Increased numbers of mast cells in human middle ear cholesteatomas: implications for treatment.

Hypothesis: Because many of the biologic phenomena in which mast cells are involved also are observed in human cholesteatoma pathology, the authors hypothesized that mast cells may play a role in this disease. The first test of this hypothesis is to determine whether there are an increased number of mast cells associated with cholesteatomas. Background: The molecular and cellular defects that result in the pathologic features observed in acquired and congenital cholesteatomas are unknown. One common feature of cholesteatoma pathogenesis is the presence of bacteria and a numerous inflammatory cytokines expressed by host inflammatory cells. The interactions between inflammatory cells and cholesteatoma epithelium could result in the induction of other aberrant biologic features of cholesteatomas. Thus, it is critical to the understanding of the pathogenesis of cholesteatomas to define the specific role of each cell type involved in this disease. Connective tissue mast cells have a complex retinue of functions mediated via the secretion of a variety of cytokines and proteinases, and many of the biologic phenomena in which mast cells are involved also are observed in cholesteatoma pathology. Methods: The authors evaluated by immunohistochemistry 36 cholesteatomas of all types (e.g., primary and secondary acquired, recurrent, and congenital) and 23 specimens of normal tissues (e.g., tympanic membrane, canal wall skin, and postauricular skin) for the expression of tryptase, a mast cell-specific protease. Results: Cholesteatomas showed approximately threefold to sevenfold increase in the concentration of mast cells when compared with that of normal tissues. In addition, 19-34% of the mast cells were found within the suprabasal layers of the squamous epithelium of cholesteatoma subgroups, a phenomenon observed only in grossly inflamed tympanic membrane specimens, but not in other control tissues including minimally inflamed tympanic membranes. Conclusions: The authors conclude from these data that mast cells may represent a previously unrecognized host inflammatory cell, which plays an important role in the development of one or more traits of cholesteatoma pathology.