Clinical meaning
Actinic keratoses (AKs) are premalignant keratinocyte neoplasms arising from cumulative ultraviolet radiation damage to epidermal keratinocytes, with an estimated 5-10% lifetime risk of progression to invasive squamous cell carcinoma per lesion. UV-B radiation (290-320 nm) causes direct DNA damage through cyclobutane pyrimidine dimer formation, while UV-A (320-400 nm) generates reactive oxygen species causing indirect DNA damage. Mutations in the p53 tumor suppressor gene (present in over 90% of AKs) impair apoptosis of UV-damaged keratinocytes, allowing clonal expansion of mutated cells. The clinician identifies AKs as rough, scaly, erythematous papules or plaques on sun-exposed skin (better felt than seen), differentiating from squamous cell carcinoma in situ (Bowen disease -- sharply demarcated, erythematous, scaly plaque), basal cell carcinoma (pearly, telangiectatic papule or nodule with rolled borders), and seborrheic keratosis (stuck-on appearance, horn cysts on dermoscopy). Treatment selection by the clinician is guided by lesion number, location, and patient factors: cryotherapy with liquid nitrogen (single or few lesions -- 10-30 second freeze-thaw-freeze cycle), topical 5-fluorouracil 5% (field therapy for widespread AKs -- applies cytotoxic effect to subclinical lesions, expected inflammatory response over 2-4...