An autopsy case of sigmoid colon cancer with multiple cerebral infarctions associated with drug-induced interstitial lung disease: a case implicating local PAI-1 overexpression.

内容摘要

A 68-year-old Japanese man receiving panitumumab-containing chemotherapy for metastatic sigmoid colon cancer presented with fever and visual field constriction. Laboratory tests revealed markedly elevated D-dimer, KL-6, and IL-6 levels. Chest computed tomography demonstrated serious diffuse interstitial infiltrates in both lungs, while brain magnetic resonance imaging revealed multiple cerebral infarctions, predominantly in the right occipital lobe. Bronchoscopy further revealed active bleeding within the airways. Despite intensive multidisciplinary treatment, including steroid pulse therapy and antibiotics, he died of respiratory failure on the 19th day of hospitalization. Autopsy findings revealed diffuse alveolar damage and multiple cerebral thrombotic infarctions. Notably, no evidence of rupture of atherosclerotic plaques in the cerebral arteries was observed, whereas multiple thromboembolic lesions were identified. Immunohistochemical analysis demonstrated positive staining for plasminogen activator inhibitor-1 (PAI-1) in alveolar macrophages as well as in macrophages within cerebral arterial thrombi. This case represents the first reported instance in which severe drug-induced interstitial lung (DI-ILD) disease led to profound coagulation-fibrinolysis abnormalities through local PAI-1 expression, resulting in multiple cerebral infarctions. In cases such as this, where anticoagulant therapy is difficult to administer due to DI-ILD associated coagulopathy, PAI-1 may represent a promising therapeutic target molecule.