Neuropathological features of pediatric laryngomalacia

Inbal Hazkani*, Matthew Schniederjan, Ching Siong Tey, Anthony N. Botros, Kristen P. Alfonso

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Laryngomalacia is the most common pediatric laryngeal anomaly. The pathophysiology of laryngomalacia is not well defined; the leading hypothesis suggests weak laryngeal tone and neuromuscular discoordination. Only a few studies explored the histopathology of the laryngeal submucosal nerves, with reported nerve hypertrophy. Our study aims to describe the histopathology of submucosal nerves in specimens obtained from children with severe laryngomalacia compared to pediatric cadaveric controls. Study design: Prospective study. Settings: Tertiary care children's hospital. Methods: Histologic and immunohistochemical sections of supraglottic tissue from 26 children with severe laryngomalacia and six pediatric autopsies were digitally scanned and assessed with image analysis software (QuPath), resulting in the identification and measurement of 4561 peripheral nerves and over 100,000 foci of neurofilaments. Results: Chronic inflammation was noted in all patients. Eosinophils were rare. The mean nerve area and perimeter were significantly smaller for patients with laryngomalacia compared to the control group (1594.0 ± 593.2 μm^2 vs. 2612.1 ± 2824.0 μm^2, p < 0.0001, and 158.8 ± 30.3 μm vs. 217.6 ± 165.0 μm, p < 0.0001). Nerve-per-area unit was significantly greater for patients with laryngomalacia compared to controls (1.39E-05 vs. 6.19 E−06, p = 0.009). The mean area and the number of neurofilaments per total nerve area were similar. Immunohistochemistry for calretinin, a marker for intestinal ganglion cells in Hirschsprung disease, was absent from all specimens. Conclusions: This series includes a comparison of all identifiable nerve fibers obtained from children with severe laryngomalacia and shows that the mucosal nerves are smaller on average than controls. These findings fail to provide support for significant morphologic peripheral nerve pathology in laryngomalacia.

Original languageEnglish (US)
Article number112012
JournalInternational journal of pediatric otorhinolaryngology
Volume182
DOIs
StatePublished - Jul 2024

Keywords

  • Histopathology
  • Laryngomalacia
  • Nerve hypertrophy
  • Neurologic theory

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Otorhinolaryngology

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