Evidence-based review of aetiopathogenic theories of congenital and acquired cholesteatoma

Abstract

Cholesteatoma is a non-neoplastic, keratinising lesion which has two forms: congenital and acquired. Congenital cholesteatoma develops behind a normal, intact tympanic membrane, whilst acquired cholesteatoma is associated with a defect in the tympanic membrane. The pathological substrate of cholesteatoma is keratinising stratified squamous epithelium, but the origin of this epidermal tissue in the middle ear is controversial. Here, we review the most relevant and recent evidence for the principal aetiopathogenic theories of both forms of cholesteatoma, in the light of recent otopathological findings. Congenital cholesteatoma is most plausibly explained by the persistence of fetal epidermoid formation. Conclusive 'proof' awaits the unambiguous demonstration of the metamorphosis of an epidermoid nidus into a lesion in vivo. Acquired cholesteatoma may develop by various mechanisms: immigration, basal hyperplasia, retraction pocket and/or trauma (iatrogenic or non-iatrogenic). However, squamous metaplasia of the normal cuboidal epithelium of the middle ear is a highly unlikely explanation. Chronic inflammation seems to play a fundamental role in multiple aetiopathogenic mechanisms of acquired cholesteatoma. Therefore early treatment of inflammatory conditions might reduce their sequelae, perhaps by preventing the development of hyperplastic papillary protrusions. Continued otopathological, cellular and molecular research would enhance our limited understanding of cholesteatoma and may lead to new therapeutic strategies for this erosive disease, which often defies surgical treatment.

The Diagnostic Accuracy of Non-Echo-Planar Diffusion-Weighted Imaging in the Detection of Residual and/or Recurrent Cholesteatoma of the Temporal Bone

“…1,2 If the cholesteatoma becomes large enough, it will displace and eventually destroy the ossicles and erode the wall of the middle ear cavity (typically the lateral wall and the scutum). In children, even a small cholesteatoma can cause ossicular chain erosions and, consequently, conductive hearing loss.…”

An Iatrogenic Cholesteatoma of the Squamous Part of the Temporal Bone

“…There are several theories to explain an acquired cholesteatoma [6] , e.g., implantation, invasion, metaplasia, and invasive hyperplasia. Of these, the implantation theory explains an iatrogenic cholesteatoma.…”

Cholesteatoma Definition and Classification: A Literature Review

“…It is universally accepted that cholesteatoma is non-neoplastic, noncancerous, and a "histopathologically benign" lesion that is "destructive" and "locally invasive" [4,19] . Potential complications may be life-threatening, "causing damage by passive growth and active destruction of adjacent structures" [20] .…”

“…Alterations of specific molecule expression levels, as for example detected altered level of p27 in keratinocytes of cholesteatoma may influence the proliferative state of cells and suggest a molecular pathology in cholesteatoma [21] . There is an imperative need for cellular and molecular research to develop new therapeutic strategies [19,21] .…”

“…With respect to its histopathology, cholesteatoma was defined as "containing layers of keratin in a cavity lined by squamous epithelium and subepithelial connective tissue" [19] , "development of a Malpighian epithelium" [3] , lesion "formed from keratinizing stratified squamous epithelium, the matrix of which comprises epithelium that rests on a stroma with varying thickness and is called the perimatrix" [8] . Symptoms such as otorrhea, deafness, or conductive hearing loss were also suggested to be included in the definition of cholesteatoma [22] .…”