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It often presents with non-specific clinical symptoms, such as fever, chest pain, cough and weight loss, thereby complicating the diagnostic process. This narrative review provides an expert comprehensive clinical practice overview covering the following issues correlated with diagnosis and management of TPE: 1- epidemiology, clinical presentation and underlying pathophysiology; 2- limitations of conventional diagnostic procedures on pleural fluid; 3- usefulness of thoracic ultrasound (TUS) in the stepwise pathway 4- role of thoracoscopy as a golden diagnostic tool, with the proposal of a step by step algorithm. 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