Definition/General
Introduction:
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by continuous mucosal inflammation limited to the colon and rectum
It shows superficial inflammation affecting mucosa and superficial submucosa
Demonstrates skip lesion absence and rectal involvement
Associated with increased colorectal cancer risk.
Origin:
Results from dysregulated immune response to luminal antigens in genetically susceptible individuals
Shows loss of immune tolerance to commensal bacteria
Involves Th2 and Th17 inflammatory pathways
Demonstrates epithelial barrier dysfunction
Associated with autoimmune phenomena.
Classification:
Extent-based classification: Proctitis (rectum only)
Left-sided colitis (to splenic flexure)
Extensive colitis (beyond splenic flexure)
Pancolitis (entire colon)
Severity: Mild, moderate, severe
Fulminant colitis (toxic megacolon).
Epidemiology:
Bimodal age distribution: peak at 20-40 years and 60-70 years
Increasing incidence in India and developing countries
Urban predominance
Genetic predisposition (HLA associations)
Environmental triggers important
10-15% family history.
Clinical Features
Presentation:
Bloody diarrhea (hallmark symptom)
Abdominal cramping
Urgency and tenesmus
Mucus in stools
Weight loss
Fatigue
Low-grade fever
Extraintestinal manifestations.
Symptoms:
Diarrhea with blood and mucus (95% cases)
Abdominal pain (cramping, left-sided)
Urgency and frequency
Tenesmus
Constitutional symptoms (fever, weight loss)
Arthralgia
Skin lesions (erythema nodosum, pyoderma gangrenosum).
Risk Factors:
Genetic susceptibility (HLA-DRB1, HLA-DQB1)
Family history
Environmental factors (diet, stress)
Smoking paradox (protective in UC)
Appendectomy may be protective
Westernized lifestyle
Antibiotic exposure.
Screening:
Colonoscopy with biopsies for diagnosis
Surveillance colonoscopy for dysplasia (after 8-10 years)
Chromoendoscopy for enhanced detection
Stool calprotectin for activity monitoring
Serum inflammatory markers (CRP, ESR).
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Gross Description
Appearance:
Continuous mucosal inflammation starting from rectum
Erythematous, granular mucosa
Loss of vascular pattern
Pseudopolyps in chronic cases
Shortened, narrowed colon
Lead pipe appearance in severe cases.
Characteristics:
Mucosal ulceration with undermined edges
Friable, hemorrhagic mucosa
Absence of skip lesions
Rectal involvement constant
Proximal extension in continuous manner
Inflammatory polyps common.
Size Location:
Rectum always involved
Continuous proximal extension
Proctitis (30% cases)
Left-sided disease (40%)
Pancolitis (30%)
Backwash ileitis in severe pancolitis
No small bowel involvement primarily.
Multifocality:
Continuous disease without skip lesions
Uniform severity in involved segments
Rectum most severely affected
Decreasing severity proximally
Sharp demarcation between normal and diseased bowel.
Microscopic Description
Histological Features:
Chronic active colitis with surface epithelial damage
Crypt architectural distortion
Increased chronic inflammation in lamina propria
Crypt abscesses
Surface erosions and ulceration
Basal plasmacytosis.
Cellular Characteristics:
Surface epithelial depletion
Increased lymphocytes and plasma cells
Neutrophils in crypts (cryptitis)
Eosinophils moderately increased
Mucin depletion in goblet cells
Paneth cell metaplasia in left colon.
Architectural Patterns:
Crypt branching and shortening
Crypt loss in severe cases
Villiform surface may develop
Surface irregularity
Mucin depletion pattern
Submucosal fibrosis in chronic cases.
Grading Criteria:
Quiescent colitis: architectural distortion only
Mild activity: cryptitis, minimal surface damage
Moderate activity: surface erosions, crypt abscesses
Severe activity: extensive ulceration, marked inflammation
Dysplasia grading (low-grade, high-grade).
Immunohistochemistry
Positive Markers:
Not routinely required for diagnosis
CD68 highlights macrophages
Tryptase for mast cells
CD3/CD20 for lymphocyte subsets
Ki-67 in dysplasia evaluation
p53 in dysplasia assessment.
Negative Markers:
CMV immunostain negative (excludes viral colitis)
HSV immunostain negative
No specific negative markers for UC
Histiocyte markers help exclude specific infections.
Diagnostic Utility:
Mainly morphological diagnosis
IHC helps exclude infections
p53 and Ki-67 useful in dysplasia
MLH1, MSH2, MSH6, PMS2 in cancer surveillance
Exclude other colitides.
Molecular Subtypes:
No specific molecular subtypes
Microsatellite stable cancers usually
p53 pathway alterations in dysplasia-carcinoma sequence
APC mutations less common than sporadic cancers.
Molecular/Genetic
Genetic Mutations:
Complex polygenic disorder
HLA associations (DRB1*0103, DQB1*0601)
NOD2 mutations less common than Crohns
IL23R polymorphisms
CARD9 mutations
Multiple susceptibility loci (>200 identified).
Molecular Markers:
Increased TNF-α
IL-13 pathway activation
Th2/Th17 cytokines
Epithelial barrier dysfunction
Oxidative stress markers
Calprotectin elevation.
Prognostic Significance:
Extent of disease predicts outcome
Early age onset more aggressive
Pancolitis higher cancer risk
Duration >8-10 years surveillance needed
Dysplasia indicates cancer risk
Genetic markers predict therapy response.
Therapeutic Targets:
Anti-TNF therapy (infliximab, adalimumab)
Anti-integrin therapy (vedolizumab)
JAK inhibitors (tofacitinib)
IL-12/23 inhibitors
5-ASA compounds
Immunosuppressives (azathioprine, methotrexate).
Differential Diagnosis
Similar Entities:
Crohns disease - transmural inflammation, skip lesions, granulomas
Infectious colitis - acute onset, organisms identified
Ischemic colitis - watershed areas, older patients
Microscopic colitis - normal endoscopy, thickened subepithelial collagen
Drug-induced colitis - medication history.
Distinguishing Features:
Crohns disease: granulomas, transmural, skip lesions, small bowel involvement
Infectious colitis: acute onset, self-limited, organisms
Ischemic colitis: watershed distribution, ghost cells
Microscopic colitis: thickened subepithelial layer, normal endoscopy
NSAID colitis: medication history, diaphragm disease.
Diagnostic Challenges:
Early disease may lack characteristic features
Quiescent colitis vs normal mucosa
Distinguishing from Crohns (indeterminate colitis)
Dysplasia detection in inflammation
Infectious superimposition.
Rare Variants:
Fulminant colitis - toxic megacolon
Backwash ileitis - terminal ileal involvement
Left-sided UC with cecal patch
Pediatric UC - more extensive disease
Elderly-onset UC - different presentation.
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
Colorectal biopsies from [sites], [number] fragments
Diagnosis
Chronic active colitis consistent with ulcerative colitis
Activity Grade
[Quiescent/Mild/Moderate/Severe] inflammatory activity
Histological Features
Shows chronic active colitis with crypt architectural distortion, basal plasmacytosis, and [specific features]
Architectural Changes
Crypt architectural distortion: [present/absent], Crypt branching: [present/absent]
Dysplasia Assessment
Dysplasia: [absent/low-grade/high-grade/indefinite]
Special Studies
CMV immunostain: negative
No molecular testing indicated
No organisms identified
Recommendations
Continue surveillance colonoscopy. Dysplasia surveillance if >8-10 years duration.
Final Diagnosis
Ulcerative colitis with [activity grade], [dysplasia status]