Singer’s Nodules: Investigating the Etiopathogenetic Markers Progressing Their Pathogenesis and Clinical Manifestations

SIMPLE SUMMARY: Vocal nodules, together with vocal polyps, are the most common benign vocal cord structures that are thought to be caused by extensive vocal abuse (shouting, talking loudly for prolonged periods) and are routinely treated surgically. However, surgical excision of these nodules, does not exclude the possibility of recurrence of these nodules, especially if lifestyle changes are not adapted to prevent phonetic trauma. Furthermore, the etiopathogenetic pathways governing the formation and maintenance of these nodules are not known. Herein, we investigated the etiopathogenetic markers for proliferation, apoptosis, growth, ischemia (tissue hypoxia), inflammation and innervation to elucidate the causative pathways. We found a profound and significant intensification of apoptosis in tissue epithelium, which strongly correlated with proliferative, ischemic, and inflammatory changes, highlighting the underlying complex interactions between various mechanisms on a cellular and tissue level, which occur during the morpho-pathogenesis of vocal nodules. ABSTRACT: Vocal nodules (or Singer’s nodules) are benign vocal cord structures which are commonly encountered by clinicians. Though phonetic trauma/abuse is thought to be the main cause of the development of vocal nodules, the exact etiopathogenesis remains unknown. Hence, we compared the immunohistochemical markers for proliferation (Ki-67), apoptosis (TUNEL), growth (EGFR), ischemia (VEGF), inflammation (IL-1α and 10), and immunoreactive innervation (PGP 9.5), in vocal nodule tissue samples obtained from 10 females (17–56 years) and vocal cord tissue from seven controls. A statistically significant increase in Ki-67, TUNEL, EGFR, VEGF and IL-1α expression was noted (p < 0.05) between nodule tissue and control tissue in both epithelial and subepithelial layers. However, the difference was non-significant for both IL-10 and PGP 9.5 (p > 0.05). All markers demonstrated moderate to strong positive correlations, except for IL-10. These findings suggest increased cellular growth and proliferation in vocal nodules coupled with a persistent presence of inflammatory and ischemic environment. Furthermore, global prevalence of apoptotic cells and decreased anti-inflammatory cytokines highlight the presence of underlying complex mechanisms in the etiopathogenesis of vocal nodules, with age having a negligible impact on the marker levels. Our results could potentially further our knowledge in understanding the effects of different treatment modalities available at the cellular level.