Immune checkpoint inhibitor-related encephalitis overlapping with hyperprogression in metastatic lung cancer: a case report

Background: Immune checkpoint inhibitors (ICIs) have significantly improved survival in patients with advanced non-small cell lung cancer (NSCLC), but may rarely trigger severe immune-related adverse events (irAEs). Case summary: A 64-year-oldpatient with metastatic squamous NSCLC and high programmed death-ligand 1 (PD-L1) expression developed subacute neurological decline following pembrolizumab therapy, concurrent with rapid progression. Cerebrospinal fluid (CSF) analysis revealed inflammatory changes featuring markedly elevated IL-6 levels, while serological and imaging studies excluded infection, supporting a diagnosis of ICI-related encephalitis. Despite neurological symptom resolution with corticosteroids and intravenous immunoglobulin, systemic hyperprogressive disease (HPD) emerged, culminating in fatal tumor progression. Conclusion: This case underscores the need for vigilance toward the coexistence of rare neurotoxic irAEs and HPD during ICI therapy. Early recognition, multidisciplinary collaboration, and balanced therapeutic strategies are critical to optimizing outcomes.