Skin cancer is the most frequently diagnosed cancer globally and is preventable. Various risk factors contribute to different types of skin cancer, including melanoma, basal cell carcinoma, and squamous cell carcinoma. These risk factors encompass both extrinsic, such as UV exposure and behavioral components, and intrinsic factors, especially involving genetic predisposition. However, the specific risk factors vary among the skin cancer types, highlighting the importance of precise knowledge to facilitate appropriate early diagnosis and treatment for at-risk individuals. Better understanding of the individual risk factors has led to the development of risk scores, allowing the identification of individuals at particularly high risk. These advances contribute to improved prevention strategies, emphasizing the commitment to mitigating the impact of skin cancer.

Background: Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with a multifactorial aetiology involving environmental and intrinsic factors. A small subset of patients develops high-frequency BCC (HF-BCC), defined as ≥9 BCCs within 3 years. Objective: To analyse demographic, clinical, and histopathological features of non-syndromic HF-BCC in a Belgian cohort, compared with low-burden BCC patients and healthy controls. Methods: A retrospective cohort study was conducted at Erasme Hospital (Brussels) using data from the EUSCAP platform. Clinical, behavioural, and histopathological data were collected and statistically analysed. Results: Of 783 patients, 16 with HF-BCC were identified. For comparison, 32 patients with 1–2 BCCs and 117 patients without BCC were selected. HF-BCC patients showed distinct characteristics, including a higher proportion of superficial BCCs (68.3% vs. 50%, p = 0.01) and fewer nodular subtypes (43.2% vs. 63.5%, p = 0.01). Their tumours were less frequently located on the nose and ears compared with patients having 1–2 BCCs. HF-BCC was associated with a personal history of squamous cell carcinoma (SCC) and actinic keratosis (AK). Conclusions: HF-BCC patients display distinct anatomical, histopathological and clinical characteristics, with a predominance of superficial BCC and an association with a personal history of SCC and AK. They show a lower frequency of tumours on the nose and ears, with a stronger tendency for localisation on the trunk and extremities. Identifying risk factors and genetic markers may contribute to improved early detection strategies, preventive measures, and the development of targeted therapies.