In-Vivo LC-OCT Evaluation of the Downward Proliferation Pattern of Keratinocytes in Actinic Keratosis in Comparison with Histology: First Impressions from a Pilot Study

Simple Summary Actinic keratoses (AKs) are extremely common in the elderly population; they are universally recognized as precursors of invasive squamous cell carcinoma, and their risk of progression relates to the basal growth pattern of keratinocytes in the histological slides, based on a model called "PRO" classification. Since AKs can be investigated at bedside with non-invasive devices such the new line-field confocal optical coherence tomography (LC-OCT), we hypothesized that it was also possible to use such devices for reproducing the PRO classification and assessing the progression risk of AK without an invasive biopsy. In this pilot study, we demonstrated the feasibility of the LC-OCT severity grading of AKs based on the histological PRO classification, obtaining a good correlation between the two models and strong interobserver agreement. It is known that actinic keratoses (AKs) can progress to invasive squamous cell carcinoma (SCC). The histological PRO grading of AKs is based on the growth pattern of basal keratinocytes and relates to their progression risk. AKs can be non-invasively characterized by line-field confocal optical coherence tomography (LC-OCT). The aim of the study was to define criteria for an LC-OCT grading of AKs based on the PRO classification and to correlate it with its histological counterpart. To evaluate the interobserver agreement for the LC-OCT PRO classification, fifty AKs were imaged by LC-OCT and biopsied for histopathology. PRO histological grading was assessed by an expert consensus, while two evaluator groups separately performed LC-OCT grading on vertical sections. The agreement between LC-OCT and histological PRO grading was 75% for all lesions (weighted kappa 0.66, 95% CI 0.48-0.83, p <= 0.001) and 85.4% when comparing the subgroups PRO I vs. PRO II/III (weighted kappa 0.64, 95% CI 0.40-0.88, p <= 0.001). The interobserver agreement for LC-OCT was 90% (Cohen's kappa 0.84, 95% CI 0.71-0.91, p <= 0.001). In this pilot study, we demonstrated that LC-OCT is potentially able to classify AKs based on the basal growth pattern of keratinocytes, in-vivo reproducing the PRO classification, with strong interobserver agreement and a good correlation with histopathology.