Summary Background  The field cancerization concept in photodamaged patients suggests that the entire sun‐exposed surface of the skin has an increased risk for the development of (pre)‐malignant lesions, mainly epithelial tumours. Topical photodynamic therapy (PDT) is a noninvasive therapeutic method for multiple actinic keratosis (AK) with excellent outcome. Objectives  To evaluate the clinical, histological and immunohistochemical changes in human skin with field cancerization after multiple sessions of PDT with methylaminolaevulinate (MAL). Methods  Twenty‐six patients with photodamaged skin and multiple AK on the face received three consecutive sessions of MAL‐PDT with red light (37 J cm−2), 1 month apart. Biopsies before and 3 months after the last treatment session were taken from normal‐appearing skin on the field‐cancerized area. Immunohistochemical stainings were performed for TP‐53, procollagen‐I, metalloproteinase‐1 (MMP‐1) and tenascin‐C (Tn‐C). Results  All 26 patients completed the study. The global score for photodamage improved considerably in all patients (P < 0·001). The AK clearance rate was 89·5% at the end of the study. Two treatment sessions were as effective as three MAL‐PDT sessions. A significant decrease in atypia grade and extent of keratinocyte atypia was observed histologically (P < 0·001). Also, a significant increase in collagen deposition (P = 0·001) and improvement of solar elastosis (P = 0·002) were noticed after PDT. However, immunohistochemistry showed only a trend for decreased TP‐53 expression (not significant), increased procollagen‐I and MMP‐1 expressions (not significant) and an increased expression of Tn‐C (P = 0·024). Conclusions  Clinical and histological improvement in field cancerization after multiple sessions of MAL‐PDT is proven. The decrease in severity and extent of keratinocyte atypia associated with a decreased expression of TP‐53 suggest a reduced carcinogenic potential of the sun‐damaged area. The significant increase of new collagen deposition and the reduction of solar elastosis explain the clinical improvement of photodamaged skin.

The concept of "field cancerization" was first introduced by Slaughter in 1953 when studying the presence of histologically abnormal tissue surrounding oral squamous cell carcinoma. It was proposed to explain the development of multiple primary tumors and locally recurrent cancer. Organ systems in which field cancerization has been described since then are: head and neck (oral cavity, oropharynx, and larynx), lung, vulva, esophagus, cervix, breast, skin, colon, and bladder. Recent molecular studies support the carcinogenesis model in which the development of a field with genetically altered cells plays a central role. An important clinical implication is that fields often remain after the surgery for the primary tumor and may lead to new cancers, designated presently as "a second primary tumor" or "local recurrence," depending on the exact site and time interval. In conclusion, the development of an expanding pre-neoplastic field appears to be a critical step in epithelial carcinogenesis with important clinical consequences. Diagnosis and treatment of epithelial cancers should not only be focused on the tumor but also on the field from which it developed. The most important etiopathogenetic, clinical, histopathological and therapeutic aspects of field cancerization are reviewed in this article.

Microneedling-assisted PDT is a safe and effective method and can produce superior cosmetic results to conventional MAL-PDT for improving photodamaged skin. Further larger prospective studies are needed to determine whether the addition of MN decreases actinic keratosis.

CAL-assisted PDT proved to be safe and more effective than conventional MAL-PDT for the treatment of AKs on the scalp. CAL pretreatment increased PpIX accumulation within the skin and may have enhanced the efficacy in this first human trial.

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