Grade 3 cholestatic immune-related hepatitis under cemiplimab for high-risk locally advanced cutaneous squamous cell carcinoma: a case report from Germany

Cutaneous squamous cell carcinoma (cSCC) is one of the most common types of skin cancer. While most cSCC are cured by surgery, those with high-risk features such as perineural invasion, infiltration of deep structures or bones, or incomplete resection carry a substantial risk of recurrence. Until recently, no systemic adjuvant treatment had demonstrated clinical benefit in terms of prolongation of relapse-free survival in this high-risk setting. The phase-3 randomized clinical trial C-POST demonstrated that adjuvant checkpoint immunotherapy with cemiplimab, a programmed cell death protein 1 (PD-1) inhibitor, prolongs disease-free survival after surgery and radiotherapy, thus leading to regulatory approval by the European Commission in 2025. We report the case of an 81-year-old male from Germany with type-2 diabetes and hypertension who presented with a rapidly enlarging cSCC of the right cheek. Histopathology showed a tumor thickness of 10.0 mm with infiltration of the subcutaneous tissue and mimetic muscles, perineural growth, and incomplete resection status. Imaging demonstrated involvement of the facial vein and infraorbital canal with bone destruction and maxillary sinus extension (pT3 cN0 cM0, stage III by AJCCv8). As complete resection was not feasible, definitive radiotherapy (60 Gy) was delivered to the residual tumor, followed by cemiplimab (350 mg every 3 weeks) with adjuvant intent, following the C-POST regimen. Treatment was complicated by grade 2 immune-related hepatitis with a cholestatic component that improved with oral corticosteroid therapy. However, the hepatitis recurred and, together with grade 3 fatigue, progressed to a grade 3 immune-related hepatitis with a predominantly cholestatic pattern, leading to hospital admission. Cross-sectional imaging and ultrasound excluded biliary obstruction and tumor relapse. Intravenous corticosteroids produced prompt biochemical improvement. Adjuvant cemiplimab was discontinued. This case illustrates the real-world translation of recently approved adjuvant immunotherapy to an elderly patient and highlights the recognition and management of a severe, cholestatic pattern of immune-related liver inflammation under anti-PD-1 checkpoint immunotherapy.