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Gastric adenocarcinoma: intestinal vs diffuse

  • Lesion

Stomach cancer comes in two forms: one forms bulky gland masses after long gastritis; the other spreads silently through the wall as single cells.

Updated

What it is

Adenocarcinoma makes up more than nine in ten gastric cancers. The intestinal type grows as cohesive glands and arises through the gastritis–atrophy–metaplasia–dysplasia sequence, so it tracks H. pylori and diet. The diffuse type is made of discohesive signet-ring cells that infiltrate the wall; it has no known precursor and is driven by loss of E-cadherin. Incidence is up to twenty times higher in Japan, Chile, Costa Rica and the Andean countries, including Colombia, than in North America.

Structure

  • Mucin lakes can form in either type and dissect tissue planes.
  • Diffuse tumours provoke desmoplasia that stiffens the wall and flattens rugae.
  • Signet-ring cells can be mistaken for inflammatory cells at low power.

Intestinal vs diffuse gastric adenocarcinoma

FeatureIntestinal typeDiffuse type
GrowthCohesive glands; bulky mass or ulcer with heaped edgesSingle discohesive cells infiltrating the wall
CellColumnar gland-forming cellsSignet-ring cells: mucin pushes the nucleus aside
PrecursorAtrophy, intestinal metaplasia, dysplasia, adenomaNone identified
Key geneChromosomal instability, MSI or EBV groupsCDH1 (E-cadherin) loss; RHOA
EpidemiologyHigh-risk regions, H. pylori; fallingUniform worldwide; not falling
Gross extremeFungating polypoid tumourLinitis plastica

Markers

  • E-cadherin loss (diffuse)
  • HER2 (some intestinal)
  • Mismatch-repair proteins
  • EBV-encoded RNA

Clinical notes

  • Early symptoms mimic dyspepsia, so most are found advanced, with weight loss, early satiety (diffuse type), anaemia and bleeding.
  • Depth of invasion and nodal and distant spread are the strongest prognostic factors; early gastric cancer (mucosa and submucosa) has excellent survival after resection.
  • Endoscopic screening programmes in Japan and Korea detect many early cancers; Colombia has high mortality, especially in the Andean departments.

Test yourself

Think of the answer, then tap the question to see it.

Which gene is lost in diffuse gastric cancer and what does it encode?

CDH1, which encodes the adhesion protein E-cadherin; its loss lets cells infiltrate singly.

What is linitis plastica?

A rigid, thickened, leather-bottle stomach from diffusely infiltrating signet-ring carcinoma with desmoplasia.

What is a Krukenberg tumour?

Bilateral ovarian metastases of signet-ring adenocarcinoma, classically from the stomach.

Which gastric cancer type has declined with falling H. pylori rates?

The intestinal type.

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: Gastric Cancer (StatPearls (NCBI Bookshelf), 2025); Hereditary diffuse gastric cancer: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025); Gastric Cancer Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2025).

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Representative model, for educational purposes only.