Pathology · Year 2 · from Pathology
Case 2: Pulmonary Tuberculosis - Granulomatous Inflammation
Patient Demographics
- Age: 35 years old
- Sex: Male
- Occupation: Healthcare worker (originally from the Philippines)
Chief Complaint
"Cough with blood-streaked sputum for 3 weeks"
History of Present Illness
A 35-year-old male healthcare worker presents with a 3-week history of productive cough that has recently become blood-streaked. He reports drenching night sweats requiring multiple changes of bedclothes, unintentional 15-pound weight loss over 2 months, low-grade fevers, and progressive fatigue. He emigrated from the Philippines 5 years ago and remembers receiving BCG vaccination as a child. He works as a nurse's aide at a long-term care facility. He has no HIV risk factors and takes no medications.
Physical Examination
- Vital Signs: BP 110/68 mmHg, HR 92 bpm, RR 18/min, Temp 38.1°C (100.6°F), SpO2 94% on room air
- General: Thin, cachectic-appearing male
- HEENT: No lymphadenopathy
- Lungs: Decreased breath sounds and crackles at right upper lobe posteriorly
- Heart: Tachycardic, regular rhythm
- Abdomen: Soft, non-tender, no hepatosplenomegaly
- Extremities: No clubbing, edema, or skin lesions
Diagnostic Workup
Laboratory Studies:
| Test | Result | Reference Range |
|---|---|---|
| WBC | 9,800/μL | 4,500-11,000/μL |
| Lymphocytes | 18% | 20-40% |
| Hemoglobin | 10.8 g/dL | 13.5-17.5 g/dL |
| Albumin | 2.9 g/dL | 3.5-5.5 g/dL |
| ESR | 78 mm/hr | <20 mm/hr |
| HIV test | Negative | Negative |
Imaging:
- Chest X-ray: Right upper lobe infiltrate with cavitation, tree-in-bud nodular opacities
- CT Chest: 3 cm cavitary lesion in right upper lobe with thick irregular walls, centrilobular nodules, mediastinal lymphadenopathy
Microbiology:
| Test | Result |
|---|---|
| Sputum AFB smear | Positive (3+) for acid-fast bacilli |
| Sputum AFB culture | Positive for M. tuberculosis (4 weeks) |
| Nucleic acid amplification | Positive for M. tuberculosis complex |
| Drug susceptibility | Susceptible to all first-line drugs |
| Interferon-gamma release assay | Positive |
Bronchoscopy with BAL and Transbronchial Biopsy:
- Histopathology:
- Multiple caseating granulomas
- Central zones of caseous (cheesy) necrosis
- Surrounding epithelioid macrophages
- Langhans-type multinucleated giant cells (horseshoe nuclear arrangement)
- Lymphocyte collar at periphery
- Acid-fast bacilli identified on Ziehl-Neelsen stain
Pathology Correlation
This case demonstrates caseating granulomatous inflammation:
- Granuloma Formation:
- Central caseous necrosis (eosinophilic, acellular material)
- Epithelioid macrophages (activated, transformed appearance)
- Langhans giant cells (fused macrophages with horseshoe nuclei)
- Surrounding lymphocyte collar
- Peripheral fibrosis
- Pathogenesis:
- M. tuberculosis survives within macrophages
- T cells (Th1) produce IFN-gamma to activate macrophages
- Activated macrophages transform into epithelioid cells
- TNF-alpha essential for granuloma maintenance
- Caseous necrosis from hypoxia and immune-mediated cytotoxicity
- Disease Manifestations:
- Cavitation results from liquefaction of caseous material
- Upper lobe predilection due to higher oxygen tension
- Constitutional symptoms from TNF-alpha and IL-1 (fever, weight loss, night sweats)
- Hemoptysis from erosion into blood vessels
- Comparison with Non-Caseating Granulomas:
- Sarcoidosis: Non-caseating, no necrosis
- TB: Caseating necrosis is characteristic
Clinical Image
Chest radiograph demonstrating active pulmonary tuberculosis with a cavitary lesion in the right upper lobe. The cavity represents liquefied caseous necrosis that has been expectorated, leaving an air-filled space. Upper lobe involvement is characteristic of reactivation TB due to higher oxygen tension favoring mycobacterial growth.
Image Source: Wikimedia Commons - "Tuberculosis X-ray" License: Public Domain URL: https://commons.wikimedia.org/wiki/File:Tuberculosis-x-ray-1.jpg
Diagnosis
Active Pulmonary Tuberculosis - Cavitary, drug-susceptible
Treatment
- Respiratory isolation with negative pressure room
- Directly observed therapy (DOT)
- Four-drug initial regimen: Rifampin, Isoniazid, Pyrazinamide, Ethambutol (RIPE)
- Vitamin B6 (pyridoxine) supplementation with isoniazid
- Monthly sputum monitoring until culture-negative
- Contact investigation for exposed individuals
- Treatment duration: 6 months minimum
Teaching Points
- Granulomatous inflammation represents a specialized form of chronic inflammation against persistent antigens
- Caseating necrosis strongly suggests tuberculosis (or endemic fungi)
- Epithelioid transformation of macrophages reflects IFN-gamma-mediated activation
- Langhans giant cells result from macrophage fusion under cytokine influence
- TNF-alpha is essential for granuloma formation and maintenance (anti-TNF therapy can reactivate TB)
- The upper lobe predilection reflects higher oxygen tension favoring M. tuberculosis
- Constitutional symptoms result from circulating cytokines (TNF, IL-1, IL-6)