Malignant versus paramalignant pleural effusions: prognosis, classification, and biomarker perspectives

Background: Malignant pleural effusions (MPE) are classified as M1 disease in the TNM system and stage IV in the UICC classification, strongly influencing clinical decision-making. In contrast, paramalignant pleural effusions (PMPE) are often considered less severe due to negative cytology. Given the limited sensitivity of cytopathology, it is unclear whether this distinction truly reflects prognosis. This study aimed to compare clinical characteristics and survival between patients with MPE and PMPE and to explore whether cytopathological distinction mirrors survival outcomes. Methods: In this multi-center prospective study, 215 patients (104 with MPE, 111 with PMPE) undergoing thoracentesis or thoracic surgery between March 2021 and March 2025 at LMU Munich University Hospital and Asklepios Lung Clinic Gauting were enrolled. From each patient, 100 ml of pleural fluid was collected for ELISA analysis. Baseline clinical, cytopathological, and pleural fluid characteristics were compared between groups, and survival was assessed for at least one year or until death. Kaplan-Meier curves and Cox proportional hazard models were used for survival analysis. Results: Survival analysis showed poor outcomes in both MPE and PMPE, with a 1-year mortality of 40–45%. No significant survival difference was observed between the two groups (HR 0.83, 95% CI: 0.56–1.23, p=0.36). Baseline demographics, tumour type and stage distribution, as well as most blood and pleural fluid biochemical parameters, were comparable between MPE and PMPE. Patients with MPE only had significantly lower serum CRP and pleural fluid pH, and significantly higher pleural fluid lactate and protein levels compared to PMPE. Conclusion: Both MPE and PMPE were associated with similarly poor survival in our cohort, with no major differences in clinical or biochemical characteristics. This finding challenges the prognostic implications of PEs in the current staging classifications, in which only MPE,are defined as stage IV disease. Our findings suggest that PMPE patients should not be considered to have a more favourable prognosis solely based on negative cytology. Further ELISA-based biomarker analyses are planned may help to refine prognostic stratification of MPE and PMPE and guide clinical decision-making. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany