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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 Nov 12, 2026

## Key points

- Intestinal type: bulky exophytic or ulcerated mass, glands, often antrum and lesser curvature; male predominance; incidence falling with fewer H. pylori infections.
- Diffuse type: signet-ring cells, linitis plastica (leather-bottle stomach); incidence stable worldwide; CDH1 (E-cadherin) loss.
- Germline CDH1 mutations cause hereditary diffuse gastric cancer (also lobular breast cancer); prophylactic gastrectomy is often advised.
- Molecular groups: chromosomal instability (HER2, EGFR, MET, KRAS), microsatellite instability (MLH1 methylation), EBV-positive (PIK3CA, PD-L1, heavy methylation), genomically stable (diffuse).
- Risks: H. pylori, nitrosamines, salted and smoked food, atrophic gastritis, gastric stump after partial gastrectomy, Ménétrier disease.
- Spread: Virchow node (left supraclavicular), Sister Mary Joseph nodule (umbilicus), Krukenberg tumour (ovaries), left axillary node, pouch of Douglas.

## 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

| Feature | Intestinal type | Diffuse type |
| --- | --- | --- |
| Growth | Cohesive glands; bulky mass or ulcer with heaped edges | Single discohesive cells infiltrating the wall |
| Cell | Columnar gland-forming cells | Signet-ring cells: mucin pushes the nucleus aside |
| Precursor | Atrophy, intestinal metaplasia, dysplasia, adenoma | None identified |
| Key gene | Chromosomal instability, MSI or EBV groups | CDH1 (E-cadherin) loss; RHOA |
| Epidemiology | High-risk regions, H. pylori; falling | Uniform worldwide; not falling |
| Gross extreme | Fungating polypoid tumour | Linitis 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.

## Memory aid

Intestinal makes glands and follows the germ; diffuse makes rings and follows the gene.

## 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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## Connections

## Related 8

- [Helicobacter pylori gastritis](https://durgical.com/en/general-pathology/helicobacter-pylori-gastritis/)
- [Gastric atrophy, intestinal metaplasia and dysplasia](https://durgical.com/en/general-pathology/gastric-atrophy-intestinal-metaplasia-and-dysplasia/)
- [Gastric polyps](https://durgical.com/en/general-pathology/gastric-polyps/)
- [Oesophageal adenocarcinoma: from Barrett to invasive cancer](https://durgical.com/en/general-pathology/oesophageal-adenocarcinoma-from-barrett-to-invasive-cancer/)
- [Oncogenic viruses and H. pylori: the table to know](https://durgical.com/en/general-pathology/oncogenic-viruses-and-h-pylori-the-table-to-know/)
- [Pathways of spread and the usual metastatic sites](https://durgical.com/en/general-pathology/pathways-of-spread-and-the-usual-metastatic-sites/)
- [Hereditary cancer syndromes: the table to know](https://durgical.com/en/general-pathology/hereditary-cancer-syndromes-the-table-to-know/)
- [Cancer epidemiology: age, environment, predisposing conditions (and Colombia)](https://durgical.com/en/general-pathology/cancer-epidemiology-age-environment-predisposing-conditions/)

## Related conditions 5

- [Gastric cancer](https://durgical.com/en/conditions/gastric-cancer/)
- [Helicobacter pylori gastritis](https://durgical.com/en/conditions/helicobacter-pylori-gastritis/)
- [Ovarian cancer](https://durgical.com/en/conditions/ovarian-cancer/)
- [Breast cancer](https://durgical.com/en/conditions/breast-cancer/)
- [Lynch syndrome (hereditary non-polyposis colorectal cancer)](https://durgical.com/en/conditions/lynch-syndrome/)

## Microorganisms 2

- [Helicobacter pylori](https://durgical.com/en/microbiology/helicobacter-pylori/)
- [Epstein–Barr virus](https://durgical.com/en/microbiology/epstein-barr-virus/)

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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](https://www.ncbi.nlm.nih.gov/books/NBK459142/) (StatPearls (NCBI Bookshelf), 2025); [Hereditary diffuse gastric cancer: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/hereditary-diffuse-gastric-cancer/) (MedlinePlus, US National Library of Medicine, 2025); [Gastric Cancer Treatment (PDQ®)–Health Professional Version](https://www.cancer.gov/types/stomach/hp/stomach-treatment-pdq) (National Cancer Institute, 2025).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/gastric-adenocarcinoma-intestinal-vs-diffuse/