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The diagnosis of neoplastic pleurisies remains difficult because of frequent false negative cytological analysis. Thoracoscopy remains the gold standard to distinguish benign from malignant pleural effusion, but it is invasive and not suitable for all patients. Microparticles (MPs) are promising potential biomarkers and could represent a new approach to identify patients with malignant pleural effusions. We have recently reported the presence of EpCAM-positive-MPs (EpCAM+MPs) in malignant pleurisies that could be routinely used as a complementary tool with cytology for the diagnosis of pleural malignancy. Here we describe three cases of pleural cancer patients negative for cancer cells but positive for EpCAM+MPs in the pleural fluid. This study confirmed the possibility to apply in clinical practice recent data about EpCAM+MPs, detected in pleural fluid, as a non-invasive pleural biomarker useful to increase sensitivity of cytology. In particular, we suggest in patients with a strong suspicion of pleural cancer to search pleural EpCAM+-MPs as a complementary diagnostic tool in case of negative cytological analysis of pleural fluid.

False Negative Pleural Cytology in Patient with Malignant Pleurisies: Is Pleural EpCAM-Positive Microparticles a Complementary Tool for Diagnosis?