Pathology and pathobiology of the actinic (solar) keratosis

The term actinic keratosis (AK) literally means a thickened, scaly growth caused by damage induced by a ray, generally taken to be electromagnetic irradiation. The name refers to the texture of the lesion and sun‐induced damage with no regard to the biology, histopathology or other features. Although historically AKs have been characterized as ‘precancerous’ or ‘premalignant’ lesions, the concept of AK existing on the same continuum as Bowen's disease and squamous cell carcinoma (SCC) has gained increasing support and acceptance in recent years. More than 5 million Americans are known to have AKs. Furthermore, studies have shown that up to 60% of SCCs begin as AKs, and of those that arose on sun‐damaged skin, there was histological evidence of contiguous AK in 97% of lesions.1, 2 Ultraviolet (UV)B radiation (wavelength 290–320 nm) from sunlight is the most important cause of AK formation. UVB radiation causes thymidine dimer formation in DNA and RNA, resulting in mutations that cause neoplastic transformation in keratinocytes. Two sites of mutations of particular interest in AK formation occur in telomerase and in the tumour suppressor gene p53, located on chromosome 17p132. Increase in telomerase activity delays apoptosis and prolongs cell lifespan, possibly even to the point of immortality. Mutations in p53 tend to occur at sites where DNA repair is diminished, allowing damage to propagate through cell divisions. These mutations render p53 unable to perform its task of driving severely damaged cells to undergo apoptosis. These mutant DNA cells are more resistant to apoptotic death and can continue to accumulate genetic injury. The same mutations in the p53 gene that are found in AKs occur in SCC. This genetic link supports the malignant nature of AKs from the time of inception.