https://doi.org/10.4081/monaldi.2026.3731
Utility of pleural fluid biomarkers in differentiating malignant and benign pleural effusion: a cross-sectional study
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Published: 6 August 2026
As cytopathological examination of the pleural fluid (PF) has a low yield, it is difficult to differentiate benign from malignant pleural effusions (PEs). There is still a lack of biomarkers in PF that can reliably help in diagnosing malignant PEs. Diagnostic accuracy in diagnosing malignant PEs is enhanced by the presence of tumor markers in PE. This would raise the likelihood of diagnosing malignant PEs with an unclear cause and starting treatment interventions early to lower morbidity and death rates in the patient. Thus, in an effort to enhance the PE diagnosis, novel PF biomarkers such as cancer ratio, cancer ratio plus, carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125), and calprotectin were evaluated. A total of 108 patients with PEs were taken, and after applying inclusion and exclusion criteria, 83 patients with exudative PE were evaluated. After clinical history and routine blood investigations, PF was sent for cytopathology, biochemical examinations, microbiological examinations for aerobic culture, fungal culture, mycobacterial culture, and biomarker (CEA, CA-125, calprotectin) analyses. Out of 83 patients with exudative PE, malignant effusion was diagnosed in 40 patients, while 43 had benign effusions. PF biomarkers adenosine deaminase (ADA), CEA, cancer ratio, calprotectin, age/ADA and serum lactate dehydrogenase (LDH)/calprotectin ratio showed a statistically significant (p<0.0001) difference between benign and malignant PE. PF CEA showed the highest specificity (97.67%) at the cut-off point of 1.96 ng/mL and age/ADA ratio showed the highest sensitivity (97.5%) at the cut-off point of 1.56 for prediction of malignancy. Cancer ratio, PL calprotectin and serum LDH/calprotectin ratio also showed good sensitivity and specificity for the prediction of malignancy. PF CA-125 showed poor sensitivity (50%) and cancer ratio plus did not reveal any statistically significant difference for prediction of malignancy from benign effusion (p=0.486). PF biomarkers (cancer ratio, CEA, age/ADA ratio, calprotectin, and serum LDH/calprotectin ratio) are reliable indicators of malignancy in exudative pleural effusions. Patients with exudative lymphocytic with unexplained pleural effusion can be addressed early using inexpensive and generally available biochemical indicators, such as pleural fluid CEA, calprotectin, cancer ratio, and serum LDH/calprotectin ratio.
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