Pulmonary veno-occlusive disease after immune checkpoint inhibitor therapy: an autopsy case report

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ID: 317523
2026
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Abstract
Abstract Background Immune checkpoint inhibitors, including nivolumab and ipilimumab, have revolutionized cancer therapy by enhancing immune-mediated antitumor activity. While some cardiovascular immune-related adverse events manifest as various phenotypes, such as myocarditis and pericarditis, pulmonary veno-occlusive disease is a particularly rare complication. Case Summary An 80-year-old man with chronic obstructive pulmonary disease, hypertension, and a history of heavy smoking underwent lobectomy for lung cancer. Histopathological examination of pulmonary tissue, including the vasculature, showed no evidence of pulmonary veno-occlusive disease at the time of surgery. Following disease recurrence, he received combination therapy with nivolumab and ipilimumab. Shortly after treatment initiation, he developed respiratory failure and a renal immune-related adverse event, which improved with oral corticosteroid therapy. Ipilimumab was discontinued due to its higher risk of severe immune-related adverse events, and nivolumab monotherapy was continued for 22 months until the 14th cycle, when the patient presented with progressive dyspnoea and severe hypoxaemia. Echocardiography and right heart catheterization confirmed pulmonary hypertension. Pulmonary vasodilator therapy was initiated, but the respiratory failure rapidly progressed and the patient died on hospital day 53. Autopsy revealed intimal fibrous thickening and smooth muscle proliferation of interlobular pulmonary veins, consistent with pulmonary veno-occlusive disease. Discussion This case highlights pulmonary veno-occlusive disease as a rare but potentially fatal pulmonary vascular complication associated with immune checkpoint inhibitor therapy. In patients receiving immune checkpoint inhibitors who develop unexplained pulmonary hypertension and severe hypoxaemia, pulmonary veno-occlusive disease should be considered as a differential diagnosis.
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Authors Saki Hasegawa-Tamba, Tsugumi Sato, Takahide Arai, Shintaro Nakano
Journal European Heart Journal - Case Reports
Year 2026
DOI
10.1093/ehjcr/ytag459
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