Endoscopic ultrasound-guided fine-needle aspiration staging of lung cancer: is it time to go beyond cytology?

15% (this means that 85% of the subjects with a positive test result will not have a TPE).9 The incidence of TPE is generally associated with the regional prevalence of tuberculosis.2 In the United States, only a small proportion of exudative pleural effusions are caused by tuberculosis.10 In TPE, a lymphocyte-dominant pleurisy, ADA is released in the presence of live intracellular Mycobacterium tuberculosis. It is thought that false-positive diagnoses of TPE by ADA level determination can be significantly reduced if ADA measurement is limited to lymphocytic pleural fluids. Theoretically, however, other lymphocyte-rich pleural effusions associated with live intracellular microorganisms also could have elevated ADA pleural fluid levels,11 including those caused by coccidioidomycosis and histoplasmosis, which are endemic mycoses in vast areas of the United States. High levels of ADA also have been reported in noninfectious conditions associated with pleural fluid lymphocytosis, including malignant conditions (eg, adenocarcinomas, leukemias, and lymphomas) and collagen vascular diseases (eg, rheumatoid pleuritis and systemic lupus erythematosus),5,7 which make the test less useful in countries with a low prevalence of tuberculosis.12,13 Therefore, an increased ADA level should not be considered as an equivalent to the presence of mycobacteria in the pleural fluid or pleural biopsy specimens.2 A higher rate of falsepositive test results can lead to the unnecessary administration of antituberculous therapy or a delay in making an alternative diagnosis. In areas with a high prevalence of tuberculosis, the proportion of false-positive results will be obviously lower. However, a limitation of the test in this setting, as a sole method of diagnosis, is that culture results will not be available to guide antituberculosis chemotherapy. Culture results are particularly necessary if drug-resistant tuberculosis is prevalent,10 an increasingly frequent scenario in countries with high rates of tuberculosis. Patients with drug-resistant tuberculosis may receive treatment with inefficient drugs due to the lack of availability of culture and drug-sensitivity results. With the decline in the prevalence of TPE, the positive predictive value of pleural fluid ADA also declines, but the negative predictive value actually increases. Therefore, the measurement of the pleural fluid ADA level could be used to rule out a tuberculous etiology of lymphocytic pleural effusions, regardless of the rate of prevalence of the disease.2,4 In conclusion, the ADA assay should not be considered as an alternative to biopsy and culture, but rather as a screening test to guide further diagnostic procedures and management of an exudative pleural effusion of unknown origin.2,3