Radiation Fibrosis of the Epiglottis: Histopathology and Multiphoton Imaging of Collagen and Elastin.

Abstract

Dysphagia attributed to radiation-induced fibrosis (RIF) is common among patients treated with radiation for head and neck cancer. In this study, we characterize RIF in the epiglottis. This has not been previously described. Our cohort included 26 patients who underwent partial epiglottidectomy for symptomatic dysphagia due to epiglottic dysfunction. Eighteen patients had a history of radiation therapy. Epiglottis tissue sections were stained with H&E, and the ratio of epiglottic cartilage thickness to total epiglottis thickness was measured. Imaging for elastin and collagen was performed with multiphoton microscopy, and the density of each in the lamina propria layer was quantified. Radiated epiglottis had a higher prevalence of dilated vasculature, chronic inflammation, focal hyalinization-like changes in the elastic cartilage, and atrophic seromucous glands. In addition, a lower ratio of elastic cartilage to total epiglottis thickness was found (0.36 in radiated versus 0.45 in non-radiated, p < 0.01), attributable to increased thickness of the lamina propria layer due to fibrosis. In the radiated samples, the density of collagen was higher, 46.51% versus 36.78% (p < 0.01), and the density of elastin was lower, 5.11% versus 8.27% (p < 0.01). Elastic fibers were straighter, shorter, and more fragmented in radiated samples. This first characterization of RIF and pilot use of multiphoton microscopy in the epiglottis identified key histopathologic characteristics associated with radiation, notably higher density of collagen, lower density of elastin, and fragmentation of elastic fibers. These findings provide a pathophysiologic explanation for the relationship between epiglottic dysfunction, dysphagia, and radiation. Level 3.