CD34-positive fibroblasts in Reinke's edema

Abstract

In Reinke’s edema, the entire length of the membranous vocal fold is filled with fluid (swelling of Reinke’s space). Several histologic modifications are involved in this lesion, including modified stromal cell activity, microvasculature alteration (with greater permeability, resulting in increased exudative fluid in the extracellular matrix), and disarrangement of collagenous and elastic fibers.1–9 Risk factors in Reinke’s edema include smoking, vocal abuse, and gastroesophageal reflux.10,11 Of the stromal cells, fibroblasts are a major component of normal vocal folds.12 Fibroblasts produce extracellular matrix components, including glycosaminoglycans (hyaluronic acid), proteoglycans, glycoproteins (fibronectin and laminin), collagen, and elastin. Vocal fold fibroblasts (VFFs) have been extensively studied, including methods for identification in culture,13 senescence in primary culture,14 paracrine potential and signaling,15,16 immunoregulation,16 mesenchymal potential,17 interaction with adipose-derived stem/stromal cells,18 transdifferentiation and deactivation,19 influence of growth factors,20–23 agerelated changes,24–26 changes after mechanical (vibration27) or chemical (smoking15) action, characterization of those immortalized,23,28,29 or derived from chronic scars,30,31 and their biological activity, such as maintaining the correct viscosity and elasticity of the vocal folds.32 Furthermore, VFFs are considered as playing an important role in different lesions, including Reinke’s edema and vocal fold wound healing and scarring.12,23,26,30,31,33–36 A subset of fibroblasts, CD341 fibroblasts (so-called CD341 fibrocytes, CD341 dendritic cells, and CD341 stromal cells), has been reported in normal tissue around different structures, such as vessels (the main cellular constituent of the vessel adventitia), nerves, glands, and skin annexes, and within capsules, septa, fibrous tracts, and interstitial reticular networks, including the upper respiratory tract (see Barth et al.37,38), although the vocal folds have not been specifically considered. CD341 fibroblasts are also the major cell component of some benign and malignant tumors.39 Furthermore, several groups of authors have reported the presence of CD341 fibroblasts in other pathologic processes, such as repair and tumor stroma formation,37,40,41 and some lesions with myxoid and edematous changes.42–44 To our knowledge, CD341 fibroblasts have not been investigated in Reinke’s edema. The aim of this study therefore was to analyze CD341 fibroblasts in normal human vocal folds and in Reinke’s edema, especially around the edematous spaces in the subepithelial tissue.