Severe oral mucosal immune-related adverse events are uncommon complications of immune checkpoint inhibitors and may compromise treatment continuation in patients with head and neck cancer.

A 77-year-old man with recurrent/metastatic head and neck squamous cell carcinoma and a PD-L1 combined positive score of 95 developed grade 3 oral mucositis after six months of pembrolizumab. Histopathological findings were compatible with immune-mediated lichenoid mucositis associated with anti-PD-1 therapy. Systemic corticosteroids achieved complete clinical resolution. However, mucositis recurred after pembrolizumab rechallenge, leading to permanent treatment discontinuation. Complete radiological response was subsequently documented and persisted for more than one year after treatment cessation.

This case highlights the importance of early recognition and multidisciplinary management of severe oral immune-related toxicity. Rechallenge may result in recurrent severe mucositis, while durable oncological remission may persist after immunotherapy discontinuation.