Definition/General
Introduction:
Autoimmune gastritis is a chronic inflammatory condition characterized by autoantibodies against gastric parietal cells
It leads to progressive oxyntic gland atrophy
It results in achlorhydria and intrinsic factor deficiency
It is associated with pernicious anemia and vitamin B12 deficiency.
Origin:
Results from autoimmune destruction of gastric parietal cells
Mediated by anti-parietal cell antibodies (90% cases)
Anti-intrinsic factor antibodies (60% cases)
Involves type IV hypersensitivity reaction
Leads to loss of acid production and intrinsic factor.
Classification:
Type A gastritis: autoimmune etiology
Involves corpus and fundus predominantly
Associated with hypergastrinemia
Classified by severity: mild, moderate, severe atrophy
Often associated with other autoimmune conditions.
Epidemiology:
Prevalence: 0.5-2% general population
Higher in Northern Europeans
Female predominance (3:1 ratio)
Peak incidence in 5th-6th decades
Strong family clustering
Associated with other autoimmune diseases (thyroid, diabetes).
Clinical Features
Presentation:
Megaloblastic anemia (B12 deficiency)
Neurological symptoms (peripheral neuropathy, dementia)
Glossitis and angular cheilitis
Achlorhydria
Iron deficiency (gastric atrophy)
Weight loss and fatigue.
Symptoms:
Fatigue and weakness (anemia)
Neurological symptoms: paresthesias, ataxia, cognitive impairment
Glossitis (smooth, red tongue)
Dyspepsia (less common)
Weight loss
Premature graying of hair.
Risk Factors:
Female sex (3:1 predominance)
Advanced age (>50 years)
Family history of autoimmune gastritis
Other autoimmune diseases: Hashimoto thyroiditis, type 1 diabetes, Addison disease
Northern European ancestry.
Screening:
Vitamin B12 levels
Anti-parietal cell antibodies (APCA)
Anti-intrinsic factor antibodies (AIFA)
Serum gastrin levels (elevated)
Pepsinogen I/II ratio (low)
Complete blood count (megaloblastic anemia).
Master Autoimmune Gastritis Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Corpus and fundus atrophy with mucosal thinning
Antral sparing (characteristic)
Loss of normal rugal folds in body
Visible submucosal vessels
Pale, smooth mucosal surface
Nodular hyperplasia may be present.
Characteristics:
Severe mucosal atrophy in corpus/fundus
Antral preservation (pathognomonic)
Loss of normal gastric fold pattern
Thin, atrophic mucosa
Endocrine cell hyperplasia (G-cell, ECL-cell).
Size Location:
Corpus-fundus predominant involvement
Antral sparing is characteristic
Transition zone at incisura angularis
Progressive proximal extension
May involve entire corpus in severe cases.
Multifocality:
Diffuse involvement of oxyntic mucosa
Antral-sparing pattern
Uniform distribution in affected areas
Associated neuroendocrine hyperplasia
Potential for carcinoid tumor development.
Microscopic Description
Histological Features:
Progressive oxyntic gland loss
Replacement by connective tissue and intestinal metaplasia
Chronic inflammation with lymphocytes and plasma cells
Parietal cell loss
Enterochromaffin-like (ECL) cell hyperplasia.
Cellular Characteristics:
Chronic inflammatory infiltrate
Loss of parietal and chief cells
Intestinal metaplasia (complete and incomplete)
Pseudopyloric metaplasia
ECL cell hyperplasia and dysplasia
Neuroendocrine micronests.
Architectural Patterns:
Glandular atrophy with crypt shortening
Intestinal metaplasia with goblet cells
Pseudopyloric metaplasia
Fibrosis replacing normal lamina propria
Neuroendocrine proliferation.
Grading Criteria:
OLGA/OLGIM staging
Atrophy grade: 0 (none) to 3 (severe)
Intestinal metaplasia grade: 0-3
Neuroendocrine changes: hyperplasia to dysplasia
ECL cell assessment.
Immunohistochemistry
Positive Markers:
Chromogranin A (ECL cell hyperplasia)
Synaptophysin (neuroendocrine cells)
CDX2 (intestinal metaplasia)
MUC2 (goblet cells)
Ki-67 (proliferation index)
Gastrin (G-cell hyperplasia).
Negative Markers:
H+/K+-ATPase (parietal cell loss)
Pepsinogen I (chief cell loss)
MUC5AC (gastric mucin loss)
MUC6 (pyloric gland mucin)
Intrinsic factor (lost).
Diagnostic Utility:
Confirms parietal cell loss
Identifies ECL cell hyperplasia
Assesses neuroendocrine proliferation
Evaluates intestinal metaplasia
Monitors carcinoid development
Distinguishes from H
pylori gastritis.
Molecular Subtypes:
Type I gastric carcinoids: associated with autoimmune gastritis
ECL cell hyperplasia: linear, micronodular, adenomatoid, dysplastic
Intestinal metaplasia: complete vs incomplete types.
Molecular/Genetic
Genetic Mutations:
MEN1 gene mutations (multiple endocrine neoplasia)
ATP4A gene (H+/K+-ATPase alpha subunit)
ATP4B gene (H+/K+-ATPase beta subunit)
CTLA-4 polymorphisms
IL-1β gene polymorphisms.
Molecular Markers:
Hypergastrinemia (>1000 pg/ml)
Low pepsinogen I/II ratio
Anti-parietal cell antibodies (H+/K+-ATPase)
Anti-intrinsic factor antibodies
Elevated chromogranin A.
Prognostic Significance:
Severe atrophy: increased gastric cancer risk
ECL cell hyperplasia: carcinoid tumor risk
Hypergastrinemia duration: neuroendocrine tumor development
Intestinal metaplasia: adenocarcinoma risk.
Therapeutic Targets:
Vitamin B12 supplementation
Iron supplementation
Proton pump inhibitors (symptom control)
Octreotide (severe hypergastrinemia)
Surveillance endoscopy
Carcinoid resection when indicated.
Differential Diagnosis
Similar Entities:
H
pylori gastritis (antral-predominant)
Environmental atrophic gastritis
Drug-induced gastritis (PPIs, H2 blockers)
Hypergastrinemia from other causes
Neuroendocrine tumors
Zollinger-Ellison syndrome.
Distinguishing Features:
Autoimmune gastritis: corpus-predominant, antral sparing, ECL hyperplasia
H
pylori: antral-predominant, organisms present
Environmental: multifocal pattern
Drug-induced: reversible changes
ZES: duodenal ulcers, gastrinoma.
Diagnostic Challenges:
Distinguishing from environmental gastritis
Identifying early neuroendocrine changes
Differentiating ECL hyperplasia from carcinoid tumor
Correlation with serological markers
Assessment of cancer risk.
Rare Variants:
Juvenile autoimmune gastritis (early onset)
Familial clusters
Association with polyglandular syndrome
Concurrent H
pylori infection
Progression to gastric adenocarcinoma.
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 [corpus/fundus/antrum], [number] fragments
Diagnosis
Autoimmune gastritis with oxyntic atrophy
Distribution Pattern
Corpus-fundus involvement with antral sparing
Atrophy Grade
Oxyntic gland atrophy: [mild/moderate/severe]
Intestinal Metaplasia
Intestinal metaplasia: [present/absent], type: [complete/incomplete]
Neuroendocrine Changes
ECL cell hyperplasia: [linear/micronodular/adenomatoid/dysplastic]
Inflammation
Chronic inflammation: [grade], predominantly lymphoplasmacytic
Special Studies
Chromogranin A: [result], H+/K+-ATPase: [result]
APCA: [positive/negative], AIFA: [positive/negative]
Gastrin level: [value] pg/ml
Risk Assessment
Increased risk for gastric carcinoid and adenocarcinoma
Final Diagnosis
Autoimmune gastritis with [grade] atrophy and ECL cell hyperplasia