Anti-striated muscle antibody positive anti-PD-1 antibody related myositis and cardiomyositis: an instructive autopsy case report with discussion for trigger of irAE

Immune checkpoint inhibitors (ICIs) can cause severe immune-related adverse events (irAEs), including life-threatening myositis and myocarditis. Characterizing the immunopathological features of these conditions is essential for improving clinical recognition and management. We report a case of a 76-year-old man with metastatic renal cell carcinoma who developed fatigue, elevated creatine kinase, and complete atrioventricular block after receiving nivolumab. Despite pacemaker implantation and plasmapheresis, the patient died of respiratory failure. Notably, serum tests were positive for anti-Kv1.4 and anti-titin antibodies, although typical myasthenia gravis features were absent. Autopsy revealed CD8-positive T-cell and CD163-positive macrophage infiltration in the myocardium and skeletal muscles, while also confirming a pathological complete response of the carcinoma. Spatial analysis using digital pathology demonstrated that Human leukocyte antigen (HLA) class I expression in cardiomyocytes was closely apposed to infiltrating CD8-positiveT cells in a patchy distribution. This observation suggests a potential local feedback loop where activated T cells may induce HLA class I upregulation in adjacent muscle fibers, sustaining focal inflammation. This case provides important insights into the complex pathophysiology of fatal irAEs and underscores the value of postmortem examination in irAEs.