We describe the case of a neglected cutaneous squamous cell carcinoma with extensive facial involvement. The patient is a male in his late 70s who presented to dermatology with a large destructive facial mass that had increased in size gradually over 3 years and then rapidly proliferated, consuming a large portion of his left maxillofacial region. While the immediate reaction was referral to hospice care, medical oncology recommended treatment with cemiplimab, an immune checkpoint inhibitor. Collaboration with multiple providers facilitated the delivery of a multidisciplinary approach utilizing immunotherapy with QUAD shot radiotherapy. The immunotherapy treatment resulted in a dramatic disease regression, but the large facial anatomical defect caused by the carcinoma remained. The patient is undergoing reconstructive surgeries. This case illustrates the potential for significant response with immune checkpoint inhibitors delivered in combination with cyclical hypofractionated radiation therapy for patients with cutaneous squamous cell carcinoma, even in very advanced disease.

Cutaneous squamous cell carcinoma (CSCC) is the second most common non-melanoma skin cancer. A majority of patients present with localized disease, but some can present with locally advanced or metastatic disease. Most of these advanced cases occur in the anatomical head and neck region and are associated with more aggressive disease, necessitating prompt and effective treatment. Prior to the emergence of immunotherapy, systemic treatment options were limited to platinum-based chemotherapy and salvaged with targeted epidermal growth factor therapy. These therapies were associated with poor efficacy and increased toxicity in an often frail, older population. Immunotherapy has dramatically improved outcomes in this patient population due to its favorable side effect profile, durable treatment response, and improved overall outcomes. In this review, an overview of the recent advances of immunotherapy in the management of CSCC in the anatomical head and neck region is provided, with a focus on advanced presentations.