Diagnostic and Treatment Aspects of Actinic Keratoses. Summary of the Doctoral Thesis

Abstract

Actinic keratoses (AK) are common keratinocyte intraepithelial neoplastic disordersthat serve as a general marker of chronic sun damage. These lesions can directly progress into invasive squamous cell carcinoma (SCC), while simultaneously, their presence serves as a general marker of all skin cancer development risks. Therefore, knowledge in diagnosing and treating AK is of great clinical relevance. The aim of this Thesis was to explore different clinically relevant aspects of diagnosingand treating AK. The aim was reached with seven tasks and six peer-reviewed publications. The initial part of the study focused on identifying clinical and dermatoscopic parameters that are indicative of histological and immunohistochemical alterations in the skin, typical of the disease. This was accomplished through a systematic review aimed at pinpointing the clinical characteristics of AK that were known to progress into invasive SCCs, as evidenced in prospective studies. The review followed the Prisma guidelines and was registered in the Prospero database. As a result, long-standing and large or merging AK were concluded to be the most important clinical risk factors for the development of SCC. Furthermore, the study summarized the most prevalent dermatoscopic features of AK and evaluated the significance of various immunohistochemical markers – namely p53, p63, p16, Ki67, cyclin D1, Bcl-2, and CD31. This evaluation aimed to discern their expression in samples of AK and intraepithelial carcinomas as opposed to samples of clinically normal but sun-damaged skin. To accomplish this objective, the study collected AK and intraepithelial carcinoma samples, as well as healthy skin samples from sun-exposed facial areas, from patients within the same age cohort. These samples were then stained with haematoxylin and eosin, along with specific immunohistochemical markers. The findings revealed distinct differences in the presence of amorphous masses and the intensity of staining for p53. Moreover, there was a variation in the expression of Bcl-2 and CD31 markers between clinically healthy, chronically sun-damaged skin and the samples of AK and intraepidermal carcinomas. In a subsequent phase of the research, an analysis was conducted to elucidate the correlation between identified clinical and dermatoscopic parameters and the observed histological and immunohistochemical alterations. This analysis revealed that dermatoscopically typical AK, particularly those featuring the hallmark small interfollicular blood capillaries, were more likely to be associated with the presence of amorphous masses in histopathological samples. Additionally, these typical AKs exhibited a lower expression of the CD31 marker. Conversely, the absence of follicular structures correlated with an increased expression of the Bcl-2 marker in the subepidermal 5 layers. The identified associations underscore the significance of neoangiogenesis and subepidermal inflammatory cell infiltration in the recognized progression from AK to SCC. Furthermore, these findings emphasize the utility of dermatoscopy as a tool for selecting lesions that exhibit greater severity and may therefore require closer monitoring or more aggressive management. The investigation into the correlation between dermatoscopic and histopathological findings is set to continue in future studies.