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  • Squamous cell carcinoma (SCC) is the second most common skin cancer, after basal cell carcinoma, in immunocompetent white individuals, and the most common skin cancer in immunosuppressed organ transplantation recipients worldwide.

  • SCC development in the skin is considered a multistep process, most invasive SCCs develop from preinvasive lesions or in situ tumors such as actinic keratosis or Bowen disease.

  • Risk factors for SCC include ultraviolet (UV) radiation, genetic predisposition, physical and chemical carcinogens, immunosuppression, drugs, viral infection, chronic inflammation, and chronic injury of the skin.

  • Diagnosis of SCC is established histologically. Histologic subtypes include spindle-cell, acantholytic, verrucous, and desmoplastic SCCs, and keratoacanthoma.

  • High-risk features for local recurrence and the development of metastatic disease include >2 mm thickness; Clark level higher than IV; perineural invasion; lip or ear as primary site; poorly or undifferentiated tumor.

  • The primary mode of therapy for localized SCC is complete surgical excision, preferentially microscopically controlled surgery (Mohs surgery). Nonsurgical interventions include topical therapy, and for locally advanced, unresectable or metastatic SCC, radiation therapy and systemic treatment with chemotherapy or targeted therapy.

  • Primary prevention for the development of SCC is based on decreasing UV radiation exposure and concomitant risk factors, and the effective treatment of precursor lesions. Systemic retinoids, niacinamide, as well as change of the immunosuppressive regimen in solid-organ transplantation recipients may be options for the secondary prevention of SCC in high-risk patients.


An accurate incidence of squamous cell carcinoma (SCC) is unknown, but the cancer is among the most common and costly malignancies in populations of European ancestry.1 The morbidity and mortality of SCC seem to be rather underestimated public health issues,2 and the health burden is considerable, particularly when considering high-risk populations, such as immunosuppressed patients, in which a 65-fold to 250-fold increased incidence of SCC has been reported.3,4


The accurate incidence of SCC is unknown as the majority of cancer registries in most countries do not generally document nonmelanoma skin cancers (NMSCs) and statistics frequently fail to include any subsequent tumors after the first SCC and to discriminate between cutaneous and mucosal SCC. However, assuming that 20% of NMSCs are SCCs,5,6 the estimated annual incidence of SCC in the United States is 700,000 cases. Therefore, SCC is, after basal cell carcinoma (BCC), the second most common skin cancer in immunocompetent white individuals and the most common skin cancer in immunosuppressed organ transplantation recipients worldwide.7 The incidence of SCC is steadily rising, with reported increases of 50% to 200% over the past 3 decades; this rise is largely attributed to a greater lifetime ultraviolet radiation (UVR) exposure as a result of greater longevity, ozone depletion, and increased voluntary exposure to UVR.8


The vast majority of SCC patients present with early-stage disease, and prognosis ...

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