TB Granuloma

Definition

A tuberculous granuloma is a classic caseating (necrotic) granuloma caused by Mycobacterium tuberculosis. It consists of central caseous necrosis surrounded by epithelioid macrophages and Langhans giant cells, rimmed by lymphocytes and outer collagen fibrosis — representing a type IV delayed hypersensitivity reaction.

General / Essential Features

• Central caseous (cheese-like) necrosis — amorphous eosinophilic acellular material
• Langhans giant cells: peripheral horseshoe arrangement of nuclei
• Surrounding epithelioid macrophages (transformed from monocytes)
• Rim of lymphocytic infiltration around the granuloma
• Collagen strands (fibrosis) forming the outer boundary
• ZN (Ziehl–Neelsen) stain demonstrates acid-fast bacilli (AFB)

Sites

• Lung (primary complex: subpleural focus + hilar lymph node)
• Lymph nodes (cervical, mediastinal, mesenteric)
• Pleura, peritoneum (miliary/disseminated TB)
• Gut (ileocaecal junction — most common GI site)
• Bone and joints (Pott's spine: vertebral TB)
• Kidneys, adrenal glands, CNS (tuberculomas)

Pathophysiology

M. tuberculosis is phagocytosed by alveolar macrophages but resists killing via inhibition of phagosome–lysosome fusion. Antigen presentation activates CD4+ Th1 cells, which release IFN-γ, activating macrophages to form epithelioid cells and fuse into giant cells. Cytokine-mediated hypoxia and direct bacterial toxins cause central caseation. Containment failure leads to cavitation and dissemination.

Etiology

• Mycobacterium tuberculosis: aerobic, acid-fast bacillus
• Mycobacterium bovis: zoonotic, from unpasteurised dairy
• Risk factors: HIV/AIDS, malnutrition, diabetes, crowded living
• Immunosuppressive therapy (corticosteroids, TNF-α inhibitors)

Clinical Features

• Primary TB: usually asymptomatic; Ghon complex on CXR
• Post-primary TB: productive cough, haemoptysis, fever, night sweats, weight loss
• Pleural effusion: exudative, lymphocyte-predominant
• Extrapulmonary: lymphadenopathy, cold abscess, spinal pain (Pott's)
• Miliary TB: bilateral fine nodular shadows on CXR ('millet seeds')

Diagnosis

• Sputum AFB smear and culture (Lowenstein–Jensen medium — 6–8 weeks)
• GeneXpert MTB/RIF: rapid PCR with rifampicin resistance detection
• Histopathology: caseating granuloma + ZN stain
• Tuberculin skin test (TST/Mantoux) and IGRA (QuantiFERON)
• CXR: upper lobe cavitation, hilar lymphadenopathy

Treatment

• HRZE: Isoniazid + Rifampicin + Pyrazinamide + Ethambutol for 2 months
• Then HR: Isoniazid + Rifampicin for 4 months (total 6 months)
• MDR-TB: longer regimens with second-line drugs (fluoroquinolones, linezolid)
• Corticosteroids: adjunctive in TB meningitis and pericarditis