Molecular biology of cholesteatoma.
Cholesteatoma is a non-neoplastic, keratinizing lesion, characterized by the proliferation of epithelium with aberrant micro-architecture into the middle ear and mastoid cavity. The exact pathogenic molecular mechanisms behind the formation and propagation of cholesteatoma remain unclear. 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. Currently, the most widely acknowledged pathogenesis of acquired cholesteatoma is the theory that negative pressure, dysfunction of the Eustachian tube, causes a deepening retraction pocket that, when obstructed, desquamated keratin cannot be cleared from the recess, and a cholesteatoma results. 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. Bacteria inside the retraction pocket produce some antigens, which will activate different cytokines and lytic enzymes. These cytokines lead to activation and maturing of osteoclasts with the consequence of degradation of extracellular bone matrix and hyperproliferation, bone erosion and finally progression of the disease. Further research is necessary for a better understanding of the pathogenetic mechanisms and to expand the spectrum of therapeutic options.
Department of Otolaryngology, Head and Neck Surgery, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania; almacjro@yahoo.com.
Alma
A
Maniu
Oana
O
Harabagiu
Maria
M
Perde Schrepler
Andreea
A
Cătană
Bogdan
B
Fănuţă
Carmen Aurelia
CA
Mogoantă
D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002781:Cholesteatoma / Q000151:congenital / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D006801:Humans; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D018384:Oxidative Stress
D015415:Biomarkers; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins