Impact of Photodynamic Therapy on Mast Cell-Associated Inflammation and Angiogenesis in Actinic Keratosis

Background/Objectives: Actinic keratosis (AK) is a common ultraviolet-induced intraepidermal neoplasm with a recognized potential to progress to cutaneous squamous cell carcinoma (cSCC). Although photodynamic therapy (PDT) is an established field-directed treatment for AK, its effects on the inflammatory and angiogenic tumor microenvironment, particularly regarding mast cell (MC) infiltration and microvascular remodeling, remain incompletely understood. This study aimed to investigate the impact of PDT on mast cell (MC) count and CD31-associated microvessel density (MVD) in AK lesions. Methods: In this prospective single-center study, 31 patients with histopathologically confirmed AK underwent three sessions of 5-aminolevulinic acid-based PDT. Each patient contributed samples of clinically uninvolved skin, the target AK lesion before PDT, and the same AK lesion after PDT. Repeated tissue measurements were analyzed using the Friedman test followed by exact Wilcoxon signed-rank tests with Holm correction. Associations between MC count and MVD were assessed using Spearman rank correlations. Clinical and dermoscopic grades were analyzed as paired ordinal outcomes. Results: Significant clinical and dermoscopic improvement was observed in the majority of patients following PDT, with complete lesion clearance achieved in 17 of 31 patients (54.84%). Both MC count and MVD were significantly higher in AK lesions compared with clinically uninvolved skin (p < 0.05). PDT resulted in a significant reduction in both parameters (p < 0.05), although post-treatment levels remained elevated relative to clinically uninvolved skin. MC count and MVD were positively correlated both before and after PDT, with a stronger association observed after treatment. Conclusions: PDT demonstrates not only cytotoxic effects against dysplastic keratinocytes but also may significantly modulate the inflammatory and angiogenic microenvironment in AK. The persistent correlation between MC infiltration and neovascularization after therapy may reflect incomplete normalization of the local microenvironment despite clinical improvement. These findings suggest that MC count and MVD may merit further evaluation as adjunctive biomarkers of response in PDT-treated AK.