Phlegmasia Cerulea Dolens and Pulmonary Embolism in a Patient With NSCLC Receiving Dual EGFR/MET Targeted Therapy: A Case Report.

Although venous thromboembolism is common in NSCLC, phlegmasia cerulea dolens, the most severe form of deep vein thrombosis, is exceedingly rare. We describe a 43-year-old man with metastatic EGFR-mutated NSCLC who developed extensive phlegmasia cerulea dolens and pulmonary embolism while receiving dual targeted therapy with osimertinib and tepotinib for acquired MET amplification. He presented with painful swelling of all limbs progressing to cyanosis and venous gangrene. Imaging confirmed widespread venous thrombosis and pulmonary embolism. Despite thrombectomy, fasciotomy, and therapeutic heparin infusion, ischemia progressed, necessitating right above-knee amputation and right elbow disarticulation. Pathology revealed ischemic necrosis and organized venous thrombi without tumor emboli. This case highlights the potential for catastrophic thrombotic events in patients receiving combined EGFR/MET inhibition. Early recognition of atypical limb swelling and prompt vascular assessment are essential to distinguish drug-related edema from evolving thrombosis. Further pharmacovigilance and clinical studies are needed to clarify the thrombotic safety of dual targeted therapy in NSCLC.