2. 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

3. Classification
 Congenital
 Acquired
 Primary
 Secondary

4. 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

5. Congenital cholesteatoma
 Ongoing debate
 Epithelial rest theory
 Microperforation from chronic inflammation
 Tos:

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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’

13. 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

14. 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

15. Molecular models
 Preneoplastic transformation events
 Defective wound-healing process
 Collision between host inflammatory
response, normal middle ear epithelium, and
bacterial infection

16. 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

17. 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

18. 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

19. 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

20. 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