Objectives/Hypothesis Although the migration of its squamous outer surface of the tympanic membrane has been well characterized, there is a paucity of data available concerning the migratory behavior of its medial mucosal surface. Existing theories of primary acquired cholesteatoma pathogenesis do not adequately explain the observed characteristics of the disease. We propose a new hypothesis, based upon a conjecture that mucosal membrane interactions are the driving force in cholesteatoma. Study Design A retrospective chart review and a prospective observational cohort study in rats. Methods After developing the new theory, it was tested through both clinical and experimental observations. To evaluate whether impairment of middle ear mucociliary migration would influence cholesteatoma formation, a retrospective chart review evaluating cholesteatoma occurrence in a sizable population of patients with either primary ciliary dyskinesia (PCD) or cystic fibrosis (CF) was performed. To study mucosal migration on the medial aspect of the tympanic membrane, ink tattoos were monitored over time in a rat model. Results No cholesteatomas were identified in either PCD patients (470) or in CF patients (1,910). In the rat model, mucosa of the posterior pars tensa migrated toward the posterior superior quadrant, whereas the mucosa of the anterior pars tensa migrated radially toward the annulus. Conclusion Mucosal coupling with traction generated by interaction of migrating opposing surfaces provides the first comprehensive theory that explains the observed characteristics of primary acquired cholesteatoma. The somewhat counterintuitive hypothesis that cholesteatoma is fundamentally a mucosal disease has numerous therapeutic implications.
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