The Laryngoscope V C 2015 The American Laryngological, Rhinological and Otological Society, Inc. Letter to the Editor In Response to A New Theory on the Pathogenesis of Acquired Cholesteatoma: Mucosal Traction In Reply: The authors welcome the thoughtful and pertinent comments of Professors Chole and Lim. We agree that histological evidence shows a paucity of cilia on the mucosa surface of the normal tympanic membrane, espe- cially the pars flaccida. Cholesteatomas, however, do not arise in normal middle ears. Albiin et al. reviewed a number of studies showing that in pathological condi- tions, large numbers of ciliated cells appear in regions of the middle ear that do not typically possesses them. 1 Grote et al. showed that infection causes increased cilia coverage of the pars flaccida in response to infection. 2 Hermansson et al. demonstrated that the pars flaccida, which was devoid of cilia in the normal state, becomes populated with ciliated cells following acute otitis media, and that they remain for at least 2 months following the resolution of the infection. 3 Our theory that mucosal interactions may underlie primary acquired cholesteatoma formation is not entirely dependent upon the presence of cilia. As described in our article, 4 opposing moist mucosal surfaces may interact in a number of ways not driven by mucociliary blanket motil- ity such as sequential adhesion and epithelial migration. Although ciliation varies, cells containing secretory granules occur throughout the middle ear. 1 All surfaces of the tympanic cavity are diffusely moistened with mucus. As the tympanic cavity has a robust clearance system, it seems unlikely that the moist medial surface of the pars flaccida is entirely stagnant. We agree that this needs to be investigated in humans. Aside from infection, there may be other circum- stances under which mucosal hypermobility arises. A substantial fraction of cholesteatomas arise in older children during a period when the extent of temporal bone pneumatization normally increases considerably. This process is driven by hyperactive mucosa invading marrow spaces, thus creating mucosally lined air cells. If impeded by obstructing disease or unyielding calcifica- tion, this developmentally programmed mucosal activa- tion, set into motion to seek open pathways but confined to the epitympanum and antrum, could conceivably cata- lyze cholesteatoma formation. We enthusiastically endorse the notion that addi- tional research into the potential role of the mucosa in cholesteatoma formation is needed. We hope that our proposal will stimulate interest in studies designed to determine whether or not our hypothesis that cholestea- toma invagination may be primarily driven by mucosal interactions is valid. ROBERT K. JACKLER, MD PETER LUKE SANTA MARIA, MBBS, PhD YASIN KURSAD VARSAK, MD NIKOLAS H. BLEVINS, MD Department of Otolaryngology–Head and Neck Surgery Stanford University School of Medicine Stanford, California ANH NGUYEN, MD, PhD Department of Otolaryngology–Head and Neck Surgery University of Oregon Health and Science University Portland, Oregon BIBLIOGRAPHY 1. Albiin N, Hellstrom S, Stenfors LE, Cerne A. Middle ear mucosa in rats and humans. Ann Otol Rhinol Laryngol Suppl 1986;126:2–15. 2. Grote JJ, Bakker D, Hesseling SC, van Blitterswijk CA. Tympanic mem- brane structure during a Staphylococcus aureus-induced middle ear infection. Acta Otolaryngol 1989;107:225–234. 3. Hermansson A, Prellner K, Hellstrom S. Persistent structural changes in the middle ear mucosa of the rat, after an experimentally induced episode of pneumococcal otitis media. Acta Otolaryngol 1990;109:421– 430. 4. Jackler RK, Santa Maria PL, Varsak YK, Nguyen A, Blevins NH. A new theory on the pathogenesis of acquired cholesteatoma: mucosal traction. Laryngoscope 2015;125(suppl 4):S1–S14. DOI: 10.1002/lary.25654 Laryngoscope 126: March 2016 Jackler et al.: Letter to the Editor E131