Sensorineural hearing loss can be caused by lesions to the inner ear during development. Understanding the events and signaling pathways that drive inner ear formation is crucial for determining the possible causes of congenital hearing loss. We have analyzed the innervation and expression of SOX2, JAGGED1, β-catenin (CTNNB1), and vitamin D receptor (VDR) in the inner ears of human conceptuses aged 5 to 10 weeks after fertilization (W) using immunohistochemistry. The prosensory domains of the human inner ear displayed SOX2 and JAGGED1 expression throughout the analyzed period, with SOX2 expression being more extensive in all the analyzed timepoints. Innervation of vestibular prosensory domains was present at 6 W and extensive at 10 W, while nerve fibers reached the base of the cochlear prosensory domain at 7–8 W. CTNNB1 and VDR expression was mostly membranous and present during all analyzed timepoints in the inner ear, being the strongest in the non-sensory epithelium. Their expression was stronger in the vestibular region compared to the cochlear duct. CTNNB1 and VDR expression displayed opposite expression trends during the analyzed period, but additional studies are needed to elucidate whether they interact during inner ear development.
Patients with laryngeal squamous cell carcinoma (LSCC) often develop other malignancies, most commonly second primary lung cancer (SPLC). This study aimed to estimate the incidence of SPLC in LSCC patients and evaluate whether pulmonary nodules on baseline thoracic computed tomography (CT) predict SPLC development. In this single-center retrospective cohort study, 243 patients with LSCC diagnosed from 2017 to 2024 at the University Hospital of Split, Croatia, were followed, of whom 26 (10.7%) developed SPLC. The median time from LSCC to SPLC diagnosis was approximately 1.2 years. Patients with LSCC had an approximately eightfold higher risk of developing an SPLC than the general population (standardized incidence ratio [SIR] 8.40; 95% confidence interval [CI] 5.48–12.30). Pulmonary nodules at diagnosis were the only predictor associated with the development of an SPLC (hazard ratio [HR] 2.37; 95% CI 1.09–5.13; p = 0.029), although this association weakened and lost significance when the analysis was restricted to metachronous tumors (HR 1.84; 95% CI 0.71–4.77; p = 0.207). Metachronous tumors were predominantly squamous cell carcinomas (83.3%), whereas adenocarcinoma was the most common histological type among synchronous tumors (50.0%; p = 0.022). Patients with SPLC had a shorter overall survival than those without it (median 5.4 vs. 8.0 years; log-rank p = 0.016). The presence of pulmonary nodules at LSCC diagnosis was associated with a higher risk of SPLC. However, these findings originate from a single center, and further studies are needed to determine whether stratification based on initial radiological findings can improve early detection of SPLC in patients with LSCC.