Definition/General

Introduction:
-Small intestinal tuberculosis is a chronic granulomatous infection caused by Mycobacterium tuberculosis
-It represents extrapulmonary tuberculosis
-It is endemic in developing countries including India
-It shows granulomatous inflammation with caseation necrosis.
Origin:
-Caused by Mycobacterium tuberculosis complex
-Spread by hematogenous route from pulmonary focus
-Lymphatic spread from adjacent lymph nodes
-Direct ingestion of infected sputum
-Results in chronic granulomatous inflammation.
Classification:
-Primary intestinal TB: no evidence of pulmonary TB
-Secondary intestinal TB: associated with pulmonary TB
-Location: ileocecal region most common (85%)
-Small bowel involvement: terminal ileum predominantly.
Epidemiology:
-High prevalence in India (endemic region)
-Young adults most affected (20-40 years)
-No gender predilection
-Malnutrition and immunosuppression predispose
-Associated with HIV coinfection.

Clinical Features

Presentation:
-Chronic abdominal pain (most common)
-Fever and weight loss
-Diarrhea or constipation
-Small bowel obstruction
-Right iliac fossa mass
-Intestinal perforation (rare).
Symptoms:
-Right iliac fossa pain (mimics appendicitis)
-Constitutional symptoms: fever, night sweats, weight loss
-Altered bowel habits
-Anorexia and malaise
-Abdominal distension
-Symptoms of intestinal obstruction.
Risk Factors:
-Immunocompromised states: HIV, diabetes, malnutrition
-Poverty and overcrowding
-Contact with active TB
-Corticosteroid therapy
-Alcoholism
-Previous history of tuberculosis.
Screening:
-CT abdomen (bowel wall thickening, lymphadenopathy)
-Colonoscopy with biopsy
-Tuberculin skin test
-Interferon-gamma release assays (IGRA)
-Chest X-ray (pulmonary TB)
-Histopathological examination.

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Gross Description

Appearance:
-Bowel wall thickening and rigidity
-Ulcerative lesions with undermined edges
-Strictures and scarring
-Mesenteric lymphadenopathy
-Caseating lymph nodes
-Perforation (complications).
Characteristics:
-Terminal ileum and ileocecal valve involvement
-Transverse ulcers (characteristic)
-Skip lesions pattern
-Bowel wall thickening up to 2-3 cm
-Serosal nodules
-Adhesions and matting.
Size Location:
-Terminal ileum (85% cases)
-Ileocecal valve commonly involved
-Right colon extension
-Jejunal involvement (10-15%)
-Multiple sites possible
-Segmental distribution.
Multifocality:
-Ileocecal region predilection
-Skip lesions characteristic
-Multifocal involvement common
-Mesenteric lymph node involvement
-Peritoneal seedling possible.

Microscopic Description

Histological Features:
-Epithelioid granulomas with caseation necrosis
-Langhans giant cells
-Chronic inflammation
-Transmural involvement
-Mucosal ulceration
-Fibrosis and scarring.
Cellular Characteristics:
-Epithelioid cells (activated macrophages)
-Langhans-type giant cells
-Lymphocytes and plasma cells
-Caseation necrosis (pathognomonic)
-Neutrophilic infiltrate (secondary infection)
-Eosinophils may be present.
Architectural Patterns:
-Well-formed granulomas
-Transmural inflammation
-Mucosal destruction and ulceration
-Submucosal fibrosis
-Lymphatic obstruction
-Neural involvement (myenteric plexus).
Grading Criteria:
-Granuloma maturity: well-formed vs poorly-formed
-Caseation presence: typical vs atypical
-Bacterial load: paucibacillary vs multibacillary
-Inflammatory activity: active vs healing.

Immunohistochemistry

Positive Markers:
-CD68 (macrophages/epithelioid cells)
-CD163 (M2 macrophages)
-Lysozyme (macrophages)
-CD3 (T-lymphocytes)
-CD20 (B-lymphocytes in mantle).
Negative Markers:
-Cytokeratins (excludes epithelial cells)
-CD30 (excludes lymphoma)
-S-100 (excludes nerve sheath tumors)
-Melanin (excludes melanoma).
Diagnostic Utility:
-Confirms macrophage nature of epithelioid cells
-Demonstrates granulomatous inflammation
-Excludes other causes of granulomas
-Assesses inflammatory cell composition
-Identifies mycobacteria when combined with special stains.
Molecular Subtypes:
-Classical granulomatous TB
-Atypical presentations: minimal granulomas
-Drug-resistant TB: altered inflammatory response
-HIV-associated TB: reduced granuloma formation.

Molecular/Genetic

Genetic Mutations:
-Host genetic factors: HLA associations, cytokine gene polymorphisms
-Mycobacterial drug resistance: rpoB, katG, inhA genes
-MDR-TB markers: resistance to rifampin and isoniazid
-XDR-TB markers: additional fluoroquinolone resistance.
Molecular Markers:
-Interferon-γ production
-TNF-α elevation
-IL-12 and IL-18 upregulation
-Th1 immune response markers
-Bacterial DNA/RNA detection.
Prognostic Significance:
-Early diagnosis: better treatment outcomes
-Drug resistance: worse prognosis
-Immunocompromised hosts: higher mortality
-Complications: perforation, obstruction affect prognosis.
Therapeutic Targets:
-Anti-TB therapy: DOTS regimen (6 months)
-First-line drugs: rifampin, isoniazid, ethambutol, pyrazinamide
-MDR-TB treatment: second-line drugs
-Surgical intervention: complications
-Nutritional support.

Differential Diagnosis

Similar Entities:
-Crohn disease
-Adenocarcinoma
-Lymphoma
-Other granulomatous infections
-Sarcoidosis
-Foreign body reaction.
Distinguishing Features:
-TB: caseating granulomas, AFB positive, endemic area
-Crohn: non-caseating granulomas, skip lesions, transmural
-Cancer: malignant cells, no granulomas
-Other infections: specific organisms identified.
Diagnostic Challenges:
-Distinguishing from Crohn disease (both show granulomas)
-Identifying mycobacteria (paucibacillary cases)
-Culture confirmation (slow growth)
-Correlation with clinical presentation
-Drug resistance testing.
Rare Variants:
-Hypertrophic TB
-Ulcerative TB
-Ulcerohypertrophic TB
-Fibrous stricture (healed TB)
-Miliary TB (disseminated form).

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

Small bowel biopsy/resection from [terminal ileum/jejunum], [number] fragments

Diagnosis

Chronic granulomatous inflammation consistent with tuberculosis

Granulomas

Epithelioid granulomas with caseation necrosis and Langhans giant cells

Distribution

Transmural involvement with mucosal ulceration

Special Stains

Ziehl-Neelsen stain: [positive/negative] for acid-fast bacilli

Associated Changes

Chronic inflammation with fibrosis and mucosal destruction

Molecular Studies

TB PCR: [positive/negative/pending]

Mycobacterial culture: [pending/positive/negative]

Drug susceptibility: [pending if culture positive]

Recommendations

Clinical correlation, anti-tubercular therapy, culture confirmation

Final Diagnosis

Small intestinal tuberculosis with chronic granulomatous inflammation