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Skin cancer is the most common type of cancer in the United States, with one in five Americans predicted to develop some form of cutaneous malignancy in their lifetime.1–4 The most common skin cancers are basal cell carcinoma, squamous cell carcinoma, and melanoma. The vast majority of cutaneous malignancies are derived from cellular components that comprise the outermost layer of the skin, or epidermis, the most abundant of which are keratinocytes and melanocytes (Figure 14.1). Malignant transformation of keratinocytes (basal cell keratinocytes and squamous epithelial keratinocytes) leads to the development of basal cell and squamous cell carcinomas, while mutations in neural-crest derived melanocytes, which are interspersed in regular intervals throughout the basal layer of the epidermis, give rise to melanoma.5


Components of the epidermis.

The skin is comprised of a wide range of cell types so it is not surprising that skin cancer genetics itself is a broad topic. The epidermis, dermis, adnexal structures, and subcutis can develop malignant transformation at different stages of differentiation. The etiology of most skin cancers is multifactorial, often requiring environmental exposure. The impact is magnified in patients with an underlying genetic predisposition. Identification of skin cancer risk factors have resulted in general risk avoidance principles and screening recommendations.5–7

In general, patients with increased genetic susceptibility tend to develop skin cancers at an earlier age, in greater number, and may develop tumors that behave more aggressively compared to patients who develop sporadic tumors. Despite this, results of studies that inquire whether patients with familial melanoma practice risk-reducing and early-detection behaviors suggest inconsistent adoption and maintenance of risk-avoidance behaviors.8,9 Thus, current recommendations for exposure avoidance and risk modification are the same for higher-risk populations and the general population.5,6 Overall assessment of risk, both genetic and environmental, is critical so that the proper screening recommendations can be made for each individual patient and family. Selection of the correct patient cohort is important to avoid unnecessary procedures, false positive results, and to best allocate finite resources in a productive and cost-effective manner.

The fundamental principles of risk assessment in general also apply to dermatology. They include a thorough patient history and physical examination.10 Patients should be asked about their history of sun exposure, personal and family history of prior skin cancers, pre-cancers, or abnormal or congenital moles, sun protective behaviors, occupational exposures, tobacco use, exposure to HPV or HIV, and whether they have noticed any lesions that are changing, painful, bleeding, or not healing. Additional relevant history includes a patient’s gender and age, immunosuppression status, and medications, as some may promote or accelerate the development of skin cancers. Other risk factors specific to the most common types of skin cancer are listed in Table 14.1. ...

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