Pleural Fluid Ratios Aid Early Diagnosis of Malignant Pleural Effusion: Study

A new study published in The American Journal of Medicine showed that pleural fluid total protein-to-adenosine deaminase (ADA) and lactate dehydrogenase-to-ADA ratios have significant diagnostic value in identifying malignant pleural effusion. Cut-off values of >3.34 for the protein/ADA ratio and >19.87 for the LDH/ADA ratio effectively differentiate malignant from benign pleural effusions, helping enable earlier diagnosis and reducing unnecessary invasive procedures.

Pleural effusion can develop from a wide range of causes, including infections, heart failure, inflammatory diseases, and cancer. Determining whether the fluid is benign or malignant is crucial as cancer-related pleural effusion often indicates advanced disease and requires rapid treatment planning. However, current diagnostic methods can sometimes be inconclusive, leading to repeated testing or invasive procedures such as thoracoscopy and pleural biopsy.

Adenosine deaminase is commonly used in pleural fluid analysis, particularly to help diagnose tuberculosis-related pleural effusion. The new study suggests that combining ADA with protein and LDH measurements may significantly expand its diagnostic utility in oncology. 

This study analyzed clinical and laboratory data from 251 patients with pleural effusion. Among them, 49 patients were diagnosed with cancer-related malignant pleural effusion, while 202 patients had benign causes of fluid accumulation.

This research evaluated multiple serum and pleural fluid biomarkers to identify combinations with the greatest diagnostic accuracy. Through statistical modeling and receiver operating characteristic (ROC) curve analysis, this research identified several key indicators associated with malignant pleural effusion, including pleural fluid lactate dehydrogenase (LDH), total protein, adenosine deaminase (ADA), and glucose levels.

Among all tested parameters, the pleural fluid total protein-to-adenosine deaminase ratio and the pleural fluid lactate dehydrogenase-to-adenosine deaminase ratio demonstrated the strongest diagnostic performance.

Also, a total protein-to-ADA ratio greater than 3.34 effectively differentiated malignant from benign pleural effusions, achieving a sensitivity of nearly 80% and specificity of 72%. Similarly, an LDH-to-ADA ratio above 19.87 demonstrated sensitivity over 81% with a specificity of 71%. The diagnostic accuracy of these ratios was reflected in strong area under the curve (AUC) values of 0.833 and 0.802, respectively.

Overall, the findings of this study suggest that early differentiation between malignant and benign pleural effusion can influence treatment decisions, reduce delays in diagnosis, and potentially spare some patients from unnecessary invasive procedures.

Reference:

Chen, D., Jiang, F., Liu, Q., & Wang, Q. (2026). A retrospective study of the usefulness of pleural effusion and blood indicators and ratios in detecting benign and malignant pleural effusion. The American Journal of Medicine. https://doi.org/10.1016/j.amjmed.2026.05.001