[Current concepts of the pathogenesis of acquired middle ear cholesteatoma].

The pathogenesis of acquired middle ear cholesteatoma is still unknown and subject of controversial discussions. Based on clinical and histological findings, several theories for cholesteatoma pathogenesis have been developed: 1) retraction pocket theory; 2) proliferation theory; 3) immigration theory, and 4) metaplasia theory. Additionally cholesteatoma development was grouped in particular stages. Immunohistochemical examinations of the matrix and perimatrix have considerably improved the knowledge of cholesteatoma pathogenesis. In this review the current concepts of cholesteatoma pathogenesis are discussed: a retraction pocket occurs due to a tubal dysfunction. Local infection leads to a disturbance of self-cleaning mechanisms, with cell debris and keratinocytes accumulate inside the retraction pocket, and this is followed by an immigration of immune cells, i. e. Langerhans' cells, T-cells, macrophages. There is an imbalance and a vicious circle of epithelial proliferation, keratinocyte differentiation and maturation, prolonged apoptosis, and disturbance of self-cleaning mechanisms. The inflammatory stimulus will induce an epithelial proliferation along with expression of lytic enzymes and cytokines. As a consequence, some "microcholesteatoma" occur which will confluent. Bacteria inside the retraction pocket produce some antigens which will activate different cytokines and lytic enzymes, i. e. ICAM, RANKL, IL-1, IL-2, IL-6, MMP-2, and MMP-9. These cytokines lead to activation and maturing of osteoclasts with the consequence of degradation of extracellular bone matrix and hyperproliferation, bone arrosion and finally progression of the disease. The question why not all cholesteatomas show the same progression process is still unclear. A probable explanation could be that in most retraction pockets migration and self-cleansing mechanisms for keratinocytes are well functioning, with normal migration of the squamous epithelium from the basal layers to the surface. Nevertheless, future research will have to evaluate this topic which might be crucial for the understanding of cholesteatoma pathogenesis and for therapy.