Difference between revisions of "Stomach"

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'''Stomach''' is an important organ for pathologists.  It is often inflamed and may be a site that cancer arises from.  Gastroenterologists often biopsy the organ.  Surgeon take-out the organ.  It connects the [[esophagus]] to the [[duodenum]].  An introduction to gastrointestinal pathology is in the ''[[gastrointestinal pathology]]'' article.
[[Image:Gray1051.png|thumb|300px|A drawing of the stomach.]]
'''Stomach''' is an important organ for pathologists.  It is often inflamed and may be a site that cancer arises from.  Gastroenterologists often biopsy the organ.  Surgeons take-out the organ.  It connects the [[esophagus]] to the [[duodenum]].  An introduction to gastrointestinal pathology is in the ''[[gastrointestinal pathology]]'' article.


=Normal=
=Normal stomach=
==Gross anatomy==
==Gross anatomy==
*Cardia - first part of the stomach; joins with [[esophagus]].
*Cardia - first part of the stomach; joins with [[esophagus]].
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**[[AKA]] antrum.  
**[[AKA]] antrum.  


Image: [http://en.wikipedia.org/wiki/File:Illu_stomach.jpg Stomach anatomy (WP)].
===Image===
<gallery>
Image:Illu_stomach.jpg | Stomach anatomy (WC)
</gallery>


==Microscopic==
==Microscopic==
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*Foveolar cells - eosinophilic contents.
*Foveolar cells - eosinophilic contents.


===Stomach vs. intestine<ref>ALS. 4 Feb 2009.</ref> <!-- I think this may be screwed-up -->===
===Stomach versus intestine===
{| class="wikitable"
A tabular comparison:<ref>ALS. 4 Feb 2009.</ref> <!-- I think this part may be screwed-up -->
|
{| class="wikitable sortable"
|'''Intestine'''
! Feature
|'''Stomach'''
! Intestine
! Stomach
|-
|-
|Spacing
|Spacing
Line 36: Line 41:
|PAS-D
|PAS-D
| -ve (???)
| -ve (???)
| +ve (???)
| +ve<ref>{{Cite journal  | last1 = Rubio | first1 = CA. | title = Gastric duodenal metaplasia in duodenal adenomas. | journal = J Clin Pathol | volume = 60 | issue = 6 | pages = 661-3 | month = Jun | year = 2007 | doi = 10.1136/jcp.2006.039388 | PMID = 16837629 | PMC = 1955048 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955048/ }}</ref>
|-
|-
|Villin stain<ref name=pmid2459839>{{cite journal |author=Osborn M, Mazzoleni G, Santini D, Marrano D, Martinelli G, Weber K |title=Villin, intestinal brush border hydrolases and keratin polypeptides in intestinal metaplasia and gastric cancer; an immunohistologic study emphasizing the different degrees of intestinal and gastric differentiation in signet ring cell carcinomas |journal=Virchows Arch A Pathol Anat Histopathol |volume=413 |issue=4 |pages=303–12 |year=1988 |pmid=2459839 |doi= |url=}}</ref>
|Villin stain<ref name=pmid2459839>{{cite journal |author=Osborn M, Mazzoleni G, Santini D, Marrano D, Martinelli G, Weber K |title=Villin, intestinal brush border hydrolases and keratin polypeptides in intestinal metaplasia and gastric cancer; an immunohistologic study emphasizing the different degrees of intestinal and gastric differentiation in signet ring cell carcinomas |journal=Virchows Arch A Pathol Anat Histopathol |volume=413 |issue=4 |pages=303–12 |year=1988 |pmid=2459839 |doi= |url=}}</ref><ref>{{Cite journal  | last1 = Braunstein | first1 = EM. | last2 = Qiao | first2 = XT. | last3 = Madison | first3 = B. | last4 = Pinson | first4 = K. | last5 = Dunbar | first5 = L. | last6 = Gumucio | first6 = DL. | title = Villin: A marker for development of the epithelial pyloric border. | journal = Dev Dyn | volume = 224 | issue = 1 | pages = 90-102 | month = May | year = 2002 | doi = 10.1002/dvdy.10091 | PMID = 11984877 }}</ref>
| +ve
| +ve
| -ve
| -ve
Line 44: Line 49:
|Images
|Images
|[http://commons.wikimedia.org/wiki/File:Tubular_adenoma_2_high_mag.jpg Tubular adenoma - goblet<br> cells on right of image (WC)]
|[http://commons.wikimedia.org/wiki/File:Tubular_adenoma_2_high_mag.jpg Tubular adenoma - goblet<br> cells on right of image (WC)]
|[http://www.microscopy-uk.org.uk/mag/imgaug01/Fig8.jpg Gastric biopsy (microscopy-uk.org.uk)]
|[http://www.microscopy-uk.org.uk/mag/imgaug01/Fig8.jpg Gastric biopsy (microscopy-uk.org.uk)], <br>[http://commons.wikimedia.org/wiki/File:Gastric_signet_ring_cell_carcinoma_histopatholgy_%282%29_PAS_stain.jpg Stomach with cancer - PAS (WC)], [http://commons.wikimedia.org/wiki/File:Normal_gastric_mucosa_intermed_mag.jpg Stomach (WC)]
|}
|}


Notes:
Notes:
*Intraepithelial lymphocytes in the gastric mucosa have a clear halo around 'em.<ref>Sternberg H4P 2nd Ed., P.484</ref>
*Intraepithelial lymphocytes in the gastric mucosa have a clear halo around 'em.<ref>Sternberg H4P 2nd Ed., P.484</ref>
*Memory device: '''F'''olveolar cells have '''f'''riends, i.e. they are close to other foveolar cells.
*Memory device: '''F'''oveolar cells have '''f'''riends, i.e. they are close to other foveolar cells.


Ref.
===Gastric antrum versus gastric body===
*PMID 11984877.
 
===Gastric antrum vs. gastric body===
{| class="wikitable sortable"
{| class="wikitable sortable"
! Cell
! Cell
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| few or none
| few or none
| parietal cells: intensely<br> eosinophilic cytoplasm
| parietal cells: intensely<br> eosinophilic cytoplasm
| [http://commons.wikimedia.org/wiki/File:Parietal_cells.jpg], [http://commons.wikimedia.org/wiki/File:Normal_gastric_mucosa_intermed_mag.jpg]
| [[Image:Normal_gastric_mucosa_intermed_mag.jpg|thumb|center|60px|Parietal cells. (WC)]]
|-
|-
| '''Chief cell'''
| '''Chief cell'''
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| absent
| absent
| chief cells: basophilic cytoplasm, <br>[[IHC]]: +ve for ''pepsinogen I''
| chief cells: basophilic cytoplasm, <br>[[IHC]]: +ve for ''pepsinogen I''
| [http://commons.wikimedia.org/wiki/File:Chief_cells.JPG]
| [[Image:Chief_cells.JPG|thumb|center|100px|Chief cells. (WC)]]
|-
|-
| '''G cell'''
| '''G cell'''
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| present
| present
| fried egg appearance (clear cytoplasm,<br> round nucleus); look at high power - <br>usu. middle 1/3 of gland,<ref>URL: [http://www.lab.anhb.uwa.edu.au/mb140/CorePages/GIT/git.htm http://www.lab.anhb.uwa.edu.au/mb140/CorePages/GIT/git.htm]. Accessed on: 3 December 2010.</ref><br> IHC: +ve for ''gastrin''.
| fried egg appearance (clear cytoplasm,<br> round nucleus); look at high power - <br>usu. middle 1/3 of gland,<ref>URL: [http://www.lab.anhb.uwa.edu.au/mb140/CorePages/GIT/git.htm http://www.lab.anhb.uwa.edu.au/mb140/CorePages/GIT/git.htm]. Accessed on: 3 December 2010.</ref><br> IHC: +ve for ''gastrin''.
| [http://commons.wikimedia.org/wiki/File:G_cell_hyperplasia_-_very_high_mag.jpg]
| [[Image:G_cell_hyperplasia_-_very_high_mag.jpg|thumb|center|60px|G cell hyperplasia. (WC)]]
|-
|-
| '''Surface'''
| '''Surface'''
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| blunted villi
| blunted villi
| antrum is somewhat <br>duodenum-like
| antrum is somewhat <br>duodenum-like
| [http://commons.wikimedia.org/wiki/File:Normal_gastric_mucosa_intermed_mag.jpg body - flat]
| [[Image:Normal_gastric_mucosa_intermed_mag.jpg |thumb|center|60px|Body - flat. (WC)]]
|-
|-
| '''Gastric glands <br>/ mucosa'''
| '''Gastric glands <br>/ mucosa'''
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===Sign out===
===Sign out===
====Short version====
====Short version====
<pre>
Stomach, Biopsy:
- Antral-type gastric mucosa within normal limits.
</pre>
<pre>
Stomach, Biopsy:
- Body and antral-type gastric mucosa within normal limits.
</pre>
<pre>
Stomach, Biopsy:
- Antral-type gastric mucosa within normal limits.
- NEGATIVE for Helicobacter-like organisms.
</pre>
=====Block letters=====
<pre>
STOMACH, BIOPSY:
- BODY AND ANTRAL-TYPE GASTRIC MUCOSA WITHIN NORMAL LIMITS.
</pre>
<pre>
<pre>
STOMACH, BIOPSY:
STOMACH, BIOPSY:
- BODY AND ANTRAL-TYPE GASTRIC MUCOSA WITHIN NORMAL LIMITS.
- BODY AND ANTRAL-TYPE GASTRIC MUCOSA WITHIN NORMAL LIMITS.
- NEGATIVE FOR HELICOBACTER-LIKE ORGANISMS.
</pre>
</pre>


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- INTESTINAL METAPLASIA: ABSENT.
- INTESTINAL METAPLASIA: ABSENT.
- HELICOBACTER-LIKE ORGANISMS: NOT IDENTIFIED WITH ROUTINE STAINS.
- HELICOBACTER-LIKE ORGANISMS: NOT IDENTIFIED WITH ROUTINE STAINS.
- NEGATIVE FOR DSYPLASIA AND NEGATIVE FOR MALIGNANCY.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
</pre>
</pre>


====Sleeve gastrectomy====
====Sleeve gastrectomy====
*Indication: morbid obesity.
{{Main|Sleeve gastrectomy}}
<pre>
STOMACH, GREATER CURVE, SLEEVE GASTRECTOMY:
- STOMACH WALL WITHIN NORMAL LIMITS.
</pre>


=Introduction=
=Introduction=
==Useful stains for stomach==
==Useful stains for stomach==
*Cresyl violet stain<ref>[http://www.histology-world.com/stains/stains.htm http://www.histology-world.com/stains/stains.htm]</ref> - used to find H. pylori.<ref name=pmid10210995>{{cite journal |author=Goggin N, Rowland M, Imrie C, Walsh D, Clyne M, Drumm B |title=Effect of Helicobacter pylori eradication on the natural history of duodenal ulcer disease |journal=Arch. Dis. Child. |volume=79 |issue=6 |pages=502-5 |year=1998 |month=December |pmid=10210995 |pmc=1717771 |doi= |url=http://adc.bmj.com/cgi/pmidlookup?view=long&pmid=10210995}}</ref>
*[[Cresyl violet stain]]<ref>[http://www.histology-world.com/stains/stains.htm http://www.histology-world.com/stains/stains.htm]</ref> - used to find H. pylori.<ref name=pmid10210995>{{cite journal |author=Goggin N, Rowland M, Imrie C, Walsh D, Clyne M, Drumm B |title=Effect of Helicobacter pylori eradication on the natural history of duodenal ulcer disease |journal=Arch. Dis. Child. |volume=79 |issue=6 |pages=502-5 |year=1998 |month=December |pmid=10210995 |pmc=1717771 |doi= |url=http://adc.bmj.com/cgi/pmidlookup?view=long&pmid=10210995}}</ref>
*Alcian blue - used to find mucin<ref>[http://www.histology-world.com/stains/stains.htm http://www.histology-world.com/stains/stains.htm]</ref> which is present in intestinal metaplasia
*[[Alcian blue stain]] - used to find mucin<ref>[http://www.histology-world.com/stains/stains.htm http://www.histology-world.com/stains/stains.htm]</ref> which is present in intestinal metaplasia
**Other mucins stains:<ref>[http://www.histology-world.com/stains/stains.htm http://www.histology-world.com/stains/stains.htm]</ref> mucicarmine, PAS, PASD (doesn't stain glycogen)
**Other mucins stains:<ref>[http://www.histology-world.com/stains/stains.htm http://www.histology-world.com/stains/stains.htm]</ref> mucicarmine, [[PAS]], [[PAS-D stain|PASD]] (doesn't stain glycogen)


==Things to look for...==
==Things to look for...==
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**Can be ''very'' easy to miss in some biopsies.
**Can be ''very'' easy to miss in some biopsies.
*Inflammation + small bacteria = suspect H. pylori gastritis.
*Inflammation + small bacteria = suspect H. pylori gastritis.
=Some patterns=
==Gastric atrophy==
===General===
*Has a wide differential diagnosis.
===Microscopic===
Can take three general forms:
#Intestinal metaplasia - see ''intestinal metaplasia'' section.
#Pseudopyloric metaplasia; gastric body looks like gastric antrum.
#*Characterized by ''foveolar hyperplasia''.
#Cell loss without replacement.
#*Clue is deep inflammation in the body.
==Plasma cells in the stomach==
DDx of plasmacytosis:
*[[Plasma cell neoplasm]].
*[[Syphilis]].
*Chronic [[gastritis]].
==Granulomatous gastritis==
*Usual DDx of granulomatous disease (see ''[[Basics]]'' article):
**DNF AAII:
***Drugs, Neoplasms, Foreign body, Autoimmune, Allergic, Infectious, Idiopathic.
Important ones:
*Autoimmune - [[Crohn's disease]].
*Infectious - [[Tuberculosis]].
*Idiopathic - [[Sarcoidosis]].


=Non-neoplastic disease=
=Non-neoplastic disease=
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Note:
Note:
*Heaped edges - suggestive of cancer.
*Heaped edges - suggestive of [[stomach cancer|cancer]].


Image:
====Endoscopic image====
*[http://commons.wikimedia.org/wiki/File:Deep_gastric_ulcer.png Gastric ulcer (WC)].
<gallery>
Image:Deep_gastric_ulcer.png | Gastric ulcer. (WC)
</gallery>


===Microscopic===
===Microscopic===
Line 175: Line 227:


==Gastritis==
==Gastritis==
===Etiology===
{{Main|Gastritis}}
A specific cause is uncommonly identified histologically.
{{Main|Chronic gastritis}}
 
{{Main|Acute gastritis}}
Gastritis causes:<ref name=Ref_PBoD812-3>{{Ref PBoD|812-3}}</ref>
*Infectious:
**H. pylori infection.
**[[Tuberculosis]].
**Salmonellosis.
**[[CMV]].
*Endocrine-related:
**[[Pernicious anemia]].
**[[Diabetes mellitus]] - gastric atony.
*Trauma, e.g. NG tube.
*Vascular, ischemia.
*Autoimmune:
**[[Crohn's disease]].
*Toxins:
**[[Alcohol]].
**Medications (NSAIDS).
**Medications.
**Uremia.
**[[Smoking]] (heavy).
*Radiation.
 
===Endoscopic appearance===
*Erythematous.
 
===Microscopic===
*Inflammatory cells - see below.
 
====Acute gastritis====
*[[AKA]] ''active gastritis''.
 
Features:
*Neutrophils - especially when intraepithelial.
 
=====Focal active gastritis=====
DDx:
#Drugs,<ref>{{Cite journal  | last1 = Parfitt | first1 = JR. | last2 = Driman | first2 = DK. | title = Pathological effects of drugs on the gastrointestinal tract: a review. | journal = Hum Pathol | volume = 38 | issue = 4 | pages = 527-36 | month = Apr | year = 2007 | doi = 10.1016/j.humpath.2007.01.014 | PMID = 17367604 }}
</ref> esp. NSAIDs.
#Infectious.
#Inflammatory bowel disease.
 
====Chronic gastritis====
Features:
*[[Plasma cells]] (in lamina propria).
**Various criteria:
**#Two plasma cells kissing, i.e. two plasma cells touching/overlapping.
**#Three is a crowd, i.e. three plasma cells in close proximity.
 
=====Lymphocytic gastritis=====
The DDx is limited:
#[[Helicobacter gastritis]].
#[[Celiac disease]].
#[[NSAID]]s.
#Idiopathic.
 
====Sydney criteria for gastritis====
A bunch of pathologists in Sydney came-up with criteria... and these were revised in Houston.<ref name=pmid8827022>{{cite journal |author=Dixon MF, Genta RM, Yardley JH, Correa P |title=Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994 |journal=Am. J. Surg. Pathol. |volume=20 |issue=10 |pages=1161-81 |year=1996 |month=October |pmid=8827022 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0147-5185&volume=20&issue=10&spage=1161}}</ref>
 
=====Classification=====
Updated Sydney classification:<ref name=pmid8827022/>
{| class="wikitable"
| || '''Non-atrophic Helicobacter''' || '''Atrophic Helicobacter''' || '''Autoimmune'''
|-
| Inflammation pattern || antral or diffuse || antrum & corpus, mild inflammation || corpus only
|-
| Atrophy & metaplasia || nil || atrophy present, metaplasia at incisura || corpus only
|-
|}
Notes:
*''Corpus'' = gastric body.
*''Incisura'' = angular incisure, incisura angularis (Latin) - notched transition point on lesser curvature of the stomach between pylorus and body.<ref>[http://en.wikipedia.org/wiki/Angular_incisure http://en.wikipedia.org/wiki/Angular_incisure]</ref>
 
=====Severity=====
The Sydney group suggests grading severity with the following language:<ref name=pmid8827022/>
*Mild.
*Moderate.
*Marked.
 
These terms are applied to the parameters described in a biopsy.  The Sydney criteria lists ''H. pylori'', ''neutrophils'', ''mononuclear cells'', ''antrum (atrophy)'', ''corpus (atrophy)'' and ''intestinal metaplasia''.  The paper that discusses this also give a visual analogue scale.
 
Parameters & Severity (adapted from Dixon et al.<ref name=pmid8827022/>):
{| class="wikitable sortable"
! Feature
! Mild
! Moderate
! Marked
|-
| H. pylori
| few touching
| many touching 
| piles
|-
| Neutrophils
| few
| bunches 
| crowded
|-
| Mononuclear cells
| not touching
| kissing 
| partying
|-
|}
 
===Sign out===
<pre>
STOMACH, BIOPSY:
- BODY AND ANTRAL-TYPE MUCOSA WITH MILD CHRONIC GASTRITIS.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR HELICOBACTOR-LIKE ORGANISMS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
</pre>
 
====Micro====
The sections show gastric body type mucosa with small clusters of plasma cells. There are no intraepithelial neutrophils. Goblet cells are not identified. The epithelium matures normally to the surface. No Helicobacter organisms are seen.


==Helicobacter gastritis==
==Helicobacter gastritis==
*Often abbreviated ''[[HP]]''.
{{Main|Helicobacter gastritis}}
===General===
*Several Helicobacter species can cause gastritis:
**''[[Helicobacter pylori]]'' - most common.
**''Helicobacter heilmannii''.
 
Epidemiologic associations - ''Helicobacter'' infections are associated with:<ref>{{Ref PBoD|814}}</ref>
*Gastritis.
*Peptic ulcers.
*Cancer.
**Carcinoma.
**[[MALT lymphoma]].
 
===Microscopic===
Features:
*Small - smaller than the nucleus of the gastric foveolar cell.
**On 400x they are still possible to miss.
*Look close to the opening of the gastric glands.
*Are often are found in groups.
*Location - can be antrum and/or body.<ref>{{cite journal |author=Maaroos HI, Kekki M, Villako K, Sipponen P, Tamm A, Sadeniemi L |title=The occurrence and extent of Helicobacter pylori colonization and antral and body gastritis profiles in an Estonian population sample |journal=Scand. J. Gastroenterol. |volume=25 |issue=10 |pages=1010-7 |year=1990 |month=October |pmid=2263873 |doi= |url=}}</ref>
*Helicobacter don't like the intestinal mucosa or mucosa that has undergone intestinal metaplasia -- you're unlikely to find 'em there.
*''Helicobacter pylori'':
**Typically have a "v" shape ''or'' a comma-like shape.
*''Helicobacter heilmannii'':
**Corkscrew appearance.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Immunohistochemical_detection_of_Helicobacter_%281%29_histopatholgy.jpg H. pylori - IHC (WC)].
*Helicobacter gastritis:
**[http://commons.wikimedia.org/wiki/File:Gastritis_helicobacter_-_high_mag.jpg Gastritis due to HP (WC)].
**[http://commons.wikimedia.org/wiki/File:Gastritis_helicobacter_-_very_high_mag_cropped.jpg HP visible (WC)].
*[http://commons.wikimedia.org/wiki/Category:Helicobacter_gastritis Set of images - HP gastritis (WC)].
*[http://gut.bmj.com/content/58/12/1669/F2.large.jpg Helicobacter heilmannii (bmj.com)].<ref>URL: [http://gut.bmj.com/content/58/12/1669.extract http://gut.bmj.com/content/58/12/1669.extract]. Accessed on: 2 March 2012.</ref>
 
===Stains===
*[[Cresyl violet stain]] - background and organisms blue.
*[[Warthin-Starry stain]] - background yellow, organisms black.
 
===IHC===
*Helicobacter pylori IHC stain +ve.
 
===Sign out===
<pre>
STOMACH, BIOPSY:
- BODY-TYPE MUCOSA WITH MODERATE CHRONIC ACTIVE GASTRITIS.
- ABUNDANT HELICOBACTER-LIKE ORGANISMS PRESENT.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
</pre>


==Intestinal metaplasia of the stomach==
==Intestinal metaplasia of the stomach==
*[[AKA]] ''gastric [[intestinal metaplasia]]''.
{{Main|Intestinal metaplasia of the stomach}}
*Abbreviated ''IM''.
===General===
*Often part of surgical pathology report, e.g. "negative for intestinal metaplasia" or "intestinal metaplasia present".
*May be associated with Helicobacter spp. infection -- though Helicobacter don't like intestinal type mucosa, i.e. H. pylori are not typically found in regions with intestinal metaplasia.
*May be reversible - some epidemiological evidence.<ref name=pmid12477745>{{Cite journal  | last1 = Walker | first1 = MM. | title = Is intestinal metaplasia of the stomach reversible? | journal = Gut | volume = 52 | issue = 1 | pages = 1-4 | month = Jan | year = 2003 | doi =  | PMID = 12477745 | PMC = 1773527
}}</ref>
 
Significance:
*Moderate risk increase for carcinoma; risk less than for Barrett's esophagus.<ref name=pmid20203636>{{cite journal |author=Correa P, Piazuelo MB, Wilson KT |title=Pathology of gastric intestinal metaplasia: clinical implications |journal=Am. J. Gastroenterol. |volume=105 |issue=3 |pages=493–8 |year=2010 |month=March |pmid=20203636 |pmc=2895407 |doi=10.1038/ajg.2009.728 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895407/?tool=pubmed}}</ref>
**Odds ratio for corpus (~5.8x) higher than antrum (2.3x) when compared to individuals without IM.<ref name=pmid21575058>{{Cite journal  | last1 = Sakitani | first1 = K. | last2 = Hirata | first2 = Y. | last3 = Watabe | first3 = H. | last4 = Yamada | first4 = A. | last5 = Sugimoto | first5 = T. | last6 = Yamaji | first6 = Y. | last7 = Yoshida | first7 = H. | last8 = Maeda | first8 = S. | last9 = Omata | first9 = M. | title = Gastric cancer risk according to the distribution of intestinal metaplasia and neutrophil infiltration. | journal = J Gastroenterol Hepatol | volume = 26 | issue = 10 | pages = 1570-5 | month = Oct | year = 2011 | doi = 10.1111/j.1440-1746.2011.06767.x | PMID = 21575058 }}</ref>
 
===Microscopic===
Features:
*Goblet cells are present in the stomach - '''key feature'''.<ref>URL: [http://esynopsis.uchc.edu/eAtlas/GI/1280.htm http://esynopsis.uchc.edu/eAtlas/GI/1280.htm]. Accessed on: 16 August 2010.</ref>
**In [[H&E stain|H&E]] the vacuole often stains light grey.
*Paneth cells are present - deep in the glands.<ref name=pmid19918317/>
**Very rarely present.
**Very uncommon in isolation.
 
Image:
*[http://en.wikipedia.org/wiki/File:Gastric_adenocarcinoma.jpg Intestinal metaplasia in the stomach - crappy quality (WC)].
 
===Stains===
*Alcian blue (pH 2.5)/PAS +ve.<ref name=pmid14736279>{{Cite journal  | last1 = Rivera-Hueto | first1 = F. | last2 = Lag-Asturiano | first2 = E. | last3 = Utrilla-Alcolea | first3 = JC. | last4 = Herrerías-Gutiérrez | first4 = JM. | title = Advanced gastric carcinoma with a complete intestinal metaplasia phenotype associated with early intestinal-type carcinoma. | journal = Arch Pathol Lab Med | volume = 128 | issue = 2 | pages = 218-21 | month = Feb | year = 2004 | doi = 10.1043/1543-2165(2004)128218:AGCWAC2.0.CO;2 | PMID = 14736279 }}</ref>
**May be used to divide into ''complete'' (type I) and ''incomplete'' (type II).<ref name=pmid7139576>{{Cite journal  | last1 = Iida | first1 = F. | last2 = Kusama | first2 = J. | title = Gastric carcinoma and intestinal metaplasia. Significance of types of intestinal metaplasia upon development of gastric carcinoma. | journal = Cancer | volume = 50 | issue = 12 | pages = 2854-8 | month = Dec | year = 1982 | doi =  | PMID = 7139576 }}</ref><ref>{{Ref Odze|276}}</ref>
*Alican blue stain +ve.{{fact}}
 
Image:
*[http://commons.wikimedia.org/wiki/File:Barrett%27s_mucosa,_Alcian_blue_stain.jpg  Barrett's mucosa - Alcian blue stain (WC)].
 
===IHC===
*CDX2 +ve (-ve in normal stomach).<ref name=pmid12477745>{{Cite journal  | last1 = Walker | first1 = MM. | title = Is intestinal metaplasia of the stomach reversible? | journal = Gut | volume = 52 | issue = 1 | pages = 1-4 | month = Jan | year = 2003 | doi =  | PMID = 12477745 | PMC = 1773527
}}</ref>
**Strong assoc. with ''[[Helicobacter gastritis]]'' as well as IM.<ref name=pmid12047325>{{Cite journal  | last1 = Satoh | first1 = K. | last2 = Mutoh | first2 = H. | last3 = Eda | first3 = A. | last4 = Yanaka | first4 = I. | last5 = Osawa | first5 = H. | last6 = Honda | first6 = S. | last7 = Kawata | first7 = H. | last8 = Kihira | first8 = K. | last9 = Sugano | first9 = K. | title = Aberrant expression of CDX2 in the gastric mucosa with and without intestinal metaplasia: effect of eradication of Helicobacter pylori. | journal = Helicobacter | volume = 7 | issue = 3 | pages = 192-8 | month = Jun | year = 2002 | doi =  | PMID = 12047325 }}</ref>
 
Others:
*Lysozyme +ve - marks paneth cells.<ref name=pmid19918317>{{Cite journal  | last1 = Rubio | first1 = CA. | last2 = Befrits | first2 = R. | title = Increased lysozyme expression in gastric biopsies with intestinal metaplasia and pseudopyloric metaplasia. | journal = Int J Clin Exp Med | volume = 2 | issue = 3 | pages = 248-53 | month =  | year = 2009 | doi =  | PMID = 19918317 }}</ref>
 
===Sign out===
<pre>
STOMACH, BIOPSY:
- BODY-TYPE MUCOSA WITH INTESTINAL METAPLASIA, FOCAL.
- MINIMAL CHRONIC GASTRITIS (BODY OF STOMACH).
- NEGATIVE FOR HELICOBACTER-LIKE ORGANISMS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
</pre>
 
<pre>
STOMACH, BIOPSY:
- ANTRAL-TYPE MUCOSA WITH INTESTINAL METAPLASIA, EXTENSIVE.
- MILD CHRONIC (ANTRAL) GASTRITIS.
- NEGATIVE FOR HELICOBACTER-LIKE ORGANISMS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
</pre>


==Inflammatory bowel disease & the stomach==
==Inflammatory bowel disease and the stomach==
:See ''[[inflammatory bowel disease]]''.
:See ''[[inflammatory bowel disease]]''.
*Histopathologic findings are usually non-specific.
*Histopathologic findings are usually non-specific.
*Conventional thinking ''was'' upper GI involvement = Crohn's disease; this is changing.<ref name=pmid20962621>{{cite journal |author=Lin J, McKenna BJ, Appelman HD |title=Morphologic findings in upper gastrointestinal biopsies of patients with ulcerative colitis: a controlled study |journal=Am. J. Surg. Pathol. |volume=34 |issue=11 |pages=1672–7 |year=2010 |month=November |pmid=20962621 |doi=10.1097/PAS.0b013e3181f3de93 |url=}}</ref>
*Conventional thinking ''was'' upper GI involvement = [[Crohn's disease]]; this is changing.<ref name=pmid20962621>{{cite journal |author=Lin J, McKenna BJ, Appelman HD |title=Morphologic findings in upper gastrointestinal biopsies of patients with ulcerative colitis: a controlled study |journal=Am. J. Surg. Pathol. |volume=34 |issue=11 |pages=1672–7 |year=2010 |month=November |pmid=20962621 |doi=10.1097/PAS.0b013e3181f3de93 |url=}}</ref>
 
===Endoscopic/gross===
Features - Crohn's:<ref name=Ref_GLP80>{{Ref GLP|80}}</ref>
*+/-Linear fissures, erosions, ulcers, cobblestoning.
*May mimic ''[[linitis plastica]]''.


===Microscopic===
===Microscopic===
Features:<ref>RK. 13 December 2010.</ref>
Features:<ref>Kirsch R. 13 December 2010.</ref>
*Focal inflammation.
*Focal inflammation.
**Common finding - non-specific.
**Common finding - non-specific.
*+/-[[Granulomas]].
*+/-[[Granulomas]].
Note:
*Granulomas in Crohn's gastritis present 7-34% of the time.<ref name=Ref_GLP80>{{Ref GLP|80}}</ref>
====Images====
<gallery>
Image: Crohn's gastritis -- low mag.jpg | CG - low mag. (WC)
Image: Crohn's gastritis -- intermed mag.jpg | CG - intermed. mag. (WC)
Image: Crohn's gastritis -- high mag.jpg | CG - high mag. (WC)
Image: Crohn's gastritis -- very high mag.jpg | CG - very high mag. (WC)
</gallery>


=Miscellaneous=
=Miscellaneous=
This is a grab bag of stuff seen in the stomach.  Some of it is quite rare.
This is a grab bag of stuff seen in the stomach.  Some of it is quite rare.
==Gastric antral vascular ectasia==
==Gastric antral vascular ectasia==
*Abbreviated ''GAVE''.
{{Main|Gastric antral vascular ectasia}}
*[[AKA]] ''watermelon stomach'' - due to characteristic endoscopic appearance.<ref name=pmid18625989>{{cite journal |author=Chatterjee S |title=Watermelon stomach |journal=CMAJ |volume=179 |issue=2 |pages=162 |year=2008 |month=July |pmid=18625989 |pmc=2443230 |doi=10.1503/cmaj.080461 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18625989}}</ref>
===General===
*Lesion of the antrum - due to dilated capillaries.
 
===Gross/endoscopic appearance===
* Linear red streaks in antrum - oriented toward the pyloric valve... vaguely resembles a watermelon.
 
Endoscopic images:
*[http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2443230&rendertype=figure&id=f1-19 Watermelon stomach (pubmedcentral.nih.gov)].
*[http://en.wikipedia.org/wiki/File:Gave.png GAVE (WP)].
 
===Microscopic===
Features:<ref name=Ref_GLP118>{{Ref GLP|118}}</ref>
*Fibrin thrombi - '''characteristic feature'''.
*Dilated capillaries in lamina propria.
*+/-Foveollar hyperplasia.<ref name=Ref_GLP119>{{Ref GLP|119}}</ref>
 
DDx:
*[[Portal hypertensive gastropathy]] - predominantly in the gastric body, usu. associated with [[cirrhosis]], do not have fibrin thrombi.<ref name=Ref_GLP120-1>{{Ref GLP|120-1}}</ref>
 
Images:
*[http://commons.wikimedia.org/wiki/File:Gastric_antral_vascular_ectasia_-_2_-_intermed_mag.jpg GAVE - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Gastric_antral_vascular_ectasia_-_2_-_very_high_mag.jpg GAVE - very high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Gastric_antral_vascular_ectasia_-_very_high_mag.jpg GAVE - two thrombi - very high mag. (WC)].
 
===Sign out===
<pre>
STOMACH, BIOPSY:
- GASTRIC ANTRAL VASCULAR ECTASIA WITH FOVEOLAR HYPERPLASIA.
- MILD CHRONIC ACTIVE ANTRAL GASTRITIS.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA.
- NEGATIVE FOR HELICOBACTER ORGANISMS.
</pre>
 
====Micro====
The sections show antral-type gastric mucosa with dilated lamina propria blood vessels and intravascular fibrin thrombi. There is mild foveolar hyperplasia. Numerous neutrophils are present between the foveollar cells and within the lamina propria.  Several large clusters of plasma cells are present in the lamina propria.


==Reactive gastropathy==
==Reactive gastropathy==
*[[AKA]] ''chemical gastropathy'',<ref name=pmid16939055>{{Cite journal  | last1 = Genta | first1 = RM. | title = Differential diagnosis of reactive gastropathy. | journal = Semin Diagn Pathol | volume = 22 | issue = 4 | pages = 273-83 | month = Nov | year = 2005 | doi =  | PMID = 16939055 }}</ref> incorrectly referred to as ''chemical gastritis'' (see below).
{{Main|Reactive gastropathy}}
===General===
*May be seen in the context of a previous resection/surgical reconstruction, e.g. Billroth II.
 
====Epidemiology====
General assocations:
*Increases with age.<ref name=pmid22928604>{{Cite journal  | last1 = Maguilnik | first1 = I. | last2 = Neumann | first2 = WL. | last3 = Sonnenberg | first3 = A. | last4 = Genta | first4 = RM. | title = Reactive gastropathy is associated with inflammatory conditions throughout the gastrointestinal tract. | journal = Aliment Pharmacol Ther | volume =  | issue =  | pages =  | month = Aug | year = 2012 | doi = 10.1111/apt.12031 | PMID = 22928604 }}</ref>
 
Etologic factors - associated with:<ref>ALS. 5 February 2009.</ref>
*Excess acid.
*EtOH.
*Bile.
*H. pylori.
*Drugs:<ref name=pmid16939055>{{Cite journal  | last1 = Genta | first1 = RM. | title = Differential diagnosis of reactive gastropathy. | journal = Semin Diagn Pathol | volume = 22 | issue = 4 | pages = 273-83 | month = Nov | year = 2005 | doi =  | PMID = 16939055 }}</ref>
**Iron (brown pigment on histology).
**NSAIDs - synergistic effect with corticosteroids.
 
Drugs that cause erosions and/or ulcers -- adapted from ''Genta'':<ref name=pmid16939055>{{Cite journal  | last1 = Genta | first1 = RM. | title = Differential diagnosis of reactive gastropathy. | journal = Semin Diagn Pathol | volume = 22 | issue = 4 | pages = 273-83 | month = Nov | year = 2005 | doi =  | PMID = 16939055 }}</ref>
 
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Drug
! Comment
! Indication for Rx
|-
| NSAIDs
| common cause
| pain, reduce cardiovascular risk
|-
| Corticosteroids
| synergistic effect with NSAIDs
| rheumatologic diseases + others
|-
| Potassium (KCl)
| common cause
| renal failure
|-
| Bisphophonates
| uncommon cause
| [[osteoporosis]]
|-
| Ferrous sulfate
| very common if symptomatic
| iron deficiency anemia
|-
| Chloroquine
| uncommon
| only in the context of [[malaria]]
|-
| Sodium polystyrene sulfonate (Kayexalate)
| rare
| renal failure patients
|}
 
====Relation to gastritis====
*May mimic a (true) gastritis symptomatically and visually in an endoscopic examination.
*"Chemical gastritis" is misnomer. Etymologically, the ''-itis'' in ''gastritis'', implies an inflammatory process.  Chemical gastropathy is not (predominantly) an inflammatory process.
**This type of confusion is not uncommon. [[Steatohepatitis]] is another example of this; it is not a process with significant inflammation yet, confusingly, carries the ''-itis'' ending.
 
===Gross/endoscopic===
Features:<ref>{{Ref GLP|69}}</ref>
*Antral erythema +/- erosions.
*+/-Bile.
 
===Microscopic===
Features - triad:<ref>El-Zimaity. 18 October 2010.</ref><ref name=pmid16939055/>
#Foveolar hyperplasia.
#*Tortuosity of glands in the "neck" region of the gastric glands.
#*Associated with "mucin depletion" - cytoplasm not clear -- as is usual.
#Smooth muscle fibre hyperplasia.
#*Abundant eosinophilic lamina propria.
#Scant acute & chronic inflammatory cells.
Additional features.
*+/-Edema.
*+/-Erosions.
 
Notes:
*Triad rarely present; mild inflammation common.
 
DDx:
*[[Amyloidosis]].
*[[Collagenous gastritis]].
*[[Hyperplastic polyp of the stomach]].<ref name=Ref_GLP69>{{Ref GLP|69}}</ref>
 
Images:
*[http://commons.wikimedia.org/wiki/File:Reactive_gastropathy_-_low_mag.jpg RG - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Reactive_gastropathy_-_high_mag.jpg RG - high mag. (WC)].
 
===Sign out===
<pre>
STOMACH, BIOPSY:
- ANTRAL-TYPE GASTRIC MUCOSA WITH REACTIVE GASTROPATHY, SEE COMMENT.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR HELICOBACTER ORGANISMS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
 
COMMENT:
This nonspecific finding may be due to a number of causes, including medications (especially NSAIDs), alcohol and bile reflux.
</pre>
 
====Not well-developed====
<pre>
STOMACH, BIOPSY:
- BODY-TYPE GASTRIC MUCOSA WITHIN NORMAL LIMITS.
- ANTRAL-TYPE GASTRIC MUCOSA WITH SMOOTH MUSCLE HYPERPLASIA AND FOCAL GASTRIC GLAND TORTUOSITY, SEE COMMENT.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR HELICOBACTER ORGANISMS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
 
COMMENT:
These findings are suggestive of a reactive gastropathy; however, gland corkscrewing is not evident.
</pre>
 
<pre>
STOMACH, BIOPSY:
- ANTRAL-TYPE GASTRIC MUCOSA WITH PROMINENT SMOOTH MUSCLE, OTHERWISE WITHIN NORMAL
LIMITS.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR HELICOBACTER ORGANISMS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
</pre>
 
==Gastric atrophy==
===General===
*Has a wide differential diagnosis.
 
===Microscopic===
Can take three general forms:
#Intestinal metaplasia - see ''intestinal metaplasia'' section.
#Pseudopyloric metaplasia; gastric body looks like gastric antrum.
#*Characterized by ''foveolar hyperplasia''.
#Cell loss without replacement.
#*Clue is deep inflammation in the body.
 
==Lymphocytic gastritis==
===General===
DDx:
*Celiac disease.
**Check [[duodenum]].
*H. pylori.
*HIV/AIDS.
 
===Microscopic===
Features:<ref>El-Zimaity. 18 October 2010.</ref>
*25 lymphocytes / 100 epithelial cells.
 
==Pernicious anemia==
===General===
*Pathology: loss of parietal cells, gastric atrophy, [[macrocytic anemia]].
*Etiology: autoimmune.
 
Diagnosis based on serology for antibodies to:<ref name=pmid12643357>{{Cite journal  | last1 = Oh | first1 = R. | last2 = Brown | first2 = DL. | title = Vitamin B12 deficiency. | journal = Am Fam Physician | volume = 67 | issue = 5 | pages = 979-86 | month = Mar | year = 2003 | doi =  | PMID = 12643357 }}</ref>
*Parietal cells.
*Intrinsic factor.
 
Others:
*Gastrin level (increased).<ref name=pmid21947876>{{Cite journal  | last1 = Annibale | first1 = B. | last2 = Lahner | first2 = E. | last3 = Fave | first3 = GD. | title = Diagnosis and management of pernicious anemia. | journal = Curr Gastroenterol Rep | volume = 13 | issue = 6 | pages = 518-24 | month = Dec | year = 2011 | doi = 10.1007/s11894-011-0225-5 | PMID = 21947876 }}</ref>
**Normal < 100 pg/mL.<ref>URL: [http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8512 http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8512]. Accessed on: 14 August 2012.</ref>
 
Note:
*Parietal cells produce ''intrinsic factor'' (important for vitamin B12 absorption) and ''hydrogen chloride'', i.e. stomach acid.
 
===Microscopic===
Features:
*Corpus predominant inflammation - usu. moderate or severe - '''key feature'''
*Loss of parietal cells.
*Increased G cells in the antrum.
**Produce gastrin to stimulate the (missing) parietal cells.
 
DDx:
*[[Gastric neuroendocrine tumour]].


Notes:
==Autoimmune metaplastic atrophic gastritis==
*Compare with other types of ''[[gastric atrophy]]''.
*[[AKA]] ''autoimmune gastritis''.
 
{{Main|Autoimmune metaplastic atrophic gastritis}}
===IHC===
Features:<ref name=pmid20975338>{{Cite journal  | last1 = Park | first1 = JY. | last2 = Cornish | first2 = TC. | last3 = Lam-Himlin | first3 = D. | last4 = Shi | first4 = C. | last5 = Montgomery | first5 = E. | title = Gastric lesions in patients with autoimmune metaplastic atrophic gastritis (AMAG) in a tertiary care setting. | journal = Am J Surg Pathol | volume = 34 | issue = 11 | pages = 1591-8 | month = Nov | year = 2010 | doi = 10.1097/PAS.0b013e3181f623af | PMID = 20975338 }}</ref>
*Chromogranin A +ve (demonstrates ''nodular enterochromaffin-like cell hyperplasia'').
*Gastrin -ve (body of stomach).


==Collagenous gastritis==
==Collagenous gastritis==
===General===
{{Main|Collagenous gastritis}}
*Very rare.
*Associated with ''[[collagenous colitis]]''.
 
===Microscopic===
Features:
*Eosinophilic material (collagen) expands lamina propria.
**Band of collagen must be ~thick as RBC diameter.
***Proven by [[trichrome stain]] that highlights collagen.
 
==Granulomatous gastritis==
*Usual DDx of granulomatous disease (see ''[[Basics]]'' article):
**DNF AAII:
***Drugs, Neoplasms, Foreign body, Autoimmune, Allergic, Infectious, Idiopathic.
 
Important ones:
*Autoimmune - [[Crohn's disease]].
*Infectious - Tuberculosis.
*Idiopathic - Sarcoidosis.
 
==Plasma cells in the stomach==
DDx of plasmacytosis:
*[[Plasma cell neoplasm]].
*[[Syphilis]].
*Chronic [[gastritis]].


==Gastritis cystitis profunda==
==Gastritis cystitis profunda==
Line 673: Line 291:


==Ménétrier's disease==
==Ménétrier's disease==
*[[AKA]] ''diffuse foveolar cell hyperplasia''.<ref name=Ref_PCPBoD8_410>{{Ref PCPBoD8|410}}</ref>
{{Main|Ménétrier's disease}}
===General===
*Super rare.
*Increased risk of gastric adenocarcinoma.<ref name=Ref_PCPBoD8_410>{{Ref PCPBoD8|410}}</ref>
 
Clinical:<ref>{{Cite journal  | last1 = Rich | first1 = A. | last2 = Toro | first2 = TZ. | last3 = Tanksley | first3 = J. | last4 = Fiske | first4 = WH. | last5 = Lind | first5 = CD. | last6 = Ayers | first6 = GD. | last7 = Piessevaux | first7 = H. | last8 = Washington | first8 = MK. | last9 = Coffey | first9 = RJ. | title = Distinguishing Ménétrier's disease from its mimics. | journal = Gut | volume = 59 | issue = 12 | pages = 1617-24 | month = Dec | year = 2010 | doi = 10.1136/gut.2010.220061 | PMID = 20926644 }}</ref>
*Classic: nausea, emesis, abdominal pain and peripheral edema.
 
Other:
*Gastric mass (may mimic cancer).
*Hypochlorhydria.
*Protein loss - leads to peripheral edema.
 
===Microscopic===
Features:<ref name=Ref_PCPBoD8_410>{{Ref PCPBoD8|410}}</ref>
*Foveolar cell hyperplasia - '''key feature'''.
 
DDx:
*[[Cronkhite-Canada syndrome]].<ref name="pmid11428328">{{cite journal |author=Junnarkar SP, Sloan JM, Johnston BT, Laird JD, Irwin ST |title=Cronkhite-Canada syndrome |journal=The Ulster medical journal |volume=70 |issue=1 |pages=56–8 |year=2001 |month=May |pmid=11428328 |pmc=2449205 |doi= |url=}}</ref>
*[[Hyperplastic polyp of the stomach]].
 
Images:
*[http://path.upmc.edu/cases/case36.html Ménétrier's disease - crappy images (upmc.edu)].


==Gastric xanthoma==
==Gastric xanthoma==
Line 701: Line 297:
*[[AKA]] ''xanthelasma''.
*[[AKA]] ''xanthelasma''.
*[[AKA]] ''stomach lipidosis''.
*[[AKA]] ''stomach lipidosis''.
===General===
{{Main|Gastric xanthoma}}
*Uncommon.
*Benign.
 
===Gross/endoscopic===
*Yellowish nodule or plaque.<ref name=Ref_GLP111>{{Ref GLP|111}}</ref>
**Classically lesser curvature and antrum.<ref name=pmid6284833/>
 
===Microscopic===
Features:<ref name=Ref_GLP111>{{Ref GLP|111}}</ref>
*Collections of gastric lamina propria with lipid-laden macrophages.
 
DDx:
*[[Signet ring cell carcinoma]].<ref name=pmid6284833>{{Cite journal  | last1 = Drude | first1 = RB. | last2 = Balart | first2 = LA. | last3 = Herrington | first3 = JP. | last4 = Beckman | first4 = EN. | last5 = Burns | first5 = TW. | title = Gastric xanthoma: histologic similarity to signet ring cell carcinoma. | journal = J Clin Gastroenterol | volume = 4 | issue = 3 | pages = 217-21 | month = Jun | year = 1982 | doi =  | PMID = 6284833 }}</ref>
*[[Whipple disease]].
*MAC infection.
 
Images:
*[http://www.flickr.com/photos/hemeguy/2911032670/in/photostream/ GX - low mag. (flickr.com)].
*[http://www.flickr.com/photos/hemeguy/2911031464/in/photostream GX - high mag. (flickr.com)].
 
===IHC===
*CD68 +ve.
*Panker (AE1/AE3) -ve.


==Gastric ischemia==
==Gastric ischemia==
Line 742: Line 315:
*[https://www.thieme-connect.com/media/endoscopy/2011S02/097cl2.jpg Gastric necrosis (thieme-connect.com)].<ref name=pmid22020717>{{Cite journal  | last1 = Papanikolaou | first1 = IS. | last2 = Foukas | first2 = PG. | last3 = Sioulas | first3 = A. | last4 = Beintaris | first4 = I. | last5 = Panagopoulos | first5 = P. | last6 = Karamanolis | first6 = G. | last7 = Panayiotides | first7 = IG. | last8 = Dimitriadis | first8 = G. | last9 = Triantafyllou | first9 = K. | title = A case of gastric ischemic necrosis. | journal = Endoscopy | volume = 43 Suppl 2 UCTN | issue =  | pages = E342 | month =  | year = 2011 | doi = 10.1055/s-0030-1256795 | PMID = 22020717 }}</ref>
*[https://www.thieme-connect.com/media/endoscopy/2011S02/097cl2.jpg Gastric necrosis (thieme-connect.com)].<ref name=pmid22020717>{{Cite journal  | last1 = Papanikolaou | first1 = IS. | last2 = Foukas | first2 = PG. | last3 = Sioulas | first3 = A. | last4 = Beintaris | first4 = I. | last5 = Panagopoulos | first5 = P. | last6 = Karamanolis | first6 = G. | last7 = Panayiotides | first7 = IG. | last8 = Dimitriadis | first8 = G. | last9 = Triantafyllou | first9 = K. | title = A case of gastric ischemic necrosis. | journal = Endoscopy | volume = 43 Suppl 2 UCTN | issue =  | pages = E342 | month =  | year = 2011 | doi = 10.1055/s-0030-1256795 | PMID = 22020717 }}</ref>


=Gastric polyps=
==Portal hypertensive gastropathy==
Similar to colonic polyps - see [[intestinal polyps]].
*Abbreviated ''PHG''.
{{Main|Portal hypertensive gastropathy}}


DDx polyp (similar to colon & rectum):
==Amyloidosis of the stomach==
*Hyperplastic - most common, characterised by abundant elongated foveola + glands.
*[[AKA]] ''gastric amyloidosis''.
*[[Hamartomatous polyps|Hamartomatous]] - weriod stuff.
{{Main|Amyloidosis}}
*[[Inflammatory fibroid polyp]] - inflammation, [[myxoid stroma]].
*[[Fundic gland polyp]] - cystic dilation, flat epithelium.
*Adenomatous polyp.
 
==Inflammatory fibroid polyp==
===General===
===General===
*Benign.
*Very rare.
*Through-out GI tract.
*Etiologies: various - see [[amyloidosis]].
*Can be thought of as granulation tissue-like.<ref name=Ref_DCHH138/>
===Microscopic===
Features:<ref name=pmid20393746>{{Cite journal  | last1 = Daum | first1 = O. | last2 = Hatlova | first2 = J. | last3 = Mandys | first3 = V. | last4 = Grossmann | first4 = P. | last5 = Mukensnabl | first5 = P. | last6 = Benes | first6 = Z. | last7 = Michal | first7 = M. | title = Comparison of morphological, immunohistochemical, and molecular genetic features of inflammatory fibroid polyps (Vanek's tumors). | journal = Virchows Arch | volume = 456 | issue = 5 | pages = 491-7 | month = May | year = 2010 | doi = 10.1007/s00428-010-0914-8 | PMID = 20393746 }}</ref>
*Proliferating spindle cells (fibroid) - '''key feature'''.
**Loosely arranged, concentrically, around blood vessels.<ref name=Ref_GLP115>{{Ref GLP|115}}</ref>
**Perivascular hypocellular zones.<ref name=Ref_DCHH138>{{Ref DCHH|138}}</ref>
*Inflammation:
**Eosinophils - often prominent.
*+/-Leiomyoma/schwannoma-like areas - with nuclear palisading.<ref name=Ref_DCHH138>{{Ref DCHH|138}}</ref>
*+/-Vascular for fibrous tissue.
*Poorly circumscribed/infiltrates into the lamina propria.
 
DDx:
*[[Inflammatory myofibroblastic tumour]].
*[[GIST]] - usually sharply demarcated border.
 
Notes:
*Concentric = share the same centre.<ref>URL: [http://dictionary.reference.com/browse/concentric http://dictionary.reference.com/browse/concentric]. Accessed on: 29 November 2011.</ref>
 
Images:
*[http://commons.wikimedia.org/wiki/File:Inflammatory_fibroid_polyp_-_low_mag.jpg IFP - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Inflammatory_fibroid_polyp_-_high_mag.jpg IFP - high mag. (WC)].
 
===IHC===
Features:<ref name=pmid20393746/>
*CD34 +ve.
**There is a CD34 -ve variant.
*Vimentin +ve -- diffuse.<ref>{{Cite journal  | last1 = Kolodziejczyk | first1 = P. | last2 = Yao | first2 = T. | last3 = Tsuneyoshi | first3 = M. | title = Inflammatory fibroid polyp of the stomach. A special reference to an immunohistochemical profile of 42 cases. | journal = Am J Surg Pathol | volume = 17 | issue = 11 | pages = 1159-68 | month = Nov | year = 1993 | doi =  | PMID = 8214261 }}</ref>
 
Others:
*CD117 -ve.<ref name=pmid15163021>{{Cite journal  | last1 = Ozolek | first1 = JA. | last2 = Sasatomi | first2 = E. | last3 = Swalsky | first3 = PA. | last4 = Rao | first4 = U. | last5 = Krasinskas | first5 = A. | last6 = Finkelstein | first6 = SD. | title = Inflammatory fibroid polyps of the gastrointestinal tract: clinical, pathologic, and molecular characteristics. | journal = Appl Immunohistochem Mol Morphol | volume = 12 | issue = 1 | pages = 59-66 | month = Mar | year = 2004 | doi =  | PMID = 15163021 }}
</ref>
*S100 -ve.


===Molecular===
===Gross/endoscopy===
*A subset have mutations in PDGFRA.<ref name=pmid20393746>{{Cite journal  | last1 = Daum | first1 = O. | last2 = Hatlova | first2 = J. | last3 = Mandys | first3 = V. | last4 = Grossmann | first4 = P. | last5 = Mukensnabl | first5 = P. | last6 = Benes | first6 = Z. | last7 = Michal | first7 = M. | title = Comparison of morphological, immunohistochemical, and molecular genetic features of inflammatory fibroid polyps (Vanek's tumors). | journal = Virchows Arch | volume = 456 | issue = 5 | pages = 491-7 | month = May | year = 2010 | doi = 10.1007/s00428-010-0914-8 | PMID = 20393746 }}</ref>
*Red/swollen gastric folds.<ref name=pmid22863214>{{Cite journal  | last1 = Kamata | first1 = T. | last2 = Suzuki | first2 = H. | last3 = Yoshinaga | first3 = S. | last4 = Nonaka | first4 = S. | last5 = Fukagawa | first5 = T. | last6 = Katai | first6 = H. | last7 = Taniguchi | first7 = H. | last8 = Kushima | first8 = R. | last9 = Oda | first9 = I. | title = Localized gastric amyloidosis differentiated histologically from scirrhous gastric cancer using endoscopic mucosal resection: a case report. | journal = J Med Case Rep | volume = 6 | issue = 1 | pages = 231 | month = | year = 2012 | doi = 10.1186/1752-1947-6-231 | PMID = 22863214 | PMC = 3438062 | URL = http://www.jmedicalcasereports.com/content/6/1/231 }} </ref>


==Hyperplastic polyp of the stomach==
Endoscopic DDx:
{{Main|Hyperplastic polyp}}
*[[Stomach cancer]].<ref name=pmid14606114>{{Cite journal  | last1 = Wu | first1 = D. | last2 = Lou | first2 = JY. | last3 = Chen | first3 = J. | last4 = Fei | first4 = L. | last5 = Liu | first5 = GJ. | last6 = Shi | first6 = XY. | last7 = Lin | first7 = HT. | title = A case report of localized gastric amyloidosis. | journal = World J Gastroenterol | volume = 9 | issue = 11 | pages = 2632-4 | month = Nov | year = 2003 | doi =  | PMID = 14606114 }}</ref><ref name=pmid22814919>{{Cite journal  | last1 = Sawada | first1 = T. | last2 = Adachi | first2 = Y. | last3 = Akino | first3 = K. | last4 = Arimura | first4 = Y. | last5 = Ishida | first5 = T. | last6 = Ishii | first6 = Y. | last7 = Endo | first7 = T. | title = Endoscopic features of primary amyloidosis of the stomach. | journal = Endoscopy | volume = 44 Suppl 2 UCTN | issue =  | pages = E275-6 | month =  | year = 2012 | doi = 10.1055/s-0032-1309750 | PMID = 22814919 | URL = https://www.thieme-connect.com/DOI/DOI?10.1055/s-0032-1309750 }}</ref>
*[[AKA]] ''gastric hyperplastic polyp''.
===General===
*Benign.
*Most common gastric polyp.<ref name=pmid19037727/>


===Microscopic===
===Microscopic===
Features:<ref>URL: [http://pathologyoutlines.com/stomach.html#hyperplastic http://pathologyoutlines.com/stomach.html#hyperplastic]. Accessed on: 26 July 2011.</ref>
Features:
*Abundant foveolar cells and elongated glands - '''key feature'''.
*Lamina propria expanded by amorphous paucicellular material.
*+/-Gland dilation.


Negatives:
Image:
*No atypical nuclei.
*[http://www.jmedicalcasereports.com/content/6/1/231/figure/F5 Stomach amyloidosis (jmedicalcasereports.com)].<ref name=pmid22863214/>
*No hyperchromasia.
*No loss of pseudostratification.


Notes:
===Stains===
*No serrations - as in the colon.
*[[Congo red stain]] +ve.


DDx:
==Eosinophilic gastritis==
*[[Ménétrier's disease]]<ref name=pmid18384215>{{Cite journal  | last1 = Park | first1 = do Y. | last2 = Lauwers | first2 = GY. | title = Gastric polyps: classification and management. | journal = Arch Pathol Lab Med | volume = 132 | issue = 4 | pages = 633-40 | month = Apr | year = 2008 | doi = 10.1043/1543-2165(2008)132[633:GPCAM]2.0.CO;2 | PMID = 18384215 | url=http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2008)132%5B633:GPCAM%5D2.0.CO;2 }}</ref> (hyperplastic hypersecretory gastropathy).
{{Main|Eosinophilic gastritis}}
*[[Juvenile polyp]]<ref name=pmid19037727>{{Cite journal  | last1 = Jain | first1 = R. | last2 = Chetty | first2 = R. | title = Gastric hyperplastic polyps: a review. | journal = Dig Dis Sci | volume = 54 | issue = 9 | pages = 1839-46 | month = Sep | year = 2009 | doi = 10.1007/s10620-008-0572-8 | PMID = 19037727 }}</ref> - abundant lamina propria, dilated glands may have neutrophils.<ref name=Ref_GLP102>{{Ref GLP|102}}</ref>
*[[Peutz-Jeghers polyp]] - thick superficial muscle.


Images:
==Proton pump inhibitor effect==
*www:
*Abbreviated ''PPI effect''.
**[http://www.flickr.com/photos/jian-hua_qiao_md/3953137621/ Gastric hyperplastic polyp (flickr.com)].
{{Main|Proton pump inhibitor effect}}
**[http://www.flickr.com/photos/jian-hua_qiao_md/3953138195/in/photostream/ Gastric hyperplastic polyp (flickr.com)].
*[[WC]]:
**[http://en.wikipedia.org/wiki/File:Gastric_hyperplastic_polyp_%281%29_foveolar_type.jpg Gastric hyperplastic polyp - low mag. (WC)].
**[http://en.wikipedia.org/wiki/File:Gastric_hyperplastic_polyp_%283%29_foveolar_type.jpg Gastric hyperplastic polyp - high mag. (WC)].


==Adenomatous polyps==
=Gastric polyps=
===General===
Similar to colonic polyps - see [[intestinal polyps]].
Common subclassification:<ref>URL: [http://surgpathcriteria.stanford.edu/gitumors/gastric-adenoma/printable.html http://surgpathcriteria.stanford.edu/gitumors/gastric-adenoma/printable.html]. Accessed on: 18 December 2012.</ref>
*Intestinal: goblet cells or Paneth cells.
*Gastric: foveolar epithelium.


Foveolar:
DDx polyp (similar to colon & rectum):
*Associated with [[familial adenomatous polyposis]] (FAP).
*Hyperplastic - most common, characterised by abundant elongated foveola + glands.
*[[Hamartomatous polyps|Hamartomatous]] - weriod stuff.
*[[Inflammatory fibroid polyp]] - inflammation, [[myxoid stroma]].
*[[Fundic gland polyp]] - cystic dilation, flat epithelium.
*[[Gastric adenoma]] - polypoid [[gastric dysplasia]].


Intestinal:
==Inflammatory fibroid polyp==
*Not associated with FAP.
{{Main|Inflammatory fibroid polyp}}


Note:
==Hyperplastic polyp of the stomach==
*These polyps can be grouped various ways.<ref name=pmid18384215>{{Cite journal  | last1 = Park | first1 = do Y. | last2 = Lauwers | first2 = GY. | title = Gastric polyps: classification and management. | journal = Arch Pathol Lab Med | volume = 132 | issue = 4 | pages = 633-40 | month = Apr | year = 2008 | doi = 10.1043/1543-2165(2008)132[633:GPCAM]2.0.CO;2 | PMID = 18384215 | url=http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2008)132%5B633:GPCAM%5D2.0.CO;2 }}</ref>
{{Main|Hyperplastic polyp of the stomach}}
 
===Microscopic===
====Foveolar type adenomatous polyp====
Features:
*Hyperchromasia at the surface - '''key feature'''.
*Cytoplasm with (shortened) champagne flute-like luminal aspect (apical mucin caps).
*Nuclear changes:
**Hyperchromasia.
**Enlargement.
*No intestinal metaplasia.
 
DDx:
*[[Gastric carcinoma]].
*[[Reactive changes]].
 
====Intestinal type adenomatous polyp====
Features - intestinal:
*[[Intestinal metaplasia of the stomach|Intestinal metaplasia]].
*Hyperchromasia of cytoplasm.
*Nuclear changes:
**Loss of nuclear polarity.
**Increased [[NC ratio]].
**Elongation of nucleus and pseudostratification.
 
DDx:
*[[Gastric carcinoma]].
*[[Reactive changes]].
*[[Intestinal metaplasia of the stomach|Intestinal metaplasia]].
 
===Sign out===
====Foveolar type====
<pre>
STOMACH POLYP, BIOPSY:
- ADENOMATOUS POLYP, FOVEOLAR TYPE.
- NEGATIVE FOR HIGH-GRADE DYSPLASIA.
</pre>


==Fundic gland polyp==
==Fundic gland polyp==
*Abbreviated ''FGP''.
{{Main|Fundic gland polyp}}
===General===
*Most common stomach polyp.<ref name=pmid20567540/>
*''Fundic'' location usually.
**May be in the body.<ref name=pmid20567540>{{Cite journal  | last1 = Spiegel | first1 = A. | last2 = Stein | first2 = P. | last3 = Patel | first3 = M. | last4 = Patel | first4 = R. | last5 = Lebovics | first5 = E. | title = A report of gastric fundic gland polyps. | journal = Gastroenterol Hepatol  (N Y) | volume = 6 | issue = 1 | pages = 45-8 | month = Jan | year = 2010 | doi =  | PMID = 20567540 }}</ref>
 
====Clinical significance====
*Weak association with FAP ([[familial adenomatous polyposis]]).<ref name=pmid20567540/><ref name=pmid18322941>{{cite journal |author=Freeman HJ |title=Proton pump inhibitors and an emerging epidemic of gastric fundic gland polyposis |journal=World J. Gastroenterol. |volume=14 |issue=9 |pages=1318-20 |year=2008 |month=March |pmid=18322941 |doi= |url=http://www.wjgnet.com/1007-9327/14/1318.asp}}</ref>
*Associated with chronic proton pump inhibitors (PPI) use -- approximately 4x risk.<ref>{{cite journal |author=Jalving M, Koornstra JJ, Wesseling J, Boezen HM, DE Jong S, Kleibeuker JH |title=Increased risk of fundic gland polyps during long-term proton pump inhibitor therapy |journal=Aliment. Pharmacol. Ther. |volume=24 |issue=9 |pages=1341-8 |year=2006 |month=November |pmid=17059515 |doi=10.1111/j.1365-2036.2006.03127.x |url=}}</ref>
 
Notes:
*Animal studies suggested PPIs cause [[neuroendocrine tumour]]s -- but this has not been found in humans.<ref>{{cite journal |author=Masaoka T, Suzuki H, Hibi T |title=Gastric epithelial cell modality and proton pump inhibitor |journal=J Clin Biochem Nutr |volume=42 |issue=3 |pages=191-6 |year=2008 |month=May |pmid=18545640 |pmc=2386521 |doi=10.3164/jcbn.2008028 |url=}}</ref>
 
===Microscopic===
Features:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/A2B001-PQ01-M.htm http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/A2B001-PQ01-M.htm]. Accessed on: 19 October 2010.</ref>
*Polypoid shape (may not be appreciated on microscopy).
*Dilated gastric glands.
**Flatted epithelial lining (consisting of normal foveolar epithelium) - '''key feature'''.
 
Image:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/A2B001-PQ01-M.htm Fundic gland polyp (ouhsc.edu)].
 
Notes:
*The presence of dysplastic changes should prompt consideration of ''FAP''.


=Neoplastic=
=Neoplastic=
Line 911: Line 376:
#Gastric carcinoma.
#Gastric carcinoma.


==Gastric columnar dysplasia==
==Gastric dysplasia==
*[[AKA]] ''gastric dysplasia''.
{{Main|Stomach adenoma}}
===General===
*Criteria similar to columnar dysplasia in the [[esophagus]].
**The threshold is much lower than in the colon and rectum.
 
Divided into:
*Low grade.
*High grade.
 
===Microscopic===
 
====Low-grade gastric columnar dysplasia====
Features:
*Nuclear changes:
**Nuclear crowding/pseudostratification with hyperchromasia.
**Elongation of nuclei (cigar-shaped nuclei).
**Nuclear stratification intact; nuclei close to the basement membrane.
*Architecture:
**Focal irregularities in the glandular contours.
 
Negatives:
*No desmoplasia.
*No necrosis.
*No surface maturation.
 
DDx:
*Indefinite for dysplasia.
*High-grade gastric columnar dysplasia - see below.
**The threshold is much lower than in the colon and rectum!
 
Images:
*[http://path.upmc.edu/cases/case431.html Low-grade gastric columnar dysplasia - several images (upmc.edu)].
 
====High-grade gastric columnar dysplasia====
Features:
*Nuclear changes:
**Round hyperchromatic nuclei.
**Loss of normal nuclear stratification.
*Architecture:
**Irregularities in the glandular contours.
**Back-to-back glands.
**Cribriforming of the glands.
**+/-Necrosis.
 
Negatives:
*No desmoplasia.
 
DDx:
*Low-grade gastric columnar dysplasia.
*[[Gastric adenocarcinoma]].
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/w/index.php?title=File:High_grade_gastric_dysplasia_-_low_mag.jpg High grade gastric dysplasia - low mag. (WC)].
**[http://commons.wikimedia.org/w/index.php?title=File:High_grade_gastric_dysplasia_-_very_high_mag.jpg High grade gastric dysplasia - very high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Gastric_adenoma_(2).jpg Gastric adenoma (WC)].
*www:
**[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404600/figure/F8/ Gastric gigh-grade dysplasia (nih.gov)].<ref name=pmid22188910>{{Cite journal  | last1 = Correa | first1 = P. | last2 = Piazuelo | first2 = MB. | title = The gastric precancerous cascade. | journal = J Dig Dis | volume = 13 | issue = 1 | pages = 2-9 | month = Jan | year = 2012 | doi = 10.1111/j.1751-2980.2011.00550.x | PMID = 22188910 }}</ref>


==Gastric neuroendocrine tumour==
==Gastric neuroendocrine tumour==
*[[AKA]] ''neuroendocrine tumour of the stomach''.
*[[AKA]] ''neuroendocrine tumour of the stomach'' and ''gastric NET''.
===General===
===General===
*Behaviour dependent on the subtype.
*Behaviour dependent on the subtype.
Line 1,053: Line 461:
Features:
Features:
*Sheets of lymphoid cells.
*Sheets of lymphoid cells.
*"Lymphoepithelial lesion" - gastric crypts invaded by a monomorphous population of lymphocytes.<ref>DB. 6 August 2010.</ref>
*"[[Lymphoepithelial lesion]]" - gastric crypts invaded by a monomorphous population of lymphocytes.<ref>Bailey, D. 6 August 2010.</ref>
**Features:
**Features:
**# Cluster of lymphocytes - three cells or more - '''key feature'''.
**# Cluster of lymphocytes - three cells or more - '''key feature'''.
Line 1,069: Line 477:
Others:
Others:
*CD3 (T cells) - scatter positivity.
*CD3 (T cells) - scatter positivity.
*CD20 (B cells) +ve.
*[[CD20]] (B cells) +ve.
*CD138 (plasma cells).
*CD138 (plasma cells).
*kappa, lambda -- often one is predominant, suggesting clonality.
*kappa, lambda -- often one is predominant, suggesting clonality.
Line 1,088: Line 496:
! Other
! Other
|-
|-
| Hereditary diffuse gastric cancer (HDGC) syndrome  
| [[Hereditary diffuse gastric cancer syndrome|Hereditary diffuse gastric cancer (HDGC) syndrome]]
| CDH1 (E-cadherin)<ref>{{OMIM|192090}}</ref>
| CDH1 (E-cadherin)<ref>{{OMIM|192090}}</ref>
| diffuse - more specifically [[signet ring cell carcinoma]]
| diffuse - more specifically [[signet ring cell carcinoma]]
Line 1,114: Line 522:
|-
|-
| Familial breast and ovarian cancer 2<ref name=omim600185>{{OMIM|600185}}</ref>
| Familial breast and ovarian cancer 2<ref name=omim600185>{{OMIM|600185}}</ref>
| BRCA2
| [[BRCA2]]
| ?
| ?
| ?
| ?
|}
|}


==Gastric adenocarcinoma==
==Gastric carcinoma==
===General===
:Includes ''gastric adenocarcinoma''.
Epidemiology:
{{Main|Gastric carcinoma}}
*Prognosis is often poor as it is discovered at a late stage.
*Higher prevalence in countries in the far east (e.g. Japan) - thought to be environmental, e.g. diet.
 
Risk factors:
*Associated with helicobacter infections, i.e. [[Helicobacter gastritis]].
*Alcohol - heavy use.<ref name=pmid21993435>{{Cite journal  | last1 = Duell | first1 = EJ. | last2 = Travier | first2 = N. | last3 = Lujan-Barroso | first3 = L. | last4 = Clavel-Chapelon | first4 = F. | last5 = Boutron-Ruault | first5 = MC. | last6 = Morois | first6 = S. | last7 = Palli | first7 = D. | last8 = Krogh | first8 = V. | last9 = Panico | first9 = S. | title = Alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. | journal = Am J Clin Nutr | volume = 94 | issue = 5 | pages = 1266-75 | month = Nov | year = 2011 | doi = 10.3945/ajcn.111.012351 | PMID = 21993435 }}</ref>
*Genetic syndromes - see [[hereditary gastric cancer]].
 
Note:
*Possible association with tobacco use - dependent on the study.<ref>{{Cite journal  | last1 = Nomura | first1 = A. | last2 = Grove | first2 = JS. | last3 = Stemmermann | first3 = GN. | last4 = Severson | first4 = RK. | title = Cigarette smoking and stomach cancer. | journal = Cancer Res | volume = 50 | issue = 21 | pages = 7084 | month = Nov | year = 1990 | doi =  | PMID = 2208177 | URL = http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=2208177}}</ref>
 
Treatment:
*Surgical excision. 
**Proximal tumours may require a complete gastrectomy as the stomach is innervated from its proximal part.
 
====Classification====
*Two different classification schemes.
**Lauren<ref name=pmid14320675>{{cite journal |author=LAUREN P |title=THE TWO HISTOLOGICAL MAIN TYPES OF GASTRIC CARCINOMA: DIFFUSE AND  SO-CALLED INTESTINAL-TYPE CARCINOMA. AN ATTEMPT AT A HISTO-CLINICAL CLASSIFICATION |journal=Acta Pathol Microbiol Scand |volume=64 |issue= |pages=31–49 |year=1965 |pmid=14320675 |doi= |url=}}</ref> - two types:
***Intestinal type (mass forming).
***Diffuse type (infiltrative).
**WHO classification - 6 subtypes for adenocarcinoma:<ref name=Ref_PBoD823>{{Ref PBoD |823}}</ref>
**#Papillary carcinoma.
**#Tubular carcinoma.
**#Mucinous carcinoma.
**#Signet-ring carcinoma.
**#Undifferentiated carcinoma.
**#Adenosquamous carcinoma.
 
Lame memory device ''STOMACH'':
*'''S'''ignet ring, '''T'''ubular, '''O'''h papillary, '''M'''ucinous, '''A'''denosquamouas, '''C'''rappy '''H'''igh grade (Undifferentiated).
 
===Gross===
Location:
*Large carcinomas preferentially involve the lesser curvature.<ref name=pmid2550682>{{Cite journal  | last1 = Yamagawa | first1 = H. | last2 = Onishi | first2 = T. | title = [A clinicopathological study of early gastric cancers with a diameter larger than five centimeters]. | journal = Gan No Rinsho | volume = 35 | issue = 10 | pages = 1114-8 | month = Sep | year = 1989 | doi =  | PMID = 2550682 }}</ref>
*Ulceration with heaped (raised) edges.
**Appearance of the typical intestinal type tumour.
*Diffuse wall thickening with loss of the rugae - called ''linitis plastica''.
**Typically due to diffuse carcinoma.
 
Main DDx of ulcer:
*[[Peptic ulcer disease]] - have a "punched-out" appearance: sharp edge, no granularity of surrounding mucosa.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Linitis_plastica.jpg Linitis plastica - endoscopic image (WC)].
*[http://commons.wikimedia.org/wiki/File:Adenocarcinoma_of_the_stomach.jpg Ulcerating gastric carcinoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Adenocarcinoma,_stomach,_gross_pathology_IMG0037a_lores.jpg Ulcerating gastric carcinoma (WC)].
 
===Microscopic===
Features - variable, either of the two following:
#"Typical adenocarcinoma":
#*Gland-forming lesion that infiltrates into the lamina propria or beyond.
#*Nuclear pleomorphism - common.
#+/-Signet ring carcinoma.
#*Scattered single cells in the lamina propria or beyond with:
#**Abundant cytoplasm containing one large (mucin-filled) vacuole.
#**A peripheral nucleus (displaced by the vacuole).
 
DDx:
*[[Gastric xanthoma]] - may mimic signet ring cell carcinoma.
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Gastric_adenocarcinoma.jpg Gastric adenocarcinoma (WC)].
**[http://commons.wikimedia.org/wiki/File:Signet_ring_cells_5.jpg SRC - breast (WC)].
**[http://en.wikipedia.org/wiki/File:Gastric_signet_ring_cell_carcinoma_histopatholgy_%282%29_PAS_stain.jpg Gastric SRC - PAS stain (WC)].
*www:
**[http://path.upmc.edu/cases/case196.html Gastric adenocarcinoma - several images (upmc.edu)].
 
===IHC===
*CK7 +ve.
*CK20 -ve, occasionally +ve.
 
===Molecular===
*May have HER2 over expression - more common in intestinal-type tumours.<ref name=pmid22213295>{{Cite journal  | last1 = Romiti | first1 = A. | last2 = Di Rocco | first2 = R. | last3 = Milione | first3 = M. | last4 = Ruco | first4 = L. | last5 = Ziparo | first5 = V. | last6 = Zullo | first6 = A. | last7 = Duranti | first7 = E. | last8 = Sarcina | first8 = I. | last9 = Barucca | first9 = V. | title = Somatostatin receptor subtype 2 A (SSTR2A) and HER2 expression in gastric adenocarcinoma. | journal = Anticancer Res | volume = 32 | issue = 1 | pages = 115-9 | month = Jan | year = 2012 | doi =  | PMID = 22213295 }}</ref>
**Poor prognosis - like in breast cancer.
**Scoring system different than in breast cancer - complete membrane staining is not required.


=See also=
=See also=

Latest revision as of 15:51, 26 January 2022

A drawing of the stomach.

Stomach is an important organ for pathologists. It is often inflamed and may be a site that cancer arises from. Gastroenterologists often biopsy the organ. Surgeons take-out the organ. It connects the esophagus to the duodenum. An introduction to gastrointestinal pathology is in the gastrointestinal pathology article.

Normal stomach

Gross anatomy

  • Cardia - first part of the stomach; joins with esophagus.
  • Fundus - superior portion - not attached directly to the esophagus.
  • Body - contains parietal cells.
  • Pylorus - distal (think pyloric stenosis); it joins with the duodenum.

Image

  • Stomach anatomy (WC)

Microscopic

Foveolar cells versus intestinal goblet cells

  • Intestinal goblet cells - clear mucin.
  • Foveolar cells - eosinophilic contents.

Stomach versus intestine

A tabular comparison:[1]

Feature Intestine Stomach
Spacing Goblets cell - spaced Foveolar cells - beside one another
Morphology of epithelial cells columnar tall columnar (Champagne flute)
Vesicle at luminal surface touching/small opening wide open
PAS-D -ve (???) +ve[2]
Villin stain[3][4] +ve -ve
Images Tubular adenoma - goblet
cells on right of image (WC) 		Gastric biopsy (microscopy-uk.org.uk),
Stomach with cancer - PAS (WC), Stomach (WC)

Notes:

  • Intraepithelial lymphocytes in the gastric mucosa have a clear halo around 'em.[5]
  • Memory device: Foveolar cells have friends, i.e. they are close to other foveolar cells.

Gastric antrum versus gastric body

Cell Body Antrum Histology Image
Parietal cell abundant few or none parietal cells: intensely
eosinophilic cytoplasm
Parietal cells. (WC)
Chief cell present absent chief cells: basophilic cytoplasm,
IHC: +ve for pepsinogen I
Chief cells. (WC)
G cell absent present fried egg appearance (clear cytoplasm,
round nucleus); look at high power -
usu. middle 1/3 of gland,[6]
IHC: +ve for gastrin.
G cell hyperplasia. (WC)
Surface flat blunted villi antrum is somewhat
duodenum-like
Body - flat. (WC)
Gastric glands
/ mucosa 		thick thin not so useful for
discrimination 		body - thick, body & antrum

Notes:

  • G cells may superficially resemble intraepithelial lymphocytes.
    • G cell nucleus is usu. perfectly round and slightly larger (diameter of 12 micrometers?) than a lymphocyte nucleus (diameter ~ 9-10 micrometers?).

Sign out

Short version

Stomach, Biopsy:
- Antral-type gastric mucosa within normal limits.

Stomach, Biopsy:
- Body and antral-type gastric mucosa within normal limits.

Stomach, Biopsy:
- Antral-type gastric mucosa within normal limits.
- NEGATIVE for Helicobacter-like organisms.
Block letters
STOMACH, BIOPSY:
- BODY AND ANTRAL-TYPE GASTRIC MUCOSA WITHIN NORMAL LIMITS.

STOMACH, BIOPSY:
- BODY AND ANTRAL-TYPE GASTRIC MUCOSA WITHIN NORMAL LIMITS.
- NEGATIVE FOR HELICOBACTER-LIKE ORGANISMS.

STOMACH, BIOPSY:
- ANTRAL-TYPE GASTRIC MUCOSA WITHIN NORMAL LIMITS.
- NEGATIVE FOR HELICOBACTER-LIKE ORGANISMS.

Long version

STOMACH, BIOPSY:
- BODY/ANTRAL-TYPE GASTRIC MUCOSA.
- INFLAMMATION: ABSENT.
- ATROPHY: ABSENT.
- INTESTINAL METAPLASIA: ABSENT.
- HELICOBACTER-LIKE ORGANISMS: NOT IDENTIFIED WITH ROUTINE STAINS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

Sleeve gastrectomy

Main article: Sleeve gastrectomy

Introduction

Useful stains for stomach

Things to look for...

  • Parietal cells (indicate you're in the body of the stomach) - pink (eosinophilic) cytoplasm.
    • Lack of parietal cells -- DDx: Bx of antrum (pylorus), Bx of cardia, pernicious anemia.
  • Goblet cells = intestinal metaplasia.
  • Architectural distortion of gastric glands - suspect cancer.
  • Signet ring cells = (usually) gastric carcinoma.
    • Can be very easy to miss in some biopsies.
  • Inflammation + small bacteria = suspect H. pylori gastritis.

Some patterns

Gastric atrophy

General

  • Has a wide differential diagnosis.

Microscopic

Can take three general forms:

  1. Intestinal metaplasia - see intestinal metaplasia section.
  2. Pseudopyloric metaplasia; gastric body looks like gastric antrum.
    • Characterized by foveolar hyperplasia.
  3. Cell loss without replacement.
    • Clue is deep inflammation in the body.

Plasma cells in the stomach

DDx of plasmacytosis:

Granulomatous gastritis

  • Usual DDx of granulomatous disease (see Basics article):
    • DNF AAII:
      • Drugs, Neoplasms, Foreign body, Autoimmune, Allergic, Infectious, Idiopathic.

Important ones:

Non-neoplastic disease

Peptic ulcer disease

  • Abbreviated PUD.
For duodenal manifestations see Peptic duodenitis.

General

  • Benign.

Complications:

  • Hemorrhage.
  • Obstruction.
  • Perforation - can be fatal.

Etiology - typically:[11]

Gross

Features:

  • Typically in the duodenum; duodenum:stomach = ~4:1.
    • Epithelial defect with punched-out edges (suggestive of a benign process).

Note:

  • Heaped edges - suggestive of cancer.

Endoscopic image

  • Gastric ulcer. (WC)

Microscopic

Features:

Gastritis

Main article: Gastritis
Main article: Chronic gastritis
Main article: Acute gastritis

Helicobacter gastritis

Main article: Helicobacter gastritis

Intestinal metaplasia of the stomach

Main article: Intestinal metaplasia of the stomach

Inflammatory bowel disease and the stomach

See inflammatory bowel disease.
  • Histopathologic findings are usually non-specific.
  • Conventional thinking was upper GI involvement = Crohn's disease; this is changing.[12]

Endoscopic/gross

Features - Crohn's:[13]

  • +/-Linear fissures, erosions, ulcers, cobblestoning.
  • May mimic linitis plastica.

Microscopic

Features:[14]

  • Focal inflammation.
    • Common finding - non-specific.
  • +/-Granulomas.

Note:

  • Granulomas in Crohn's gastritis present 7-34% of the time.[13]

Images

  • CG - low mag. (WC)

  • CG - intermed. mag. (WC)

  • CG - high mag. (WC)

  • CG - very high mag. (WC)

Miscellaneous

This is a grab bag of stuff seen in the stomach. Some of it is quite rare.

Gastric antral vascular ectasia

Main article: Gastric antral vascular ectasia

Reactive gastropathy

Main article: Reactive gastropathy

Autoimmune metaplastic atrophic gastritis

  • AKA autoimmune gastritis.
Main article: Autoimmune metaplastic atrophic gastritis

Collagenous gastritis

Main article: Collagenous gastritis

Gastritis cystitis profunda

General

  • May be associated with glandular proliferation as well.[15] (???)
  • Super rare.
  • Similar to cystitis cystica.

Microscopic

Features:

  • Cystic spaces lined by foveolar epithelium.

Ménétrier's disease

Main article: Ménétrier's disease

Gastric xanthoma

  • Abbreviated GX.
  • AKA xanthelasma.
  • AKA stomach lipidosis.
Main article: Gastric xanthoma

Gastric ischemia

Gastric necrosis redirects here.

General

  • Rare.
  • May arise due to:
    • Small bowel obstruction.[16]
    • Therapeutic embolization.[17]

Microscopic

Features:

  • +/-Pseudomembrane formation.[18]
  • Necrosis of the epithelium lining the gastric pits.

Image:

Portal hypertensive gastropathy

  • Abbreviated PHG.
Main article: Portal hypertensive gastropathy

Amyloidosis of the stomach

  • AKA gastric amyloidosis.
Main article: Amyloidosis

General

Gross/endoscopy

  • Red/swollen gastric folds.[19]

Endoscopic DDx:

Microscopic

Features:

  • Lamina propria expanded by amorphous paucicellular material.

Image:

Stains

Eosinophilic gastritis

Main article: Eosinophilic gastritis

Proton pump inhibitor effect

  • Abbreviated PPI effect.
Main article: Proton pump inhibitor effect

Gastric polyps

Similar to colonic polyps - see intestinal polyps.

DDx polyp (similar to colon & rectum):

Inflammatory fibroid polyp

Main article: Inflammatory fibroid polyp

Hyperplastic polyp of the stomach

Main article: Hyperplastic polyp of the stomach

Fundic gland polyp

Main article: Fundic gland polyp

Neoplastic

The spectrum from benign to malignant is divided into five:[22]

  1. Benign.
  2. Indefinite for gastric epithelial dysplasia.
  3. Low-grade gastric epithelial dysplasia.
  4. High-grade gastric epithelial dysplasia.
  5. Gastric carcinoma.

Gastric dysplasia

Main article: Stomach adenoma

Gastric neuroendocrine tumour

  • AKA neuroendocrine tumour of the stomach and gastric NET.

General

  • Behaviour dependent on the subtype.
  • Uncommon.

Overview of subtypes

Divided into four types:[23]

Tumour type Relative prevalence Multifocality Tumour size Typical location Clinical Other Histology
Type 1 ~75% yes small (5-10 mm) body benign typically, female:male ~ 4:1, 50-60 years chronic atrophic gastritis - usu. autoimmune WDNET, WDNEC
Type 2 rare yes small ~15 mm body aggressive, ~50 years old assoc. MEN I, hyperchlorhydia WDNEC, WDNET
Type 3 10-15% no small and large variable location aggressive if >2.0 cm, males > females normal gastrin levels WDNET
Type 4 extremely rare no large variable location aggressive (mets usu. at time of Dx), males > females elevated gastrin d/t parietal cell dysfunction PDNEC

Notes:

  • WDNET = well-differentiated neuroendocrine tumour.
  • WDNEC = well-differentiated neuroendocrine carcinoma.
  • PDNEC = poorly-differentiated neuroendocrine carinoma.

Microscopic

See neuroendocrine tumours

Neoplastic rare

Gastric calcifying fibrous tumour

Main article: Calcifying fibrous tumour

Gastric cancer

Gastric lymphoma

Main article: MALT lymphoma

General

  • Associated with helicobacter infection.[24]
  • Usually MALT lymphoma (mucosa-associated lymphoid tissue lymphoma).

Microscopic

Features:

  • Sheets of lymphoid cells.
  • "Lymphoepithelial lesion" - gastric crypts invaded by a monomorphous population of lymphocytes.[25]
    • Features:
      1. Cluster of lymphocytes - three cells or more - key feature.
        • Single lymphocytes don't count.
      2. Clearing around the lymphocyte cluster.
    • Associated with MALT lymphoma;[26] however, not specific.

DDx:

IHC

  • Panker -- most useful.

Others:

  • CD3 (T cells) - scatter positivity.
  • CD20 (B cells) +ve.
  • CD138 (plasma cells).
  • kappa, lambda -- often one is predominant, suggesting clonality.
  • BCL2 +ve.

Treatment

  • Triple therapy (two antibiotics, proton pump inhibitor (PPI)).[29]
  • Surgery - if triple therapy fails.

Review paper: PMID 16950858.

Hereditary gastric cancer

Several syndromes are associated with gastric cancer:[30]

Disease Gene Histology Other
Hereditary diffuse gastric cancer (HDGC) syndrome CDH1 (E-cadherin)[31] diffuse - more specifically signet ring cell carcinoma most important; assoc. invasive lobular carcinoma[32]
Lynch syndrome MSH2, MLH1, others ? colorectal carcinoma, endometrial carcinoma
Familial adenomatous polyposis APC ? adenomatous polyps
Peutz-Jeghers syndrome STK11 ? stomach hamartomas - not precursor
Li-Fraumeni syndrome TP53 (p53) ? AKA SBLA syndrome = sarcomas, breast, brain, leukemia, laryngeal, lung, adrenocortical carcinoma
Familial breast and ovarian cancer 2[33] BRCA2 ? ?

Gastric carcinoma

Includes gastric adenocarcinoma.
Main article: Gastric carcinoma

See also

References

  1. ↑ ALS. 4 Feb 2009.
  2. ↑ Rubio, CA. (Jun 2007). "Gastric duodenal metaplasia in duodenal adenomas.". J Clin Pathol 60 (6): 661-3. doi:10.1136/jcp.2006.039388. PMC 1955048. PMID 16837629. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955048/.
  3. ↑ Osborn M, Mazzoleni G, Santini D, Marrano D, Martinelli G, Weber K (1988). "Villin, intestinal brush border hydrolases and keratin polypeptides in intestinal metaplasia and gastric cancer; an immunohistologic study emphasizing the different degrees of intestinal and gastric differentiation in signet ring cell carcinomas". Virchows Arch A Pathol Anat Histopathol 413 (4): 303–12. PMID 2459839.
  4. ↑ Braunstein, EM.; Qiao, XT.; Madison, B.; Pinson, K.; Dunbar, L.; Gumucio, DL. (May 2002). "Villin: A marker for development of the epithelial pyloric border.". Dev Dyn 224 (1): 90-102. doi:10.1002/dvdy.10091. PMID 11984877.
  5. ↑ Sternberg H4P 2nd Ed., P.484
  6. ↑ URL: http://www.lab.anhb.uwa.edu.au/mb140/CorePages/GIT/git.htm. Accessed on: 3 December 2010.
  7. ↑ http://www.histology-world.com/stains/stains.htm
  8. ↑ Goggin N, Rowland M, Imrie C, Walsh D, Clyne M, Drumm B (December 1998). "Effect of Helicobacter pylori eradication on the natural history of duodenal ulcer disease". Arch. Dis. Child. 79 (6): 502-5. PMC 1717771. PMID 10210995. http://adc.bmj.com/cgi/pmidlookup?view=long&pmid=10210995.
  9. ↑ http://www.histology-world.com/stains/stains.htm
  10. ↑ http://www.histology-world.com/stains/stains.htm
  11. ↑ Malfertheiner, P.; Chan, FK.; McColl, KE. (Oct 2009). "Peptic ulcer disease.". Lancet 374 (9699): 1449-61. doi:10.1016/S0140-6736(09)60938-7. PMID 19683340.
  12. ↑ 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.
  13. ↑ 13.0 13.1 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. 80. ISBN 978-0443066573.
  14. ↑ Kirsch R. 13 December 2010.
  15. ↑ URL: http://www.springerlink.com/content/u2v2525241754557/ Accessed on: 19 November 2010.
  16. ↑ Steen, S.; Lamont, J.; Petrey, L. (Jan 2008). "Acute gastric dilation and ischemia secondary to small bowel obstruction.". Proc (Bayl Univ Med Cent) 21 (1): 15-7. PMC 2190544. PMID 18209748. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190544/.
  17. ↑ 17.0 17.1 Papanikolaou, IS.; Foukas, PG.; Sioulas, A.; Beintaris, I.; Panagopoulos, P.; Karamanolis, G.; Panayiotides, IG.; Dimitriadis, G. et al. (2011). "A case of gastric ischemic necrosis.". Endoscopy 43 Suppl 2 UCTN: E342. doi:10.1055/s-0030-1256795. PMID 22020717.
  18. ↑ Herman, J.; Chavalitdhamrong, D.; Jensen, DM.; Cortina, G.; Manuyakorn, A.; Jutabha, R. (Apr 2011). "The significance of gastric and duodenal histological ischemia reported on endoscopic biopsy.". Endoscopy 43 (4): 365-8. doi:10.1055/s-0030-1256040. PMID 21360426.
  19. ↑ 19.0 19.1 Kamata, T.; Suzuki, H.; Yoshinaga, S.; Nonaka, S.; Fukagawa, T.; Katai, H.; Taniguchi, H.; Kushima, R. et al. (2012). "Localized gastric amyloidosis differentiated histologically from scirrhous gastric cancer using endoscopic mucosal resection: a case report.". J Med Case Rep 6 (1): 231. doi:10.1186/1752-1947-6-231. PMC 3438062. PMID 22863214. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438062/.
  20. ↑ Wu, D.; Lou, JY.; Chen, J.; Fei, L.; Liu, GJ.; Shi, XY.; Lin, HT. (Nov 2003). "A case report of localized gastric amyloidosis.". World J Gastroenterol 9 (11): 2632-4. PMID 14606114.
  21. ↑ Sawada, T.; Adachi, Y.; Akino, K.; Arimura, Y.; Ishida, T.; Ishii, Y.; Endo, T. (2012). "Endoscopic features of primary amyloidosis of the stomach.". Endoscopy 44 Suppl 2 UCTN: E275-6. doi:10.1055/s-0032-1309750. PMID 22814919.
  22. ↑ Rugge, M.; Correa, P.; Dixon, MF.; Hattori, T.; Leandro, G.; Lewin, K.; Riddell, RH.; Sipponen, P. et al. (Feb 2000). "Gastric dysplasia: the Padova international classification.". Am J Surg Pathol 24 (2): 167-76. PMID 10680883.
  23. ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/StomachNET_11protocol.pdf. Accessed on: 29 March 2012.
  24. ↑ Mbulaiteye, SM.; Hisada, M.; El-Omar, EM. (2009). "Helicobacter Pylori associated global gastric cancer burden.". Front Biosci 14: 1490-504. PMID 19273142.
  25. ↑ Bailey, D. 6 August 2010.
  26. ↑ Papadaki, L.; Wotherspoon, AC.; Isaacson, PG. (Nov 1992). "The lymphoepithelial lesion of gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): an ultrastructural study.". Histopathology 21 (5): 415-21. PMID 1452124.
  27. ↑ Kim, K.; Kim, EJ.; Kim, MJ.; Song, HJ.; Lee, YS.; Jung, KW.; Yu, E. (Dec 2009). "Clinicopathological features of syphilitic gastritis in Korean patients.". Pathol Int 59 (12): 884-9. doi:10.1111/j.1440-1827.2009.02462.x. PMID 20021615.
  28. ↑ Long, BW.; Johnston, JH.; Wetzel, W.; Flowers, RH.; Haick, A. (Sep 1995). "Gastric syphilis: endoscopic and histological features mimicking lymphoma.". Am J Gastroenterol 90 (9): 1504-7. PMID 7661178.
  29. ↑ Zullo, A.; Hassan, C.; Andriani, A.; Cristofari, F.; De Francesco, V.; Ierardi, E.; Tomao, S.; Morini, S. et al. (Aug 2009). "Eradication therapy for Helicobacter pylori in patients with gastric MALT lymphoma: a pooled data analysis.". Am J Gastroenterol 104 (8): 1932-7; quiz 1938. doi:10.1038/ajg.2009.314. PMID 19532131.
  30. ↑ Sereno, M.; Aguayo, C.; Guillén Ponce, C.; Gómez-Raposo, C.; Zambrana, F.; Gómez-López, M.; Casado, E. (Sep 2011). "Gastric tumours in hereditary cancer syndromes: clinical features, molecular biology and strategies for prevention.". Clin Transl Oncol 13 (9): 599-610. PMID 21865131.
  31. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 192090
  32. ↑ Guilford, P.; Hopkins, J.; Harraway, J.; McLeod, M.; McLeod, N.; Harawira, P.; Taite, H.; Scoular, R. et al. (Mar 1998). "E-cadherin germline mutations in familial gastric cancer.". Nature 392 (6674): 402-5. doi:10.1038/32918. PMID 9537325.
  33. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 600185
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