Cholesteatoma: a molecular and cellular puzzle.

Abstract

The authors' published and unpublished studies to date support several suppositions concerning the pathology of cholesteatomas. First, cholesteatoma epithelium behaves more like a wound-healing process than a neoplasm. The available evidence to date does not indicate that cholesteatomas have inherent genetic instability, a critical feature of all malignant lesions. Second, the induction of hyperproliferative cells in all layers of the cholesteatoma epidermis implicates a potential idiopathic response to both internal events as well as external stimuli in the form of cytokines released by infiltrating inflammatory cells. Third, the presence of bacteria may provide a critical link between the cholesteatoma and the host, which prevents the cholesteatoma epithelium from terminating specific differentiation programs and returning to a quiescent state in which it becomes minimally proliferative, nonmigratory, and noninvasive. Fourth, none of our data suggest that there are any obvious molecular or cellular differences among the various types of cholesteatomas (e.g., primary and secondary acquired, recidivistic, and congenital). Continued research should delineate the precise molecular and cellular dysfunction involved in the pathogenesis of cholesteatomas and how this knowledge can be useful in the clinical management of cholesteatomas.