Definition/General
Introduction:
Lymphocytic colitis is a form of microscopic colitis characterized by chronic watery diarrhea and increased intraepithelial lymphocytes
Part of microscopic colitis spectrum
Shows normal endoscopic appearance with characteristic histologic changes
Chronic inflammatory condition of unknown etiology.
Origin:
Results from abnormal immune response in colonic mucosa
Associated with increased mucosal permeability
Shows T-lymphocyte infiltration
Linked to autoimmune mechanisms
Drug-induced cases well recognized
Genetic predisposition possible.
Classification:
Lymphocytic colitis (increased intraepithelial lymphocytes)
Collagenous colitis (thickened subepithelial collagen)
Incomplete microscopic colitis (partial features)
Drug-induced microscopic colitis
WHO recognizes as distinct entities.
Epidemiology:
Peak incidence in middle-aged women (50-70 years)
Female predominance (5:1 ratio)
Increasing recognition worldwide
Association with autoimmune diseases
Indian data limited but cases increasingly reported.
Clinical Features
Presentation:
Chronic watery diarrhea (hallmark symptom)
Normal colonoscopy
Crampy abdominal pain
Urgency and incontinence
Weight loss (variable)
No rectal bleeding.
Symptoms:
Large-volume watery diarrhea (3-20 stools/day)
Nocturnal diarrhea (40-50% cases)
Fecal incontinence
Abdominal cramping
Dehydration
Fatigue.
Risk Factors:
Female gender
Advanced age (>50 years)
Autoimmune diseases (celiac disease, thyroid disorders)
Medications (NSAIDs, PPIs, SSRIs)
Smoking
HLA associations.
Screening:
Colonoscopy with biopsy (essential)
Normal endoscopic appearance
Multiple colonic biopsies
Stool studies (exclude infection)
Celiac serology
Thyroid function tests.
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Gross Description
Appearance:
Normal gross appearance (endoscopically)
No visible mucosal abnormalities
Normal colonic mucosa color and texture
No ulceration or mass lesions
Pseudomelanosis coli (if laxative use).
Characteristics:
Macroscopically normal colonic mucosa
No inflammatory changes visible grossly
Normal mucosal folds
No strictures or dilatation
Biopsy sites only visible abnormality.
Size Location:
Pan-colonic involvement (histologically)
Right-sided predominance (some studies)
Cecum to rectum affected
Small bowel sparing
Uniform distribution.
Multifocality:
Diffuse colonic involvement
Patchy severity possible
Right and left colon affected
Rectal involvement consistent
No segmental sparing.
Microscopic Description
Histological Features:
Increased intraepithelial lymphocytes (>20 per 100 epithelial cells)
Surface epithelial damage
Chronic inflammation in lamina propria
Normal crypt architecture
No significant subepithelial collagen thickening.
Cellular Characteristics:
Intraepithelial CD8+ T lymphocytes
Surface epithelial flattening
Increased chronic inflammatory cells in lamina propria
Plasma cells and lymphocytes
Minimal neutrophils.
Architectural Patterns:
Preserved crypt architecture
Surface epithelial damage with lymphocytic infiltration
Normal subepithelial collagen (<7 micrometers)
Minimal crypt distortion
No increased mitoses.
Grading Criteria:
Intraepithelial lymphocyte count (>20 per 100 epithelial cells diagnostic)
Surface epithelial damage assessment
Chronic inflammation degree
Subepithelial collagen thickness (<7 μm)
No formal grading system.
Immunohistochemistry
Positive Markers:
CD3 (intraepithelial T lymphocytes)
CD8 (predominant intraepithelial subset)
CD68 (lamina propria macrophages)
CD20 (B lymphocytes in lamina propria)
Cytokeratin (epithelium).
Negative Markers:
CD4 (fewer intraepithelial cells)
Specific infectious agents
Malignancy markers
Neuroendocrine markers (unless incidental)
Mesenchymal markers.
Diagnostic Utility:
CD3/CD8 highlights intraepithelial lymphocytes
Confirms T-cell nature
Excludes other lymphoid proliferations
Usually not required for diagnosis
Research applications.
Molecular Subtypes:
Drug-induced subtype
Idiopathic subtype
Autoimmune-associated
Post-infectious
HLA-DQ2/DQ8 associated.
Molecular/Genetic
Genetic Mutations:
HLA-DQ2 association
HLA-DQ8 association
TNF gene polymorphisms
IL-10 gene variants
No specific driver mutations
Polygenic predisposition.
Molecular Markers:
Increased TNF-α
Interferon-γ
IL-15 (intraepithelial lymphocyte activation)
Increased intestinal permeability markers
Tight junction proteins (claudins, occludin).
Prognostic Significance:
Chronic relapsing course
Variable response to treatment
Spontaneous remission possible (30-50%)
Drug withdrawal may lead to improvement
No malignant potential.
Therapeutic Targets:
Budesonide (first-line treatment)
Cholestyramine (bile acid sequestrant)
Loperamide (symptomatic)
Prednisolone (refractory cases)
Immunosuppressants (severe cases).
Differential Diagnosis
Similar Entities:
Collagenous colitis (thickened subepithelial collagen)
Celiac disease (small bowel involvement)
Infectious colitis (organisms present)
Drug-induced colitis (specific drugs)
Inflammatory bowel disease (early stages).
Distinguishing Features:
Lymphocytic colitis: Increased intraepithelial lymphocytes, normal collagen
Collagenous colitis: Thickened subepithelial collagen band
Celiac disease: Small bowel villous atrophy
Infectious: Organisms identified
IBD: Crypt architectural distortion.
Diagnostic Challenges:
Distinguishing from collagenous colitis (collagen band thickness)
Differentiating from reactive changes
Recognizing drug-induced cases
Quantifying intraepithelial lymphocytes accurately
Normal endoscopy with abnormal histology.
Rare Variants:
Incomplete microscopic colitis
Drug-induced lymphocytic colitis
Post-infectious lymphocytic colitis
Lymphocytic gastroenterocolitis
Paucicellular lymphocytic colitis.
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
[specimen type] from [anatomical location]
Clinical Information
Chronic watery diarrhea. Normal colonoscopy. Drug history: [specify medications]
Intraepithelial Lymphocytes
Intraepithelial lymphocytes: [X] per 100 epithelial cells (normal <20, diagnostic >20)
Epithelial Changes
Surface epithelial damage: [present/absent]. Epithelial flattening: [present/absent]
Inflammatory Features
Chronic inflammation in lamina propria: [mild/moderate]. Plasma cell infiltration: [present/absent]
Subepithelial Collagen
Subepithelial collagen thickness: [X] micrometers (normal <7 μm)
Crypt Architecture
Crypt architecture: [preserved/minimally distorted]. No significant architectural distortion
Final Diagnosis
Lymphocytic Colitis - Microscopic colitis with increased intraepithelial lymphocytes