Abstract

Background and Clinical Significance: Cutaneous squamous cell carcinoma (CSCC) is a common non-melanoma skin cancer, and while most cases are curable, a small proportion progresses to locally advanced or metastatic disease. As neoadjuvant immunotherapy with PD-1 inhibitors such as cemiplimab becomes more widely adopted, understanding real-world patterns of response remains essential. Case Presentation: We report a case of a man in his 50s with a large, locally advanced CSCC of the left hand in whom neoadjuvant cemiplimab was chosen to reduce tumor burden and preserve hand function when margin-negative resection was unlikely. The patient received four cycles of cemiplimab and demonstrated marked clinical improvement followed by complete pathological response at the primary site upon wide local excision. However, metastatic involvement of the epitrochlear and axillary lymph nodes was identified at surgery despite initial benign imaging. Postoperative PET/CT showed no additional disease, and the patient subsequently underwent axillary dissection and adjuvant cemiplimab with good functional recovery. Conclusions: This case highlights the potential for neoadjuvant cemiplimab to achieve substantial local tumor control and functional preservation while emphasizing the need for careful nodal assessment and ongoing surveillance in patients with very-high-risk CSCC. In cases where baseline cross-sectional staging is not performed, pre-existing occult nodal disease cannot be excluded.

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