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

Microscopic

Foveolar cells versus intestinal goblet cells

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

Stomach versus intestine

A tabular comparison:[1]

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[2]
Villin stain[3][4] +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.[5]
  • 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,[6]
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

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.

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:

Granulomatous gastritis

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

Important ones:

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:[11]

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

Microscopic

Features:

Gastritis

Helicobacter gastritis

Intestinal metaplasia of the stomach

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.[12]

Microscopic

Features:[13]

  • 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

Reactive gastropathy

Autoimmune metaplastic atrophic gastritis

  • AKA autoimmune gastritis.

Collagenous gastritis

General

Microscopic

Features:

  • Eosinophilic material (collagen) expands lamina propria.
    • Band of collagen must be ~thick as RBC diameter.

DDx:

Gastritis cystitis profunda

General

  • May be associated with glandular proliferation as well.[14] (???)
  • Super rare.
  • Similar to cystitis cystica.

Microscopic

Features:

  • Cystic spaces lined by foveolar epithelium.

Ménétrier's disease

Gastric xanthoma

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

General

  • Uncommon.
  • Benign.

Gross/endoscopic

  • Yellowish nodule or plaque.[15]
    • Classically lesser curvature and antrum.[16]

Microscopic

Features:[15]

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

DDx:

Images

www:

IHC

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

Gastric ischemia

Gastric necrosis redirects here.

General

  • Rare.
  • May arise due to:
    • Small bowel obstruction.[17]
    • Therapeutic embolization.[18]

Microscopic

Features:

  • +/-Pseudomembrane formation.[19]
  • Necrosis of the epithelium lining the gastric pits.

Image:

Portal hypertensive gastropathy

  • Abbreviated PHG.

General

Gross

Features:[21]

Note:

  • May mimic eosinophilic gastritis.[22]

Images

Microscopic

Features:[23]

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

Notes:

DDx:

Sign out

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.

General

Gross/endoscopy

  • Red/swollen gastric folds.[25]

Endoscopic DDx:

Microscopic

Features:

  • Lamina propria expanded by amorphous paucicellular material.

Image:

Stains

Gastric polyps

Similar to colonic polyps - see intestinal polyps.

DDx polyp (similar to colon & rectum):

Inflammatory fibroid polyp

Hyperplastic polyp of the stomach

  • AKA gastric hyperplastic polyp.

General

  • Benign.
  • Most common gastric polyp.[28]

Microscopic

Features:[29]

  • 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

www:

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POLYP, STOMACH (ANTRUM), EXCISION:
- HYPERPLASTIC POLYP.

Micro

The sections show antral-type gastric mucosa with hyperplastic gastric pits. No gland dilation is apparent. The epithelium matures to the surface. The lamina propria is not expanded.

Focal neutrophilic inflammation is present. No Helicobacter-like organisms are identified. No intestinal metaplasia is present. No mitotic activity or nuclear atypia is apparent.

Fundic gland polyp

Neoplastic

The spectrum from benign to malignant is divided into five:[32]

  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.[32]
  • Polypoid forms are grouped various ways.[30]

Grading

Like in the colon - they are divided into:

  • Low grade.
  • High grade.

Subclassification

One subclassification:[33]

  • 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

www:

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:

DDx:

Images

www:

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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, 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:[36]

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.[37]
  • 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.[38]
    • 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;[39] 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)).[42]
  • Surgery - if triple therapy fails.

Review paper: PMID 16950858.

Hereditary gastric cancer

Several syndromes are associated with gastric cancer:[43]

Disease Gene Histology Other
Hereditary diffuse gastric cancer (HDGC) syndrome CDH1 (E-cadherin)[44] diffuse - more specifically signet ring cell carcinoma most important; assoc. invasive lobular carcinoma[45]
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[46] 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.[48]

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[49] - two types:
      • Intestinal type (mass forming).
      • Diffuse type (infiltrative).
    • WHO classification - 6 subtypes for adenocarcinoma:[50]
      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.[51]
  • 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:

Stains

  • Mucicarmine +ve.

IHC

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

Others:

  • p53 +ve in upto 75% of cases.[52]

Molecular

  • May have HER2 over expression - more common in intestinal-type tumours.[53]
    • 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.
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.

See also

References

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