3.3.1 Actinic Keratosis

The frequency is dependent of skin type and life conditions. Prevalence in the US is 10% in females and 26% in males, however, in UK it is 6% in females and 15% in males. Total prevalence of AK in Germany, standardized for age and sex, was 2.66%; the age-standardized rate was higher for men (3.85%) than for women (1.45%). In the group of 60-70 years old males it is 11.5%. The highest incidence rates are found in Queensland /Australia.

Actinic keratosis, a non-melanoma skin cancer precursor, is mainly induced by chronic UV exposure, and genetic predisposition such as skin types I-III. In some patients, human papilloma virus (HPV) infective types or immunosuppression after transplantation or in HIV patients may play an important role. Chemical agents including tar may play also a role. AK`s may slowly progress over years and in 1 out of 10 cases progress after several years to an invasive squamous cell carcinoma. First molecular changes are the occurrence of p53. At this point, some AKs may even regress. Further oncogenic changes with occurrence of, for example c-myc, turns the process on and single mutated keratinocytes may aggregate to a clonal expansion in the epidermis.

Lesions present as circumscribed hyperkeratotic yellow-brown or red papules and plaques. Finally, they may be confluent and involve large areas of lesions (field cancerisation). Other lesions may be flat and atrophic, some are hyperpigmented.

Cornu cutaneum (cutaneous horns) are conical projections, made of hyperkeratotic material and look similar to animal horns.

They are mainly located on sun-exposed areas (scalp, face - preferentially over the brows and on the cheeks, back of hands, shins, forearms, helix).

Actinic keratoses are usually classified in grades 1 to 3 which relates to increasing atypia of keratinocytes in the different layers of the epidermis. However, involvement of the perifollicular and periacrosyringeal layers of keratinocyte can already move towards invasion. Actinic keratosis may evolve from all grades towards a squamous cell carcinoma.

The histology shows hyperkeratosis, epidermal disarray, and atypical keratinocytes, assembled in different layers of the epidermis, and around the acroinfundibula. A strong inflammatory infiltrate is present in the upper dermis, which usually shows actinic elastosis.

The evolution is chronic and long-lasting. Actinic keratosis may regress spontaneously or evolve towards a squamous cell carcinoma.

A transition to squamous cell carcinoma is possible, with an estimation of a frequency of 5% per year. Resistance or recurrence after topical or ablative treatments, fast growth and pain are reliable signs of transformation. Field cancerisation is an additional risk factor of transition to squamous cell carcinoma.

The diagnosis relies on clinical features and is proven by histology. Physical examination is usually sufficient for the diagnosis. However, in some cases (thicker AK, pigmented AK) dermoscopy is useful for the diagnosis. If a squamous invasive skin carcinoma or other malignancy cannot be ruled out a biopsy is mandatory.

Actinic keratoses must be differentiated from Bowen’s disease, seborrhoeic or HPV keratoses, adnexal tumors of the skin, and superficial basal cell carcinoma. Pigmented seborrhoeic or viral keratosis must be differentiated form lentigo maligna and lentigo maligna melanoma

Prevention relies on sun protection (sunscreens, textile UV protective clothes, UV glasses, umbrella, avoidance of high UV energy exposure times such as 11 am to 3 pm). Oral daily supplementation with niacin is proven to be a preventive measurement. Lesions can be destroyed by curettage, cryosurgery or photodynamic therapy. Topical treatments are with 5-fluorouracil or immune modifiers such as imiquimod cream, diclofenac or ingenol mebutate. Suspicious lesions must be biopsied and may need to be excised.

Dietary supplements may be useful in the prevention and/or treatment of actinic keratosis and field cancerization.

Any patients undergoing transplantation and long-term immunosuppression should be examined before transplantation and offered regular follow-up examination.