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Theories of cholesteatoma

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Theories of cholesteatoma

  1. 1. Definition cystic lesion formed from keratinizing stratified squamous epithelium in the temporal bone the matrix composed of epithelium that rests on the perimatrix the resulting hyperkeratosis and shedding of keratin debris results in surrounding inflammatory reaction
  2. 2. Classification Congenital Acquired  Primary  Secondary
  3. 3. Congenital Cholesteatoma Korner’s 1965:  pearly white mass behind an intact TM in the absence of history of otitis or otorrhea, TM perforation, or previous otologic procedures Levenson 1986:  presence of prior bouts of otitis media does not necessarily exclude the presence of congenital cholesteatoma
  4. 4. Congenital cholesteatoma Ongoing debate Epithelial rest theory Microperforation from chronic inflammation Tos:
  5. 5. Primary acquired cholesteatoma Represent the vast majority seen clinically Deep retraction pockets in which desquamated keratin deposits and does not migrate These retraction pockets are considered precursors to cholesteatomas Bacteria can infect the keratin matrix, forming biofilms leading to chronic infection and epithelial proliferation
  6. 6. Primary acquired cholesteatoma Invagination:  Eustachian tube dysfunction causes negative middle ear pressure  Fluctuating negative and positive pressures combined with inflammation can lead to loss of structural support and atelectasis  Pars flaccida the most susceptible  Retraction pocket may form leading to alteration of normal epithelial migration patterns
  7. 7. Primary acquired cholesteatoma basal cell hyperplasia or papillary ingrowth  Papillary ingrowth of keratinizing epithelium into the lamina propria of the TM  Basal lamina of the TM  separates the connective tissue of the lamina propria from the keratinising epithelium of the lateral layer of the TM  Breaks in the basal lamina in spontaneous and induced cholesteatoma
  8. 8. Primary acquired cholesteatoma Metaplasia  Low cuboidal and simple squamous epithelium can be changed to stratified squamous epithelium in patients with chronic or recurrent ear infection  Epithelial cells pluripotent and can differentiate into other cell types in the presence of inflammation  Clinically there is little support for this theory
  9. 9. Primary acquired cholesteatoma epithelial invasion  Epithelial pseudopods  seen within the lamina propria which form epithelial cones and microcholesteatomas  Inflammation in Prussaks space  causes breaks in the basal lamina allowing epithelial invasion and cholesteatoma formation
  10. 10. Primary acquired cholesteatoma Sudhoff &Tos 2000  Proposed a combination of both theories  4 stages  Retraction pocket stage  Proliferation stage of retraction pocket  Expansion stage of retraction pocket  Bone resorption
  11. 11. Secondary acquired cholesteatoma Perforations from infection or trauma can cause cholesteatoma Posterior marginal perforation Epithelial cells migrate across a denuded surface ‘contact guidance’ and stop when they encounter another epithelial surface ‘contact inhibition’
  12. 12. Alternatively Primary acquired  Eustachian tube dysfunction  Poor aeration of the epitympanic space  Retraction of the pars flaccida  Normal migratory pattern altered  Accumulation of keratin, enlargement of sac
  13. 13. Alternatively Secondary acquired  Implantation – surgery, foreign body, blast injury  Metaplasia – transformation of cuboidal epithelium to squamous epithelium from chronic infection  Invasion/Migration – medial migration along permanent perforation of TM  Papillary ingrowth – intact pars flaccida, inflammation in Prussack’s space, break in the basal membrane, cords of epithelium migrate inward
  14. 14. Molecular models Preneoplastic transformation events Defective wound-healing process Collision between host inflammatory response, normal middle ear epithelium, and bacterial infection
  15. 15. Preneoplastic transformation events Hyperproliferative keratinocytes  Increased proliferation  Decreased terminal differentiation Expression of epithelial markers in the basal and suprabasal layers (cytokeratins – 10,13,16, filaggrin, involucrin); confirm they arise from pars flaccida and overlying EAC skin High expression of epidermal growth factor receptor, transforming growth factor Upregulation of p53
  16. 16. Defective wound-healing process Chronic inflammatory response around matrix (granulation/perimatrix) Infiltration of activated T-cells and macrophages Production of cytokines (TGF,TNF,IL-1,IL-2,FGF,PDGF) Causes increased migration and invasion of cholesteatoma epithelium and fibroblasts
  17. 17. Host inflammatory response Bacterial related antigens producing host inflammatory response may stimulate the migrating epithelium’s uncoordinated proliferation Granulation induces invasion of keratinocytes Granulation – contains proteases, acid phosphatases, bone resorption proteins, osteoclast- activating factors, prostaglandins Keratin implanted into mouse calvaria was shown by Chole, et. al., to activate osteoclasts and produce a localized inflammatory bone remodeling similar to cholesteatomas
  18. 18. Cytokines Cytokines TNF-alpha lysosomal enzymes, acid phosphatase (total and tartrate resistant), cathepsin B, leucyl aminopeptidase lysozyme together with non-lysosomal enzymes calpain I and II It is likely that TNF-alpha acts both directly by causing bone erosion and indirectly by stimulating the release of lysosomal enzymes. The non-lysosomal enzymes calpain I and II seem to participate in the bone erosion associated with cholesteatoma by their involvement in collagen destruction. bacterial endotoxin
  19. 19. Summary Complex pathogensis of cholesteatoma Congenital:  Epithelial rests  Microperforations  Tos theory Acquired:  Primary (invagination)  Secondary (implantation, migration, basal cell hyperplasia, metaplasia, invasion) Molecular biology:  Cytokines bony erosion and development of cholesteatoma

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