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 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.
  • AKA antrum.

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:

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
Villin stain	+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.
• Memory device: Folveolar 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, 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:
- 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

• Indication: morbid obesity.

STOMACH, GREATER CURVE, SLEEVE GASTRECTOMY:
- STOMACH WALL WITHIN NORMAL LIMITS.

Introduction

Useful stains for stomach

• Cresyl violet stain - used to find H. pylori.
• Alcian blue stain - 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.

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:

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

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.

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.

Endoscopic image

• 

  Gastric ulcer. (WC)

Microscopic

Features:

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

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.

Endoscopic/gross

Features - Crohn's:

• +/-Linear fissures, erosions, ulcers, cobblestoning.
• May mimic linitis plastica.

Microscopic

Features:

• Focal inflammation.
  • Common finding - non-specific.
• +/-Granulomas.

Note:

• Granulomas in Crohn's gastritis present 7-34% of the time.

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

• 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

Main article: Ménétrier's disease

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

• 

  Xanthoma. (WC)

www:

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

IHC

• CD68 +ve.
• Panker (AE1/AE3) -ve.

Gastric ischemia

Gastric necrosis redirects here.

General

• Rare.
• May arise due to:
  • Small bowel obstruction.
  • Therapeutic embolization.

Microscopic

Features:

• +/-Pseudomembrane formation.
• Necrosis of the epithelium lining the gastric pits.

Image:

• Gastric necrosis (thieme-connect.com).

Portal hypertensive gastropathy

• Abbreviated PHG.

General

• 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.

Gross

Features:

• Mosaic-like pattern.
  • May be referred to as snakeskin-like pattern.
  • Usu. body of stomach.
• +/-Red spots.

Note:

• May mimic eosinophilic gastritis.

Images

• 

  PHG. (WC/Samir)

Microscopic

Features:

• Dilated capillaries in the submucosa (prominent) and to a lesser extent in the lamina propria - key feature.

Notes:

• May be associated with hyperplastic-like polyps.
  • Subepithelial granulation tissue and vascular proliferation.
• Findings in mucosal biopsies are often nonspecific, i.e. not diagnostic.

DDx:

• Gastric antral vascular ectasia - have thrombi in the dilated blood vessels.

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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.

Amyloidosis of the stomach

• AKA gastric amyloidosis.

Main article: Amyloidosis

General

• Very rare.
• Etiologies: various - see amyloidosis.

Gross/endoscopy

• Red/swollen gastric folds.

Endoscopic DDx:

• Stomach cancer.

Microscopic

Features:

• Lamina propria expanded by amorphous paucicellular material.

Image:

• Stomach amyloidosis (jmedicalcasereports.com).

Stains

• Congo red stain +ve.

Eosinophilic gastritis

General

• Rare.

Microscopic

Features:

• Abundant eosinophils -- >=127 eosinophils/mm².

Note:

• Normal range:
  • <38 eosinophils/mm².
    • Typically ~16 eosinophils/mm².

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.
• Gastric adenoma - polypoid gastric dysplasia.

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:

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

Gastric adenoma directs here.

• AKA gastric columnar dysplasia.

General

• Lesions that protrude into the lumen and are macroscopically apparent are known as: adenomas.
• Polypoid forms are grouped various ways.

Grading

Like in the colon - they are divided into:

• Low grade.
• High grade.

Subclassification

One subclassification:

• 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.
• Hyperchromasia of cytoplasm.
• Nuclear changes:
  • Loss of nuclear polarity.
  • Increased NC ratio.
  • Elongation of nucleus and pseudostratification.

DDx:

• Gastric carcinoma.
• Reactive changes.
• Intestinal metaplasia.

Images

• 

  Gastric adenoma. (WC/KGH)

• 

  Gastric adenoma. (WC/KGH)

www:

• Gastric polyps - several images (sciencedirect.com).
• 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:

• Low-grade gastric columnar dysplasia - several images (upmc.edu).
• Gastric low-grade dysplasia (nih.gov).

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

• 

  High grade gastric dysplasia - low mag. (WC/Nephron)

• 

  High grade gastric dysplasia - very high mag. (WC/Nephron)

www:

• Gastric high-grade dysplasia - probably (nih.gov).
• Gastric high-grade dysplasia - probably (nih.gov).
• Gastric high-grade dysplasia (nih.gov).

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Indefinite for dypslasia

STOMACH, ANTRUM, BIOPSIES:
- ANTRAL-TYPE MUCOSA INDEFINITE FOR DYSPLASIA WITH MODERATE CHRONIC INFLAMMATION.
- EXTENSIVE INTESTINAL METAPLASIA.
- NEGATIVE FOR HELICOBACTER-LIKE ORGANSIMS.
- NEGATIVE FOR MALIGNANCY.

Intestinal type

 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.

Foveolar type

STOMACH POLYP, EXCISION:
- ADENOMATOUS POLYP, FOVEOLAR TYPE.
- NEGATIVE FOR HIGH-GRADE DYSPLASIA. 
- NEGATIVE FOR HELICOBACTER-LIKE ORGANISMS.

Foveolar type with high-grade dysplasia

STOMACH POLYP, EXCISION:
- LARGE ADENOMATOUS POLYP (FOVEOLAR TYPE) WITH HIGH-GRADE DYSPLASIA.
- NEGATIVE FOR MALIGNANCY.

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.
• Neuroendocrine tumour - esp. for poorly differentiated; no gland formation.

Grading

• Moderately differentiated >=50 % glands.^{[citation needed]}
• Poorly differentiated >=50% no glands (sheeting or nests).

Images

• 

  Gastric adenocarcinoma. (WC)

• 

  Gastric SRC - PAS stain. (WC)

www:

• Gastric adenocarcinoma - several images (upmc.edu).

Stains

• Mucicarmine +ve.

IHC

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

Others:

• p53 +ve in upto 75% of cases.

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.

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Biopsy

Intestinal type

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.

GASTRIC ULCER, BIOPSY:
- INVASIVE ADENOCARCINOMA, INTESTINAL-TYPE, MODERATELY DIFFERENTIATED.

Diffuse type

STOMACH, BIOPSY:
- INVASIVE ADENOCARCINOMA, DIFFUSE TYPE.

COMMENT:
A pankeratin immunostain demonstrates single (infiltrating) epithelial cells in the
lamina propria.

Micro

The tumour consists of single cells with abundant foamy-appearing cytoplasm and eccentric nuclei with mild nuclear atypia.

Poorly differentiated

 GASTRIC ULCER, BIOPSY:
- INVASIVE ADENOCARCINOMA, POORLY-DIFFERENTIATED.

See also

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