Definition/General
Introduction:
Gastric atrophic gastritis is a chronic inflammatory condition characterized by progressive loss of gastric glands
It involves replacement by connective tissue and often intestinal metaplasia
It represents the end-stage of chronic gastritis
It is a precancerous lesion associated with increased gastric adenocarcinoma risk.
Origin:
Results from chronic inflammation of gastric mucosa
Most commonly caused by Helicobacter pylori infection (80-90% cases)
Can also result from autoimmune gastritis (parietal cell antibodies)
Environmental factors and genetic predisposition contribute
Leads to progressive gland loss and mucosal architectural distortion.
Classification:
Classified by Sydney system: mild, moderate, severe
Based on extent: antral-predominant (H
pylori related)
Corpus-predominant (autoimmune)
Pangastric (multifocal)
Graded by degree of glandular loss
Associated with intestinal metaplasia classification (complete vs incomplete).
Epidemiology:
Prevalence increases with age (50-70% in elderly)
Higher in developing countries
Male predominance (2:1 ratio)
Associated with H
pylori infection (70-80% cases in India)
Family clustering suggests genetic predisposition
Environmental factors: salt intake, smoking, alcohol consumption.
Clinical Features
Presentation:
Often asymptomatic in early stages
Dyspepsia (most common symptom)
Epigastric pain or discomfort
Early satiety and bloating
Vitamin B12 deficiency symptoms (corpus involvement)
Weight loss (advanced cases)
Iron deficiency anemia.
Symptoms:
Epigastric pain (60-70%)
Dyspepsia and indigestion
Nausea and vomiting
Loss of appetite
Megaloblastic anemia (B12 deficiency)
Neurological symptoms (B12 deficiency)
Glossitis and angular cheilitis.
Risk Factors:
H
pylori infection (major risk factor)
Advanced age (>50 years)
Family history of gastric cancer
Autoimmune conditions
High salt intake
Smoking and alcohol consumption
Low socioeconomic status
Previous gastric surgery.
Screening:
Upper endoscopy with biopsy
H
pylori testing (urea breath test, stool antigen)
Serology for autoimmune gastritis (parietal cell antibodies)
Pepsinogen I/II ratio
Vitamin B12 levels
Iron studies.
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Gross Description
Appearance:
Gastric mucosa appears thinned and pale
Loss of normal rugal pattern
Flattened mucosal folds
Visible submucosal blood vessels through thin mucosa
Areas of nodularity may be present
Surface irregularities and erosions.
Characteristics:
Mucosal thinning is characteristic finding
Loss of normal gastric fold architecture
Antral involvement in H
pylori gastritis
Corpus/fundus involvement in autoimmune gastritis
Submucosal vascular pattern visible
Surface may show granular appearance.
Size Location:
Antral involvement: H
pylori-associated atrophic gastritis
Corpus/fundus: autoimmune atrophic gastritis
Pangastric involvement in severe cases
Transition zones may show mixed patterns
Pyloric gland metaplasia in corpus.
Multifocality:
Often multifocal distribution
Patchy involvement initially
Progressive involvement over time
Skip lesions may be present
Association with synchronous intestinal metaplasia
May coexist with gastric adenocarcinoma.
Microscopic Description
Histological Features:
Loss of gastric glands (oxyntic or pyloric)
Replacement by fibrous connective tissue
Chronic inflammation with lymphocytes and plasma cells
Intestinal metaplasia (complete or incomplete)
Surface epithelial changes
Mucin depletion.
Cellular Characteristics:
Surface epithelium shows regenerative changes
Chronic inflammatory cells predominate
Lymphoid follicles may be present
Eosinophils and neutrophils (active inflammation)
Intestinal-type goblet cells in metaplastic areas
Paneth cells in complete intestinal metaplasia.
Architectural Patterns:
Glandular atrophy with shortened crypts
Loss of normal gastric gland architecture
Fibrosis replacing normal lamina propria
Intestinal metaplasia with villiform architecture
Pyloric metaplasia in corpus
Surface foveolar hyperplasia.
Grading Criteria:
Sydney system grading: Grade 0 (normal)
Grade 1 (mild): <25% gland loss
Grade 2 (moderate): 25-50% loss
Grade 3 (severe): >50% loss
OLGA staging (Operative Link on Gastritis Assessment)
Combines atrophy and intestinal metaplasia.
Immunohistochemistry
Positive Markers:
CDX2 (intestinal metaplasia marker)
Villin (intestinal differentiation)
MUC2 (goblet cells)
CK20 (intestinal-type epithelium)
Lysozyme (Paneth cells)
Ki-67 (proliferation index)
p53 (dysplasia evaluation).
Negative Markers:
MUC5AC (gastric mucin, lost in atrophy)
MUC6 (pyloric gland mucin)
Pepsinogen I (oxyntic glands)
H+/K+-ATPase (parietal cells)
Gastrin (G cells)
Chromogranin A (neuroendocrine cells).
Diagnostic Utility:
Confirms intestinal metaplasia (CDX2, MUC2)
Evaluates completeness of intestinal metaplasia
Assesses proliferative activity (Ki-67)
Identifies dysplasia (p53 overexpression)
Helps differentiate from reactive changes.
Molecular Subtypes:
Complete intestinal metaplasia: CDX2+, MUC2+, Villin+
Incomplete intestinal metaplasia: Mixed MUC2/MUC5AC
Colonic-type: MUC2+, CD10+
Small intestinal-type: MUC2+, CD10-, Villin+.
Molecular/Genetic
Genetic Mutations:
APC mutations (early event)
TP53 mutations (progression to dysplasia)
KRAS mutations (intestinal metaplasia)
PIK3CA mutations
CDH1 mutations (diffuse-type progression)
SMAD4 mutations.
Molecular Markers:
Microsatellite instability (MSI)
CpG island methylation (CIMP)
Wnt pathway activation
p16 hypermethylation
RUNX3 hypermethylation
MGMT promoter methylation.
Prognostic Significance:
Extensive atrophy: higher cancer risk
Incomplete intestinal metaplasia: higher malignant potential
OLGA staging: stages III-IV high risk
p53 mutations: progression marker
Family history: genetic predisposition.
Therapeutic Targets:
H
pylori eradication: prevents progression
Antioxidants: vitamin C, E
COX-2 inhibitors: anti-inflammatory
Probiotics: microbiome modulation
Surveillance endoscopy: early detection.
Differential Diagnosis
Similar Entities:
Reactive gastropathy (NSAIDs, bile reflux)
Active H
pylori gastritis (before atrophy)
Dysplasia (low-grade, high-grade)
Intestinal-type adenocarcinoma (invasive)
Lymphoma (MALT lymphoma)
Hyperplastic polyps.
Distinguishing Features:
Atrophic gastritis: gland loss, fibrosis, intestinal metaplasia
Reactive: surface changes, no atrophy
Active H
pylori: neutrophilic infiltrate, no significant atrophy
Dysplasia: architectural distortion, nuclear atypia
Adenocarcinoma: invasion, desmoplastic response.
Diagnostic Challenges:
Distinguishing atrophy from reactive changes
Grading degree of atrophy accurately
Identifying early dysplasia
Differentiating autoimmune from H
pylori gastritis
Sampling adequacy for accurate assessment
Correlation with endoscopic findings.
Rare Variants:
Autoimmune gastritis: parietal cell antibodies, corpus predominant
Granulomatous gastritis: Crohn disease, sarcoidosis
Eosinophilic gastritis: eosinophil predominance
Lymphocytic gastritis: intraepithelial lymphocytes.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Gastric biopsy from [antrum/corpus/fundus], [number] fragments
Diagnosis
Chronic atrophic gastritis with intestinal metaplasia
Classification
Atrophy grade: [mild/moderate/severe], OLGA stage: [stage]
Histological Features
Shows [degree] loss of gastric glands with replacement by fibrous tissue and chronic inflammation
Intestinal Metaplasia
Intestinal metaplasia: [present/absent], type: [complete/incomplete]
Inflammation
Chronic inflammation: [grade], activity: [present/absent]
Helicobacter Status
H. pylori: [positive/negative/equivocal]
Dysplasia
Dysplasia: [absent/present], grade: [low/high] if present
Special Studies
CDX2: [result], MUC2: [result]
H. pylori testing: [method]: [result]
[other study]: [result]
Final Diagnosis
Chronic atrophic gastritis, [grade], with intestinal metaplasia, [H. pylori status]