Difference between revisions of "Stomach"
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==Reactive gastropathy== | ==Reactive gastropathy== | ||
===General=== | ===General=== | ||
*[[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> | |||
*May be seen in the context of a previous resection/surgical reconstruction, e.g. Billroth II. | *May be seen in the context of a previous resection/surgical reconstruction, e.g. Billroth II. | ||
| Line 277: | Line 278: | ||
===Microscopic=== | ===Microscopic=== | ||
Features -triad:<ref>El-Zimaity. 18 October 2010.</ref> | Features - triad:<ref>El-Zimaity. 18 October 2010.</ref><ref name=pmid16939055/> | ||
#Foveolar hyperplasia. | #Foveolar hyperplasia. | ||
#*Tortuosity of glands in the "neck" region of the gastric glands. | #*Tortuosity of glands in the "neck" region of the gastric glands. | ||
| Line 284: | Line 285: | ||
#*Abundant eosinophilic lamina propria. | #*Abundant eosinophilic lamina propria. | ||
#Scant acute & chronic inflammatory cells. | #Scant acute & chronic inflammatory cells. | ||
Additional features. | |||
*+/-Edema. | |||
*+/-Erosions. | |||
Notes: | Notes: | ||
*Triad rarely present. | *Triad rarely present; mild inflammation common. | ||
DDx: | DDx: | ||
*Amyloidosis. | *[[Amyloidosis]]. | ||
*Collagenous gastritis. | *[[Collagenous gastritis]]. | ||
==Gastric atrophy== | ==Gastric atrophy== | ||
Revision as of 17:50, 30 July 2011
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.
Normal
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.
- AKA antrum.
Image: Stomach anatomy (WP).
Microscopic
Foveolar cells vs. intestinal goblet cells
- Intestinal goblet cells - clear mucin.
- Foveolar cells - eosinophilic contents.
Stomach vs. intestine[1]
| 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 (???) |
| Villin stain[2] | +ve | -ve |
| Images | Tubular adenoma - goblet cells on right of image (WC) |
Gastric biopsy (microscopy-uk.org.uk) |
Notes:
- Intraepithelial lymphocytes in the gastric mucosa have a clear halo around 'em.[3]
- Memory device: Folveolar cells have friends, i.e. they are close to other foveolar cells.
Ref.
- PMID 11984877.
Gastric antrum vs. gastric body
| Body | Antrum | Histology | Image | |
| Parietal cells | abundant | few or none | parietal cells: intensely eosinophilic cytoplasm |
[1], [2] |
| Chief cells | present | absent | chief cells: basophilic cytoplasm, IHC: +ve for pepsinogen I |
[3] |
| G cells | absent | present | fried egg appearance (clear cytoplasm, round nucleus); look at high power - usu. middle 1/3 of gland,[4] IHC: +ve for gastrin. |
[4] |
| Surface | flat | blunted villi | antrum is somewhat duodenum-like |
body - flat |
| Gastric glands / mucosa |
thick | thin | not so useful for discrimination |
body - thick, body & antrum |
![[1]](http://commons.wikimedia.org/wiki/File:Parietal_cells.jpg){kind=link}
![[2]](http://commons.wikimedia.org/wiki/File:Normal_gastric_mucosa_intermed_mag.jpg){kind=link}
![[3]](http://commons.wikimedia.org/wiki/File:Chief_cells.JPG){kind=link}
![[4]](http://commons.wikimedia.org/wiki/File:Gastric_antral_vascular_ectasia_-_intermed_mag.jpg){kind=link}
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?).
Introduction
Useful stains for stomach
- Cresyl violet stain[5] - used to find H. pylori.[6]
- Alcian blue - used to find mucin[7] which is present in intestinal metaplasia
- Other mucins stains:[8] mucicarmine, PAS, PASD (doesn't stain glycogen)
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.
Non-neoplastic disease
Gastritis
Etiology
A specific cause is uncommonly identified histologically.
Gastritis causes:[9]
- Infectious:
- H. pylori infection.
- Tuberculosis.
- Salmonellosis.
- CMV.
- Endocrine-related:
- Pernicious anemia.
- Diabetes - gastric atony.
- Trauma, e.g. NG tube.
- Vascular, ischemia.
- Autoimmune:
- Crohn's disease.
- Toxins:
- Radiation.
Endoscopic appearance
- Erythematous.
Microscopic
- Inflammatory cells - in particular.
- Neutrophils (active gastritis) - especially when intraepithelial, or
- 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.
- Various criteria:
Sydney criteria for gastritis
A bunch of pathologists in Sydney came-up with criteria... and these were revised in Houston.[10]
Classification[10]
| 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.[11]
Severity
The Sydney group suggests grading severity with the following language:[10]
- 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.[10]):
| Mild | Moderate | Marked | |
| H. pylori | few touching | many touching | piles |
| Neutrophils | few | bunches | crowded |
| Mononuclear cells | not touching | kissing | partying |
Helicobacter gastritis
General
- Several Helicobacter species can cause gastritis; H. pylori most common
Finding Helicobacter
- Small - smaller than the nucleus of the gastric foveolar cell.
- On 400x they are still possible to miss.
- Commonly have a "v" shape.
- Look close to the opening of the gastric glands.
- Are often are found in groups.
- Location - can be antrum and/or body.[12]
- Helicobacter don't like the intestinal mucosa or mucosa that has undergone intestinal metaplasia -- you're unlikely to find 'em there.
Images:
- H. pylori - IHC (WC).
- Helicobacter gastritis:
- Set of images - HP gastritis (WC).
Epidemiologic associations
Helicobacter infections are associated with:[13]
- Gastritis.
- Peptic ulcers.
- Cancer.
- Carcinoma.
- MALT lymphoma.
Intestinal metaplasia
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.
Significance
- Moderate risk increase for carcinoma; risk less than for Barrett's esophagus.[14]
Microscopy
Features:
- Goblet cells are present in the stomach.[15]
- With cresyl violet vacuole stains blue.
- With H&E vacuole may stain greyish.
Inflammatory bowel disease & the stomach
- Histopathologic findings are usually non-specific.
- Conventional thinking was upper GI involvement = Crohn's disease; this is changing.[16]
Microscopic
Features:[17]
- Focal inflammation.
- Common finding - non-specific.
- +/-Granulomas.
Miscellaneous
This is a grab bag of stuff seen in the stomach. Some of it is quite rare.
Gastric antral vascular ectasia
General
- Abbreviated GAVE.
- Antrum lesion - due dilated capillaries.
- AKA watermelon stomach - due to characteristic endoscopic appearance.[18]
Gross/endoscopic appearance
- Linear red streaks in antrum - oriented toward the pyloric valve... vaguely resembles a watermelon.
Endoscopic images:
Microscopic
Features:[19]
- Fibrin thrombi - characteristic feature.
- Dilated capillaries in lamina propria.
Images:
Reactive gastropathy
General
- AKA chemical gastropathy.[20]
- May be seen in the context of a previous resection/surgical reconstruction, e.g. Billroth II.
Epidemiology
- Associated with...[21]
- Excess acid.
- EtOH.
- Bile.
- H. pylori.
- Drug:
- Iron (brown pigment on histology).
- NSAIDs.
Microscopic
- 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:
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:[23]
- 25 lymphocytes / 100 epithelial cells.
Pernicious anemia
General
- Gastric atrophy.
- Loss of parietal cells.
- Intrinsic factor antibodies present in serum.
- Intrinsic factor -- absorbs vitamin B12.
- Macrocytic anemia.
Microscopic
Features:
- Corpus predominant inflammation.
- Increased G cells in the antrum.
- Increased gastrin level to try and stimulate (missing) parietal cells.
- See gastric atrophy section.
Collagenous gastritis
General
- Very rare.
- Associated 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.
- Band of collagen must be ~thick as RBC diameter.
Granulomatous gastritis
- Usual DDx of granulomatous disease (see Basics article):
- DNF AAII:
- Drugs, Neoplasms, Foreign body, Autoimmune, Allergic, Infectious, Idiopathic.
- DNF AAII:
Important ones:
- Autoimmune - Crohn's disease.
- Infectious - Tuberculosis.
- Idiopathic - Sarcoidosis.
Miscellaneous
- DDx of Plasmacytosis:
Gastritis cystitis profunda
General
- AKA Gastritic cystica profunda. (???)
- May be assoc. with glandular proliferation as well.[24] (???)
- Super rare.
- Similar to cystitis cystica.
Microscopic
Features:
- Cystic spaces lined by foveolar epithelium.
Gastric polyps
Similar to colonic polyps - see intestinal polyps.
DDx polyp (similar to colon & rectum):
- Hyperplastic - most common, characterised by abundant elongated foveola + glands.
- Hamartomatous - weriod stuff.
- Inflammatory fibroid polyp - inflammation, myxoid stroma.
- Fundic gland polyp - cystic dilation, flat epithelium.
- Adenomatous polyp.
Hyperplastic polyp
General
- Benign.
Microscopic
Features:[25]
- Abundant foveolar cells and elongated glands.
Negatives:
- No atypical nuclei.
- No hyperchromasia.
- No loss of pseudostratification.
DDx:
- Ménétrier's disease[26] (hyperplastic hypersecretory gastropathy).
Adenomatous polyps
General
- Divided into "gastric" and "intestinal type". (???)
- Can be grouped various ways.[26] (???)
Microscopic
- Type.
- Intestinal: goblet cells or Paneth cells.
- Gastric: foveolar epithelium. (???)
- Architectural crowding of glands.
- Hyperchromasia of cytoplasm.
- Nuclear changes:
- Loss of nuclear polarity.
- Incr. NC ratio.
- Elongation of nucleus.
Fundic gland polyps
General
- Fundic location - duh!
Clinical significance
- Weak association with FAP (familial adenomatous polyposis).[27]
- Associated with chronic proton pump inhibitors (PPI) use -- approximately 4x risk.[28]
Notes:
- Animal studies suggested PPIs cause neuroendocrine tumours -- but this has not been found in humans.[29]
Microscopic
Features:[30]
- Polypoid shape (may not be appreciated on microscopy).
- Dilated gastric glands.
- Flatted epithelial lining (consisting of normal foveolar epithelium) - key feature.
Image:
Notes:
- The presence of dysplastic changes should prompt consideration of FAP.
Neoplastic
Gastric dysplasia
General
- Criteria similar to those in adenomatous colonic polyps (see Microscopic).
- Divided into:
- Low grade.
- High grade.
- Nuclei no longer stratified.
Microscopic
Features:
- Nuclear changes.
- Nuclear crowding/pseudostratification.
- Elongation of nuclei (cigar-shaped nuclei).
- Cytoplasm - hyperchromatic.
- Mitosis - particularly above the basement membrane.
Images:
- High grade gastric dysplasia - low mag. (WC).
- High grade gastric dysplasia - very high mag. (WC).
- Gastric adenoma (WC).
.jpg){kind=link}
Neoplastic rare
Gastric calcifying fibrous tumour
General
- Rare.
- Benign.
Microscopic
Features:[31]
- Submucosal circumscribed fibrocollagenous nodule.
- Psammomatous calcifications.
- Focal plasma cells at the periphery.
Gastric cancer
- GIST (see gastrointestinal stromal tumour).
- Adenocarcinoma.
- MALT lymphoma.
Gastric lymphoma
Main article: MALT lymphoma
General
- Associated with helicobacter infection.[32]
- 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.[33]
- Features:
- Cluster of lymphocytes - three cells or more - key feature.
- Single lymphocytes don't count.
- Clearing around the lymphocyte cluster.
- Cluster of lymphocytes - three cells or more - key feature.
- Associated with MALT lymphoma;[34] however, not specific.
- Features:
IHC - work-up
- Panker -- most useful.
Others:
- CD3, CD20, CD138, kappa, lambda, BCL2.
Treatment
- Triple therapy (two antibiotics, proton pump inhibitor (PPI)).[35]
- Surgery - if triple therapy fails.
Review paper: PMID 16950858.
Gastric adenocarcinoma
General
Epidemiology:
- Associated with helicobacter infections.
- 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.
Treatment:
- Surgical excision.
- Proximal tumours may require a complete gastrectomy as the stomach is innervated from its proximal part.
Classification
- Two different classification schemes.
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).
- Scattered single cells in the lamina propria or beyond with:
Images:
IHC
CK7 +ve. CK20 -ve, occasionally +ve.
See also
References
- ↑ ALS. 4 Feb 2009.
- ↑ 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.
- ↑ Sternberg H4P 2nd Ed., P.484
- ↑ URL: http://www.lab.anhb.uwa.edu.au/mb140/CorePages/GIT/git.htm. Accessed on: 3 December 2010.
- ↑ http://www.histology-world.com/stains/stains.htm
- ↑ 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.
- ↑ http://www.histology-world.com/stains/stains.htm
- ↑ http://www.histology-world.com/stains/stains.htm
- ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 812-3. ISBN 0-7216-0187-1.
- ↑ 10.0 10.1 10.2 10.3 Dixon MF, Genta RM, Yardley JH, Correa P (October 1996). "Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994". Am. J. Surg. Pathol. 20 (10): 1161-81. PMID 8827022. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0147-5185&volume=20&issue=10&spage=1161.
- ↑ http://en.wikipedia.org/wiki/Angular_incisure
- ↑ Maaroos HI, Kekki M, Villako K, Sipponen P, Tamm A, Sadeniemi L (October 1990). "The occurrence and extent of Helicobacter pylori colonization and antral and body gastritis profiles in an Estonian population sample". Scand. J. Gastroenterol. 25 (10): 1010-7. PMID 2263873.
- ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 814. ISBN 0-7216-0187-1.
- ↑ Correa P, Piazuelo MB, Wilson KT (March 2010). "Pathology of gastric intestinal metaplasia: clinical implications". Am. J. Gastroenterol. 105 (3): 493–8. doi:10.1038/ajg.2009.728. PMC 2895407. PMID 20203636. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895407/?tool=pubmed.
- ↑ URL: http://esynopsis.uchc.edu/eAtlas/GI/1280.htm. Accessed on: 16 August 2010.
- ↑ 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.
- ↑ RK. 13 December 2010.
- ↑ Chatterjee S (July 2008). "Watermelon stomach". CMAJ 179 (2): 162. doi:10.1503/cmaj.080461. PMC 2443230. PMID 18625989. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18625989.
- ↑ 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. 118. ISBN 978-0443066573.
- ↑ 20.0 20.1 Genta, RM. (Nov 2005). "Differential diagnosis of reactive gastropathy.". Semin Diagn Pathol 22 (4): 273-83. PMID 16939055.
- ↑ ALS. 5 February 2009.
- ↑ El-Zimaity. 18 October 2010.
- ↑ El-Zimaity. 18 October 2010.
- ↑ URL: http://www.springerlink.com/content/u2v2525241754557/ Accessed on: 19 November 2010.
- ↑ URL: http://pathologyoutlines.com/stomach.html#hyperplastic. Accessed on: 26 July 2011.
- ↑ 26.0 26.1 Park, do Y.; Lauwers, GY. (Apr 2008). "Gastric polyps: classification and management.". Arch Pathol Lab Med 132 (4): 633-40. doi:10.1043/1543-2165(2008)132[633:GPCAM]2.0.CO;2. PMID 18384215. http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2008)132%5B633:GPCAM%5D2.0.CO;2.
- ↑ Freeman HJ (March 2008). "Proton pump inhibitors and an emerging epidemic of gastric fundic gland polyposis". World J. Gastroenterol. 14 (9): 1318-20. PMID 18322941. http://www.wjgnet.com/1007-9327/14/1318.asp.
- ↑ Jalving M, Koornstra JJ, Wesseling J, Boezen HM, DE Jong S, Kleibeuker JH (November 2006). "Increased risk of fundic gland polyps during long-term proton pump inhibitor therapy". Aliment. Pharmacol. Ther. 24 (9): 1341-8. doi:10.1111/j.1365-2036.2006.03127.x. PMID 17059515.
- ↑ Masaoka T, Suzuki H, Hibi T (May 2008). "Gastric epithelial cell modality and proton pump inhibitor". J Clin Biochem Nutr 42 (3): 191-6. doi:10.3164/jcbn.2008028. PMC 2386521. PMID 18545640. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386521/.
- ↑ URL: http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/A2B001-PQ01-M.htm. Accessed on: 19 October 2010.
- ↑ Attila T, Chen D, Gardiner GW, Ptak TW, Marcon NE (July 2006). "Gastric calcifying fibrous tumor". Can. J. Gastroenterol. 20 (7): 487–9. PMC 2659917. PMID 16858502. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659917/.
- ↑ Mbulaiteye, SM.; Hisada, M.; El-Omar, EM. (2009). "Helicobacter Pylori associated global gastric cancer burden.". Front Biosci 14: 1490-504. PMID 19273142.
- ↑ DB. 6 August 2010.
- ↑ 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.
- ↑ 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.
- ↑ LAUREN P (1965). "THE TWO HISTOLOGICAL MAIN TYPES OF GASTRIC CARCINOMA: DIFFUSE AND SO-CALLED INTESTINAL-TYPE CARCINOMA. AN ATTEMPT AT A HISTO-CLINICAL CLASSIFICATION". Acta Pathol Microbiol Scand 64: 31–49. PMID 14320675.
- ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 823. ISBN 0-7216-0187-1.