Cytokeratin 13, Cytokeratin 17, and Ki-67 Expression in Human Acquired Cholesteatoma and Their Correlation With Its Destructive Capacity.

OBJECTIVES: Cholesteatoma is a nonneoplastic destructive lesion of the temporal bone with debated pathogenesis and bone resorptive mechanism. Both molecular and cellular events chiefly master its activity. Continued research is necessary to clarify factors related to its aggressiveness. We aimed to investigate the expression of Ki-67, cytokeratin 13 (CK13) and cytokeratin 17 (CK17) in acquired nonrecurrent human cholesteatoma and correlate them with its bone destructive capacity. METHODS: A prospective quantitative immunohistochemical study was carried out using fresh acquired cholesteatoma tissues (n=19), collected during cholesteatoma surgery. Deep meatal skin tissues from the same patients were used as control (n=8). Cholesteatoma patients were divided into 2 groups and compared (invasive and noninvasive) according to a grading score for bone resorption based upon clinical, radiologic and intraoperative findings. To our knowledge, the role of CK17 in cholesteatoma aggressiveness was first investigated in this paper. RESULTS: Both Ki-67 and CK17 were significantly overexpressed in cholesteatoma than control tissues (P<0.001 for both Ki-67 and CK17). In addition, Ki-67 and CK17 were significantly higher in the invasive group than noninvasive group of cholesteatoma (P=0.029, P=0.033, respectively). Furthermore, Ki-67 and CK17 showed a moderate positive correlation with bone erosion scores (r=0.547, P=0.015 and r=0.588, P=0.008, respectively). In terms of CK13, no significant difference was found between cholesteatoma and skin (P=0.766). CONCLUSION: Both Ki-67 and CK17 were overexpressed in cholesteatoma tissue and positively correlated with bone resorption activity. The concept that Ki-67 can be a predictor for aggressiveness of cholesteatoma was supported. In addition, this is the first study demonstrating CK17 as a favoring marker in the aggressiveness of acquired cholesteatoma.

Pathogenesis and Bone Resorption in Acquired Cholesteatoma: Current Knowledge and Future Prospectives.

Cholesteatoma is a cystic non tumorous lesion of the temporal bone that has the ability to destroy nearby structures by its power to cause bone resorption and as a result, fatal complications prevail. We aimed to conduct a comprehensive review for pathogenesis of acquired cholesteatoma, bone resorption mechanisms, and offer a future vision of this serious disease. We have reviewed different theories for pathogenesis of acquired cholesteatoma including the most relevant and updated ones with special emphasis on the mechanisms of bone resorption through Medline/PubMed research using the keywords 'aetiopathogenesis, bone resorption, acquired cholesteatoma, temporal bone, and cytokines.' In order to strengthen our study, we searched the reference lists of identified reviews. Cholesteatoma is a subject of debate among otolaryngologists since it was prescribed firstly. Over many decades, several theories were postulated for aetiopathogenesis of cholesteatoma with a tendency to follow more than one theory to explain the proper nature of that disease. Until now, the mechanism of bone resorption has yet to be more clarified. In the last century, a leap has occurred in the field of biomolecular cholesteatoma research which improved our knowledge about its pathophysiology and bone destructive mechanism. However, surgery is still the only available treatment. We conclude that discovery of new therapeutic choices for cholesteatoma other than surgery by the use of anti-growth, anti-proliferative, apoptotic agents as well as medications that antagonize osteoclastogenesis should be the main concern in the future clinical and experimental research work. Also, searching for predictors of the aggressiveness of cholesteatoma can affect the timing of intervention and prevent occurrence of complications.

Immune cell profile in invasive cholesteatomas: preliminary findings.

BACKGROUND: Cholesteatoma consists of keratinizing squamous epithelium, granulation tissue and keratin plugs. The pathogenesis of cholesteatoma may be related to alterations in the stromal immune cell infiltrate. OBJECTIVE: To examine the immunophenotypic characteristics of the immune cell infiltrate in invasive cholesteatomas. MATERIALS AND METHODS: This study included 12 patients with invasive cholesteatomas causing wide bone erosion of the mastoid, middle ear structures, and the bony plates of middle ear cleft. Diagnosis of invasiveness was based on the clinical, radiological and intraoperative findings. Canal wall-down surgical approach was done in all cases to control the disease process. We used the cholesteatomatous tissue specimens to perform immunohistochemical stains for B cells (CD20), T cells (CD3), histiocytes (CD68) and Langerhans' cells (CD1a). Mouse monoclonal antibodies and immunoperoxidase staining methods were used. The results of immunohistology were scored as mean values of positively stained immune cells. The data were compared with findings in 10 specimens of external ear skin (control group). RESULTS: Immunohistochemistry showed highly significant (p<0.00) counts of immune cells in invasive cholesteatomas (CD3: 4.7+/-0.4, CD68:4.6+/-0.5, CD20: 0.8+/-0.1 and CD1a: 0.8 +/-0.1) compared to those in external canal skin (control group: CD3:0.8+/-0.3, CD68: 1.0+/-0.4, CD20: 0.2+/-0.1 and CD1a: 0.1+/-0.1). In cholesteatomas, the predominant of CD3(+) T lymphocytes and CD68(+) cells (histiocytes). Rare CD20(+) cells and CD1a(+) cells (Langerhans' cells) were also observed. CONCLUSIONS: This preliminary study describes the profile of the immune cell infiltrate in invasive cholesteatomas. The numeric dominance of CD3(+) cells and CD68(+) cells suggests that cell-mediated immunity has important role in the development of cholesteatoma and in its autodestructive properties. Further studies are recommended to categorize the T cell subsets in different stages of cholesteatomas.

Assessment of nasal obstruction with flexible nasal endoscopy.

OBJECTIVE: To report the value of nasal endoscopy as an outpatient procedure in the diagnosis of posterior nasal obstruction. METHODS: Over one year period, from March 2002 to March 2003, we evaluated 130 adult patients that attended the Ear, Nose and Throat Department of Sohag University Hospital in Egypt with persistent nasal obstruction via anterior rhinoscopy and flexible nasopharyngoscopy. We reported the cause and site of obstruction in relation to the choanae. We confirmed the diagnosis by CT scanning, rigid endoscopic examination under general anesthesia, and histopathological analysis of biopsies taken. RESULTS: Forty-six percent of our cases had posterior nasal obstruction, 43.5% due to post-choanal lesions (mainly adenoid), 33% due to pre-choanal lesions (mainly choanal polyps), and 23.5% due to choanal lesions (mainly choanal adenoid). CONCLUSION: We conclude that flexible nasal endoscopy is superior to visual examination in the evaluation of nasal obstruction; hence, we recommend its routine use.