[Tumor markers in the assessment of malignant and benign pericardial effusion].

BACKGROUND: The differential diagnosis of pericardial effusion is often challenging because different etiologies can be discussed. Of particular therapeutic and prognostic importance is the definitive differentiation of malignant pericardial effusion from benign effusions. The definitive diagnosis of malignant pericardial effusion is established by a positive cytological examination of the pericardial fluid. However, pericardial fluid cytology, although specific has variable sensitivity. Tumor markers are often investigated after pericardiocentesis but their utility as an aid for the diagnosis of malignant pericardial effusion is not well established. The aim of this study was to measure the concentrations of the tumor markers CEA, CA 19-9, CA 72-4, SCC and NSE in malignant and non-malignant pericardial effusions and to assess their diagnostic utility in differentiating malignant from benign pericardial effusion.

METHODS: We investigated the pericardial fluid of 29 patients with proven malignant pericardial effusion and 25 patients with non-malignant pericardial effusion. The etiology of the pericardial effusion was defined by pericardial cytology, epicardial histology and PCR for cardiotropic viruses from pericardial and epicardial tissue acquired by pericardioscopy. The group with non-malignant pericardial effusion comprised 15 patients with autoreactive effusion and 10 patients with viral pericardial effusion. We analyzed the following tumor markers in the pericardial fluid: carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, carbohydrate antigen (CA) 72-4, squamous cell carcinoma (SCC) antigen and neuron-specific enolase (NSE).

RESULTS: Of the tumor markers tested the mean concentrations of the CEA, CA 72-4 and CA 19-9 were significantly higher in malignant pericardial effusions than in non-malignant effusions (CEA 450.66 ±1620.58 µg/l vs. 0.72 ±1.49 µg/l, p<0.001; CA 19-9 1331.31 ±3420.87 kU/l vs. 58.85 ±17.53 kU/l, p=0.04; CA 72-4 707.90 ±2397.55 kU/l vs. 0.48 ±2.40 kU/l, p<0.001). ROC curve analysis showed that pericardial fluid CA 72-4 yielded an area under the curve (AUC) of 0.85 (95% confidence interval 0.74-0.95), followed by CEA with 0.80 (95% confidence interval 0.68-0.92). Pericardial fluid CA 72-4 levels >1.0 kU/l had 72% sensitivity (95% confidence interval 53%-87%) and 96% specificity (95% confidence interval 80%-99.9%) and CA 72-4 levels >2.5 kU/l had 69% sensitivity (95% confidence interval 49%-85%) and 96% specificity (95% confidence interval 80%-99.9%) in differentiating malignant pericardial effusions from effusions due to benign conditions.

CONCLUSION: Malignant pericardial effusions are associated with significantly higher pericardial concentrations of the tumor markers CEA, CA 72-4 and CA 19-9. Of the tested tumor markers, measurement of CA 72-4 levels in pericardial fluid offered the best diagnostic accuracy. Based on our data evaluation of every patient with unexplained pericardial effusion and negative pericardial fluid cytology should include the measurement of pericardial fluid CA 72-4 levels. Under these circumstances the elevation of pericardial fluid CA 72-4 levels should include malignancy as a probable diagnosis.