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 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.

Image: Stomach anatomy (WP).

Microscopic

Foveolar cells versus intestinal goblet cells

  • Intestinal goblet cells - clear mucin.
  • Foveolar cells - eosinophilic contents.

Stomach vs. intestine

A tabular comparison:[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

Cell Body Antrum Histology Image
Parietal cell abundant few or none parietal cells: intensely
eosinophilic cytoplasm
[1], [2]
Chief cell present absent chief cells: basophilic cytoplasm,
IHC: +ve for pepsinogen I
[3]
G cell 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?).

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Short version

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

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

Introduction

Useful stains for stomach

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:[9]

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:

Microscopic

Features:

Gastritis

Etiology

A specific cause is uncommonly identified histologically.

Gastritis causes:[10]

Endoscopic appearance

  • Erythematous.

Microscopic

  • Inflammatory cells - see below.

Acute gastritis

  • AKA active gastritis.

Features:

  • Neutrophils - especially when intraepithelial.
Focal active gastritis

DDx:

  1. Drugs,[11] 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.

Note:

Lymphocytic gastritis
General

The DDx is limited:

  1. Helicobacter gastritis.
  2. Celiac disease.
  3. NSAIDs.[citation needed]
  4. Idiopathic.
  5. HIV/AIDS.
Microscopic

Features:[13]

  • 25 lymphocytes / 100 epithelial cells.

Sydney criteria for gastritis

A bunch of pathologists in Sydney came-up with criteria... and these were revised in Houston.[14]

Classification

Updated Sydney classification:[14]

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.[15]
Severity

The Sydney group suggests grading severity with the following language:[14]

  • 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.[14]):

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

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Mild chronic

STOMACH, BIOPSY: 
- BODY AND ANTRAL-TYPE GASTRIC MUCOSA WITH MILD CHRONIC INFLAMMATION. 
- NEGATIVE FOR INTESTINAL METAPLASIA. 
- NEGATIVE FOR HELICOBACTOR-LIKE ORGANISMS. 
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

Moderate chronic active

STOMACH, BIOPSY: 
- BODY AND ANTRAL-TYPE GASTRIC MUCOSA WITH MODERATE CHRONIC ACTIVE INFLAMMATION. 
- NEGATIVE FOR INTESTINAL METAPLASIA. 
- NEGATIVE FOR HELICOBACTOR-LIKE 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

  • Often abbreviated HP.

General

  • Several Helicobacter species can cause gastritis:

Epidemiologic associations - Helicobacter infections are associated with:[16]

Gross

  • Thickened gastric folds.
  • Erythema.

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.[17]
  • 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:

Stains

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

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.[19]

Significance:

  • Moderate risk increase for carcinoma; risk less than for Barrett's esophagus.[20]
    • Odds ratio for corpus (~5.8x) higher than antrum (2.3x) when compared to individuals without IM.[21]

Microscopic

Features:

  • Goblet cells are present in the stomach - key feature.[22]
    • In H&E sections the vacuole often stains light grey.
    • Foveolar epithelium should be present in the same fragment.
  • +/-Paneth cells - deep in the glands.[23]
    • Very rarely present.
    • Very uncommon in isolation.

Note:

  • Intestinal metaplasia (IM) is occasionally subdivided:[24]
    • Complete IM = goblet cells and (intestinal) brush border.
    • Incomplete IM = mucus vacuoles of various sizes, no (intestinal) brush border.

DDx:

Image:

Stains

  • Alcian blue (pH 2.5)/PAS +ve.[25]
    • May be used to divide into complete (type I) and incomplete (type II).[26][27]
  • Alican blue stain +ve.[citation needed]

Image:

IHC

Others:

  • Lysozyme +ve - marks paneth cells.[23]

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STOMACH, BIOPSY:
- BODY-TYPE MUCOSA WITH INTESTINAL METAPLASIA, FOCAL.
- MINIMAL CHRONIC GASTRITIS (BODY OF STOMACH).
- NEGATIVE FOR HELICOBACTER-LIKE ORGANISMS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
STOMACH, BIOPSY:
- ANTRAL-TYPE MUCOSA WITH INTESTINAL METAPLASIA, EXTENSIVE.
- MILD CHRONIC (ANTRAL) GASTRITIS.
- NEGATIVE FOR HELICOBACTER-LIKE 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.[29]

Microscopic

Features:[30]

  • 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.[31]

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:

Microscopic

Features:[32]

  • Fibrin thrombi - characteristic feature.
  • Dilated capillaries in lamina propria.
  • +/-Foveollar hyperplasia.[33]

DDx:

Images:

Sign out

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,[35] 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.[36]

Etologic factors - associated with:[37]

  • Excess acid.
  • EtOH.
  • Bile.
  • H. pylori.
  • Drugs:[35]
    • Iron (brown pigment on histology).
    • NSAIDs - synergistic effect with corticosteroids.

Drugs that cause erosions and/or ulcers -- adapted from Genta:[35]

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:[38]

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

Microscopic

Features - triad:[39][35]

  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:

Sign out

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.
STOMACH, BIOPSY:
- ANTRAL-TYPE GASTRIC MUCOSA WITH PROMINENT SMOOTH MUSCLE, OTHERWISE WITHIN NORMAL
LIMITS.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR HELICOBACTER ORGANISMS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

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.

Autoimmune metaplastic atrophic gastritis

Pernicious anemia redirects here.

General

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

Diagnosis based on serology for antibodies to:[42]

  • Parietal cells.
  • Intrinsic factor.

Others:

  • Gastrin level (increased).[43]
    • Normal < 100 pg/mL.[44]

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:

Notes:

IHC

Features:[45]

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

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STOMACH, BIOPSY:
- SEVERE CHRONIC ACTIVE GASTRITIS WITH EXTENSIVE INTESTINAL METAPLASIA.
- NEGATIVE FOR HELICOBACTER-LIKE ORGANISMS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

COMMENT:
Parietal cells are not apparent on the H&E stained sections. Immunostains show 
rows of Chromogranin A positive cells and a lack of gastrin staining.  

These findings suggest an autoimmune gastritis; correlation with blood work 
is suggested.

Collagenous gastritis

General

Microscopic

Features:

  • Eosinophilic material (collagen) expands lamina propria.
    • 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.

Important ones:

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

Plasma cells in the stomach

DDx of plasmacytosis:

Gastritis cystitis profunda

General

  • May be associated with glandular proliferation as well.[46] (???)
  • Super rare.
  • Similar to cystitis cystica.

Microscopic

Features:

  • Cystic spaces lined by foveolar epithelium.

Ménétrier's disease

  • AKA diffuse foveolar cell hyperplasia.[47]

General

  • Super rare.
  • Increased risk of gastric adenocarcinoma.[47]

Clinical:[48]

  • Classical: nausea, emesis, abdominal pain and peripheral edema.
    • Emesis (intractable) - most important.

Other:

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

Epidemiology:

Treatment:

  • EGFR inhibitors.[49]
  • Gastrectomy.

Gross

  • "Bag of worms" appearance - very thick gastric folds.

Microscopic

Features:[47]

  • Foveolar cell hyperplasia - key feature.
  • Decreased parietal cells.
  • +/-Inflammation.

DDx:

Images:

Gastric xanthoma

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

General

  • Uncommon.
  • Benign.

Gross/endoscopic

  • Yellowish nodule or plaque.[51]
    • Classically lesser curvature and antrum.[52]

Microscopic

Features:[51]

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

DDx:

Images:

IHC

  • CD68 +ve.
  • Panker (AE1/AE3) -ve.

Gastric ischemia

Gastric necrosis redirects here.

General

  • Rare.
  • May arise due to:
    • Small bowel obstruction.[53]
    • Therapeutic embolization.[54]

Microscopic

Features:

  • +/-Pseudomembrane formation.[55]
  • Necrosis of the epithelium lining the gastric pits.

Image:

Gastric polyps

Similar to colonic polyps - see intestinal polyps.

DDx polyp (similar to colon & rectum):

Inflammatory fibroid polyp

General

  • Benign.
  • Through-out GI tract.
  • Can be thought of as granulation tissue-like.[56]

Microscopic

Features:[57]

  • Proliferating spindle cells (fibroid) - key feature.
    • Loosely arranged, concentrically, around blood vessels.[58]
    • Perivascular hypocellular zones.[56]
  • Inflammation:
    • Eosinophils - often prominent.
  • +/-Leiomyoma/schwannoma-like areas - with nuclear palisading.[56]
  • +/-Vascular for fibrous tissue.
  • Poorly circumscribed/infiltrates into the lamina propria.

DDx:

Notes:

  • Concentric = share the same centre.[59]

Images:

IHC

Features:[57]

  • CD34 +ve.
    • There is a CD34 -ve variant.
  • Vimentin +ve -- diffuse.[60]

Others:

  • CD117 -ve.[61]
  • S100 -ve.

Molecular

  • A subset have mutations in PDGFRA.[57]

Hyperplastic polyp of the stomach

  • AKA gastric hyperplastic polyp.

General

  • Benign.
  • Most common gastric polyp.[62]

Microscopic

Features:[63]

  • Abundant foveolar cells and elongated glands - key feature.
  • +/-Gland dilation.

Negatives:

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

Notes:

  • No serrations - as in the colon.

DDx:

Images:

Fundic gland polyp

  • Abbreviated FGP.

General

  • Most common stomach polyp.[66]
  • Fundic location usually.
    • May be in the body.[66]

Clinical significance

Notes:

Microscopic

Features:[70]

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

Notes:

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

DDx:

Image:

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POLYP, STOMACH, BIOPSY:
- FUNDIC GLAND POLYP.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR HELICOBACTER-LIKE ORGANISMS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

Neoplastic

The spectrum from benign to malignant is divided into five:[24]

  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.[24]
  • Polypoid forms are grouped various ways.[64]

Grading

Like in the colon - they are divided into:

  • Low grade.
  • High grade.

Subclassification

One subclassification:[71]

  • Intestinal: goblet cells or Paneth cells.
    • Not associated with FAP.
  • Gastric: foveolar epithelium.

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:

Intestinal type

Features - intestinal:

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

DDx:

Images:

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:

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:

Images:

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Foveolar type

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

Gastric neuroendocrine tumour

  • AKA neuroendocrine tumour of the stomach.

General

  • Behaviour dependent on the subtype.
  • Uncommon.

Overview of subtypes

Divided into four types:[73]

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

Gastric cancer

Gastric lymphoma

General

  • Associated with helicobacter infection.[74]
  • 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.[75]
    • 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;[76] however, not specific.

DDx:

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)).[79]
  • Surgery - if triple therapy fails.

Review paper: PMID 16950858.

Hereditary gastric cancer

Several syndromes are associated with gastric cancer:[80]

Disease Gene Histology Other
Hereditary diffuse gastric cancer (HDGC) syndrome CDH1 (E-cadherin)[81] diffuse - more specifically signet ring cell carcinoma most important; assoc. invasive lobular carcinoma[82]
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[83] 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:

Note:

  • Possible association with tobacco use - dependent on the study.[85]

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[86] - two types:
      • Intestinal type (mass forming).
      • Diffuse type (infiltrative).
    • WHO classification - 6 subtypes for adenocarcinoma:[87]
      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.[88]
  • 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:

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:

Images:

IHC

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

Molecular

  • May have HER2 over expression - more common in intestinal-type tumours.[89]
    • Poor prognosis - like in breast cancer.
    • Scoring system different than in breast cancer - complete membrane staining is not required.

See also

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