Ultraviolet radiation from sun exposure is a major risk factor, causes mutations in key genes and explains the predilection of nonmelanoma skin cancer for sun-exposed skin.
Hedgehog signalling pathway mutations are involved in basal cell carcinoma pathogenesis.
p53 Mutations are involved in both squamous cell carcinoma and basal cell carcinoma pathogenesis, as well as in the development of actinic keratoses, which are the precursors of squamous cell carcinomas.
There are several histopathologic subtypes of each nonmelanoma skin cancer.
The more infiltrative or poorly differentiated variants are more clinically aggressive (e.g., morpheaform basal cell carcinoma and spindle cell squamous cell carcinoma).
TNM staging classifications exist for most types of nonmelanoma skin cancer and depend on clinical characteristics, pathological features and radiologic evaluation of the primary tumour, adjacent structures, lymph nodes, and viscera.
Basal cell carcinomas that are large, deep, or infiltrative may be locally aggressive and recurrent, but metastasize only rarely (<0.05%).
Squamous cell carcinomas 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 treatment for both basal cell carcinomas and squamous cell carcinomas is surgical. Mohs surgery is preferred for ill-defined or aggressive lesions because it allows microscopic control of tumour margins.
The 5-year recurrence rate for basal cell carcinoma 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.
Local recurrence is a problem for large, deep, or histologically infiltrative variants. squamous cell carcinomas with these features may also metastasize. The 5-year survival for patients with metastatic squamous cell carcinoma is <50%.
The rarer forms of nonmelanoma skin cancer have a significantly more aggressive clinical course as compared with basal cell carcinoma and squamous cell carcinoma. These include sebaceous carcinoma, Merkel cell carcinoma, dermatofibrosarcoma protuberans (DFSP), and cutaneous angiosarcoma.
Combinations of surgery, radiation therapy, and chemotherapy can be used for metastatic disease.
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