What pleural fluid test differentiates tuberculosis from malignancy?

From the Guidelines

Adenosine deaminase (ADA) testing of pleural fluid is the most useful test to differentiate tuberculosis from malignancy, with an elevated ADA level above 40 U/L strongly suggesting tuberculous pleurisy, while lower levels are more consistent with malignancy. This is based on the most recent and highest quality study available, which prioritizes morbidity, mortality, and quality of life as the outcome 1. The test has high sensitivity and specificity for tuberculous pleural effusions, making it a valuable tool in clinical practice.

Key Points to Consider

• ADA testing is particularly valuable in resource-limited settings as it is relatively inexpensive and provides rapid results compared to culture methods.
• Other supportive tests include pleural fluid lymphocyte predominance, low glucose, high protein levels, and positive acid-fast bacilli staining or culture, though these are less specific.
• In clinical practice, ADA results should be interpreted alongside clinical presentation, radiological findings, and other pleural fluid parameters for optimal diagnostic accuracy.
• The British Thoracic Society guideline for pleural disease recommends the use of pleural fluid ADA and/or IFN-gamma test(s) for diagnosing tuberculous pleural effusion in high prevalence populations 1.

Limitations and Considerations

• ADA levels may not be raised if the patient has HIV and tuberculosis, which can affect the accuracy of the test 1.
• The test may not be useful in countries with a low prevalence of tuberculosis, as ADA levels can also be raised in empyema, rheumatoid pleurisy, and malignancy 1.
• The diagnostic yield of pleural fluid cytology varies depending on tumor type, tumor load, sample quality, expertise of cytologist, and availability of specific ancillary tests 1.

Clinical Application

• Pleural fluid ADA testing should be used as a diagnostic tool to differentiate tuberculosis from malignancy, taking into account the patient's clinical presentation, radiological findings, and other pleural fluid parameters.
• The test results should be interpreted in the context of the patient's overall clinical picture, and further investigation should be considered if the results are inconclusive or if there is a high suspicion of malignancy.

From the Research

Pleural Fluid Tests for Differentiating Tuberculosis from Malignancy

• Adenosine deaminase (ADA) is a useful biomarker for differentiating tuberculous pleural effusion (TPE) from malignant pleural effusion (MPE) 2, 3, 4, 5.
• The cutoff value of ADA for TPE diagnosis varies, with studies suggesting values ranging from 36 U/L to 49 U/L 2, 3.
• ADA activity below 16 U/L suggests that TPE is highly unlikely, with a sensitivity of 38.5% and specificity of 100% 2.
• The ADA effusion/serum ratio can also be used, with a cutoff value of 1.7 having a sensitivity of 84.6% and specificity of 72.2% for TPE diagnosis 2.
• Other features that can help differentiate TPE from MPE include lymphocyte percentage, lactate dehydrogenase (LD)/ADA ratio, and serum LD levels 4.
• Pleuroscopy-guided pleural biopsy is a valuable diagnostic tool for TPE, with a sensitivity of 66.7% and specificity of 100% 2.
• Cytology evaluation can also be used, with a sensitivity of 72.2% and specificity of 70.1% for TPE diagnosis 2.
• It is essential to note that ADA activity can be elevated in other conditions, such as hematologic malignancies, and therefore should be interpreted in conjunction with other diagnostic tests and clinical findings 4, 6.