Pembrolizumab therapy leads to resolution of lentigines and tumour control in a patient with xeroderma pigmentosum and advanced cutaneous squamous cell carcinoma

We describe a 54-year-old patient with xeroderma pigmentosum (XP) who developed unresectable cutaneous squamous cell carcinoma and was treated with pembrolizumab, an immune checkpoint inhibitor (ICI). The treatment led to significant tumour regression and, unexpectedly, a complete resolution of the patient’s lentigines, while vitiligo and other pigmented lesions remained unchanged. The findings suggest that ICIs may amplify immune responses against ultraviolet-induced pigmented lesions in patients with XP, potentially linked to the disease’s high mutational burden. Further studies are needed to elucidate the underlying mechanisms.