Gastric pathology

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Gastric Pathology

A comprehensive overview of the major disease processes affecting the stomach, drawn from Robbins & Kumar Basic Pathology and Robbins, Cotran & Kumar Pathologic Basis of Disease.

1. Gastritis

Acute Gastritis

Acute gastritis is a transient mucosal inflammatory process, most often associated with:

Heavy NSAID or aspirin use
Excessive alcohol intake
Heavy smoking
Uraemia, systemic infections (e.g., Staphylococcal food poisoning), severe physiological stress (burns → Curling ulcer; CNS injury → Cushing ulcer)

Mucosal injury results from imbalance between aggressive factors (acid, pepsin) and protective factors (mucus, bicarbonate, prostaglandins, blood flow). Histologically, the mucosa shows oedema, vascular congestion, and neutrophilic infiltration. Erosions may form; haemorrhage can be extensive ("haemorrhagic gastritis").

Chronic Gastritis

H. pylori–Associated Gastritis (Type B)

Helicobacter pylori is a gram-negative, flagellated, spiral bacterium that survives in the gastric mucus by producing urease, which generates an alkaline microenvironment. It is the strongest single risk factor for peptic ulcer disease and a WHO-classified carcinogen implicated in gastric adenocarcinoma and MALT lymphoma.

Key facts:

Found in 60–80% of gastric ulcers and ~95% of duodenal ulcers
Causes chronic active gastritis in almost 100% of infected persons
Primarily affects the antrum
Strains expressing CagA protein carry highest cancer/MALT lymphoma risk

Morphology:

H. pylori resides in mucus overlying foveolar cells — concentrated in the antrum
Neutrophilic infiltration of lamina propria ± pit abscesses
Dense subepithelial plasma cells; lymphoid aggregates with germinal centres (induced MALT)
Intestinal metaplasia (goblet cells + columnar absorptive cells) → precancerous
Hyperplastic and inflammatory polyps

Diagnosis: H&E/Giemsa/Warthin-Starry silver stain; rapid urease test; urea breath test; stool antigen; serology; PCR

H. pylori gastritis histology: (A) Warthin-Starry silver stain showing spiral bacilli; (B) intraepithelial neutrophils; (C) lymphoid aggregates with germinal centres; (D) intestinal metaplasia with goblet cells

H. pylori gastritis. (A) Spiral bacilli on Warthin-Starry stain. (B) Neutrophilic intraepithelial infiltrate. (C) Lymphoid aggregate with germinal centre. (D) Intestinal metaplasia (goblet cells). — Robbins & Kumar Basic Pathology, Fig. 13.14

Autoimmune Gastritis (Type A)

Accounts for <10% of chronic gastritis. Caused by CD4+ T-cell–mediated and antibody-mediated destruction of parietal cells targeting H⁺,K⁺-ATPase (the proton pump) and intrinsic factor. Antibodies to H⁺,K⁺-ATPase and intrinsic factor are present in up to 80% of patients.

Features:

Feature	H. pylori Gastritis	Autoimmune Gastritis
Location	Antrum	Body & fundus
Inflammatory infiltrate	Neutrophils, subepithelial plasma cells, germinal centres	Lymphocytes, macrophages (deeper, gland-centred)
Acid production	Increased → slightly decreased	Decreased (achlorhydria)
Gastrin	Normal → markedly increased	Markedly increased (hypergastrinemia)
Serology	Anti-H. pylori antibodies	Anti-parietal cell (H⁺,K⁺-ATPase, intrinsic factor)
Sequelae	PUD, adenocarcinoma, MALT lymphoma	Pernicious anaemia, adenocarcinoma, carcinoid tumour
Associations	Lower socioeconomic status	Hashimoto thyroiditis, T1DM, Addison disease

Morphology: Diffuse body/fundus atrophy with thinned mucosa; loss of rugal folds; parietal and chief cell loss; intestinal metaplasia; endocrine (ECL) cell hyperplasia → risk of gastric carcinoid tumours

Clinical: Pernicious anaemia (megaloblastic, B12 deficiency); atrophic glossitis; peripheral neuropathy. Median age at diagnosis 60 years, slight female predominance.

Other Forms of Gastritis

Eosinophilic gastritis: Dense eosinophilic infiltrate (antrum/pylorus), often with peripheral eosinophilia and raised IgE; associated with food allergy (milk, soy in children), parasites, systemic sclerosis
Lymphocytic gastritis: Predominantly adult females; 40% linked to coeliac disease; marked increase in intraepithelial T-lymphocytes; endoscopic "varioliform" appearance
Granulomatous gastritis: Contains granulomas; causes include Crohn disease (most common in Western populations), sarcoidosis, mycobacteria, fungi, CMV, H. pylori

2. Peptic Ulcer Disease (PUD)

PUD refers to chronic mucosal ulceration of the stomach or duodenum. Almost always associated with:

H. pylori infection (chronic antral gastritis → ↑ acid + ↓ duodenal bicarbonate)
NSAIDs (± corticosteroids; suppress prostaglandin synthesis → ↓ mucosal protection)
Cigarette smoking
Rarer: Zollinger-Ellison syndrome, CMV/HSV infection, cocaine (vasoconstriction), cirrhosis

Risk factors:

H. pylori infection
NSAIDs (especially in elderly >60 yrs)
Smoking (synergises with H. pylori)
COPD, psychological stress
Zollinger-Ellison syndrome

Epidemiology: Incidence is falling with declining H. pylori prevalence; however, NSAID-associated PUD in elderly is rising. Duodenal ulcers are ~4× more common than gastric ulcers.

Morphology of a peptic ulcer:

Round-to-oval punched-out defect with sharply demarcated, perpendicular walls ("cliff-like" edges)
4 histological zones from surface inward:
1. Necrotic debris (acute inflammatory exudate)
2. Non-specific fibrinoid necrosis
3. Granulation tissue (vascular and fibroblastic)
4. Collagenous scar (fibrosis) incorporating blood vessels with thickened walls (endarteritis obliterans)
Actively inflamed margins; regenerating epithelium at edges

Complications:

Haemorrhage (most common; posterior duodenal ulcers erode the gastroduodenal artery)
Perforation (most dangerous; anterior ulcers; peritonitis)
Obstruction (pyloric scarring → gastric outlet obstruction)
Penetration (into adjacent organs: pancreas, liver)
Malignant transformation (rare in gastric ulcers; duodenal ulcers do NOT undergo malignant change)

3. Gastric Polyps

Type	Key Features
Hyperplastic polyps	Most common; elongated foveolar glands, inflamed stroma; associated with H. pylori and autoimmune gastritis; malignant potential very low
Fundic gland polyps	Common in PPIs users and FAP (APC mutation); cystic dilation of fundic glands; very low malignant potential
Gastric adenomas	Usually solitary antral lesions; all exhibit dysplasia (low or high grade); high-grade = nuclear atypia, cribriform structures; precursor to adenocarcinoma

4. Gastric Adenocarcinoma

The most common gastric malignancy, comprising >90% of all gastric cancers.

Epidemiology

High incidence in Japan, Chile, Costa Rica, Eastern Europe (up to 20× higher than North America)
Incidence in the US has fallen ~85% since 1930 (↓ H. pylori prevalence, ↓ salt/smoked food, ↑ refrigeration)
Exception: Gastric cardia adenocarcinoma is rising (linked to Barrett oesophagus, obesity, GERD)

Molecular Subtypes

The Cancer Genome Atlas (TCGA) classifies gastric adenocarcinoma into four groups:

EBV-positive (~9%): Frequent PIK3CA mutations, DNA hypermethylation, extreme amplification of PD-L1/PD-L2
MSI-high (~22%): Hypermutated; common in older women; MLH1 silencing by methylation; better prognosis
Chromosomally unstable (CIN) (~50%): TP53 mutations, KRAS, ERBB2 amplification; predominates at gastroesophageal junction
Genomically stable (GS) (~20%): Enriched for diffuse type; CDH1 (E-cadherin) and RHOA mutations; worst prognosis

Hereditary Gastric Cancer

Hereditary diffuse gastric cancer: Loss-of-function mutations in CDH1 (E-cadherin) → up to ~30% of hereditary diffuse cases
Lynch syndrome: Mismatch repair gene mutations → MSI → intestinal-type gastric cancer risk

Morphological Classification (Lauren)

Type	Intestinal	Diffuse
Gross pattern	Bulky, polypoid or ulcerating mass	Infiltrating, thickened wall (linitis plastica)
Histology	Gland-forming; cohesive cells	Poorly cohesive/signet-ring cells; no glands
CDH1	Preserved	Lost (E-cadherin loss)
Molecular	Often CIN, MSI, or EBV	Often GS
Pathogenesis	H. pylori → intestinal metaplasia → dysplasia	Often H. pylori or CDH1 mutations
Prognosis	Slightly better	Worse

Signet-ring cells: Neoplastic cells with large mucin vacuoles displacing the nucleus to the periphery — pathognomonic of diffuse type.

Linitis plastica ("leather bottle stomach"): Extensive submucosal fibrosis from diffuse infiltration creates a shrunken, rigid stomach.

Spread and Metastases

Virchow node: Left supraclavicular sentinel lymph node
Sister Mary Joseph nodule: Periumbilical lymph node involvement
Krukenberg tumour: Metastases to ovaries (bilateral; signet-ring cells within ovarian stroma)
Blumer shelf: Deposits in the pouch of Douglas (palpable on rectal exam)
Left axillary lymph nodes (Irish node)

Staging and Prognosis

Early gastric cancer (EGC): Confined to mucosa ± submucosa, regardless of lymph node status → 90–95% 5-year survival
Advanced cancer (involving muscularis propria or beyond) → poor prognosis; <20% of cases detected early in Western countries
Workup: Endoscopy with biopsy; EUS (most reliable for T-staging); MDCT for locoregional + distant staging; PET-CT for metastases. CEA and CA-125 are of limited utility.

5. Gastric MALT Lymphoma

Low-grade extranodal marginal zone B-cell lymphoma
Arises from induced MALT secondary to H. pylori infection (especially CagA⁺ strains)
Early-stage disease can regress completely with H. pylori eradication (antibiotic + PPI)
Higher-grade transformation can occur; may acquire t(11;18) translocation — these do NOT respond to H. pylori eradication alone and require chemotherapy/rituximab

6. Other Gastric Tumours

Tumour	Notes
Gastrointestinal stromal tumour (GIST)	Most common mesenchymal gastric tumour; driven by activating KIT (CD117) or PDGFRA mutations; spindle-cell morphology; treated with imatinib (KIT inhibitor)
Gastric carcinoid (neuroendocrine tumour)	Arises from ECL cells; associated with hypergastrinemia (autoimmune gastritis, MEN-1, Zollinger-Ellison); generally low-grade
Gastric lymphoma	Second most common gastric malignancy after adenocarcinoma

Summary of Key Pathogenetic Relationships

H. pylori infection
    ├─→ Chronic antral gastritis
    │       ├─→ Peptic ulcer disease
    │       ├─→ Intestinal metaplasia → Dysplasia → Intestinal-type adenocarcinoma
    │       └─→ MALT → MALT lymphoma
    └─→ Diffuse gastritis
            └─→ Diffuse-type adenocarcinoma (via additional CDH1 loss)

Autoimmune gastritis (Type A)
    ├─→ Achlorhydria → Pernicious anaemia
    ├─→ Intestinal metaplasia → Adenocarcinoma
    └─→ ECL hyperplasia → Gastric carcinoid

Key sources: Robbins & Kumar Basic Pathology, Chapter 13 | Robbins, Cotran & Kumar Pathologic Basis of Disease, Chapter 17 | Grainger & Allison's Diagnostic Radiology | Goldman-Cecil Medicine

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