Definition/General
Introduction:
Tuberculous pleural effusion is caused by Mycobacterium tuberculosis infection of the pleural space
It represents 20-30% of all pleural effusions in India
It is predominantly a hypersensitivity reaction to mycobacterial antigens
Pleural biopsy shows higher diagnostic yield than pleural fluid cytology alone.
Origin:
Results from rupture of subpleural caseous focus into pleural space
Can occur from primary or post-primary tuberculosis
Hematogenous spread from pulmonary or extrapulmonary TB
Immune-mediated response to mycobacterial proteins causes pleural inflammation.
Classification:
Classified as exudative effusion
Protein >3 g/dL
LDH >200 U/L
Pleural fluid to serum protein ratio >0.5
Light's criteria positive for exudate
May be unilateral or bilateral.
Epidemiology:
High prevalence in endemic areas like India
Peak incidence in young adults (20-40 years)
Male predominance in most studies
Associated with HIV co-infection in 10-15% cases
Drug-resistant TB increasing in prevalence.
Clinical Features
Presentation:
Insidious onset of chest pain and dyspnea
Low-grade fever with night sweats
Weight loss and malaise
Dry cough initially, may become productive
Chest pain pleuritic in nature.
Symptoms:
Fever (60-80% cases)
Night sweats (70% cases)
Weight loss (50-70% cases)
Chest pain (80-90% cases)
Dyspnea (60-80% cases)
Cough (40-60% cases)
Constitutional symptoms prominent.
Risk Factors:
HIV infection (10-15x increased risk)
Diabetes mellitus
Immunosuppression
Malnutrition
Chronic kidney disease
Silicosis
Endemic area residence.
Screening:
Tuberculin skin test (TST)
Interferon-gamma release assays (IGRAs)
Chest X-ray and CT thorax
Sputum examination for AFB
HIV testing recommended in all cases.
Master Tuberculous Pleural Effusion Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Pleural fluid is typically straw-colored to turbid
May be hemorrhagic in some cases
Viscous consistency due to high protein content
Volume varies from small to massive
Loculated in chronic cases.
Characteristics:
Exudative characteristics
Protein >3 g/dL (usually 4-6 g/dL)
LDH >200 U/L (often >500 U/L)
Low glucose (<60 mg/dL)
Low pH (<7.35)
High ADA levels (>40 U/L).
Size Location:
Usually unilateral (80% cases)
Right-sided slightly more common
May be bilateral in disseminated TB
Free-flowing in acute cases
Loculated in chronic/complicated cases.
Multifocality:
Predominantly unilateral involvement
Bilateral effusions in 10-20% cases
Associated with pulmonary tuberculosis in 30-50% cases
May have pleural thickening and adhesions
Empyema formation in complicated cases.
Microscopic Description
Histological Features:
Pleural fluid shows lymphocytic predominance (>50%)
Total cell count 1000-6000 cells/μL
Activated lymphocytes and plasma cells
Reactive mesothelial cells
Epithelioid cells may be present.
Cellular Characteristics:
Small mature lymphocytes predominant
Large activated lymphocytes with prominent nucleoli
Plasma cells with eccentric nuclei
Mesothelial cells show reactive changes
Macrophages with vacuolated cytoplasm.
Architectural Patterns:
Dispersed cellular pattern
Lymphocytic clusters may be present
Reactive mesothelial proliferation
Epithelioid cell clusters (when present)
Background inflammatory debris.
Grading Criteria:
No specific grading system
Assessment based on lymphocyte percentage
ADA levels for diagnostic support
AFB demonstration rarely achieved
PCR positivity increases diagnostic accuracy.
Immunohistochemistry
Positive Markers:
CD3, CD20 for lymphocyte typing
CD68 positive in macrophages
Calretinin, WT1 in reactive mesothelial cells
CD138 in plasma cells
Epithelioid cells may show CD68 positivity.
Negative Markers:
Cytokeratins (except in mesothelial cells)
CEA, TTF-1 to exclude adenocarcinoma
CD15, CD30 to exclude lymphoma
Melanoma markers to exclude metastatic melanoma.
Diagnostic Utility:
IHC has limited role in TB diagnosis
Helps exclude malignancy when differential diagnosis unclear
T-cell predominance supports TB diagnosis
Mesothelial markers help identify reactive mesothelial proliferation.
Molecular Subtypes:
T-helper cell predominance (CD4+)
Th1 response characteristic of TB
Interferon-gamma production by activated T-cells
IL-2, TNF-alpha elevated in pleural fluid.
Molecular/Genetic
Genetic Mutations:
No specific mutations in host cells
Mycobacterial DNA may be detected by PCR
IS6110 sequence specific for M
tuberculosis
16S rRNA gene amplification
GeneXpert MTB/RIF for rapid diagnosis.
Molecular Markers:
Interferon-gamma elevated in pleural fluid
TNF-alpha, IL-2 increased
Adenosine deaminase (ADA) >40 U/L
Lysozyme levels elevated
Pleural fluid ADA isoenzyme ADA2 predominant.
Prognostic Significance:
Drug sensitivity pattern determines prognosis
HIV co-infection worsens prognosis
Multi-drug resistance associated with poor outcomes
Early diagnosis and treatment improve prognosis
Complete treatment prevents recurrence.
Therapeutic Targets:
Anti-tubercular therapy (ATT): HRZE regimen
Isoniazid, Rifampin, Ethambutol, Pyrazinamide
Treatment duration 6-9 months
Drug resistance testing guides therapy
Corticosteroids in complicated cases.
Differential Diagnosis
Similar Entities:
Malignant pleural effusion (adenocarcinoma, mesothelioma)
Parapneumonic effusion (bacterial pneumonia)
Viral pleuritis (lymphocytic predominance)
Rheumatoid pleuritis (autoimmune)
Fungal pleuritis (endemic mycoses).
Distinguishing Features:
TB: High ADA levels (>40 U/L)
TB: Lymphocytic predominance
TB: Low glucose, low pH
Malignant: Cytological atypia
Bacterial: Neutrophilic predominance
Viral: Normal ADA levels.
Diagnostic Challenges:
Low yield of AFB demonstration (10-20%)
Culture positivity in 20-40% cases
Overlap with other lymphocytic effusions
Reactive mesothelial proliferation mimicking malignancy
Need for pleural biopsy in many cases.
Rare Variants:
Hemorrhagic tuberculous effusion
Chylous tuberculous effusion (rare)
Fibrinous/organized tuberculous pleuritis
Tuberculous empyema
Multi-drug resistant TB effusion.
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
Pleural fluid, volume [X] mL, straw-colored to turbid
Adequacy
Adequate for cytological evaluation
Cellularity
Moderate to high cellularity with [X] cells/μL
Cell Differential
Lymphocytes: [X]% (predominantly small mature), Mesothelial cells: [X]%, Macrophages: [X]%, Neutrophils: [X]%
Morphological Features
Predominance of small mature lymphocytes with occasional large activated forms. Reactive mesothelial cells present. Background shows proteinaceous material.
AFB Staining
AFB staining: [Positive/Negative for acid-fast bacilli]
Additional Studies
ADA level: [X] U/L (>40 U/L suggestive of tuberculosis)
Malignant Cells
No malignant cells identified
Final Diagnosis
Pleural fluid cytology consistent with tuberculous pleuritis
Comment
Findings suggest tuberculous etiology. Recommend correlation with ADA levels, imaging, and clinical presentation. Consider pleural biopsy if diagnosis unclear.