From actinic keratosis to squamous cell carcinoma: pathophysiology revisited

Abstract

The precursor of most cutaneous invasive squamous cell carcinomas (iSCCs) is intraepithelial UV-induced damage, known as field cancerization, which can eventually transform into actinic keratosis (AK). Although AK is the most common precursor of iSCC, many AKs will either persist in the same stage or regress, while only a few will progress into iSCC. Nevertheless, because the progression of individual AKs cannot be predicted, it has been proposed that all AKs, regardless of the grade, should be carefully monitored and appropriately treated in clinical practice. Modern imaging techniques such as dermatoscopy, reflectance confocal microscopy (RCM) and high-definition optical coherence tomography (HD-OCT) may have potential to monitor the evolution of actinic field damage. Dermatoscopy can be used to differentiate between AK, intraepidermal carcinoma (IEC) and SCC which may help clinicians to diagnose in situ or invasive lesions at an earlier stage. HD-OCT and RCM can be used to detect cellular and histological changes characteristic of subclinical lesions, allowing visualization of previously invisible lesions. As development of invasive AK directly from the cancer field cannot be ruled out, the ideal treatment should be able to eradicate AK lesions and reverse the underlying field cancerization.

Sequential treatment of actinic keratosis with cryotherapy and ingenol mebutate: reflectance confocal microscopy monitoring of efficacy and local skin reaction

“…Actinic keratosis (AK) is the most common precursor of invasive squamous cell carcinoma. It usually appears in UV‐damaged skin known as field cancerization . Treatment of both AKs and field cancerization decreases the likelihood of AK relapse .…”

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

“…In general patients develop multiple AKs in one area and predicting which course each individual lesion will follow is impossible. Nonetheless, AK lesions are reliable markers for patients who are most predisposed to developing invasive SCC [4,[12][13].AK lesions typically appear in areas most frequently exposed to the sun such as the face, back of the hands, or bald scalp; 75% of lesions are found on the head, neck and forearms [14]. The lesions vary in appearance as well as size and can include erythematous scaly macules, rough pigmented patches and hyperkeratotic skin horns.…”

“…In general patients develop multiple AKs in one area and predicting which course each individual lesion will follow is impossible. Nonetheless, AK lesions are reliable markers for patients who are most predisposed to developing invasive SCC [4,[12][13].…”

“…These can potentially sustain and aggravate the disease state, if only visible lesions are treated [26,27]. In addition, it has been shown that mild AKs (grade I) are the most common lesion associated with invasive SCC [12,13]. Since there are no defined clinical indicators or specific genetic markers to predict progression to SCC, the expert opinion is to administer AK treatment in a field-directed manner in all patients to prevent invasive SCCs [28].…”

Non‐invasive monitoring of subclinical and clinical actinic keratosis of face and scalp under topical treatment with ingenol mebutate gel 150 mcg/g by means of reflectance confocal microscopy and optical coherence tomography: New perspectives and comparison of diagnostic techniques

“…Noninvasive diagnostic techniques are very helpful tools in the analysis of the entire cancerization field,detecting both subclinical and clinical AKs . This is helpful for the choice of the most appropriate therapeutic approach .…”