Autopsy of a patient with fatal Epstein-Barr virus-associated encephalitis after treatment with immune checkpoint inhibitors for advanced lung adenocarcinoma: A case report

Abstract

Immunotherapy using immune checkpoint inhibitors (ICIs) has improved the prognosis of many cancers, including lung cancer. The mechanisms of development of immune-related adverse events (irAEs) after treatment with ICIs are not completely understood. Because ICIs can exacerbate opportunistic infections by altering immune conditions, potential opportunistic infections such as those caused by Epstein–Barr virus (EBV) may be involved in the development of irAEs. However, there is a lack of clinical findings that indicate the relationship between irAEs and potential opportunistic infections.Herein, we present the case of a 67-year-old man with advanced lung adenocarcinoma who developed encephalitis after the third cycle of pembrolizumab administration. Polymerase chain reaction using cerebrospinal fluid and blood samples revealed positive results for EBV. An autopsy examination revealed lymphocyte infiltration in the area surrounding the EBV-infected cells in the brain.Our case suggests that immune reconstitution occurred after the administration of ICIs, followed by an enhanced immune response to EBV that resulted in fatal encephalitis. Additional findings regarding the interaction between irAEs and opportunistic infections should be acquired to confirm this speculation.

Keywords

• Lung cancer
• Immunotherapy
• Immune checkpoint inhibitors (ICIs)
• Immune-related adverse events (irAEs)
• Epstein–Barr virus (EBV)
• Encephalitis