Abstract Background Pleural effusions are common clinical findings with a broad differential, ranging from heart failure to infectious and malignant etiologies. Distinguishing between these causes is critical, as malignant pleural effusions carry major prognostic and therapeutic implications. While imaging narrows the differential, definitive diagnosis often relies on thoracentesis and fluid analysis. Cytology can establish malignancy with a relatively high yield and may prevent the need for invasive tissue biopsy. Ancillary testing, including immunocytochemistry and molecular profiling, further enhances diagnostic precision and informs therapeutic decision-making. Case Presentation A 38-year-old woman with asthma, hypertension, and prior gastric sleeve surgery presented with progressive dyspnea, cough, and wheezing. Chest imaging revealed a large right pleural effusion, a right breast mass with peau d’orange changes, and axillary lymphadenopathy. Thoracentesis drained 1560 mL of serosanguinous fluid. Analysis demonstrated an exudative effusion with elevated protein (6 g/dL), LDH (336 U/L), and lymphocyte predominance (74%). Cytology revealed atypical epithelioid cells with hyperchromatic, overlapping nuclei, diagnostic of malignant pleural effusion. These findings supported metastatic breast cancer as the source and enabled expedited oncology referral for staging and treatment planning. Discussion Malignant pleural effusions are frequently exudative, bloody, and lymphocyte-predominant. Cytology has a diagnostic yield of ∼40-60%, which improves with the use of cell blocks and ancillary studies. Immunocytochemistry can confirm lineage and origin; breast carcinoma typically expresses markers such as GATA3, ER, PR, and mammaglobin, while molecular testing provides additional prognostic and therapeutic guidance. In this case, cytology alone was sufficient to confirm metastatic disease, obviating the need for a more invasive biopsy. This underscores the evolving role of pleural fluid analysis not only in establishing malignancy but also in facilitating tumor characterization when advanced testing is employed. Conclusion This case demonstrates the diagnostic power of pleural fluid cytology in identifying malignant effusions and expediting oncologic care. For patients presenting with large exudative effusions and high suspicion for malignancy, thoracentesis provides a minimally invasive, high-yield approach that can both relieve symptoms and deliver critical diagnostic information. The integration of cytology with ancillary testing has the potential to reduce reliance on invasive procedures and align diagnosis with precision treatment strategies. This abstract is funded by: None
Reitnauer et al. (Fri,) studied this question.