Track

Clinical Studies

Abstract

Cutaneous radiation fibrosis is a delayed response to ionizing radiation therapy with significant morbidity. Currently, the published clinicopathologic characterization of this condition is limited to individual case reports and small series using murine models of disease. Accordingly, given the paucity of large case series, the spectrum of histopathologic features remains to be fully elucidated. In our study, we identified 26 cases of radiation fibrosis involving skin at our institution diagnosed between 2016 and 2023. In all cases, the most common epidermal findings were ulceration (24%), interface vacuolization (57%), and dyskeratotic keratinocytes (39%). In the dermis, all 26 cases demonstrated vascular ectasia, reactive endothelial cells, and bizarre (radiation) fibroblasts, with additional features including chronic inflammation (96%, 25/26), pigment incontinence (62%, 16/26), and collagen hyalinization (58%, 15/26). Further, fat necrosis was present in 91% of biopsies containing adipose tissue and eccrine metaplasia was identified 82% of cases in which eccrine glands were present. Interestingly, when we stratify the cases by time between initial irradiation to diagnostic procedure, we observe greater rates of epidermal atrophy (38% vs 14%) and myxoid stromal changes (80% vs 50%) in tissues biopsied > 36 months from the onset of radiation therapy than those biopsied at earlier time points. Overall, this study expands our understanding of the diverse histopathologic spectrum of cutaneous radiation fibrosis, contributing novel insights into the microscopic features present in this condition that may not only facilitate improved recognition but also potentially yield mechanistic insight into its pathogenesis.