Allergy Immunol | volume = 38 | issue = 2-3 | pages = 298-301 | month = Apr | year = 2010 | doi = 10.1007/s12016-009-8160-z | PMID = 19629760 }}</ref> | ||
*IgA deficiency - associated with celiac sprue. | |||
==Microscopic== | ==Microscopic== | ||
Features:<ref name=Ref_PBoD843>{{Ref PBoD|843}}</ref> | Features:<ref name=Ref_PBoD843>{{Ref PBoD|843}}</ref> | ||
*Intraepithelial lymphocytes - '''key feature'''. | *[[Intraepithelial lymphocytes]] (IELs) - '''key feature'''. | ||
**Should be more pronounced at tips of villi.<ref name=pmid15280404>{{cite journal |author=Biagi F, Luinetti O, Campanella J, ''et al.'' |title=Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease? |journal=J. Clin. Pathol. |volume=57 |issue=8 |pages=835–9 |year=2004 |month=August |pmid=15280404 |pmc=1770380 |doi=10.1136/jcp.2003.013607 |url=}}</ref> | **Should be more pronounced at tips of villi.<ref name=pmid15280404>{{cite journal |author=Biagi F, Luinetti O, Campanella J, ''et al.'' |title=Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease? |journal=J. Clin. Pathol. |volume=57 |issue=8 |pages=835–9 |year=2004 |month=August |pmid=15280404 |pmc=1770380 |doi=10.1136/jcp.2003.013607 |url=}}</ref> | ||
**Criteria for number varies: | |||
*** > 40 IELs / 100 enterocytes (epithelial cells).<ref name=pmid10524652>{{cite journal |author=Oberhuber G, Granditsch G, Vogelsang H |title=The histopathology of coeliac disease: time for a standardized report scheme for pathologists |journal=Eur J Gastroenterol Hepatol |volume=11 |issue=10 |pages=1185–94 |year=1999 |month=October |pmid=10524652 |doi= |url=}}</ref> | |||
*** > 25 IELs / 100 enterocytes (epithelial cells).<ref name=pmid17544877>{{cite journal |author=Corazza GR, Villanacci V, Zambelli C, ''et al.'' |title=Comparison of the interobserver reproducibility with different histologic criteria used in celiac disease |journal=Clin. Gastroenterol. Hepatol. |volume=5 |issue=7 |pages=838–43 |year=2007 |month=July |pmid=17544877 |doi=10.1016/j.cgh.2007.03.019 |url=}}</ref> | |||
*Loss of villi - '''important feature'''. | *Loss of villi - '''important feature'''. | ||
**Normal duodenal biopsy should have 3 good villi. | **Normal duodenal biopsy should have 3 good villi. | ||
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*Mitosis increased (in the crypts). | *Mitosis increased (in the crypts). | ||
*+/-Collagen band (pink material in mucosa) - "Collagenous sprue"; must encompass ~25% of mucosa. | *+/-Collagen band (pink material in mucosa) - "Collagenous sprue"; must encompass ~25% of mucosa. | ||
Notes: | Notes: | ||
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*Flat lesions without IELs are unlikely to be celiac sprue. | *Flat lesions without IELs are unlikely to be celiac sprue. | ||
*Mucosa erosions are rare in celiac sprue; should prompt consideration of an alternate diagnosis (infection, medications, Crohn's disease). | *Mucosa erosions are rare in celiac sprue; should prompt consideration of an alternate diagnosis (infection, medications, Crohn's disease). | ||
*Biagi ''et al.''<ref name=pmid15280404>{{cite journal |author=Biagi F, Luinetti O, Campanella J, ''et al.'' |title=Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease? |journal=J. Clin. Pathol. |volume=57 |issue=8 |pages=835–9 |year=2004 |month=August |pmid=15280404 |pmc=1770380 |doi=10.1136/jcp.2003.013607 |url=}}</ref> count twenty cells in five (villi) tips. | |||
===DDx=== | |||
*[[Giardiasis]]. | |||
**Have giardia organisms. | |||
**Always consider ''Giardiasis'' and especially on exams. | |||
*[[Crohn's disease]]. | |||
*[[Helicobacter gastritis]].<ref name=pmid16831028>{{Cite journal | last1 = Brown | first1 = I. | last2 = Mino-Kenudson | first2 = M. | last3 = Deshpande | first3 = V. | last4 = Lauwers | first4 = GY. | title = Intraepithelial lymphocytosis in architecturally preserved proximal small intestinal mucosa: an increasing diagnostic problem with a wide differential diagnosis. | journal = Arch Pathol Lab Med | volume = 130 | issue = 7 | pages = 1020-5 | month = Jul | year = 2006 | doi = 10.1043/1543-2165(2006)130[1020:ILIAPP]2.0.CO;2 | PMID = 16831028 }}</ref> | |||
*[[Cryptosporidiosis]].<ref name=pmid16831028/> | |||
*[[Whipple's disease]] (very rare). | |||
**Abundant macrophages should make one suspicious. | |||
*[[Autoimmune enteropathy]] - pediatric population. | |||
**Super duper rare. | |||
*Drugs - e.g. olmesartan.<ref name=pmid24852741>{{Cite journal | last1 = Fiorucci | first1 = G. | last2 = Puxeddu | first2 = E. | last3 = Colella | first3 = R. | last4 = Paolo Reboldi | first4 = G. | last5 = Villanacci | first5 = V. | last6 = Bassotti | first6 = G. | title = Severe spruelike enteropathy due to olmesartan. | journal = Rev Esp Enferm Dig | volume = 106 | issue = 2 | pages = 142-4 | month = Feb | year = 2014 | doi = | PMID = 24852741 }}</ref> | |||
*[[obesity|Morbid obesity]].<ref name=pmid17516730>{{Cite journal | last1 = Harpaz | first1 = N. | last2 = Levi | first2 = GS. | last3 = Yurovitsky | first3 = A. | last4 = Kini | first4 = S. | title = Intraepithelial lymphocytosis in architecturally normal small intestinal mucosa: association with morbid obesity. | journal = Arch Pathol Lab Med | volume = 131 | issue = 3 | pages = 344; author reply 344 | month = Mar | year = 2007 | doi = 10.1043/1543-2165(2007)131[344b:IR]2.0.CO;2 | PMID = 17516730 }}</ref> | |||
===Image=== | |||
<gallery> | |||
Image: Celiac disease - low mag.jpg | CD - low mag. (WC/Nephron) | |||
Image: Celiac disease - intermed mag.jpg | CD - intermed. mag. (WC/Nephron) | |||
Image: Celiac disease - high mag.jpg | CD - high mag. (WC/Nephron) | |||
Image: Celiac disease - very high mag.jpg | CD - very high mag. (WC/Nephron) | |||
Image:Coeliac_path.jpg | Celiac sprue. (WC) | |||
</gallery> | |||
===Refractory sprue=== | ===Refractory sprue=== | ||
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===Grading=== | ===Grading=== | ||
Many pathologists do not grade celiac sprue. | |||
The | ====Marsh==== | ||
The ''Marsh system'', also ''Marsh-Oberhuber'':<ref name=pmid10524652>{{cite journal |author=Oberhuber G, Granditsch G, Vogelsang H |title=The histopathology of coeliac disease: time for a standardized report scheme for pathologists |journal=Eur J Gastroenterol Hepatol |volume=11 |issue=10 |pages=1185–94 |year=1999 |month=October |pmid=10524652 |doi= |url=}}</ref> | |||
{| class="wikitable" | {| class="wikitable" | ||
| | | Marsh score | ||
| '''Marsh 1''' | | Descriptors | ||
| '''Marsh | | Villi | ||
| ''' | | Intraepithelial <Br>lymphocytes (IELs) | ||
| Crypts | |||
|- | |||
| Normal (Marsh 0) | |||
| normal | |||
| normal villi | |||
| '''< 40 / 100 epithelial cells''' | |||
| normal crypts | |||
|- | |||
| Marsh 1 | |||
| IELs increased | |||
| normal villi | |||
| '''> 40 / 100 epithelial cells''' | |||
| '''normal crypts''' | |||
|- | |||
| Marsh 2 | |||
| hypertrophic crypts, IELs | |||
| '''normal villi''' | |||
| > 40 / 100 epithelial cells | |||
| '''hypertrophic crypts''' | |||
|- | |- | ||
| Marsh 3a | |||
| partial villous atrophy / blunted villi (mild) | |||
| '''mild atrophy''' | |||
| > 40 / 100 epithelial cells | |||
| hypertrophic crypts | |||
|- | |||
| Marsh 3b | |||
| moderate-to-marked villous atrophy /<br> blunted villi (moderate-to-marked) | |||
| '''marked atrophy''' | |||
| > 40 / 100 epithelial cells | |||
| hypertrophic crypts | |||
|- | |||
| Marsh 3c | |||
| total villous atrophy, flattened mucosa | |||
| '''absent'''; flat as a pancake | |||
| > 40 / 100 epithelial cells | |||
| hypertrophic crypts | |||
|} | |||
====Simplified Marsh/Corazza==== | |||
A simplified Marsh system - based (only) on villous architecture:<ref name=pmid17544877>{{cite journal |author=Corazza GR, Villanacci V, Zambelli C, ''et al.'' |title=Comparison of the interobserver reproducibility with different histologic criteria used in celiac disease |journal=Clin. Gastroenterol. Hepatol. |volume=5 |issue=7 |pages=838–43 |year=2007 |month=July |pmid=17544877 |doi=10.1016/j.cgh.2007.03.019 |url=}}</ref> | |||
{| class="wikitable" | |||
| Grade | |||
| Similar Marsh grade | |||
| Descriptors | | Descriptors | ||
| | | Alternate descriptors | ||
| | |- | ||
| A | |||
| Marsh 1 | |||
| well-formed villi, IELs > 25/100 enterocytes | |||
| normal villous architecture | |||
|- | |- | ||
| | | B1 | ||
| | | Marsh 3a | ||
| | | partial villous atrophy; villous-crypt ratio < 3:1 | ||
| | | blunted villi | ||
|- | |||
| B2 | |||
| Marsh 3c | |||
| total villous atrophy | |||
| flattened mucosa | |||
|} | |} | ||
== | Notes: | ||
* | *Villous atrophy can be assessed endoscopically.<ref name=pmid20844959>{{cite journal |author=Ciaccio EJ, Bhagat G, Tennyson CA, Lewis SK, Hernandez L, Green PH |title=Quantitative Assessment of Endoscopic Images for Degree of Villous Atrophy in Celiac Disease |journal=Dig Dis Sci |volume= |issue= |pages= |year=2010 |month=September |pmid=20844959 |doi=10.1007/s10620-010-1371-6 |url=}}</ref> | ||
==IHC== | |||
*CD3 -- marks the IELs.<ref name=pmid15280404>{{cite journal |author=Biagi F, Luinetti O, Campanella J, ''et al.'' |title=Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease? |journal=J. Clin. Pathol. |volume=57 |issue=8 |pages=835–9 |year=2004 |month=August |pmid=15280404 |pmc=1770380 |doi=10.1136/jcp.2003.013607 |url=}}</ref> | |||
==Sign out== | |||
===TTG result not available=== | |||
<pre> | |||
Duodenum, Biopsy: | |||
- Small bowel mucosa with increased intraepithelial lymphocytes, villous | |||
architecture and crypt architecture within normal limits, see comment. | |||
- Brunner's glands present. | |||
- NEGATIVE for acute duodenitis. | |||
- NEGATIVE for dysplasia. | |||
Comment: | |||
Focally, there are approximately 50 lymphocytes/100 enterocytes. Increased intraepithelial | |||
lymphocytes is a nonspecific finding that may be seen in a number of conditions, including | |||
infections (e.g. Helicobacter gastritis), obesity, and autoimmune disorders (e.g. Crohn's | |||
disease). It is seen in celiac disease; correlation with serology is suggested, if not done. | |||
</pre> | |||
====Block letters==== | |||
<pre> | |||
SMALL BOWEL (DUODENUM), BIOPSY: | |||
- SMALL BOWEL MUCOSA WITH INCREASED INTRAEPITHELIAL LYMPHOCYTES, VILLOUS | |||
ARCHITECTURE AND CRYPT ARCHITECTURE WITHIN NORMAL LIMITS, SEE COMMENT. | |||
- NEGATIVE FOR ACUTE DUODENITIS. | |||
- NEGATIVE FOR DYSPLASIA. | |||
COMMENT: | |||
There are approximately 45 lymphocytes/100 enterocytes. Increased intraepithelial | |||
lymphocytes is a nonspecific finding. It is seen in celiac disease; correlation with TTG | |||
serology is suggested, if not done. | |||
</pre> | |||
=====Alternate===== | |||
<pre> | |||
DUODENUM, BIOPSY: | |||
- SMALL BOWEL MUCOSA WITH INCREASED INTRAEPITHELIAL LYMPHOCYTES, VILLOUS | |||
ARCHITECTURE AND CRYPT ARCHITECTURE WITHIN NORMAL LIMITS, SEE COMMENT. | |||
- BRUNNER'S GLANDS PRESENT. | |||
- NEGATIVE FOR ACUTE DUODENITIS. | |||
- NEGATIVE FOR DYSPLASIA. | |||
COMMENT: | |||
Focally, there are approximately 50 lymphocytes/100 enterocytes. Increased intraepithelial | |||
lymphocytes is a nonspecific finding that may be seen in a number of conditions, including | |||
infections (e.g. Helicobacter gastritis), and autoimmune disorders (e.g. Crohn's disease). | |||
It is seen in celiac disease; correlation with TTG serology is suggested, if not done. | |||
</pre> | |||
===Positive TTG=== | |||
<pre> | |||
DUODENUM, BIOPSY: | |||
- SMALL BOWEL MUCOSA WITH BRUNNER'S GLANDS AND AN INCREASE OF INTRAEPITHELIAL LYMPHOCYTES | |||
(>50 LYMPHOCYTES/100 ENTEROCYTES), A PRESERVATION OF VILLOUS ARCHITECTURE AND CRYPTS | |||
WITHIN NORMAL LIMITS, SEE COMMENT. | |||
COMMENT: | |||
The findings are consistent with celiac disease, Marsh classification 1. | |||
</pre> | |||
<pre> | |||
DUODENUM, BIOPSY: | |||
- SMALL BOWEL MUCOSA WITH BRUNNER'S GLANDS, AN INCREASE OF INTRAEPITHELIAL LYMPHOCYTES | |||
(>60 LYMPHOCYTES/100 ENTEROCYTES), AND A BLUNTED VILLOUS ARCHITECTURE, SEE COMMENT. | |||
COMMENT: | |||
The findings are consistent with celiac disease, Marsh classification 3a. | |||
</pre> | |||
====Micro==== | |||
The sections show small bowel mucosa with Brunner's glands. Increased numbers of | |||
intraepithelial lymphocytes are present ~ 50 lymphocytes/100 epithelial cells. | |||
The villous architecture is within normal limits (no apparent villous blunting). | |||
Neutrophils are present in the lamina propria; however, they are not found intraepithelial. | |||
The epithelium matures normally to the surface (no dysplasia). | |||
==See also== | ==See also== | ||
*[[Gastrointestinal pathology]]. | *[[Gastrointestinal pathology]]. | ||
*[[Duodenum]]. | *[[Duodenum]]. | ||
*[[Collagenous gastritis]]. | |||
==References== | ==References== | ||
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[[Category:Gastrointestinal pathology]] | [[Category:Gastrointestinal pathology]] | ||
[[Category:Diagnosis]] | |||
[[Category:Duodenum]] |
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