Lymphocyte to Neutrophil Ratio in Pleural Fluid Suggestive of Tuberculosis
A lymphocyte to neutrophil ratio greater than or equal to 0.75 in pleural fluid is highly suggestive of tuberculous pleuritis, with this threshold providing 88% sensitivity and 95% specificity for tuberculosis diagnosis when combined with elevated adenosine deaminase levels. 1
Diagnostic Cellular Patterns in Pleural Fluid
Lymphocyte Predominance in TB
- A lymphocyte percentage ≥25% in pleural fluid suggests granulomatous disease, including tuberculosis, sarcoidosis, or hypersensitivity pneumonitis 2, 3
- Lymphocyte percentage >50% is particularly suggestive of tuberculosis or cellular NSIP 2
- Tuberculous pleural effusions are typically characterized by:
Neutrophil Patterns
- While lymphocyte predominance is classic in TB, approximately 9.5% of tuberculous pleural effusions can be neutrophil-predominant 5
- A neutrophil differential count ≥50% typically suggests acute lung injury, aspiration pneumonia, or suppurative infection rather than TB 2
Diagnostic Value of Lymphocyte/Neutrophil Ratio
The lymphocyte to neutrophil ratio in pleural fluid provides valuable diagnostic information:
L/N ratio ≥0.75: When combined with elevated adenosine deaminase (ADA) levels (≥50 U/L), this ratio achieves:
- 88% sensitivity
- 95% specificity
- 95% positive predictive value
- 88% negative predictive value
- 92% diagnostic efficiency for tuberculosis 1
Using the L/N ratio significantly improves the specificity of ADA testing alone (which is 81% by itself) 1
Clinical Considerations
Neutrophil-Predominant TB Pleural Effusions
Neutrophil-predominant TB pleural effusions show:
- Higher inflammatory serum markers (elevated WBC count and CRP)
- Higher rates of positive AFB in sputum (36.8% vs 9.4%)
- Higher diagnostic yield of MTB culture (78.9% vs 22.7%)
- Higher detection rates by PCR (31.6% vs 5.0%) 5
Contrary to traditional belief, neutrophil-predominant TB pleural effusions may not always transition to lymphocyte-predominant forms 5
Differential Diagnosis
Lower neutrophil-lymphocyte ratio values are significantly associated with tuberculous pleural effusion compared to malignant, para-pneumonic, and para-malignant effusions 6
Similar lymphocyte-rich patterns with high adenosine deaminase levels can be seen in both tuberculosis and tularemia, suggesting analogous pathogenetic mechanisms 7
Practical Approach to Pleural Fluid Analysis
Obtain pleural fluid for:
- Cell count with differential
- Adenosine deaminase (ADA) level
- Gram stain and bacterial culture
- Acid-fast bacilli stain and TB culture
Calculate the lymphocyte to neutrophil ratio
Interpret findings:
- L/N ratio ≥0.75 + ADA ≥50 U/L: Highly suggestive of TB (95% specificity)
- Lymphocyte percentage >50%: Strongly suggests TB or hypersensitivity pneumonitis
- Neutrophil percentage ≥50%: Consider acute infection, but TB remains possible
For lymphocyte-predominant effusions with high ADA, consider TB even with negative stains/cultures, as microbiological confirmation is often difficult
For neutrophil-predominant effusions, more aggressive microbiological testing is warranted as they have higher yield for MTB detection
Remember that while lymphocyte predominance is the classic pattern in tuberculous pleural effusions, neutrophil-predominant patterns can occur in approximately 10% of cases and should not rule out TB diagnosis when other clinical features are suggestive.