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 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.[12]

Endoscopic/gross

Features - Crohn's:[13]

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

Microscopic

Features:[14]

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

Note:

  • Granulomas in Crohn's gastritis present 7-34% of the time.[13]

Images

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

Gastritis cystitis profunda

General

  • May be associated with glandular proliferation as well.[15] (???)
  • 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.

Gastric ischemia

Gastric necrosis redirects here.

General

  • Rare.
  • May arise due to:
    • Small bowel obstruction.[16]
    • Therapeutic embolization.[17]

Microscopic

Features:

  • +/-Pseudomembrane formation.[18]
  • Necrosis of the epithelium lining the gastric pits.

Image:

Portal hypertensive gastropathy

  • Abbreviated PHG.

General

Gross

Features:[20]

Note:

Images

Microscopic

Features:[22]

  • 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.[24]

Endoscopic DDx:

Microscopic

Features:

  • Lamina propria expanded by amorphous paucicellular material.

Image:

Stains

Eosinophilic gastritis

General

  • Rare.

Gross

DDx:

Microscopic

Features:

  • Abundant eosinophils -- >=127 eosinophils/mm2.[27]
    • 30 eosinophils/HPF, if the field diameter of 1 HPF is 0.55 mm.

Notes:

  • Normal range:[27]
    • <38 eosinophils/mm2.
      • Typically ~16 eosinophils/mm2.
  • Mild eosinophilia is seen in:[27]

Gastric polyps

Similar to colonic polyps - see intestinal polyps.

DDx polyp (similar to colon & rectum):

Inflammatory fibroid polyp

Hyperplastic polyp of the stomach

Fundic gland polyp

Neoplastic

The spectrum from benign to malignant is divided into five:[28]

  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.[28]
  • Polypoid forms are grouped various ways.[29]

Grading

Like in the colon - they are divided into:

  • Low grade.
  • High grade.

Subclassification

One subclassification:[30]

  • 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:

Sign out

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:[33]

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.[34]
  • 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.[35]
    • 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;[36] 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)).[39]
  • Surgery - if triple therapy fails.

Review paper: PMID 16950858.

Hereditary gastric cancer

Several syndromes are associated with gastric cancer:[40]

Disease Gene Histology Other
Hereditary diffuse gastric cancer (HDGC) syndrome CDH1 (E-cadherin)[41] diffuse - more specifically signet ring cell carcinoma most important; assoc. invasive lobular carcinoma[42]
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[43] 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.[45]

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[46] - two types:
      • Intestinal type (mass forming).
      • Diffuse type (infiltrative).
    • WHO classification - 6 subtypes for adenocarcinoma:[47]
      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.[48]
  • 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:

Grading

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

Images

www:

Stains

  • Mucicarmine +ve.

IHC

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

Others:

  • p53 +ve in upto 75% of cases.[49]

Molecular

  • May have HER2 over expression - more common in intestinal-type tumours.[50]
    • Poor prognosis - like in breast cancer.
    • Scoring system different than in breast cancer - complete membrane staining is not required.

Sign out

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

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