Defining Field Cancerization of the Skin Using Noninvasive Optical Coherence Tomography Imaging to Detect and Monitor Actinic Keratosis in Ingenol Mebutate 0.015%- Treated Patients.

Long-term, chronic exposure to ultraviolet radiation from sunlight can induce DNA damage in epidermal keratinocytes and promote the formation of skin abnormalities, including actinic keratosis (AK).1-3 AKs present as skin-colored to reddish-brown macules, papules, or plaques with superficial gritty scale. Gene expression patterns and histopathologic analysis suggest that AKs are part of a disease continuum, starting with subclinically sundamaged skin and ultimately leading to the potential development of squamous cell carcinoma (SCC).4-6 Over time, AKs may resolve, remain stable, or progress. The risk for progression to invasive SCC over a 10-year period for patients with multiple AKs has been estimated at 10 percent.7 A primary challenge in the management of AKs is the possibility of field cancerization, a term that describes a biologic process in which large areas of cells are affected by a carcinogenic alteration resulting from a prolonged period of exposure to an injurious environment. The concept of field cancerization, introduced by Slaughter et al in 1953 with reference to histologic analysis of oral cancers,8 has been adapted to describe the damaging effects of ultraviolet light on the skin. Field cancerization presupposes an increased likelihood of future AKs and their progression to SCC. Determining and predicting which AKs may progress to SCC remains difficult, especially since visual identification of AKs is the current standard of care.9 Various field-directed therapies are now available to treat not only clinically obvious lesions but also the underlying damage. it would thus be helpful to have validated, noninvasive techniques for visualizing, detecting, and monitoring the damaged field. Optical coherence tomography (OCT) is one technology that offers considerable promise for noninvasive, real-time detection of AKs. OCT yields images of the tissue microarchitecture in both the horizontal and vertical planes down to a depth of approximately 2mm. its resolution is only 5 to 10μm, however, which precludes the detection of distinct cellular features.10,11 Nevertheless, the relatively large field of view (6mm) in OCT, and the low probe-to-field-of-view ratio (1.38cm:6mm) makes it well-suited to imaging broader areas of actinic damage (Figure 1). Noninvasive imaging devices show an inverse relationship between field-of-view size and cellular resolution. An ideal device for evaluating field cancerization is one that has just enough cellular resolution without compromising the scope of the field of view. Additionally, when using an imaging technique to monitor lesions at various intervals over time, it is important to minimize any discrepancy between the probe size and the imaging field. This is key to ensuring appropriate probe positioning over time. To date, OCT is used primarily in the research setting. Figure 1. Probe size and field of view (FOV) for a commercially available OCT device. Probe size and FOV in the context of an AK (grey circle) for Fourier domain OCT (FD-OCT) is shown (A). The probe that contacts the skin is circular, whereas the imaged FOV is ... The aim of this pilot study was to further define actinic field cancerization of the skin by comparing OCT readings with conventional histopathology for the identification of clinical and subclinical AKs. The study also aimed to compare the results of clinical and OCT assessment in monitoring the effect of topical ingenol mebutate (Picato®) 0.015% gel12 treatment of AKs on the face. A final objective was to investigate the relationship between the extent of lesion clearance and the severity of local skin reactions (LSRs) observed during ingenol mebutate treatment.