A Case Series of Pleural Effusions of Extra-vascular Origin (PEEVO)

Pleural effusions are commonly encountered in clinical practice and are most frequently caused by cardiopulmonary, malignant, or inflammatory conditions.These effusions typically result from alterations in hydrostatic or oncotic pressures, pleural permeability, or lymphatic drainage.In contrast, pleural effusions of extra-vascular origin (PEEVO) arise from direct migration of non-vascular fluids into the pleural space through anatomical disruptions or fistulous connections and represent a rare but important diagnostic entity.PEEVO includes chylothorax, urinothorax, biliothorax, and pancreatic pleural effusion, each associated with characteristic pleural fluid biochemical profiles and distinct management strategies.We present a case series of four patients with PEEVO encountered at a tertiary academic medical center, illustrating the diverse clinical contexts in which these effusions occur.The cases highlight key diagnostic features, including elevated pleural fluid triglycerides in chylothorax, pleural fluid-to-serum creatinine ratios greater than one in urinothorax, pleural fluid bilirubin exceeding serum levels in biliothorax, and markedly elevated pleural fluid amylase or lipase in pancreatic pleural effusions.Diagnostic imaging modalities such as lymphangiography, computed tomography, magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography, and renal scintigraphy played critical roles in identifying the underlying sources of fluid leakage.This case series emphasizes the importance of maintaining a high index of suspicion for PEEVO in patients with recurrent or atypical pleural effusions.Early recognition through targeted pleural fluid analysis and focused imaging, combined with multidisciplinary, etiology-directed management, can reduce diagnostic delay, prevent recurrence, and improve clinical outcomes.