Cholesteatoma: Theories of Etiopathogenesis and Routes of Spread

DEFINITION

CLASSIFICATION

PART A: THEORIES OF ETIOPATHOGENESIS

1. Invagination / Retraction Pocket Theory (Most Accepted)

• Eustachian tube (ET) dysfunction leads to hypoventilation of the middle ear cleft
• Persistent negative middle ear pressure ("ex vacuo") causes the pars flaccida (which is less fibrous and less rigid) to retract inward
• The retraction pocket deepens progressively; at a critical depth, desquamated keratin can no longer self-migrate out of the pocket
• Keratin accumulates, bacteria colonize the keratin matrix forming biofilms, and a cholesteatoma results
• An atrophic or thinned TM (from previous AOM/OME) is especially susceptible

• Eustachian tube obstruction in animal models produces drum retraction and cholesteatoma
• Higher incidence in cleft palate patients (poor ET function)
• Retraction pockets are recognized clinically as precursor lesions
• Selective epitympanic dysventilation syndrome (Palva) and the Sudhoff-Tos combined retraction + basal hyperplasia model are variants of this theory

2. Epithelial Invasion / Immigration Theory (Migration Theory)

• Keratinizing squamous epithelium from the external auditory canal or outer surface of the TM migrates inward through the margins of a pre-existing tympanic membrane perforation (usually posterosuperior marginal)
• The inner mucosal lining of the TM is damaged by inflammation, losing its barrier function
• The outer keratin epithelium then migrates in by "contact guidance" along exposed connective tissue surfaces
• This produces a secondary acquired cholesteatoma, located medial to the ossicular chain

• CK-10 (cytokeratin 10, a marker of meatal epidermis) is preferentially expressed in cholesteatoma matrix
• Animal studies (Jackson and Lim) showed keratinizing epithelium can migrate into cat bulla by contact guidance
• Temporal bone fractures allowing ingrowth of EAC epithelium - Cummings, p. 2686

3. Basal Cell Hyperplasia / Papillary Ingrowth Theory

• Epithelial "prickle cells" (basal keratinocytes) of the pars flaccida invade the subepithelial connective tissue via proliferating columns/cones of epithelium ("epithelial cones")
• For this invasion, the basement membrane (basal lamina) must be disrupted - such disruptions have been documented in human and animal cholesteatomas
• Microcholesteatomas form behind an intact TM and then secondarily perforate
• Propylene glycol instillation into chinchilla middle ear induces this process experimentally

• Overexpression of CK-13 and CK-16 (hyperproliferation markers)
• Increased EGF receptor expression
• Elevated fibronectin and tenascin (extracellular matrix disruption)
• Increased ICAM-1/ICAM-2 (cell migration facilitators)
• Presence of heat shock proteins 60 and 70
• Langerhans cells promoting keratinocyte proliferation via IL-1α and TGF-β
• Caspase-8/caspase-3 activation leading to accelerated apoptosis - Cummings, p. 2687

4. Squamous Metaplasia Theory

• Simple squamous or cuboidal epithelium of the middle ear mucosal lining undergoes metaplastic transformation into keratinizing stratified squamous epithelium in response to chronic inflammation/infection
• The resulting keratinizing area enlarges due to debris accumulation, forming a pearl-like cyst
• With intercurrent infection, the cholesteatoma leads to secondary TM perforation, producing the classic appearance

• Islands of keratinizing epithelium found in biopsies from children with OME (supports)
• No convincing human or animal model support; considered the least accepted theory - Cummings, p. 2687

5. Mucosal Traction Theory (Newest)

• Opposing mucosal surfaces on the medial TM and lateral ossicles become adherent
• Mucociliary clearance propels these adherent surfaces upward into the attic, pushing the pars flaccida inward
• Net epithelial cell migration and adhesive forces from trapped mucus further deepen the retraction pocket
• This theory proposes a more active mechanical role for the mucosa in cholesteatoma genesis

Congenital Cholesteatoma - Etiopathogenesis

• Michaels (1986) described an "epidermoid formation" - a small area of keratinizing epithelium in the anterior tympanum of fetuses at 10-33 weeks' gestation (found in 37/68 temporal bones)
• These embryonic epithelial cell rests normally regress; if they persist and expand, keratinous material accumulates forming a congenital cholesteatoma, typically in the anterior middle ear
• Diagnosed by the presence of: white mass behind intact TM, no prior history of otorrhea/perforation/surgery - Scott-Brown's Vol 2, p. 200

PART B: ROUTES OF SPREAD

Starting Point: Prussak's Space

• Laterally: pars flaccida of TM
• Medially: neck and head of malleus
• Superiorly: lateral malleolar fold

Route 1: Posterosuperior (Most Common)

• The cholesteatoma spreads posteriorly through a posterior opening in the epitympanum
• Enters the posterior epitympanum lateral to the body of the incus
• Travels through the aditus ad antrum
• Reaches the mastoid antrum and progressively erodes mastoid air cell walls, forming a single large cavity

Route 2: Inferior - Into Mesotympanum

• Spreads inferiorly through the lateral pouch of von Tröltsch (anterior and posterior)
• Enters the mesotympanum proper
• Can extend to the hypotympanum (inferior to the annulus)
• Here, it may threaten the jugular bulb

Route 3: Anterior - Supratubal Route

• Extends anteriorly into the anterior epitympanic space (anterior to the malleus head/neck)
• Enters the supratubal recess (STR) - a bony cul-de-sac above the ET opening
• Here it threatens the geniculate ganglion and first genu of the facial nerve, which lie just medial to the STR
• The "cog" (bony septum based on the tegmen) must be removed surgically to visualize the STR - Cummings, p. 2613

Route 4: Medial Extension (Advanced Disease)

• Advanced disease extends medial to the ossicles (lateral chain displaced medially by pars flaccida cholesteatoma)
• Reaches the medial wall of the tympanic cavity: threatens the oval window, round window niche, and otic capsule
• Most common site of labyrinthine fistula: horizontal (lateral) semicircular canal (ampullated limb)
• Rarely: cochlear fistula

Bony Erosions and Structures Threatened

Summary: BOX - Complications Arising from Routes of Spread

• Conductive, sensorineural, or mixed hearing loss
• Labyrinthine fistula (mainly horizontal SCC, rarely cochlea)
• Facial nerve paralysis (acute or chronic)
• Intracranial infections (meningitis, brain abscess, extradural abscess)
• Brain herniation or CSF leakage (tegmen erosion)
• Lateral sinus thrombophlebitis

SUMMARY TABLE