Irradiated macula flava in the human vocal fold mucosa

Abstract

Purpose

There have been no investigations regarding radiation-induced damage on human maculae flavae (MFs) in the vocal fold mucosa (VFM) and on stellate cells (SC) in the MF. The VFM, especially MF, after irradiation was investigated histologically.

Materials and methods

The lamina propria of the irradiated VFM was investigated in 5 human adult vocal folds by light and electron microscopy.

Results

Fibroblasts in the irradiated Reinke's space (RS) showed no morphological changes. Irradiated RS was composed of fibrous tissue with increased collagenous fibers. Most of the SC in the irradiated MF had dark cytoplasm. The nucleus-cytoplasm ratio was relatively small, but there were few intracellular organelles in the cytoplasm. Some SC showed degeneration. Fewer vesicles were present at the periphery of the cytoplasm. The MF was rather deficient in fibrous components. Elastic and collagenous fibers immediately surrounding SC in the irradiated MF were lower in number than usual, but elastic fibers and collagenous fibers composed of irregular collagen fibrils could be detected at a distance from SC. It was suggested that precursors of collagenous and elastic fibers synthesized by SC were damaged by irradiation. Radiation sensitivity of SC was higher than that of conventional fibroblasts in RS, and SC appeared to decrease their level of activity.

Conclusions

Radiation sensitivity of SC was different from that of conventional fibroblasts. Radiation induced not only changes in the lamina propria of the VFM but also dysfunction of the SC in the MF, and is one of the causes of voice disorders after irradiation.

Introduction

Voice disorders are one of the complications after radiation therapy, and they are caused by radiation-induced tissue damage. Radiation therapy may be a double-edged sword with the capacity to cure tumors and also possibly cause fibrosis, necrosis, chronic edema, atrophy, and even secondary carcinomas [1]. Despite the beneficial tumoricidal effects of radiation, whenever doses of radiation sufficient to kill cancer cells are used, normal tissues are permanently affected [1].

In our previous studies, human maculae flavae (MF) located at both ends of the human vocal fold mucosa (VFM) were inferred to be involved in the metabolism of extracellular matrices in the VFM and to be responsible for forming the characteristic layered structure of the human VFM. Maculae flavae are also considered to be an important structure in the growth, development, and aging of the human VFM [2], [3], [4], [5], [6], [7], [8], [9], [10]. There have been no investigations regarding radiation-induced damage on the human MFs in the VFMs.

An interstitial cell with a starlike appearance in the human MFs, located at both ends of the human VFM, was discovered [11], [12], [13], [14]. This cell possessed lipid droplets and stored vitamin A [11], [12]. This cell had many morphological differences from conventional fibroblasts in the vocal fold and constantly synthesized extracellular matrices that are essential for the human VFM. These cells have no nomenclature and were thus designated as “vocal fold stellate cells (SCs),” for convenience in the series of our previous studies [11], [12], [13], [14]. Our past studies inferred that the vocal fold SCs in the MFs form an independent cell category that should be considered a new category of cells and is involved in the metabolism of extracellular matrices in the human VFM [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14]. There have also been no investigations regarding the radiation-induced damage of SCs or its radiation sensitivity.

In the present study, irradiated normal human VFMs were investigated by light and electron microscopy. The radiation-induced damage of the SCs in the human MFs and its influence on voice disorders after radiation, and a comparison of the radiation sensitivity between SCs and conventional fibroblasts were discussed.