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. 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

	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	+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.
• 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, 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?).

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Short version

STOMACH, BIOPSY:
- BODY AND ANTRAL-TYPE GASTRIC MUCOSA WITHIN NORMAL LIMITS.

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 DSYPLASIA AND NEGATIVE FOR MALIGNANCY.

Introduction

Useful stains for stomach

• Cresyl violet stain - used to find H. pylori.
• Alcian blue - used to find mucin which is present in intestinal metaplasia
  • Other mucins stains: 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

Peptic ulcer disease

• Abbreviated PUD.

For duodenal manifestations see Peptic duodenitis.

General

• Benign.

Complications:

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

Etiology - typically:

• Helicobacter pylori.

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.

Image:

• Gastric ulcer (WC).

Microscopic

Features:

• Loss of epithelium.
• Inflammation.
• +/-Helicobacter organisms - see Helicobacter gastritis.

Gastritis

Etiology

A specific cause is uncommonly identified histologically.

Gastritis causes:

• Infectious:
  • H. pylori infection.
  • Tuberculosis.
  • Salmonellosis.
  • CMV.
• Endocrine-related:
  • Pernicious anemia.
  • Diabetes mellitus - gastric atony.
• Trauma, e.g. NG tube.
• Vascular, ischemia.
• Autoimmune:
  • Crohn's disease.
• Toxins:
  • Alcohol.
  • Medications (NSAIDS).
  • Medications.
  • Uremia.
  • Smoking (heavy).
• Radiation.

Endoscopic appearance

• Erythematous.

Microscopic

• Inflammatory cells - see below.

Acute gastritis

• AKA active gastritis.

Features:

• Neutrophils - especially when intraepithelial.

Focal active gastritis

DDx:

1. Drugs, esp. NSAIDs.
2. Infectious.
3. Inflammatory bowel disease.

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.

Lymphocytic gastritis

The DDx is limited:

1. Helicobacter gastritis.
2. Celiac disease.
3. NSAIDs.
4. Idiopathic.

Sydney criteria for gastritis

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

Classification

Updated Sydney classification:

	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.

Severity

The Sydney group suggests grading severity with the following language:

• 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.):

	Mild	Moderate	Marked
H. pylori	few touching	many touching	piles
Neutrophils	few	bunches	crowded
Mononuclear cells	not touching	kissing	partying

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STOMACH, BIOPSY: 
- MILD CHRONIC GASTRITIS. 
- NEGATIVE FOR INTESTTINAL METAPLASIA. 
- NEGATIVE FOR HELICOBACTOR ORGANISMS. 
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

Micro

The sections show gastric body type mucosa with small clusters of plasma cells. There are no intraepithelial neutrophils. Goblet cells are not identified. The epithelium matures normally to the surface. No Helicobacter organisms are seen.

Helicobacter gastritis

General

• Several Helicobacter species can cause gastritis:
  • Helicobacter pylori - most common.
  • Helicobacter heilmannii.

Epidemiologic associations - Helicobacter infections are associated with:

• Gastritis.
• Peptic ulcers.
• Cancer.
  • Carcinoma.
  • MALT lymphoma.

Microscopic

Features:

• Small - smaller than the nucleus of the gastric foveolar cell.
  • On 400x they are still possible to miss.
• Look close to the opening of the gastric glands.
• Are often are found in groups.
• Location - can be antrum and/or body.
• Helicobacter don't like the intestinal mucosa or mucosa that has undergone intestinal metaplasia -- you're unlikely to find 'em there.
• Helicobacter pylori:
  • Typically have a "v" shape or a comma-like shape.
• Helicobacter heilmannii:
  • Corkscrew appearance.

Images:

• H. pylori - IHC (WC).
• Helicobacter gastritis:
  • Gastritis due to HP (WC).
  • HP visible (WC).
• Set of images - HP gastritis (WC).
• Helicobacter heilmannii (bmj.com).

Stains

• Cresyl violet stain - background and organisms blue.
• Warthin-Starry stain - background yellow, organisms black.

IHC

• Helicobacter pylori IHC stain +ve.

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STOMACH, BIOPSY:
- BODY-TYPE MUCOSA WITH MODERATE CHRONIC ACTIVE GASTRITIS.
- ABUNDANT HELICOBACTER-LIKE ORGANISMS PRESENT.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

Intestinal metaplasia of the stomach

• AKA gastric intestinal metaplasia.
• Abbreviated IM.

General

• Often part of surgical pathology report, e.g. "negative for intestinal metaplasia" or "intestinal metaplasia present".
• May be associated with Helicobacter spp. infection -- though Helicobacter don't like intestinal type mucosa, i.e. H. pylori are not typically found in regions with intestinal metaplasia.
• May be reversible - some epidemiological evidence.

Significance:

• Moderate risk increase for carcinoma; risk less than for Barrett's esophagus.
  • Odds ratio for corpus (~5.8x) higher than antrum (2.3x) when compared to individuals without IM.

Microscopic

Features:

• Goblet cells are present in the stomach.
  • In H&E the vacuole often stains light grey.

Image:

• Intestinal metaplasia in the stomach - crappy quality (WC).

Stains

• Alcian blue (pH 2.5)/PAS +ve.
  • May be used to divide into complete (type I) and incomplete (type II).
• Alican blue stain +ve.^{[citation needed]}

Image:

• Barrett's mucosa - Alcian blue stain (WC).

IHC

• CDX2 +ve (-ve in normal stomach).
  • Strong assoc. with Helicobacter gastritis as well as IM.

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STOMACH, BIOPSY:
- BODY-TYPE MUCOSA WITH INTESTINAL METAPLASIA, FOCAL.
- MINIMAL CHRONIC GASTRITIS (BODY OF STOMACH).
- NEGATIVE FOR HELICOBACTER ORGANISMS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

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.

Microscopic

Features:

• 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

• Abbreviated GAVE.
• AKA watermelon stomach - due to characteristic endoscopic appearance.

General

• Lesion of the antrum - due to dilated capillaries.

Gross/endoscopic appearance

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

Endoscopic images:

• Watermelon stomach (pubmedcentral.nih.gov).
• GAVE (WP).

Microscopic

Features:

• Fibrin thrombi - characteristic feature.
• Dilated capillaries in lamina propria.
• +/-Foveollar hyperplasia.

DDx:

• Portal hypertensive gastropathy - predominantly in the gastric body, usu. associated with cirrhosis, do not have fibrin thrombi.

Images:

• GAVE - intermed. mag. (WC).
• GAVE - very high mag. (WC).
• GAVE - two thrombi - very high mag. (WC).

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STOMACH, BIOPSY: 
- GASTRIC ANTRAL VASCULAR ECTASIA WITH FOVEOLAR HYPERPLASIA.
- MILD CHRONIC ACTIVE ANTRAL GASTRITIS.
- NEGATIVE FOR INTESTINAL METAPLASIA. 
- NEGATIVE FOR DYSPLASIA. 
- NEGATIVE FOR HELICOBACTER ORGANISMS.

Micro

The sections show antral-type gastric mucosa with dilated lamina propria blood vessels and intravascular fibrin thrombi. There is mild foveolar hyperplasia. Numerous neutrophils are present between the foveollar cells and within the lamina propria. Several large clusters of plasma cells are present in the lamina propria.

Reactive gastropathy

• AKA chemical gastropathy, incorrectly referred to as chemical gastritis (see below).

General

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

Epidemiology

General assocations:

• Increases with age.

Etologic factors - associated with:

• Excess acid.
• EtOH.
• Bile.
• H. pylori.
• Drugs:
  • Iron (brown pigment on histology).
  • NSAIDs - synergistic effect with corticosteroids.

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

Drug	Comment	Indication for Rx
NSAIDs	common cause	pain, reduce cardiovascular risk
Corticosteroids	synergistic effect with NSAIDs	rheumatologic diseases + others
Potassium (KCl)	common cause	renal failure
Bisphophonates	uncommon cause	osteoporosis
Ferrous sulfate	very common if symptomatic	iron deficiency anemia
Chloroquine	uncommon	only in the context of malaria
Sodium polystyrene sulfonate (Kayexalate)	rare	renal failure patients

Relation to gastritis

• May mimic a (true) gastritis symptomatically and visually in an endoscopic examination.
• "Chemical gastritis" is misnomer. Etymologically, the -itis in gastritis, implies an inflammatory process. Chemical gastropathy is not (predominantly) an inflammatory process.
  • This type of confusion is not uncommon. Steatohepatitis is another example of this; it is not a process with significant inflammation yet, confusingly, carries the -itis ending.

Gross/endoscopic

Features:

• Antral erythema +/- erosions.
• +/-Bile.

Microscopic

Features - triad:

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:

• Amyloidosis.
• Collagenous gastritis.
• Hyperplastic polyp of the stomach.

Images:

• RG - low mag. (WC).
• RG - high mag. (WC).

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STOMACH, BIOPSY:
- ANTRAL-TYPE GASTRIC MUCOSA WITH REACTIVE GASTROPATHY, SEE COMMENT.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR HELICOBACTER ORGANISMS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

COMMENT:
This nonspecific finding may be due to a number of causes, including medications (especially NSAIDs), alcohol and bile reflux.

Not well-developed

STOMACH, BIOPSY:
- BODY-TYPE GASTRIC MUCOSA WITHIN NORMAL LIMITS.
- ANTRAL-TYPE GASTRIC MUCOSA WITH SMOOTH MUSCLE HYPERPLASIA AND FOCAL GASTRIC GLAND TORTUOSITY, SEE COMMENT.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR HELICOBACTER ORGANISMS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

COMMENT:
These findings are suggestive of a reactive gastropathy; however, gland corkscrewing is not evident.

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.
  • Check duodenum.
• H. pylori.
• HIV/AIDS.

Microscopic

Features:

• 25 lymphocytes / 100 epithelial cells.

Pernicious anemia

General

• Pathology: loss of parietal cells, gastric atrophy, macrocytic anemia.
• Etiology: autoimmune.

Diagnosis based on serology for antibodies to:

• Parietal cells.
• Intrinsic factor.

Others:

• Gastrin level (increased).
  • Normal < 100 pg/mL.

Note:

• Parietal cells produce intrinsic factor (important for vitamin B12 absorption) and hydrogen chloride, i.e. stomach acid.

Microscopic

Features:

• Corpus predominant inflammation - usu. moderate or severe - key feature
• Loss of parietal cells.
• Increased G cells in the antrum.
  • Produce gastrin to stimulate the (missing) parietal cells.

DDx:

• Gastric neuroendocrine tumour.

Notes:

• Compare with other types of gastric atrophy.

IHC

Features:

• Chromogranin A +ve (demonstrates nodular enterochromaffin-like cell hyperplasia).
• Gastrin -ve (body of stomach).

Collagenous gastritis

General

• Very rare.
• Associated with collagenous colitis.

Microscopic

Features:

• Eosinophilic material (collagen) expands lamina propria.
  • Band of collagen must be ~thick as RBC diameter.
    • Proven by trichrome stain that highlights collagen.

Granulomatous gastritis

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

Important ones:

• Autoimmune - Crohn's disease.
• Infectious - Tuberculosis.
• Idiopathic - Sarcoidosis.

Plasma cells in the stomach

DDx of plasmacytosis:

• Plasma cell neoplasm.
• Syphilis.
• Chronic gastritis.

Gastritis cystitis profunda

• AKA Gastritic cystica profunda.^{[citation needed]}

General

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

Microscopic

Features:

• Cystic spaces lined by foveolar epithelium.

Ménétrier's disease

• AKA diffuse foveolar cell hyperplasia.

General

• Super rare.
• Increased risk of gastric adenocarcinoma.

Clinical:

• Classic: nausea, emesis, abdominal pain and peripheral edema.

Other:

• Gastric mass (may mimic cancer).
• Hypochlorhydria.
• Protein loss - leads to peripheral edema.

Microscopic

Features:

• Foveolar cell hyperplasia - key feature.

DDx:

• Cronkhite-Canada syndrome.
• Hyperplastic polyp of the stomach.

Images:

• Ménétrier's disease - crappy images (upmc.edu).

Gastric xanthoma

• Abbreviated GX.
• AKA xanthelasma.
• AKA stomach lipidosis.

General

• Uncommon.
• Benign.

Gross/endoscopic

• Yellowish nodule or plaque.
  • Classically lesser curvature and antrum.

Microscopic

Features:

• Collections of gastric lamina propria with lipid-laden macrophages.

DDx:

• Signet ring cell carcinoma.
• Whipple disease.
• MAC infection.

Images:

• GX - low mag. (flickr.com).
• GX - high mag. (flickr.com).

IHC

• CD68 +ve.
• Panker (AE1/AE3) -ve.

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.

Inflammatory fibroid polyp

General

• Benign.
• Through-out GI tract.
• Can be thought of as granulation tissue-like.

Microscopic

Features:

• Proliferating spindle cells (fibroid) - key feature.
  • Loosely arranged, concentrically, around blood vessels.
  • Perivascular hypocellular zones.
• Inflammation:
  • Eosinophils - often prominent.
• +/-Leiomyoma/schwannoma-like areas - with nuclear palisading.
• +/-Vascular for fibrous tissue.
• Poorly circumscribed/infiltrates into the lamina propria.

DDx:

• Inflammatory myofibroblastic tumour.
• GIST - usually sharply demarcated border.

Notes:

• Concentric = share the same centre.

Images:

• IFP - low mag. (WC).
• IFP - high mag. (WC).

IHC

Features:

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

Others:

• CD117 -ve.
• S100 -ve.

Molecular

• A subset have mutations in PDGFRA.

Hyperplastic polyp of the stomach

Main article: Hyperplastic polyp

• AKA gastric hyperplastic polyp.

General

• Benign.
• Most common gastric polyp.

Microscopic

Features:

• Abundant foveolar cells and elongated glands - key feature.

Negatives:

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

Notes:

• No serrations - as in the colon.

DDx:

• Ménétrier's disease (hyperplastic hypersecretory gastropathy).
• Juvenile polyp.
• Peutz-Jeghers polyp.

Images:

• www:
  • Gastric hyperplastic polyp (flickr.com).
  • Gastric hyperplastic polyp (flickr.com).
• WC:
  • Gastric hyperplastic polyp - low mag. (WC).
  • Gastric hyperplastic polyp - high mag. (WC).

Adenomatous polyps

General

• Divided into "gastric" and "intestinal type". (???)

• Can be grouped various ways. (???)

Microscopic

• Type.
  • Intestinal: goblet cells or Paneth cells.
  • Gastric: foveolar epithelium. (???)
• Architectural crowding of glands.
• Hyperchromasia of cytoplasm.
• Nuclear changes:
  • Loss of nuclear polarity.
  • Increased NC ratio.
  • Elongation of nucleus.

Fundic gland polyp

General

• Most common stomach polyp.
• Fundic location - duh!
  • May be in the body.

Clinical significance

• Weak association with FAP (familial adenomatous polyposis).
• Associated with chronic proton pump inhibitors (PPI) use -- approximately 4x risk.

Notes:

• Animal studies suggested PPIs cause neuroendocrine tumours -- but this has not been found in humans.

Microscopic

Features:

• Polypoid shape (may not be appreciated on microscopy).
• Dilated gastric glands.
  • Flatted epithelial lining (consisting of normal foveolar epithelium) - key feature.

Image:

• Fundic gland polyp (ouhsc.edu).

Notes:

• The presence of dysplastic changes should prompt consideration of FAP.

Neoplastic

The spectrum from benign to malignant is divided into five:

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

Gastric columnar dysplasia

• AKA gastric dysplasia.

General

• Criteria similar to columnar dysplasia in the esophagus.
  • The threshold is much lower than in the colon and rectum.

Divided into:

• Low grade.
• High grade.

Microscopic

Low-grade gastric columnar dysplasia

Features:

• Nuclear changes:
  • Nuclear crowding/pseudostratification with hyperchromasia.
  • Elongation of nuclei (cigar-shaped nuclei).
  • Nuclear stratification intact; nuclei close to the basement membrane.
• Architecture:
  • Focal irregularities in the glandular contours.

Negatives:

• No desmoplasia.
• No necrosis.
• No surface maturation.

DDx:

• Indefinite for dysplasia.
• High-grade gastric columnar dysplasia - see below.
  • The threshold is much lower than in the colon and rectum!

Images:

• Low-grade gastric columnar dysplasia - several images (upmc.edu).

High-grade gastric columnar dysplasia

Features:

• Nuclear changes:
  • Round hyperchromatic nuclei.
  • Loss of normal nuclear stratification.
• Architecture:
  • Irregularities in the glandular contours.
  • Back-to-back glands.
  • Cribriforming of the glands.
  • +/-Necrosis.

Negatives:

• No desmoplasia.

DDx:

• Low-grade gastric columnar dysplasia.
• Gastric adenocarcinoma.

Images:

• WC:
  • High grade gastric dysplasia - low mag. (WC).
  • High grade gastric dysplasia - very high mag. (WC).
  • Gastric adenoma (WC).
• www:
  • Gastric gigh-grade dysplasia (nih.gov).

Gastric neuroendocrine tumour

• AKA neuroendocrine tumour of the stomach.

General

• Behaviour dependent on the subtype.
• Uncommon.

Overview of subtypes

Divided into four types:

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

• Gastrointestinal stromal tumour (GIST).
• Gastric adenocarcinoma.
• MALT lymphoma.

Gastric lymphoma

Main article: MALT lymphoma

General

• Associated with helicobacter infection.
• 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.
  • 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; however, not specific.

DDx:

• Reactive lymphoid hyperplasia.
• Syphilis.

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)).
• Surgery - if triple therapy fails.

Review paper: PMID 16950858.

Hereditary gastric cancer

Several syndromes are associated with gastric cancer:

Disease	Gene	Histology	Other
Hereditary diffuse gastric cancer (HDGC) syndrome	CDH1 (E-cadherin)	diffuse - more specifically signet ring cell carcinoma	most important; assoc. invasive lobular carcinoma
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	BRCA2	?	?

Gastric adenocarcinoma

General

Epidemiology:

• 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.
• Genetic syndromes - see hereditary gastric cancer.

Note:

• Possible association with tobacco use - dependent on the study.

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 - two types:
    • Intestinal type (mass forming).
    • Diffuse type (infiltrative).
  • WHO classification - 6 subtypes for adenocarcinoma:
    1. Papillary carcinoma.
    2. Tubular carcinoma.
    3. Mucinous carcinoma.
    4. Signet-ring carcinoma.
    5. Undifferentiated carcinoma.
    6. Adenosquamous carcinoma.

Lame memory device STOMACH:

• Signet ring, Tubular, Oh papillary, Mucinous, Adenosquamouas, Crappy High grade (Undifferentiated).

Gross

Location:

• Large carcinomas preferentially involve the lesser curvature.
• 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:

• Linitis plastica - endoscopic image (WC).
• Ulcerating gastric carcinoma (WC).
• Ulcerating gastric carcinoma (WC).

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).

DDx:

• Gastric xanthoma - may mimic signet ring cell carcinoma.

Images:

• WC:
  • Gastric adenocarcinoma (WC).
  • SRC - breast (WC).
  • Gastric SRC - PAS stain (WC).
• www:
  • Gastric adenocarcinoma - several images (upmc.edu).

IHC

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

Molecular

• May have HER2 over expression - more common in intestinal-type tumours.
  • Poor prognosis - like in breast cancer.
  • Scoring system different than in breast cancer - complete membrane staining is not required.

See also

• Esophagus.
• Duodenum.
• Granulation tissue.
• Intestinal polyps.