Definition/General
Introduction:
Microscopic colitis is a chronic inflammatory disorder characterized by watery diarrhea with normal colonoscopic appearance but abnormal histology
Comprises lymphocytic colitis and collagenous colitis
Shows clinical-pathologic correlation essential for diagnosis
Underrecognized condition requiring biopsy for diagnosis.
Origin:
Results from abnormal immune response in colonic mucosa
Associated with increased intestinal permeability
Shows mucosal inflammation without gross changes
Linked to drug-induced mechanisms
Autoimmune component suspected
Multifactorial etiology.
Classification:
Lymphocytic colitis: increased intraepithelial lymphocytes (>20 per 100 epithelial cells)
Collagenous colitis: thickened subepithelial collagen band (>10 μm)
Incomplete microscopic colitis: partial features of both
Paucicellular variant: minimal inflammation.
Epidemiology:
Peak incidence in middle-aged to elderly (50-70 years)
Strong female predominance (3-9:1 ratio)
Increasing incidence worldwide
Association with autoimmune diseases
Drug-induced cases common
Indian data emerging.
Clinical Features
Presentation:
Chronic watery diarrhea (hallmark)
Normal colonoscopic appearance
Crampy abdominal pain
Urgency and fecal incontinence
Weight loss (variable)
No rectal bleeding or mucus.
Symptoms:
Large-volume watery stools (3-20 per day)
Nocturnal diarrhea (40-60% cases)
Fecal incontinence (50-80% cases)
Lower abdominal cramping
Dehydration
Fatigue and malaise.
Risk Factors:
Female gender
Advanced age (>50 years)
Medications (NSAIDs, PPIs, SSRIs, statins)
Autoimmune diseases (celiac, thyroid, arthritis)
Smoking (variable association)
Genetic predisposition.
Screening:
Colonoscopy with multiple biopsies (essential)
Normal endoscopic mucosa
Right and left colon sampling
Special stains (trichrome)
Stool analysis (exclude infection)
Drug history review.
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Gross Description
Appearance:
Normal colonoscopic appearance (defining feature)
No mucosal abnormalities
Normal vascular pattern
No ulceration, erosions, or mass lesions
Pseudomelanosis coli (if laxative use)
Biopsy sites only visible finding.
Characteristics:
Macroscopically unremarkable colonic mucosa
Normal mucosal color and texture
No inflammatory changes visible grossly
Normal haustral pattern
No strictures or dilatation.
Size Location:
Pan-colonic involvement (histologically)
Uniform distribution
Cecum to rectum affected
Right-sided symptoms often predominant
Small bowel typically spared.
Multifocality:
Diffuse colonic involvement
Consistent microscopic changes
No segmental variation
Both subtypes affect entire colon
Rectal involvement universal.
Microscopic Description
Histological Features:
Lymphocytic colitis: increased intraepithelial lymphocytes, surface epithelial damage
Collagenous colitis: thickened subepithelial collagen band, surface changes
Chronic inflammation in lamina propria
Normal crypt architecture (typically preserved).
Cellular Characteristics:
CD8+ intraepithelial lymphocytes (lymphocytic type)
Subepithelial myofibroblasts (collagenous type)
Chronic inflammatory cells
Surface epithelial flattening
Plasma cell infiltration.
Architectural Patterns:
Preserved crypt architecture
Surface epithelial damage
Homogeneous collagen band (collagenous type)
Normal goblet cell distribution
Minimal crypt distortion.
Grading Criteria:
Lymphocytic colitis: >20 intraepithelial lymphocytes per 100 epithelial cells
Collagenous colitis: >10 μm subepithelial collagen band
Surface epithelial damage assessment
Inflammatory cell density
No formal grading systems.
Immunohistochemistry
Positive Markers:
CD3 and CD8 (intraepithelial lymphocytes)
Smooth muscle actin (myofibroblasts in collagen band)
CD68 (macrophages)
CD20 (B lymphocytes)
Cytokeratin (epithelium).
Negative Markers:
CD4 (fewer intraepithelial)
Specific infectious agents
Malignancy markers
Neuroendocrine markers
Mesenchymal markers.
Diagnostic Utility:
CD3/CD8 highlight intraepithelial lymphocytes
Smooth muscle actin shows myofibroblasts
Usually morphology sufficient
Special stains more useful (trichrome)
Research applications.
Molecular Subtypes:
Drug-induced microscopic colitis
Idiopathic microscopic colitis
Autoimmune-associated
Post-infectious
Incomplete microscopic colitis.
Molecular/Genetic
Genetic Mutations:
HLA-DQ2/DQ8 associations
TNF gene polymorphisms
IL-10 gene variants
TGF-β pathway genes
No specific driver mutations
Polygenic inheritance pattern.
Molecular Markers:
TNF-α and IFN-γ (inflammatory cytokines)
TGF-β1 (fibroblast activation)
IL-15 (lymphocyte activation)
Intestinal permeability markers
Tight junction proteins.
Prognostic Significance:
Chronic relapsing course (both subtypes)
Variable treatment response
Spontaneous remission (20-50% cases)
Drug withdrawal beneficial
No malignant potential.
Therapeutic Targets:
Budesonide (first-line therapy)
Cholestyramine (bile acid sequestrant)
Anti-diarrheal agents
Prednisolone (refractory)
Immunosuppressants (severe disease).
Differential Diagnosis
Similar Entities:
Infectious colitis (organisms present)
Inflammatory bowel disease (architectural changes)
Drug-induced colitis (specific agents)
Irritable bowel syndrome (normal histology)
Celiac disease (small bowel).
Distinguishing Features:
Microscopic colitis: Normal endoscopy, specific histologic changes
Infectious colitis: Organisms identified, acute changes
IBD: Endoscopic abnormalities, crypt distortion
IBS: Normal histology
Celiac: Small bowel villous atrophy.
Diagnostic Challenges:
Distinguishing lymphocytic from collagenous subtypes
Recognizing drug-induced cases
Quantifying diagnostic criteria accurately
Correlating clinical and pathologic findings
Adequate biopsy sampling.
Rare Variants:
Incomplete microscopic colitis
Paucicellular lymphocytic colitis
Gastric microscopic colitis
Mixed lymphocytic-collagenous patterns
Drug-specific variants.
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 multiple colonic sites
Clinical Information
Chronic watery diarrhea with normal colonoscopy. Drug history: [medications]
Endoscopic Correlation
Normal colonoscopic appearance (characteristic of microscopic colitis)
Histologic Subtype
Subtype: [Lymphocytic colitis/Collagenous colitis/Incomplete microscopic colitis]
Quantitative Features
Intraepithelial lymphocytes: [X] per 100 epithelial cells. Collagen band: [X] micrometers
Inflammatory Features
Surface epithelial damage: [present]. Chronic inflammation in lamina propria: [mild/moderate]
Special Stains
Trichrome stain: [highlights collagen band/not performed as not indicated]
Final Diagnosis
Microscopic Colitis - [Lymphocytic/Collagenous] subtype