Pathology · Year 2 · from Pathology

Case 1: Pulmonary Tuberculosis with Caseating Granulomas

Patient Demographics

• Age: 35 years old
• Sex: Male
• Occupation: Recent immigrant, construction worker

Chief Complaint

"Cough with blood-tinged sputum, night sweats, and weight loss for 2 months"

History of Present Illness

A 35-year-old male from the Philippines presents with a 2-month history of productive cough, initially with yellow sputum that has recently become blood-streaked. He reports drenching night sweats requiring him to change his shirt, fevers, and unintentional weight loss of 8 kg. He has mild shortness of breath with exertion. He immigrated to the United States 1 year ago. He has no known HIV risk factors and denies prior TB diagnosis or treatment. He lives in a shared housing arrangement with 5 other individuals.

Physical Examination

• Vital Signs: BP 118/72 mmHg, HR 96 bpm, RR 20/min, Temp 38.4C, SpO2 95% on room air
• General: Thin male, appears chronically ill, mild respiratory distress
• HEENT: No oral lesions, mild cervical lymphadenopathy
• Respiratory: Decreased breath sounds in right upper lobe with bronchial breath sounds, few crackles
• Cardiovascular: Tachycardia, no murmurs
• Abdomen: Soft, non-tender
• Extremities: No clubbing or edema

Diagnostic Workup

Laboratory Studies:

Imaging:

• Chest X-ray: Right upper lobe cavitary lesion (3.5 cm) with surrounding infiltrate, additional nodular opacities in right middle lobe
• CT Chest: Cavitary lesion in right upper lobe with tree-in-bud nodularity, mediastinal lymphadenopathy with central hypodensity

Microbiology:

• Sputum AFB smear: 3+ acid-fast bacilli
• GeneXpert MTB/RIF: Mycobacterium tuberculosis detected, rifampin resistance not detected
• Sputum culture: Pending (Mycobacterium tuberculosis grew at 3 weeks)

Tuberculin Skin Test:

• 22 mm induration at 48 hours (strongly positive)

Pathology Correlation

This case demonstrates the characteristic pathology of tuberculosis infection:

Primary TB vs. Reactivation TB:

Primary TB (Ghon Complex):

• Initial infection, usually childhood
• Ghon focus: Subpleural granuloma, typically middle or lower lung
• Ghon complex: Ghon focus + involved hilar lymph nodes
• Usually asymptomatic, heals with fibrosis and calcification
• May progress to primary progressive TB in immunocompromised

Reactivation TB (Secondary TB):

• Reactivation of latent infection
• Typically involves apical and posterior segments of upper lobes
• Higher oxygen tension favors M. tuberculosis growth
• Cavitation common (as in this patient)
• Highly contagious

Histopathology of TB:

Caseating Granuloma:

1. Central caseating necrosis - "cheesy" appearance, acellular, eosinophilic
2. Epithelioid macrophages - activated macrophages with elongated, "footprint-shaped" nuclei
3. Langhans giant cells - multinucleated giant cells with nuclei arranged in horseshoe/peripheral pattern
4. Lymphocyte collar - surrounding rim of lymphocytes and fibroblasts

Why Caseation?

• Result of Type IV hypersensitivity (delayed-type) response
• T cells release IFN-gamma activating macrophages
• TNF-alpha mediates granuloma formation
• Central necrosis represents killed bacteria and dead immune cells

Special Stains:

• Ziehl-Neelsen or Kinyoun stain: Acid-fast bacilli (red rods)
• Organisms often sparse in tissue; culture more sensitive

Clinical Image

Gross pathology of pulmonary tuberculosis showing caseating granulomas with characteristic "cheesy" white necrotic centers. The caseous material has a soft, friable consistency. Cavitation may develop when this material is expectorated.

Image Source: Wikimedia Commons - "Tuberculosis pathology" License: CC BY-SA 3.0 URL: https://commons.wikimedia.org/wiki/File:Tuberculosis_-_Teknisk_Museum_01.jpg

Diagnosis

Pulmonary Tuberculosis, Cavitary, Sputum Smear-Positive

• Active, infectious disease
• Drug-susceptible (based on molecular testing)

Treatment

Initial Phase (2 months):

• RIPE therapy:
• Rifampin
• Isoniazid (+ pyridoxine to prevent neuropathy)
• Pyrazinamide
• Ethambutol

Continuation Phase (4 months):

• Rifampin + Isoniazid

Public Health:

1. Respiratory isolation until 3 negative AFB smears
2. Directly Observed Therapy (DOT)
3. Contact investigation for all close contacts
4. Report to public health authorities

Teaching Points

1. Caseating granulomas are the histologic hallmark of TB
2. Langhans giant cells with peripheral horseshoe nuclei are characteristic (but not pathognomonic)
3. Reactivation TB typically involves upper lobes (higher PO2)
4. Type IV hypersensitivity mediates granuloma formation and tissue damage
5. AFB smear detects highly infectious patients; culture is gold standard for diagnosis
6. The tuberculin skin test detects delayed-type hypersensitivity, not active disease

All cases for this lecture as Markdown