Neuropathological Features of Pediatric Laryngomalacia

Introduction: Laryngomalacia (LM) is the most common pediatric laryngeal anomaly; however, the pathophysiology is not well defined. The leading hypothesis suggests weak laryngeal tone and neuromuscular discoordination of the peripheral nervous system. Only a handful of studies have explored the histopathology of the laryngeal submucosal nervous system with reported nerve hypertrophy. The goal of our study was to report the neuropathological features of specimens obtained from children with LM compared to controls

Methods: Histologic and immunohistochemical sections of supraglottic tissue from 26 children with severe LM and 6 pediatric autopsies were digitally scanned and assessed with image analysis software (QuPath), resulting in the identification and measurement of 4,561 peripheral nerves and over 100,000 foci of neurofilaments

Results: Chronic inflammation was noted in 20 patients. Eosinophilia was rare. The mean nerve area and perimeter were significantly smaller for patients with LM compared to the control group (1594.0±593.2µm^2 vs 2612.1±2824.0 µm^2, p< 0.0001, and 158.8±30.3µm vs 217.6±165.0µm, p< 0.0001). Nerve-per-area unit was significantly greater for patients with LM compared to controls (1.39E-05 vs 6.19 E-06, p= 0.009). The mean area of neurofilaments was similar (5.2±10.1 µm^2 vs 5.5±13.8 µm^2, p=0.9). Immunohistochemistry for calretinin, a marker for Hirschsprung disease, was absent from all specimens.

Conclusions: Increased size of mucosal nerves has been reported in smaller studies of LM. This series includes a comparison of all identifiable nerve fibers and shows the mucosal nerves in laryngomalacia are smaller on average than controls. These findings fail to provide support for significant morphologic peripheral nerve pathology in LM.