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 stomach=
=Normal stomach=
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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.


===Gastric antrum versus gastric body===
===Gastric antrum versus gastric body===
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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>
<pre>
STOMACH, BIOPSY:
STOMACH, BIOPSY:
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====Sleeve gastrectomy====
====Sleeve gastrectomy====
*Indication: morbid [[obesity]].
{{Main|Sleeve gastrectomy}}
<pre>
STOMACH, GREATER CURVE, SLEEVE GASTRECTOMY:
- STOMACH WALL WITHIN NORMAL LIMITS.
</pre>


=Introduction=
=Introduction=
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Note:
Note:
*Granulomas in Crohn's gastritis present 7-34% of the time.<ref name=Ref_GLP80>{{Ref GLP|80}}</ref>
*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=
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*[[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====
<gallery>
image:Xanthoma_histology.jpg | Xanthoma. (WC)
</gallery>
www:
*[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==
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==Portal hypertensive gastropathy==
==Portal hypertensive gastropathy==
*Abbreviated ''PHG''.
*Abbreviated ''PHG''.
===General===
{{Main|Portal hypertensive gastropathy}}
*Due to [[portal hypertension]].
**Usually secondary to [[liver cirrhosis]] which is typically due to [[alcoholism]].
***Reported in approximately 65% of cirrhotics with portal hypertension in one paper.<ref name=pmid15648238>{{Cite journal  | last1 = Mesihovic | first1 = R. | last2 = Prohic | first2 = D. | last3 = Gribajcevic | first3 = M. | last4 = Vanis | first4 = N. | last5 = Gornjakovic | first5 = S. | last6 = Sarac | first6 = A. | title = Portal hypertensive gastropathy (PHG). | journal = Med Arh | volume = 58 | issue = 6 | pages = 377-9 | month =  | year = 2004 | doi =  | PMID = 15648238 }}
</ref>
 
===Gross===
Features:<ref name=pmid12492178>{{Cite journal  | last1 = Thuluvath | first1 = PJ. | last2 = Yoo | first2 = HY. | title = Portal Hypertensive gastropathy. | journal = Am J Gastroenterol | volume = 97 | issue = 12 | pages = 2973-8 | month = Dec | year = 2002 | doi = 10.1111/j.1572-0241.2002.07094.x | PMID = 12492178 }}</ref>
*Mosaic-like pattern.
**May be referred to as [[Gastric snakeskin appearance|snakeskin-like pattern]].<ref name=pmid22211417/>
**Usu. body of stomach.
*+/-Red spots.
 
Note:
*May mimic [[eosinophilic gastritis]].<ref name=pmid22211417>{{Cite journal  | last1 = Sikanderkhel | first1 = S. | last2 = Luthra | first2 = M. | last3 = Chavalitdhamrong | first3 = D. | title = Snakeskin-like pattern mimicking portal hypertensive gastropathy in patient with eosinophilic gastritis. | journal = Dig Endosc | volume = 24 | issue = 1 | pages = 53 | month = Jan | year = 2012 | doi = 10.1111/j.1443-1661.2011.01155.x | PMID = 22211417 }}</ref>
 
====Images====
<gallery>
Image:PHGastro.jpg | PHG. (WC/Samir)
</gallery>
 
===Microscopic===
Features:<ref name=Ref_GLP120-1>{{Ref GLP|120-1}}</ref>
*Dilated capillaries in the submucosa (prominent) and to a lesser extent in the lamina propria - '''key feature'''.
 
Notes:
*May be associated with [[hyperplastic polyp of the stomach|hyperplastic]]-like polyps.<ref name=pmid22002002>{{Cite journal  | last1 = Lam | first1 = MC. | last2 = Tha | first2 = S. | last3 = Owen | first3 = D. | last4 = Haque | first4 = M. | last5 = Chatur | first5 = N. | last6 = Gray | first6 = JR. | last7 = Yoshida | first7 = EM. | title = Gastric polyps in patients with portal hypertension. | journal = Eur J Gastroenterol Hepatol | volume = 23 | issue = 12 | pages = 1245-9 | month = Nov | year = 2011 | doi = 10.1097/MEG.0b013e32834c15cf | PMID = 22002002 }}</ref>
**Subepithelial [[granulation tissue]] and vascular proliferation.
*Findings in mucosal biopsies are often [[specificity|nonspecific]], i.e. not diagnostic.<ref name=Ref_GLP120-1>{{Ref GLP|120-1}}</ref>
 
DDx:
*[[Gastric antral vascular ectasia]] - have thrombi in the dilated blood vessels.
 
===Sign out===
<pre>
STOMACH, BIOPSY:
- ANTRAL-TYPE AND BODY-TYPE GASTRIC MUCOSA WITH PROMINENT CAPILLARIES
AND MODERATE CHRONIC INACTIVE INFLAMMATION.
- NEGATIVE FOR HELICOBACTER-LIKE ORGANISMS.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
 
COMMENT:
No fibrin thrombi are seen.  The findings are compatible with portal hypertension.
Clinical correlation is required.
</pre>


==Amyloidosis of the stomach==
==Amyloidosis of the stomach==
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==Eosinophilic gastritis==
==Eosinophilic gastritis==
===General===
{{Main|Eosinophilic gastritis}}
*Rare.


===Microscopic===
==Proton pump inhibitor effect==
Features:
*Abbreviated ''PPI effect''.
*Abundant eosinophils -- >=127 eosinophils/mm<sup>2</sup>.<ref name=pmid21169993/>
{{Main|Proton pump inhibitor effect}}
 
Note:
*Normal range:<ref name=pmid21169993>{{Cite journal  | last1 = Lwin | first1 = T. | last2 = Melton | first2 = SD. | last3 = Genta | first3 = RM. | title = Eosinophilic gastritis: histopathological characterization and quantification of the normal gastric eosinophil content. | journal = Mod Pathol | volume = 24 | issue = 4 | pages = 556-63 | month = Apr | year = 2011 | doi = 10.1038/modpathol.2010.221 | PMID = 21169993 }}</ref>
**<38 eosinophils/mm<sup>2</sup>.
***Typically ~16 eosinophils/mm<sup>2</sup>.


=Gastric polyps=
=Gastric polyps=
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==Gastric dysplasia==
==Gastric dysplasia==
:''Gastric adenoma'' directs here.
{{Main|Stomach adenoma}}
*[[AKA]] ''gastric columnar dysplasia''.
===General===
*Lesions that protrude into the lumen ''and'' are macroscopically apparent are known as: ''adenomas''.<ref name=pmid10680883>{{Cite journal  | last1 = Rugge | first1 = M. | last2 = Correa | first2 = P. | last3 = Dixon | first3 = MF. | last4 = Hattori | first4 = T. | last5 = Leandro | first5 = G. | last6 = Lewin | first6 = K. | last7 = Riddell | first7 = RH. | last8 = Sipponen | first8 = P. | last9 = Watanabe | first9 = H. | title = Gastric dysplasia: the Padova international classification. | journal = Am J Surg Pathol | volume = 24 | issue = 2 | pages = 167-76 | month = Feb | year = 2000 | doi =  | PMID = 10680883 }}</ref>
*Polypoid forms are 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>
 
====Grading====
Like in the colon - they are divided into:
*Low grade.
*High grade.
 
====Subclassification====
One 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.
**Not associated with FAP.
*Gastric: foveolar epithelium.
**Associated with [[familial adenomatous polyposis]] (FAP).
 
===Microscopic===
*Histologic criteria similar to columnar dysplasia in the [[esophagus]].
**The threshold is much lower than in the colon and rectum.
 
====Foveolar type====
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====
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]].
 
=====Images=====
<gallery>
Image:Gastric_adenoma_(1).jpg | Gastric adenoma. (WC/KGH)
Image:Gastric_adenoma_(2).jpg | Gastric adenoma. (WC/KGH)
</gallery>
www:
*[http://www.sciencedirect.com/science/article/pii/S1756231710001878 Gastric polyps - several images (sciencedirect.com)].
*[http://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165%282008%29132%5B633%3AGPCAM%5D2.0.CO%3B2 Gastric polyps - several images (achivesofpathology.org)].
 
====Grading====
=====Low-grade gastric 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)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204467/figure/F4/ Gastric low-grade dysplasia (nih.gov)].<ref name=pmid22076218>{{Cite journal  | last1 = Kushima | first1 = R. | last2 = Kim | first2 = KM. | title = Interobserver Variation in the Diagnosis of Gastric Epithelial Dysplasia and Carcinoma between Two Pathologists in Japan and Korea. | journal = J Gastric Cancer | volume = 11 | issue = 3 | pages = 141-5 | month = Sep | year = 2011 | doi = 10.5230/jgc.2011.11.3.141 | PMID = 22076218 }}</ref>
=====High-grade gastric 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=====
<gallery>
Image:High_grade_gastric_dysplasia_-_low_mag.jpg | High grade gastric dysplasia - low mag. (WC/Nephron)
Image:High_grade_gastric_dysplasia_-_very_high_mag.jpg | High grade gastric dysplasia - very high mag. (WC/Nephron)
</gallery>
www:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404600/figure/F8/ Gastric high-grade dysplasia - probably (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>
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204467/figure/F7/ Gastric high-grade dysplasia - probably (nih.gov)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204467/figure/F6/ Gastric high-grade dysplasia (nih.gov)].<ref name=pmid22076218/>
 
===Sign out===
====Indefinite for dypslasia====
<pre>
STOMACH, ANTRUM, BIOPSIES:
- ANTRAL-TYPE MUCOSA INDEFINITE FOR DYSPLASIA WITH MODERATE CHRONIC INFLAMMATION.
- EXTENSIVE INTESTINAL METAPLASIA.
- NEGATIVE FOR HELICOBACTER-LIKE ORGANSIMS.
- NEGATIVE FOR MALIGNANCY.
</pre>
 
====Intestinal type====
<pre>
STOMACH, ANTRUM, BIOPSIES:
- ANTRAL-TYPE MUCOSA WITH FOCUS OF LOW-GRADE DYSPLASIA (INTESTINAL TYPE).
- EXTENSIVE INTESTINAL METAPLASIA.
- MODERATE CHRONIC INFLAMMATION.
- NEGATIVE FOR HELICOBACTER-LIKE ORGANSIMS.
- NEGATIVE FOR MALIGNANCY.
</pre>
 
====Foveolar type====
<pre>
STOMACH POLYP, EXCISION:
- ADENOMATOUS POLYP, FOVEOLAR TYPE.
- NEGATIVE FOR HIGH-GRADE DYSPLASIA.
- NEGATIVE FOR HELICOBACTER-LIKE ORGANISMS.
</pre>
 
====Foveolar type with high-grade dysplasia====
<pre>
STOMACH POLYP, EXCISION:
- LARGE ADENOMATOUS POLYP (FOVEOLAR TYPE) WITH HIGH-GRADE DYSPLASIA.
- NEGATIVE FOR MALIGNANCY.
</pre>


==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.
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Features:
Features:
*Sheets of lymphoid cells.
*Sheets of lymphoid cells.
*"Lymphoepithelial lesion" - gastric crypts invaded by a monomorphous population of lymphocytes.<ref>Bailey, D. 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'''.
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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.
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! 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 720: 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.
*[[Neuroendocrine tumour]] - esp. for poorly differentiated; no gland formation.
 
====Grading====
*Moderately differentiated >=50 % glands.{{fact}}
*Poorly differentiated >=50% no glands (sheeting or nests).
 
====Images====
<gallery>
Image:Gastric_adenocarcinoma.jpg | Gastric adenocarcinoma. (WC)
Image:Gastric_signet_ring_cell_carcinoma_histopatholgy_%282%29_PAS_stain.jpg | Gastric SRC - PAS stain. (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case196.html Gastric adenocarcinoma - several images (upmc.edu)].
 
===Stains===
*Mucicarmine +ve.
 
===IHC===
*CK7 +ve.
*CK20 -ve, occasionally +ve.
 
Others:
*p53 +ve in upto 75% of cases.<ref name=pmid21772890>{{Cite journal  | last1 = Zali | first1 = MR. | last2 = Moaven | first2 = O. | last3 = Asadzadeh Aghdaee | first3 = H. | last4 = Ghafarzadegan | first4 = K. | last5 = Ahmadi | first5 = KJ. | last6 = Farzadnia | first6 = M. | last7 = Arabi | first7 = A. | last8 = Abbaszadegan | first8 = MR. | title = Clinicopathological significance of E-cadherin, β-catenin and p53 expression in gastric adenocarinoma. | journal = J Res Med Sci | volume = 14 | issue = 4 | pages = 239-47 | month = Jul | year = 2009 | doi =  | PMID = 21772890 }}</ref>
 
===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.
 
===Sign out===
====Biopsy====
=====Intestinal type=====
<pre>
STOMACH, BIOPSY:
- INVASIVE ADENOCARCINOMA, INTESTINAL TYPE, MODERATELY DIFFERENTIATED.
- Gastric mucosa with moderate chronic active inflammation and extensive
  intestinal metaplasia.
- Benign small bowel mucosa with erosions.
</pre>
 
<pre>
GASTRIC ULCER, BIOPSY:
- INVASIVE ADENOCARCINOMA, INTESTINAL-TYPE, MODERATELY DIFFERENTIATED.
</pre>
 
=====Diffuse type=====
<pre>
STOMACH, BIOPSY:
- INVASIVE ADENOCARCINOMA, DIFFUSE TYPE.
 
COMMENT:
A pankeratin immunostain demonstrates single (infiltrating) epithelial cells in the
lamina propria.
</pre>
 
=====Micro=====
The tumour consists of single cells with abundant foamy-appearing cytoplasm and eccentric
nuclei with mild nuclear atypia.
 
=====Poorly differentiated=====
<pre>
GASTRIC ULCER, BIOPSY:
- INVASIVE ADENOCARCINOMA, POORLY-DIFFERENTIATED.
</pre>


=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?).

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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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