Definition/General
Introduction:
Inflammatory bowel disease (IBD) comprises chronic inflammatory disorders of the gastrointestinal tract
Includes ulcerative colitis and Crohn disease
Characterized by relapsing-remitting course
Shows immune-mediated inflammation
Increased cancer risk with longstanding disease.
Origin:
Results from dysregulated immune response to intestinal microbiota
Involves genetic predisposition and environmental factors
Shows loss of immune tolerance
Associated with barrier dysfunction
Multifactorial etiology.
Classification:
Ulcerative colitis: continuous mucosal inflammation limited to colon
Crohn disease: transmural, skip lesions, any GI segment
IBD unclassified: features of both
Microscopic colitis: lymphocytic and collagenous
WHO classification recognizes distinct entities.
Epidemiology:
Peak incidence in young adults (20-40 years)
Bimodal distribution (second peak 60-70 years)
Rising incidence in developing countries including India
Urban predominance
Familial clustering (genetic factors).
Clinical Features
Presentation:
Chronic diarrhea (most common)
Rectal bleeding (ulcerative colitis)
Abdominal pain (cramping)
Weight loss
Fever (active disease)
Extraintestinal manifestations.
Symptoms:
Bloody diarrhea (ulcerative colitis >90%)
Mucus passage
Urgency and tenesmus
Crampy abdominal pain
Fatigue
Perianal disease (Crohn disease).
Risk Factors:
Genetic predisposition (family history)
Environmental factors (Western lifestyle)
Smoking (protective in UC, harmful in CD)
Appendectomy (protective in UC)
NSAIDs (may trigger).
Screening:
Colonoscopy (diagnosis and surveillance)
Histological examination (essential)
Stool studies (exclude infection)
Imaging (CT/MRI enterography)
Dysplasia surveillance (long-standing disease).
Master Inflammatory Bowel Disease Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Ulcerative colitis: continuous mucosal inflammation, granular surface, loss of haustrations
Crohn disease: skip lesions, cobblestone mucosa, deep ulcers, strictures
Pseudopolyps common
Mucosal edema and hyperemia.
Characteristics:
Diffuse involvement (ulcerative colitis) vs patchy (Crohn)
Superficial ulceration (UC) vs deep fissures (CD)
Lead pipe colon (chronic UC)
String sign (CD strictures)
Fistula formation (CD).
Size Location:
Ulcerative colitis: always involves rectum, extends proximally
Left-sided colitis (most common in Asia)
Pancolitis (extensive disease)
Crohn disease: any segment, ileocolonic most common.
Multifocality:
Continuous involvement (ulcerative colitis)
Skip lesions (Crohn disease)
Rectal sparing (uncommon in UC, may occur with treatment)
Backwash ileitis (severe UC)
Upper GI involvement (Crohn only).
Microscopic Description
Histological Features:
Chronic inflammation in lamina propria
Cryptitis and crypt abscesses
Crypt architectural distortion
Surface epithelial damage
Increased chronic inflammatory cells
Basal lymphoplasmacytosis.
Cellular Characteristics:
Lymphocytes, plasma cells, and eosinophils in lamina propria
Neutrophils in crypts (active inflammation)
Surface epithelial regeneration
Goblet cell depletion
Paneth cell metaplasia (left-sided colon).
Architectural Patterns:
Crypt branching and shortening
Irregular crypt spacing
Surface villiform change
Basal lymphoid aggregates
Transmural inflammation (Crohn disease)
Granulomas (Crohn disease, 60% cases).
Grading Criteria:
Quiescent: minimal inflammation, architectural distortion only
Mild activity: cryptitis, few crypt abscesses
Moderate activity: numerous crypt abscesses, surface erosion
Severe activity: extensive ulceration, marked inflammation.
Immunohistochemistry
Positive Markers:
CD3 (T lymphocytes)
CD20 (B lymphocytes)
CD68 (macrophages)
Cytokeratins (epithelium)
Ki-67 (increased proliferation).
Negative Markers:
CMV (unless superinfection)
HSV (unless superinfection)
Specific pathogens (excluded by special stains)
Malignancy markers (unless dysplasia/carcinoma).
Diagnostic Utility:
Excludes infectious etiology
Assesses inflammatory cell types
Evaluation for dysplasia (p53, Ki-67)
CMV inclusion bodies (immunocompromised)
Usually not required for IBD diagnosis.
Molecular Subtypes:
Ulcerative colitis: Th2-mediated
Crohn disease: Th1/Th17-mediated
Genetic susceptibility genes: NOD2, IL23R, ATG16L1
Pharmacogenomics: TPMT, NUDT15.
Molecular/Genetic
Genetic Mutations:
NOD2 mutations (Crohn disease)
IL23R variants (both UC and CD)
ATG16L1 mutations (autophagy defects)
CARD9 variants
FUT2 gene (secretor status).
Molecular Markers:
Increased TNF-α
IL-23/IL-17 axis
Interferon-γ (Crohn)
IL-13 (ulcerative colitis)
Autophagy dysfunction
Barrier function genes.
Prognostic Significance:
Extent of disease (prognosis factor)
Age at onset (<18 years worse prognosis)
Extraintestinal manifestations
Steroid dependency
Dysplasia development (cancer risk).
Therapeutic Targets:
Anti-TNF agents (infliximab, adalimumab)
Anti-integrin (vedolizumab)
JAK inhibitors (tofacitinib)
Anti-IL23 (ustekinumab)
Ozanimod (S1P receptor modulator).
Differential Diagnosis
Similar Entities:
Infectious colitis (bacterial, viral, parasitic)
Ischemic colitis
Radiation colitis
Drug-induced colitis
Microscopic colitis
Solitary rectal ulcer syndrome.
Distinguishing Features:
IBD: Chronic changes, architectural distortion
Infectious: Acute inflammation, organisms
Ischemic: Watershed areas, hyalinized stroma
Radiation: Atypical fibroblasts, vascular changes
Drug-induced: Eosinophilia, history.
Diagnostic Challenges:
Distinguishing UC from CD (10% indeterminate)
Differentiating from infectious colitis
Recognizing dysplasia vs regenerative atypia
Assessing response to treatment
Clinical correlation essential.
Rare Variants:
Microscopic colitis (lymphocytic, collagenous)
Diversion colitis
Pouchitis (post-IPAA)
Drug-induced microscopic colitis
IBD unclassified.
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
History of [IBD type/duration]. Current symptoms: [symptoms]
Activity Grade
Activity: [Quiescent/Mild/Moderate/Severe]
Chronic Changes
Architectural distortion: [present/absent]. Basal lymphoplasmacytosis: [present/absent]. Crypt branching and shortening noted.
Acute Inflammation
Cryptitis: [present/absent]. Crypt abscesses: [present/absent]. Surface erosion: [present/absent]
Special Features
Granulomas: [present/absent]. Transmural inflammation: [present/absent]. Fissuring ulceration: [present/absent]
Dysplasia Assessment
Dysplasia: [Negative/Indefinite/Low-grade/High-grade]
Final Diagnosis
Chronic colitis, [active/quiescent], consistent with [ulcerative colitis/Crohn disease/IBD unclassified]