Cholesteatomas are bone destructive expansions of keratinizing squamous epithelium in the middle ear and temporal bone. Today, surgery is the only treatment. There are several controversies regarding cholesteatomas, including the definition, the pathogenesis and the surgical method. Intense efforts have been made searching for a comprehension of the cholesteatoma process at a cellular and molecular level. Recurrent infections and inflammation seem to be contributing factors for the cholesteatomas to expand. The innate immunity, essential to keep a healthy middle ear environment and to protect the middle ear from intruding pathogens, is therefore a matter of interest. In this thesis, results are presented from a cohort of cholesteatoma surgeries in Östergötland from a 16-year period. A group of patients also filled in a questionnaire to assess changes in health-related quality of life (HRQoL) after surgery. According to the findings in this thesis, the residual and recurrence frequencies are low, and the hearing and HRQoL are improved in the majority of cases. This thesis also presents an investigation of the innate immunity in ears with acquired cholesteatoma, in comparison with healthy controls. The expression of mRNA of toll-like receptors 2 and 4, participants of the Janus kinase/signal transducer and activator of transcription pathway, and nitric oxide synthases in middle ear mucosa, were investigated with quantitative polymerase chain reaction. An investigation of nitric oxide (NO) in the middle ear, with chemiluminescence measurements, is also presented. A derangement of the innate immune system is seen in ears with cholesteatoma, which supports the idea that the innate immunity participates in the cholesteatoma process, though the underlying mechanisms are still unclear. The suggestion of NO production in the middle ear sheds light on NOs possible participation in the healthy middle ear environment.

Acquired aural cholesteatoma poses a unique procedural dilemma with regard to pathogenetic research and theory building. Because cholesteatoma spontane ously occurs only in the poorly pneumatized human ear, its pathogenesis is specific to humans. Nonetheless, because of the ethical questions surrounding human experimentation, pathogenetic study has almost exclusively involved nonhuman subjects. Indeed, attempts have failed in almost all animal expe riments except with the gerbil, and even here experimental designs have been improbable compared with human cholesteatoma. Cholesteatoma in the gerbil is useful, therefore, only for the study of pathology and not for human pathogenesis. I hold that the pathogenesis of cholesteatoma will be understood by studying the cholesteatomatous ear, that is, the malpneumatized ear of the human. The anatomical difference between the normal and malpneumatized ear is a probable cause of cholesteatoma. This difference may be found clinically in facial nerve decompression and cholesteatoma surgery, as, for example, facial nerve palsy occurs usually in the normal, well-pneumatized ear. Of course, conventional animal experimentation will not confirm this clinical difference since there is no ideal animal model for the poorly pneumatized human ear. Present surgical techniques for cholesteatoma vary greatly according to indi vidual otosurgeon's opinion. The most extreme difference of opinion is focused on whether to remove the external ear canal wall. Normally, the best option would be not to remove the canal wall if cholesteatoma recurrence can be prevented. Simply put, recurrence of cholesteatoma comes about when its cause has not been removed during primary surgery.

A reference for tackling diagnostic dilemmas that pathologists and clinicians encounter when assessing pediatric head and neck disease.