Ectopic rabphilin-3A expression in lung adenocarcinoma associated with paraneoplastic arginine vasopressin deficiency during anti-PD-L1 therapy: a case report

Immune checkpoint inhibitors (ICIs) can cause endocrine immune-related adverse events affecting multiple endocrine organs, including the pituitary, yet arginine vasopressin deficiency (AVP-D) remains rare. Lymphocytic infundibuloneurohypophysitis, the principal cause of AVP-D, is an autoimmune inflammatory disorder of the posterior pituitary and stalk in which anti-RPH3A antibodies serve as a specific marker, and RPH3A as a pathogenic autoantigen, yet its relationship to cancer and ICI therapy remains unclear. We report a 63-year-old man with lung adenocarcinoma treated with carboplatin, paclitaxel, bevacizumab, and atezolizumab who developed AVP-D without obvious anterior pituitary dysfunction. Serum testing demonstrated the presence of anti-RPH3A antibodies. Lung tumor specimens showed ectopic RPH3A expression with prominent CD8+ T-cell infiltration by immunohistochemistry and in situ hybridization chain reaction. Given prior evidence that RPH3A is a pathogenic autoantigen in AVP neurons, these findings support a paraneoplastic mechanism in which PD-L1 blockade unleashes RPH3A-reactive T cells primed against ectopic tumor expression, leading to collateral injury of AVP neurons and consequent AVP-D.