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.

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.

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

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:
  • Trauma, e.g. NG tube.
  • Vascular, ischemia.
  • Autoimmune:
  • Toxins:
  • Radiation.

Endoscopic appearance

  • Erythematous.

Microscopic

  • Inflammatory cells - see below.

Acute gastritis

  • AKA active gastritis.

Features:

  • Neutrophils - especially when intraepithelial.

Chronic gastritis

Features:

  • Plasma cells (in lamina propria).
    • Various criteria:
      1. Two plasma cells kissing, i.e. two plasma cells touching/overlapping.
      2. Three is a crowd, i.e. three plasma cells in close proximity.

Sydney criteria for gastritis

A bunch of pathologists in Sydney came-up with criteria... and these were revised in Houston.[10]

Classification

Updated Sydney 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:

Epidemiologic associations

Helicobacter infections are associated with:[13]

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

See inflammatory bowel disease.
  • 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] incorrectly referred to as chemical gastritis (see below).
  • 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.
  • Drugs:[20]
    • Iron (brown pigment on histology).
    • NSAIDs - synergistic effect with corticosteroids.

Drugs that cause erosions and/or ulcers -- adapted from Genta:[20]

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.

Microscopic

Features - triad:[22][20]

  1. Foveolar hyperplasia.
    • Tortuosity of glands in the "neck" region of the gastric glands.
    • Associated with "mucin depletion" - cytoplasm not clear -- as is usual.
  2. Smooth muscle fibre hyperplasia.
    • Abundant eosinophilic lamina propria.
  3. Scant acute & chronic inflammatory cells.

Additional features.

  • +/-Edema.
  • +/-Erosions.

Notes:

  • Triad rarely present; mild inflammation common.

DDx:

Images:

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.

Lymphocytic gastritis

General

DDx:

  • Celiac disease.
  • 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

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:

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.

Ménétrier's disease

  • AKA diffuse foveolar cell hyperplasia.[25]

General

  • Super rare.
  • Increased risk of gastric adenocarcinoma.[25]

Microscopic

Features:[25]

  • Foveolar cell hyperplasia - key feature.

DDx:

Gastric polyps

Similar to colonic polyps - see intestinal polyps.

DDx polyp (similar to colon & rectum):

Inflammatory fibroid polyp

General

  • Benign.
  • Through-out GI tract.

Microscopic

Features:[27]

  • Proliferating spindle cells (fibroid) - key feature.
    • +/-"Concentric" arrangement.
  • Inflammation:
    • Eosinophils - often prominent.

IHC

Features:[27]

  • CD34 +ve.
    • There is a CD34 -ve variant.


Hyperplastic polyp

General

  • Benign.

Microscopic

Features:[28]

  • Abundant foveolar cells and elongated glands.

Negatives:

  • No atypical nuclei.
  • No hyperchromasia.
  • No loss of pseudostratification.

DDx:

  • Ménétrier's disease[29] (hyperplastic hypersecretory gastropathy).

Adenomatous polyps

General

  • Divided into "gastric" and "intestinal type". (???)
  • Can be grouped various ways.[29] (???)

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 polyp

General

  • Fundic location - duh!

Clinical significance

Notes:

Microscopic

Features:[33]

  • 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:

Neoplastic rare

Gastric calcifying fibrous tumour

Main article: Calcifying fibrous tumour

Gastric cancer

Gastric lymphoma

Main article: MALT lymphoma

General

  • Associated with helicobacter infection.[34]
  • 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.[35]
    • 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;[36] however, not specific.

IHC - work-up

  • Panker -- most useful.

Others:

  • CD3, CD20, CD138, kappa, lambda, BCL2.

Treatment

  • Triple therapy (two antibiotics, proton pump inhibitor (PPI)).[37]
  • Surgery - if triple therapy fails.

Review paper: PMID 16950858.

Familial gastric carcinoma

  • Signet ring carcinoma - associated with E-cadherin (CDH1[38]) mutation.[39]

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.
    • Lauren[40] - two types:
      • Intestinal type (mass forming).
      • Diffuse type (infiltrative).
    • WHO classification - 6 subtypes for adenocarcinoma (papillary, tubular, mucinous, signet-rign, undifferentiated, adenosquamous).[41]

Microscopic

Features - variable, either of the two following:

  1. "Typical adenocarcinoma":
    • Gland-forming lesion that infiltrates into the lamina propria or beyond.
    • Nuclear pleomorphism - common.
  2. +/-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).

Images:

IHC

CK7 +ve. CK20 -ve, occasionally +ve.

See also

References

  1. ↑ ALS. 4 Feb 2009.
  2. ↑ 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.
  3. ↑ Sternberg H4P 2nd Ed., P.484
  4. ↑ URL: http://www.lab.anhb.uwa.edu.au/mb140/CorePages/GIT/git.htm. Accessed on: 3 December 2010.
  5. ↑ http://www.histology-world.com/stains/stains.htm
  6. ↑ 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.
  7. ↑ http://www.histology-world.com/stains/stains.htm
  8. ↑ http://www.histology-world.com/stains/stains.htm
  9. ↑ 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. ↑ 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.
  11. ↑ http://en.wikipedia.org/wiki/Angular_incisure
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ URL: http://esynopsis.uchc.edu/eAtlas/GI/1280.htm. Accessed on: 16 August 2010.
  16. ↑ 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.
  17. ↑ RK. 13 December 2010.
  18. ↑ 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.
  19. ↑ 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. ↑ 20.0 20.1 20.2 20.3 Genta, RM. (Nov 2005). "Differential diagnosis of reactive gastropathy.". Semin Diagn Pathol 22 (4): 273-83. PMID 16939055.
  21. ↑ ALS. 5 February 2009.
  22. ↑ El-Zimaity. 18 October 2010.
  23. ↑ El-Zimaity. 18 October 2010.
  24. ↑ URL: http://www.springerlink.com/content/u2v2525241754557/ Accessed on: 19 November 2010.
  25. ↑ 25.0 25.1 25.2 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 410. ISBN 978-1416054542.
  26. ↑ Junnarkar SP, Sloan JM, Johnston BT, Laird JD, Irwin ST (May 2001). "Cronkhite-Canada syndrome". The Ulster medical journal 70 (1): 56–8. PMC 2449205. PMID 11428328. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2449205/.
  27. ↑ 27.0 27.1 Daum, O.; Hatlova, J.; Mandys, V.; Grossmann, P.; Mukensnabl, P.; Benes, Z.; Michal, M. (May 2010). "Comparison of morphological, immunohistochemical, and molecular genetic features of inflammatory fibroid polyps (Vanek's tumors).". Virchows Arch 456 (5): 491-7. doi:10.1007/s00428-010-0914-8. PMID 20393746.
  28. ↑ URL: http://pathologyoutlines.com/stomach.html#hyperplastic. Accessed on: 26 July 2011.
  29. ↑ 29.0 29.1 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.
  30. ↑ 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.
  31. ↑ 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.
  32. ↑ 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/.
  33. ↑ URL: http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/A2B001-PQ01-M.htm. Accessed on: 19 October 2010.
  34. ↑ Mbulaiteye, SM.; Hisada, M.; El-Omar, EM. (2009). "Helicobacter Pylori associated global gastric cancer burden.". Front Biosci 14: 1490-504. PMID 19273142.
  35. ↑ DB. 6 August 2010.
  36. ↑ 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.
  37. ↑ 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.
  38. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 192090
  39. ↑ 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.
  40. ↑ 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.
  41. ↑ 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.
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