[Role of perimatrix fibroblasts in development of acquired middle ear cholesteatoma. A hypothesis].

The epithelial pathogenesis of acquired cholesteatoma has been widely accepted, but clinical and experimental data have not been able to answer questions like: How does a cholesteatoma start or grow or how is bone resorption of conducted? From our own experiments and literature a new hypothesis of cholesteatoma origin and growth is drawn. Three prerequisites are necessary for development: (1) the unique anatomical situation at the ear-drum (two different epithelial layers close together); (2) chronic destruction of the submucosal tissue in the middle ear (infection, inflammation); (3) wound healing (proliferation phase). Destruction of the submucosal space by middle ear infection and cell necrosis starts the wound healing cascade. In wound healing generally the connective tissue fibroblasts and macrophages play a pivotal role. Cytokines of the wound healing thought to promote the re-epithelization of the mucosal defect and scar tissue development act upon the intact squamous cell layer of the outer surface of the ear-drum at the same time. Thereby a proliferation of the undamaged epithelial layer is induced. Cholesteatoma matrix is always surrounded by a layer of connective tissue, the perimatrix. Persistence of the inflammation causes permanent wound healing in the perimatrix, proliferation of the fibroblasts (granulation tissue) and proliferation of the epithelium (matrix). It is speculated that by virtue of wound healing cytokines of fibroblasts and macrophages are the driving forces of cholesteatoma origin, growth and bone destruction.