Stomach

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Stomach is an important organ for pathologists. It is often inflammed and may be a site that cancer arises from. Gastroenterologists often biopsy the organ. Surgeon take-out the organ.

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 (wikipedia.org).

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 Notes 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); look at high power,
IHC: +ve for gastrin. 		NEED IMAGE
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

Introduction

Useful stains for stomach

  • Cresyl violet stain[4] - used to find H. pylori.[5]
  • Alcian blue - used to find mucin[6] which is present in intestinal metaplasia
    • Other mucins stains:[7] 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:[8]

  • 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:
    • Alcohol.
    • Medications (NSAIDS).
    • Medications.
    • Uremia.
    • Smoking (heavy).
  • Radiation.

Endoscopic appearance

  • Erythematous.

Microscopic

  • Inflammatory cells - in particular.
    • Neutrophils (active gastritis) - especially when intraepithelial, or
    • 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.[9]

Classification[9]

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.[10]

Severity

The Sydney group suggests grading severity with the following language:[9]

  • 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.[9]):

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.[11]
  • 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:[12]

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.[13]

Microscopy

Features:

  • Goblet cells are present in the stomach.[14]
    • With cresyl violet vacuole stains blue.
    • With H&E vacuole may stain greyish.

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.[15]

Gross/endoscopic appearance

  • Linear red streaks in antrum - oriented toward the pyloric valve... vaguely resembles a watermelon.

Endoscopic images:

Microscopic

Features:[16]

  • Fibrin thrombi - characteristic feature.
  • Dilated capillaries in lamina propria.

Images:

Reactive gastropathy

General

  • May be seen in the context of a previous resection/surgical reconstruction, e.g. Billroth II.

Epidemiology

  • Associated with...[17]
    • Excess acid.
    • EtOH.
    • Bile.
    • H. pylori.
    • Drug:
      • Iron (brown pigment on histology).
      • NSAIDs.

Microscopic

Features -triad:[18]

  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.

Notes:

  • Triad rarely present.

DDx:

  • Amyloidosis.
  • Collagenous gastritis.

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:[19]

  • 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.

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.

Miscellaneous

Gastritis cystitis profunda

General

  • AKA Gastritic cystica profunda. (???)
  • May be assoc. with glandular proliferation as well.[20] (???)
  • 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

Histology

Features:[21]

  • Abundant foveolar cells and elongated glands

Negatives:

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

Links

Adenomatous polyps

Divided into 'gastric' and 'intestinal type'[22]

Histology

  • 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).[23]
  • Associated with chronic proton pump inhibitors (PPI) use -- approximately 4x risk.[24]

Notes:

Microscopic

Features:[26]

  • 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

  • Nuclear changes.
    • Nuclear crowding/pseudostratification.
    • Elongation of nuclei (cigar-shaped nuclei).
  • Cytoplasm - hyperchromatic.
  • Mitosis - particularily above the basement membrane.

Image: Gastric adenoma (WC).

Neoplastic rare

Gastric calcifying fibrous tumour

General

  • Rare.
  • Benign.

Microscopic

Features:[27]

  • Submucosal circumscribed fibrocollagenous nodule.
  • Psammomatous calcifications.
  • Focal plasma cells at the periphery.

Gastric cancer

Gastric lymphoma

Main article: MALT lymphoma

General

  • Associated with helicobacter infection.[28]
  • 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.[29]
    • 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;[30] 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)).[31]
  • Surgery - if triple therapy fails.

Review paper: PMID 16950858.

Gastric adenocarcinoma

General

  • Two different classification schemes.
    • Lauren[32] - two types:
      • Intestinal type (mass forming).
      • Diffuse type (infiltrative).
    • WHO classification - 6 subtypes for adenocarcinoma (papillary, tubular, mucinous, signet-rign, undifferentiated, adenosquamous).[33]

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.

Microscopy

  • Adenocarcinoma - gland-forming lesion.
  • Signet ring carcinoma.

Treatment

  • Surgical excision.
    • Proximal tumours may require a complete gastrectomy as the stomach is innervated from its proximal part.

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. ↑ http://www.histology-world.com/stains/stains.htm
  5. ↑ 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.
  6. ↑ http://www.histology-world.com/stains/stains.htm
  7. ↑ http://www.histology-world.com/stains/stains.htm
  8. ↑ 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.
  9. ↑ 9.0 9.1 9.2 9.3 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.
  10. ↑ http://en.wikipedia.org/wiki/Angular_incisure
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ URL: http://esynopsis.uchc.edu/eAtlas/GI/1280.htm. Accessed on: 16 August 2010.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ ALS. 5 February 2009.
  18. ↑ El-Zimaity. 18 October 2010.
  19. ↑ El-Zimaity. 18 October 2010.
  20. ↑ URL: http://www.springerlink.com/content/u2v2525241754557/ Accessed on: 19 November 2010.
  21. ↑ http://pathologyoutlines.com/stomach.html#hyperplastic
  22. ↑ NEED ONE
  23. ↑ 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.
  24. ↑ 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.
  25. ↑ 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/.
  26. ↑ URL: http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/A2B001-PQ01-M.htm. Accessed on: 19 October 2010.
  27. ↑ 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/.
  28. ↑ Mbulaiteye, SM.; Hisada, M.; El-Omar, EM. (2009). "Helicobacter Pylori associated global gastric cancer burden.". Front Biosci 14: 1490-504. PMID 19273142.
  29. ↑ DB. 6 August 2010.
  30. ↑ 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.
  31. ↑ 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.
  32. ↑ 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.
  33. ↑ 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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