What is the pathophysiology of cholesteatoma?

Pathophysiology of Cholesteatoma

Cholesteatoma develops through distinct mechanisms depending on whether it is congenital or acquired, with the acquired form arising primarily from chronic inflammation and eustachian tube dysfunction leading to tympanic membrane retraction, while congenital cholesteatoma originates from persistent fetal epidermoid formations behind an intact tympanic membrane.

Congenital Cholesteatoma Pathogenesis

• Congenital cholesteatoma most plausibly develops from the persistence of fetal epidermoid formations that fail to regress during embryonic development 1.
• These lesions characteristically develop behind a normal, intact tympanic membrane without any history of prior ear disease or perforation 1.
• The pathological substrate consists of keratinizing stratified squamous epithelium that becomes trapped in the middle ear during fetal development 1.

Acquired Cholesteatoma Pathogenesis

Primary Mechanisms

Acquired cholesteatoma develops through multiple pathways, with chronic inflammation playing a fundamental role in disease initiation and progression 1:

• Immigration theory: Squamous epithelium migrates through a tympanic membrane perforation into the middle ear space 1.
• Basal hyperplasia: Chronic inflammation stimulates hyperplastic papillary protrusions of epithelium that extend into the middle ear 1.
• Retraction pocket formation: Eustachian tube dysfunction creates negative middle ear pressure, causing tympanic membrane retraction that traps desquamating epithelium 1.
• Traumatic implantation: Iatrogenic or non-iatrogenic trauma can introduce squamous epithelium into the middle ear (such as following tympanostomy tube placement) 2.

Critical Pathophysiologic Note

• Squamous metaplasia of normal middle ear cuboidal epithelium is highly unlikely and should not be considered a viable mechanism 1.
• Chronic otitis media and persistent inflammation are the main culprits driving acquired cholesteatoma formation 3.

Cellular and Molecular Mechanisms

Stem Cell Contribution

• Stem cells expressing Nestin and S100B markers reside within cholesteatoma tissue and contribute to disease progression through self-renewal and differentiation capabilities 4.
• Cholesteatoma-derived stem cells show enhanced susceptibility to inflammatory stimuli compared to normal auditory canal skin stem cells, perpetuating the inflammatory microenvironment 4.
• These stem cells can differentiate into keratinocyte-like cells, contributing to the accumulation of keratinous debris 4.

Infectious Component

• The trapped keratinous debris becomes secondarily infected with polymicrobial bacterial flora, most commonly including Haemophilus influenzae, Staphylococcus aureus, and Pseudomonas aeruginosa 5.
• This secondary infection drives the characteristic foul-smelling, purulent otorrhea seen clinically 5.

Progressive Destructive Process

Bone Erosion Mechanisms

Cholesteatoma is a benign but progressive cystic lesion that causes extensive bone erosion through enzymatic activity and pressure effects 6:

• The expanding mass of keratinizing squamous epithelium exerts direct pressure on surrounding bone 3.
• Inflammatory mediators and enzymatic degradation contribute to ossicular erosion, scutum erosion, lateral semicircular canal erosion, facial canal dehiscence, and tegmen erosion 7, 6.

Clinical Implications

• Early treatment of inflammatory conditions might reduce sequelae by preventing the development of hyperplastic papillary protrusions that initiate cholesteatoma formation 1.
• The invasive nature and rapid growth potential make surgical excision the only effective treatment, as there are no effective nonsurgical options currently available 5, 3.

Common Pitfall

• Do not confuse cholesteatoma with simple acute otitis media or ventilation tube-associated otorrhea, as cholesteatoma requires immediate surgical referral and is characterized by white keratinous debris visible on examination 5.