Definition/General
Introduction:
Lymphocytic gastritis is a rare form of chronic gastritis characterized by increased intraepithelial lymphocytes
It is defined by >20 lymphocytes per 100 epithelial cells
It may be associated with celiac disease and other autoimmune conditions
It represents a distinct histological pattern.
Origin:
Results from immune-mediated inflammation
Associated with gluten sensitivity in some cases
May represent hypersensitivity reaction to dietary or environmental antigens
T-cell mediated inflammatory response
Exact pathogenesis incompletely understood.
Classification:
Primary lymphocytic gastritis: idiopathic
Secondary forms: associated with celiac disease (40-50% cases)
Associated with H
pylori infection
Drug-induced (NSAIDs, PPIs)
Associated with autoimmune conditions.
Epidemiology:
Rare condition (<1% of gastritis cases)
Female predominance (2:1 ratio)
Middle-aged adults (40-60 years)
Strong association with celiac disease (40-50%)
Higher prevalence in Northern Europe.
Clinical Features
Presentation:
Dyspepsia (most common symptom)
Epigastric pain and discomfort
Malabsorption symptoms (celiac disease)
Diarrhea and weight loss
Iron deficiency anemia
Symptoms of associated autoimmune diseases.
Symptoms:
Abdominal pain (epigastric)
Dyspepsia and indigestion
Diarrhea (if celiac disease)
Weight loss and malnutrition
Fatigue and weakness
Dermatitis herpetiformis (celiac association).
Risk Factors:
Celiac disease (major association)
Gluten sensitivity
Family history of autoimmune diseases
Other autoimmune conditions: thyroid disease, diabetes
H
pylori infection
NSAID use.
Screening:
Upper endoscopy with biopsy
Celiac serology: anti-tTG, anti-EMA
HLA typing (DQ2/DQ8)
H
pylori testing
Gluten-free diet trial
Small bowel biopsy (celiac disease).
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Gross Description
Appearance:
Varioliform gastritis (characteristic endoscopic pattern)
Aphthous-like erosions
Mucosal nodularity and irregularity
Cobblestone appearance
Erythematous and friable mucosa
Normal appearance possible.
Characteristics:
Antral involvement most common
Diffuse mucosal changes
Multiple small erosions
Thickened folds possible
Nodular gastritis pattern
May appear normal endoscopically.
Size Location:
Antral predominance (60-70% cases)
May involve corpus and fundus
Diffuse distribution possible
Concurrent duodenal changes (celiac disease)
Patchy involvement.
Multifocality:
Multifocal distribution
Often pan-gastric involvement
Associated with duodenal changes (celiac disease)
Variable endoscopic appearance
Skip lesions possible.
Microscopic Description
Histological Features:
Increased intraepithelial lymphocytes (>20/100 epithelial cells)
Chronic inflammation in lamina propria
Surface epithelial damage and regeneration
Lymphoid follicles may be present
Minimal glandular atrophy initially.
Cellular Characteristics:
Intraepithelial T-lymphocytes (predominantly CD8+)
Surface epithelial damage
Chronic inflammatory infiltrate in lamina propria
Lymphocytes and plasma cells
Increased mitotic activity.
Architectural Patterns:
Preserved glandular architecture (early stages)
Surface epithelial irregularity
Foveolar hyperplasia
Lamina propria expansion
Progressive atrophy (chronic cases)
Intestinal metaplasia (late changes).
Grading Criteria:
Intraepithelial lymphocyte count: >20/100 epithelial cells (diagnostic)
Surface epithelial damage: mild, moderate, severe
Chronic inflammation grade: 0-3
Atrophy assessment: 0-3.
Immunohistochemistry
Positive Markers:
CD3 (T-lymphocytes)
CD8 (cytotoxic T-cells predominant)
CD20 (B-cell component)
Ki-67 (increased proliferation)
CD68 (macrophages)
CD117 (mast cells).
Negative Markers:
CD4 (fewer helper T-cells)
Chromogranin A (normal neuroendocrine cells)
H
pylori (may be absent)
Viral markers (CMV, EBV) typically negative.
Diagnostic Utility:
Confirms T-cell nature of intraepithelial lymphocytes
Demonstrates CD8+ predominance
Excludes lymphoproliferative disorders
Assesses inflammatory pattern
Evaluates for viral infections.
Molecular Subtypes:
CD8+ T-cell predominant pattern
Mixed CD4+/CD8+ pattern
Associated with celiac disease: similar IEL pattern
H
pylori-associated: mixed inflammatory pattern.
Molecular/Genetic
Genetic Mutations:
HLA-DQ2/DQ8 association (celiac-related cases)
CTLA-4 polymorphisms
IL-15 gene variants
TNF-α gene polymorphisms
T-cell receptor gene rearrangements.
Molecular Markers:
Elevated IL-15
Increased interferon-γ
T-cell activation markers
Tissue transglutaminase (celiac association)
Zonulin elevation (intestinal permeability).
Prognostic Significance:
Celiac association: responds to gluten-free diet
Idiopathic cases: variable response to treatment
H
pylori association: responds to eradication
Chronic inflammation: risk of atrophy.
Therapeutic Targets:
Gluten-free diet (celiac-associated cases)
H
pylori eradication (when present)
Corticosteroids (severe cases)
Proton pump inhibitors
Elimination diets (food sensitivities).
Differential Diagnosis
Similar Entities:
H
pylori gastritis
Autoimmune gastritis
Reactive gastropathy
Viral gastritis (CMV, EBV)
Primary gastric lymphoma
Crohn disease.
Distinguishing Features:
Lymphocytic gastritis: increased IEL >20/100, CD8+ predominance
H
pylori: organisms present, neutrophilic activity
Autoimmune: corpus involvement, ECL hyperplasia
Viral: inclusion bodies
Lymphoma: monoclonality.
Diagnostic Challenges:
Accurate IEL counting
Distinguishing from reactive changes
Identifying underlying associations
Correlation with celiac serology
Excluding viral infections
Assessment of treatment response.
Rare Variants:
Pediatric lymphocytic gastritis
Drug-induced forms
Association with tropical sprue
Concurrent with duodenal lymphocytosis
Progression to MALT lymphoma.
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 [site], [number] fragments
Diagnosis
Lymphocytic gastritis
Intraepithelial Lymphocytes
IEL count: [number]/100 epithelial cells (normal <20/100)
Histological Features
Increased intraepithelial lymphocytes with surface epithelial damage and chronic inflammation
Inflammation
Chronic inflammation: [grade], predominantly lymphoplasmacytic
Architecture
Glandular architecture: [preserved/altered]
Special Studies
CD3: [result], CD8: [result]
H. pylori: [present/absent]
[other study]: [result]
Recommendations
Consider celiac disease evaluation, H. pylori testing
Final Diagnosis
Lymphocytic gastritis with increased intraepithelial lymphocytes