Pathology of cholesteatoma: a review - Europe PMC

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Journal of the Royal Society of Medicine Volume 72 May 1979

Pathology of cholesteatoma: a review' Professor L Michaels MD FRCPath Department of Pathology and Bacteriology Institute of Laryngology and Otology 330 Gray's Inn Road, London WCIX 8EE

Cholesteatoma is a problem interpreted essentially on a clinical level; the pathologist working mainly with biopsy material and post-mortem temporal bones finds this subject a difficult one. The source of his difficulties can be resolved into two main problems: (1) There is a widespread concept among otolaryngologists that the squamous epithelium of cholesteatoma is derived by migration from the external surface of the tympanic membrane. Such a migration is a unique one in non-neoplastic squamous epithelium. A more acceptable concept would be metaplasia of the middle ear mucosa (see Sade 1978). (2) In trying to understand the effects of cholesteatoma, at almost every turn it may be questioned whether it is the chronic otitis media that invariably accompanies cholesteatoma that has done the damage. The pathology of cholesteatoma may be considered in the classical fashion of morbid anatomy under the headings of: gross appearances; light and electron microscopic appearances; and special studies such as microbiology and chemical findings. Gross appearances Cholesteatoma is characteristically described as having a pearly grey sheen. In our experience the dead keratinous material comprising the bulk of the cholesteatomatous material has a yellowish coloration. The colour of the capsule (composed of the more immature squamous cells and also a small amount of connective tissue) is rather paler. Much of the large literature on the pathogenesis and progression of cholesteatoma has been on the diagnosis by otologists of the presence of this condition by naked eye or operating microscope without histological confirmation. A diagnosis of cholesteatoma may be mistaken, and in reality other conditions such as cholesterol granuloma, mucous secretion, solidified pus, or even neoplasm such as paraganglioma may be present. It is therefore possible that some of the descriptions of the pathogenesis of cholesteatoma may be of dubious validity. The majority of descriptions of the pathogenesis of cholesteatoma seek to explain the frequent location of the condition in the upper part of the middle ear cleft with discharge through a perforation of the pars flaccida portion of the tympanic membrane (Nager 1977). The cholesteatoma may extend through the aditus into the mastoid antrum and mastoid air cells. It appears to conform in shape to normal structures, such as ossicles, that it is in contact with. Frequently such ossicles are eroded, but other bony structures are rarely involved. Occasionally cholesteatoma is said to invade the bone of the facial nerve area or the area of lateral semicircular canal, and very rarely it is said to erode the tegmen and burrow into the brain. It is impossible in these cases to dissociate these invasive properties from the effects of the chronic otitis media with which cholesteatoma is always associated.

Microscopic appearances Under the light microscope the pearly material consists of dead, fully differentiated keratin squames representing the corneal layer of the cholesteatoma. Sometimes biopsy material shows only such squames when the so-called capsule has not been removed. The capsule is composed of a fully differentiated stratified squamous epithelium similar to the epidermis of skin and resting on connective tissue. There is a basal layer of small cubical cells above which is a spinal or malpighian layer composed of five or six rows of cells in which intercellular Paper read to Section of Otology, 2 December 1977. Accepted 28 February 1978 0 1 41-0768/79/050366-04/$O 1.00/0

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'prickles' or spines are present. A thin granular layer in which the cells display prominent cytoplasmic keratohyaline granules separates the malpighian layer from the corneal layer which is very extensive. Granular and corneal layers are unusual in squamous epithelium of metaplastic origin, but are occasionally seen, e.g. in the bronchial mucosa (Figure 1). Electron microscopy confirms the light microscopic findings of a stratified squamous epithelium of typical ultrastructural appearance. The basal cells rest on a basal lamina; on the interface between the two appear occasional hemidesmosomes. Desmosomes and tonofibrils arising from them are abundant in the malpighian layer (Figure 2). Our findings confirm those of Lim & Saunders (1972) in the presence of Langerhans cells among the cells of the malpighian layer. These are cells with clear cytoplasm and no desmosomal attachments; their characteristic feature is the presence of bodies shaped like rackets in the cytoplasm with thin stalks showing a central linear core and expanded spherical tips (Figure 3). Langerhans cells are well known components of skin stratified squamous epithelium including the external auditory meatus. Their presence in the epithelium of cholesteatoma is considered to be evidence of its migration from the outer surface of the tympanic membrane rather than by local metaplasia. Langerhans cells have been found in the stratified squamous epithelium of the oral mucosa (Schenk 1975) and recent work indicates that they are specialized mesenchymal scavenger cells which are particularly prominent in stratified squamous epithelium (Shelley & Juhlin 1976). The prominence of these cells in cholesteatomatous squamous epithelium is perhaps more an index of the marked exposure of this epithelium to foreign antigens than of its mode of development. At the same time as the presence of cholesteatoma, one or more of the following pathological processes is frequently seen in the middle ear: (a) Chronic inflammatory granulation tissue; it is likely that both this tissue and the bacteria giving rise to it produce most of the destructive changes that are ascribed to cholesteatoma. (b) Glandular secretory change of the columnar epithelium of the middle ear; such glands are frequently seen beneath the squamous epithelium of the cholesteatoma. (c) Cholesterol granuloma usually associated with haemorrhage which is frequent in the middle ear; this lesion is manifested as clefts with surrounding foreign body type giant cells. (d) Tympanosclerosis, i.e. plaques of calcified hyaline collagen; these are seen in the mucosa anywhere in the middle ear. Resorption of ossicles is frequently seen in cholesteatoma. In some cases the eroded ossicles are covered by the squamous epithelium of the cholesteatoma. Under these circumstances there is always a layer of granulation tissue between the squamous epithelium and the bone. It seems likely that it is the chronic inflammatory change, not the epithelium covering, that produces the erosion. In a study of the effects of autologous transposed ossicles, Robin et al.

w^:,i^>,s" Figure 1. Section of 'capsule' of choles~~~ ~teatoma. Specimen embedded in Araldite and cut at 2 microns thickness. B, basal @ layer. M, malpighian layer; note intercellular 'prickles'. G, granular layer; note keratohyaline granules. C, corneal layer. Paragon stain x 400

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Figure 2. Electron micrograph of basal layer and lower malpighian layer of cholesteatoma. BL, basal lamina. The three basal and the malpighian cells above them show numerous intercellular ~~~connections which are interrupted by desmosomes (D). The cytoplasms of both basal and

-1_malpighian cells show dense deposits of darkly

staining tonofibrils, some of which are emanating from desmosomes. x6000

Figure 3. Electron micrograph of part of Langerhans cell from cholesteatomatous epi-

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thelium. The nuclear membrane of the cell extends from the bottom left hand corner diagonally ss the photograph. The cytoplasmic membrane of the cell extends across the right lower * corner. Between the two are two characteristic filaments of the Langerhans cell each exhibiting a central core. The upper one is rachet-shaped with J Ea hyaline bulbous extremity. x 58 000

(1976) showed that cholesteatoma may be present on the surface of the dead transposed ossicle. This lesion may well have been present before the transposition, as this procedure was done on ears already affected with cholesteatoma. Special studies In a study of the bacteriological findings in 100 cases of cholesteatoma, T A L Rees (1977, unpublished) found that proteus or pseudomonas together or singly represent the predominant source of the infection in by far the majority of cases. Staphylococcus pyogenes and betahaemolytic streptococci may be found but much more infrequently. Such an incidence of infection is similar to that found by Rees (1971) in 2470 cases of chronic otitis media. This again emphasizes the identity of certain pathological features of cholesteatoma with chronic otitis media. A number of chemical factors have been incriminated in the bone resorption of choles-


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teatoma. All of these are again derived from the accompanying chronic otitis media or the infection associated with it. Specimens of cholesteatoma which include the underlying matrix have been found to show strong collagenase activity. This enzyme has been located by immunofluorescent methods in the connective tissue, particularly around blood vessels (Abramson & Huang 1977). It is likely that this collagenase plays a part in resorption of bone. Endotoxins may also play a part and this is particularly likely because they are derived from gram-negative bacilli which, as mentioned above, are prominent in infection associated with cholesteatoma (Yin 1975).

References Abramson M & Huang C (1977) In: Cholesteatoma First International Conference. Ed. B F McCabe et al. Aesculapius Publishing Company, Birmingham, Alabama; pp 162-166 Lim D J & Saunders W H (1972) Annals of Otology, Rhinology and Laryngology 81, 1-12 Nager G T (1977) In: Cholesteatoma First International Conference. Ed. B F McCabe et al. Aesculapius Publishing Company, Birmingham, Alabama; pp 193-203 Rees T A L (1971) British Journal of Clinical Practice 25, 453-454 Robin P E, Bennett R J & Gregory M (1976) Clinical Otolaryngology 1, 295-308 Sade J (1978) Journal of the Royal Society of Medicine 71, 716-732 Schenk P (1975) Acta Otolaryngologica (Stockholm) 80, 301-311 Shelley W B & Juhlin L (1976) Nature (London) 261, 46-47 Yin E T (1975) Journal of Laboratory and Clinical Medicine 86, 430