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

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.

The life‐cycle and restoration of the human vocal fold

“…The extent of remodeling within the lamina propria is uncertain. Clinical observation mostly shows no improvement in vocal fold stiffness following fibrotic change and vocal fold nodules and polyps are known to persist in adults without surgical intervention 56 . This contrasts to observations in childhood where most vocal fold nodules resolve during puberty and fibrotic changes secondary to surgery are not always carried through into adulthood 57,58 …”

Characterization of Angiogenic, Matrix Remodeling, and Antimicrobial Factors in Preterm and Full-Term Human Umbilical Cords

“…The appearance and distribution of MMP2, TIMP2, VEGF, and HBD2 were examined in the endothelium of the umbilical arteries, the endothelium of the umbilical vein, the blood vessel wall, the extraembryonic mesenchyme, and the amniotic epithelium. Positively stained cells were counted and then graded using a scale containing the following values: 0—no positive structures (0%); 0/+—occasional positive structures (12.5%); +—few positive structures (25%); +/++—few to moderate number of positive structures (37.5%); ++—moderate number of positive structures (50%); ++/+++—moderate to numerous number of positive structures (62.5%); +++—numerous positive structures (75%); +++/++++—numerous to an abundance of positive structures (87.5%); ++++—abundance of positive structures (100%) [ 26 ].…”

Expression of Markers Ki-67, Nestin, VEGF, CD34 and Apoptosis in Relatively Healthy Lung Tissue with Non-Changed and Metaplastic Bronchial Epithelium

“…Negative and positive controls were provided to evaluate the specificity and sensitivity of the IHC. Positive control was carried out using already proved positive stainings for the specific marker: spinal ganglion of the pig for nestin [ 24 ], hyperplastic vocal noduli for Ki-67 [ 25 ], extirpated v. saphena magna for VEGF [ 26 ], subepithelial blood vessels of oral mucosa for CD34 [ 27 ]. Negative control was performed by excluding the primary antibody from the staining procedure.…”

“…Immunoreactive (positive) structures seen in the visual field were then counted. The scale that was used for the semi-quantitative method contains the following values: 0—no positive structures (0%); 0/+—occasional positive structures (12.5%); +—few positive structures (25%); +/++—few to moderate number of positive structures (37.5%); ++—moderate number of positive structures (50%); ++/+++—moderate number of to numerous positive structures (62.5%); +++—numerous positive structures (75%); +++/++++—numerous to abundance of positive structures (87.5%); ++++—abundance of positive structures (100%) [ 25 ] (see Supplementary Materials, Figure S1 ).…”