Integrating pleural fluid and peripheral blood biomarkers to improve malignant vs. tuberculous pleural effusion diagnosis: a retrospective study

Accurate differentiation between malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE) remains a critical clinical challenge, attributed to the suboptimal sensitivity of pleural effusion (PE) cytology for MPE and low microbiological positivity rate for TPE. This study evaluated the diagnostic value of individual and combined biomarkers derived from PE and peripheral blood (PB) to assist in the clinical differential diagnosis of MPE and TPE. This retrospective study included 290 patients (102 MPE, 188 TPE). Clinical and laboratory data were retrieved from electronic medical records (EMRs). Diagnostic performance of 18 individual and 74 combined biomarkers was assessed via ROC curve analysis. MPE patients were older (median 69 vs. 53 years, p < 0.001) with more females (57% vs. 29%, p < 0.001). PE-CEA showed the best single-biomarker performance (AUC = 0.95, 95% CI: 0.91–0.98), followed by PB-CYFRA21-1 (AUC = 0.91) and PB-CEA (AUC = 0.90). Eight combined biomarkers outperformed PE-CEA; PE-SPOT/PE-CEA had the highest AUC (0.98, 95% CI: 0.96–0.99). Combined PE and PB biomarker ratios show promising preliminary diagnostic potential for MPE-TPE differentiation. PE-CEA is optimal alone, PE-SPOT/PE-CEA is the best combination. These findings could inform future validation studies of stratified diagnostic approaches.