Differentiation characteristics of cholesteatoma epithelium determined by expression of transglutaminase isoenzymes.
Transglutaminase (TGase) isoenzymes are involved in the process of the differentiation and cornification of keratinocytes in the epidermis. This study investigates the presence and localization of three TGase isoenzymes to elucidate the nature and differentiation status of the squamous epithelium in human aural cholesteatoma. Twenty cholesteatoma specimens were used. The presence and localization of three TGase isoenzymes were studied by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. mRNA expression of three TGase isoenzymes were detected in the tested cholesteatomas with variable levels. The immunohistochemical staining patterns of three TGase isoenzymes showed variations within specimens, relating to keratinizing activity. TGase K is the most abundant among three isoenzymes. Keratinizing epithelium of cholesteatoma have similar expression profiles of TGase isoenzymes with those of epidermis of the skin. Other areas, particularly those showing non-keratinizing epithelium, showed weak immunostaining of TGase E and C, suggesting its different maturation status from keratinizing epithelium. The results of this study indicate that epithelium of cholesteatoma undergoes same direction of maturation and differentiation characteristics as the epidermis of skin, evidenced by similar expressions of TGases both in mRNA level and immunohistochemistry. (+info)
Expression of matrix-degrading cysteine proteinase cathepsin K in cholesteatoma.
Cholesteatoma is a nonneoplastic lesion of the middle ear space or mastoid that is histologically characterized by a progressive bone erosion of the ossicles and surrounding bone. Several matrix-degrading enzymes have been implicated as mediators of this bone erosion. Because the novel cysteine proteinase cathepsin K has been shown to play a central role in bone resorption, we examined the expression of this enzyme in tissue specimens of cholesteatoma. Tissue specimens of 9 patients with cholesteatoma were obtained during middle-ear surgery. Expression of cathepsin K mRNA was determined by RT-PCR using specific primers. Immunohistochemical analysis of cathepsin K protein expression in tissue sections was performed by using the streptavidin-alkaline phosphatase technique. Expression of both cathepsin K mRNA and protein was detected in areas affected by cholesteatoma, whereas specimens of nonaffected ear cartilage and surrounding tissue were not positive. In addition, cathepsin K was detected in numerous multinucleated giant cells, particularly osteoclasts at the site of bone degradation. In contrast, keratinized squamous epithelium was negative for cathepsin K. These data demonstrate that the matrix-degrading cysteine proteinase cathepsin K may be involved in bone erosion in cholesteatoma. Strong expression of this collagenolytic enzyme in osteoclasts suggests that these cells are mainly involved in cathepsin K-mediated bone destruction. (+info)
Diffusion-weighted imaging for differentiating recurrent cholesteatoma from granulation tissue after mastoidectomy: case report.
Identification of recurrent cholesteatoma and differentiation from postoperative granulation tissue is important in a patient who has undergone mastoidectomy for cholesteatoma. We describe the diffusion-weighted imaging findings and apparent diffusion coefficient values in a case of recurrent cholesteatoma. This case suggests possible differentiation of cholesteatoma from granulation tissue on the basis of diffusion-weighted imaging findings. (+info)
Immunohistochemical investigations of cathepsin D activity in the structures of cholesteatoma.
BACKGROUND: Cathepsin D decomposes cytoplasmic proteins, cell organelles, collagen, elastase and proteoglycans. It takes part in angiogenesis and activates osteoclasts, and is thought to play a major role in the destruction of bone tissue by cholesteatoma. The aim of the present study was to evaluate the activity of cathepsin D in the structures of cholesteatoma. MATERIAL/METHODS: Cholesteatomas were collected from 16 patients operated on for chronic inflammation of the middle ear. Specimens were fixed in formalin at pH 7.2, after which parrafin slices were made. Cathepsin D was assayed with a Dako set. Keratin was measured by the Kreyberg method. Normal skin from behind the ear was taken from the patients during the same operation. The samples included a stratified, desquamative epithelium (matrix), a streak containing connective tissue (perimatrix), and a mass of keratin debris. RESULTS: Cathepsin D demonstrates high activity in perimatrix cells adjacent to bone tissue, while it occurs in trace amounts in the matrix. A highly positive reaction was observed within keratin, which was present in the superficial layer of the epithelium. Pseudocathepsin located in desquamative epithelial cells demonstrated a high positive reaction. There were trace amounts of cathepsin D within the dermis. In the control group (the skin samples), there were trace amounts of cathepsin D within the corneous layer of the epithelium. CONCLUSIONS: Cathepsin D places a major role in bone tissue destruction due to cholesteatoma. (+info)
Expression patterns of cytokeratins in cholesteatomas: evidence of increased migration and proliferation.
Aural cholesteatoma is characterized by invading squamous epithelia with altered growth properties. Cytokeratin (CK) expression is affected in epidermal proliferative diseases and represents the alterations of keratinocyte proliferation, differentiation, and migration. In the present study, the intensity of CK immuno-expression was determined, using densitometry at various sites in experimental cholesteatoma in order to characterize changes of keratinocytes. With cholesteatoma formation, CK4, a marker for non-keratinizing epithelia, increased in the suprabasal layers of the annular external auditory canal (EAC) and at the pars tensa indicating an altered differentiation and migration of keratinocytes. CK5/6, a marker of keratinizing squamous epithelium, increased only at the pars tensa of the tympanic membrane, indicating basal keratinocyte hyperplasia. CK1/10 increased in the suprabasal layer at the annular EAC, and at the peripheral pars tensa, indicating increased terminal differentiation of keratinocytes. CK13/16, markers of differentiation and hyperproliferation, increased in suprabasal layer of the EAC, and at the peripheral pars tensa. However, it decreased in the basal layer of the EAC, indicating hyperproliferation and migration of keratinocytes. The findings of this study support the basal cell hyperplasia hypotheses for the pathogenesis of aural cholesteatoma, with regard to hyperproliferation, migration, and an altered differentiation of keratinocytes. (+info)
External auditory canal cholesteatoma: clinical and imaging spectrum.
BACKGROUND AND PURPOSE: Cholesteatoma is an inflammatory lesion of the temporal bone that uncommonly involves the external auditory canal (EAC). In this large case series, we aimed to define its imaging features and to determine the characteristics most important to its clinical management. METHODS: Thirteen cases of EAC cholesteatoma (EACC) were retrospectively reviewed. Clinical data were reviewed for the history, presentation, and physical examination findings. High-resolution temporal bone CT scans were examined for a soft-tissue mass in the EAC, erosion of adjacent bone, and bone fragments in the mass. The middle ear cavity, mastoid, facial nerve canal, and tegmen tympani were evaluated for involvement. RESULTS: Patients presented with otorrhea, otalgia, or hearing loss. Eight cases were spontaneous, and five were postsurgical or post-traumatic. CT imaging in all 13 cases showed a soft-tissue mass with adjacent bone erosion. Intramural bone fragments were identified in seven cases. This mass most often arose inferiorly (n = 8) or posteriorly (n = 8), but it was circumferential in two cases. We noted middle ear extension (n = 5), mastoid involvement (n = 4), facial canal erosion (n = 2), and tegmen tympani dehiscence (n = 1). CONCLUSION: Temporal bone CT shows EACC as a soft-tissue mass within the EAC, with adjacent bone erosion. Bone fragments may be present within the mass. The cholesteatoma may extend into the mastoid or middle ear, or it may involve the facial nerve canal or tegmen tympani. Recognition of this entity and its possible extension is important because it may influence clinical management. (+info)
Differential diagnosis and treatment of hearing loss.
Hearing loss is a common problem that can occur at any age and makes verbal communication difficult. The ear is divided anatomically into three sections (external, middle, and inner), and pathology contributing to hearing loss may strike one or more sections. Hearing loss can be categorized as conductive, sensorineural, or both. Leading causes of conductive hearing loss include cerumen impaction, otitis media, and otosclerosis. Leading causes of sensorineural hearing loss include inherited disorders, noise exposure, and presbycusis. An understanding of the indications for medical management, surgical treatment, and amplification can help the family physician provide more effective care for these patients. (+info)
Closed tympanoplasty in middle ear cholesteatoma surgery.
OBJECTIVE: To determine the effect of closed tympanoplasty surgery for middle ear cholesteatoma and to compare the postoperative results with the outcomes of canal-wall-down mastoidectomy. METHODS: Seventy patients with middle ear cholesteatoma were involved in the study. Pneumo-otoscopy, pure-tone audiometry, anamnestic and clinical data were evaluated before the surgery. Modified radical mastoidectomy was performed for 31 patients. Thirty-nine patients were treated with closed tympanoplasty surgery, including intact canal wall mastoidectomy, endaural atticotomy, lateral attic and aditus wall reconstruction and tympanoplasty. The follow-up examination was carried out 12 months after the surgery. The recurrence of cholesteatoma, otorrhea and hearing level were evaluated postoperatively. RESULTS: Otorrhea was estimated in 4 cases (10.3%) after closed tympanoplasty surgery and in 6 cases (19.4%) after modified radical mastoidectomy. Among the patients who were operated using closed tympanoplasty technique the middle ear cholesteatoma recurrence rate was 12.8% and among those, who underwent modified radical mastoidectomy recurrent disease occurred in 9.7% of the cases. The hearing improvement was found in 15 cases (38.46%) after closed tympanoplasty, while there was no hearing improvement after modified radical mastoidectomy. CONCLUSIONS: We conclude that despite the fact, that cholesteatoma recurrence rate after closed tympanoplasty is relatively high, this surgical method permits to preserve adequate hearing level and releases from postoperative cavity care problems as compared with modified radical mastoidectomy. (+info)