Case Report: Pembrolizumab unmasks a capillary leak syndrome with chylothorax in early TNBC

Pembrolizumab has become standard of care in early-stage triple-negative breast cancer (TNBC), but its expanding use may induce rare adverse events involving vascular and lymphatic endothelium. Capillary leak syndrome (CLS) remains an exceptionally rare toxicity of PD-1 blockade, scarcely reported in breast cancer, especially in the adjuvant setting. We report the case of a 40-year-old female with early-stage TNBC who presented with progressive dyspnea, diffuse subcutaneous edema and bilateral pleural and peritoneal effusions after two cycles of adjuvant pembrolizumab. Imaging confirmed polyserositis with interstitial pulmonary edema, and laboratory tests showed hypoalbuminemia without other abnormalities. Thoracentesis revealed milky pleural fluid containing chylomicrons, confirming chylothorax. Bronchoalveolar lavage, medical pleuroscopy, and pleural biopsies demonstrated a normal-appearing pleura without malignant or inflammatory infiltrates. Extensive workup ruled out infectious, neoplastic, cardiac, renal, and autoimmune causes, supporting pembrolizumab-induced vascular and lymphatic endothelial dysfunction. Corticosteroid therapy (1 mg/kg) led to rapid clinical and radiologic resolution. Pembrolizumab was permanently discontinued with no recurrence after corticosteroid tapering. This case highlights a rare but clinically significant immune-related adverse event (irAE) characterized by both vascular and lymphatic capillary leak under pembrolizumab. With PD-1 inhibitors increasingly used in curative TNBC, unexplained serous effusions and edema should prompt consideration of CLS and warrant comprehensive diagnostic evaluation to enable timely immunosuppression.