Nonmelanoma Skin Cancers
Basal Cell and Squamous Cell Carcinomas
Gary S. Wood, Yaohui Gloria Xu, Juliet L. Aylward, Vladimir Spiegelman, Erin Vanness, Joyce M.C. Teng and Stephen N. Snow
Summary of Key Points
Incidence
• More than 2 million new cases of nonmelanoma skin cancer (NMSC) occur annually in the United States, including 80% basal cell carcinomas (BCCs), 20% squamous cell carcinomas (SCCs), and a few rarer types.
• Incidence is increasing 2% to 3% per year.
• Fifteen percent to 43% of solid organ transplant recipients will develop NMSC within 10 years.
Biological Characteristics
• Ultraviolet radiation from sun exposure is a major risk factor, causes mutations in key genes and explains the predilection of NMSC for sun-exposed skin.
• Hedgehog signaling pathway mutations are involved in BCC pathogenesis.
• p53 Mutations are involved in both SCC and BCC pathogenesis, as well as in the development of actinic keratoses, which are the precursors of SCCs.
• There are several histopathologic subtypes of each NMSC.
• The more infiltrative or poorly differentiated variants are more clinically aggressive (e.g., morpheaform BCC and spindle cell SCC).
Staging Evaluation
• TNM staging classifications exist for most types of NMSC and depend on clinical characteristics, pathological features and radiologic evaluation of the primary tumor, adjacent structures, lymph nodes, and viscera.
• BCCs that are large, deep, or infiltrative may be locally aggressive and recurrent, but metastasize only rarely (<0.05%).
• SCCs have a greater metastatic rate, especially those that are large, deep, have perineural invasion, or are located on the dorsal hands, lips, ears, penis, or sites of chronic infection, ulceration, or radiation.
Primary Therapy and Results
• Primary treatment for both BCCs and SCCs is surgical. Mohs surgery is preferred for ill-defined or aggressive lesions because it allows microscopic control of tumor margins.
• The 5-year recurrence rate for BCC is 1% for Mohs surgery compared to 5% for other types of surgical excision.
• Alternative primary therapies include various forms of physical destruction and radiation therapy.
• Interferons and inducers of interferons (e.g., imiquimod) are useful in selected cases. Retinoids, hedgehog pathway agents, and difluoromethylornithine are other promising chemopreventive and adjunctive modalities.
Locally Advanced and Metastatic Disease
• Local recurrence is a problem for large, deep, or histologically infiltrative variants. SCCs with these features may also metastasize. The 5-year survival for patients with metastatic SCC is <50%.
• The rarer forms of nonmelanoma skin cancer have a significantly more aggressive clinical course as compared with BCC and SCC. These include sebaceous carcinoma, Merkel cell carcinoma, dermatofibrosarcoma protuberans (DFSP), and cutaneous angiosarcoma.
