Melanocyte localization and distribution in human cholesteatoma.Histol Histopathol. 2008 Mar;23(3):291-6.

INTRODUCTION: Melanocytes in skin are derived from the neural crest and colonize the epidermis in the first trimester of gestation. Melanocytes have been observed in the nasopharyngeal, inner ear and oral mucosa and should therefore be present in the middle ear mucosa. AIMS: To identify and determine the distribution of melanocytes in human cholesteatoma and normal meatal skin in Caucasian adults. MATERIAL AND METHODS: Human cholesteatoma (n=18) and normal meatal skin samples (n=10) were investigated immunohistochemically with anti-HMB-45 and MART-1 antibodies. Localization and distribution of melanocytes were assessed in the epidermis and cholesteatoma using an automatic analyzing system. RESULTS: Regular skin exhibited melanocytes within the epidermis and accounted for 10% of the total cell number. They occurred partly as membrane-bound clusters. Cholesteatoma matrix melanocytes were observed in the basal layer and exhibited an oval or roundmorphology. Decreased numbers of melanocytes in the basal layer correlated with keratinization within cholesteatoma samples. Melanocytes revealed monomorphous nuclei, abundant cytoplasm containing particles of melanin. Found adjacent to glands and blood vessels, melanocytes were also scattered among the mesenchymal cells. Accounting for 2-6% of the total cell number within the squamous epithelium, melanocyte density was significantly lower in cholesteatoma tissue than in skin. CONCLUSIONS: The melanocyte distribution pattern was different when comparing the epithelia of skin and cholesteatoma. The presence of melanocytes in cholesteatoma may be due to an ingrowth, consequently controlled by keratinocyte-derived signals. In terms of the pathogenesis of cholesteatoma, neither squamous metaplasia nor melanocyte metaplasia can be excluded by our data.

Cholesteatoma behind an intact tympanic membrane: histopathologic evidence for a tympanic membrane origin.Otol Neurotol. 2001 Jul;22(4):444-6.

BACKGROUND: Several theories have been proposed with respect to the origin and pathogenesis of cholesteatoma behind an intact tympanic membrane. CASE REPORT: The authors describe a case of cholesteatoma behind an intact tympanic membrane in a 71-year-old man with a history of tympanic membrane retraction fixed to the incus without evidence of a perforation. The membrane eventually became detached, and remnants of keratinizing squamous epithelium were found on the incus. DISCUSSION: Mechanisms such as metaplasia, ectopic epidermis rests, or ingrowth of meatal epidermis have been proposed to explain the pathogenesis of cholesteatoma behind an intact tympanic membrane. These findings, based on temporal bone histopathology, support the role of an acquired epidermal rest. CONCLUSIONS: This case report provides evidence that cholesteatoma behind an intact tympanic membrane can be established from a resolved retraction of the pars tensa of the tympanic membrane.

Does occurrence of keratinizing stratified squamous epithelium in the middle-ear cavity always indicate a cholesteatoma?J Laryngol Otol. 2004 Oct;118(10):757-63.

The origin and behaviour of keratinizing stratified squamous epithelium, an essential component of cholesteatoma occurring in the middle-ear cavity, has puzzled otologists for decades. In this experimental study in 16 cats, central (n = 23) and peripheral (n = 9) tympanic membrane perforations were observed for up to 63 days before sacrifice. The tympanic membranes with bony rim were excised, decalcified and embedded in Epon 812. Sections were stained with toluidine blue and examined using a light microscope. The perforation had been sealed by meatal epithelium exhibiting pronounced hyperplasia and keratin formation, lying on a bed of granulation tissue. Subtotal central perforations healed within 14 days, forming a bowl-shaped tympanic membrane and leaving parts of the handle of the malleus (with meatal epithelium) protruding freely into the middle-ear cavity. Stratified squamous epithelium, morphologically identical with that of external ear canal epidermis, could be observed on the malleus even 63 days after operation. This meatal epithelium was non-keratinizing, non-invasive, and showed no destructive properties typical of acquired cholesteatoma. During certain circumstances, the cell cycle of hyperplastic epidermal epithelium within the middle-ear cavity can evidently be arrested and inactivated by a local defence mechanism.