Micronucleus frequency in acquired middle ear cholesteatoma

OBJECTIVE: To determine the micronucleus (MN) frequency of acquired cholesteatoma tissue using an MN assay. MATERIAL AND METHODS: Eighteen patients were diagnosed as having chronic otitis media with acquired cholesteatoma and were divided into primary and secondary acquired cholesteatoma groups. Cholesteatoma tissue and normal tissue specimens from the external ear canal skin were taken from the patients during surgical operations. MN frequencies of cholesteatoma and control samples were determined according to standard criteria. RESULTS: The MN frequencies of the cholesteatoma and control tissues were 0.54%+/-0.31% and 0.24%+/-0.11%, respectively (p<0.01). MN frequencies for the primary and secondary acquired cholesteatoma groups were 0.63%+/-0.36% and 0.46%+/-0.26%, respectively (p>0.05). MN frequencies in cholesteatoma patients without and with complications were 0.42%+/-0.19% and 0.85%+/-0.37%, respectively (p<0.05). CONCLUSION: MN frequencies were found to be increased in cholesteatoma tissues when compared with external ear canal skin. The MN frequency in five cases with complications was higher than in cases without complications. These results indicate that there could be associations between MN frequency and acquired cholesteatoma and between MN frequency and complications.     

Micronucleus frequency in acquired middle ear cholesteatoma

Objective—To determine the micronucleus (MN) frequency of acquired cholesteatoma tissue using an MN assay.

Material and Methods—Eighteen patients were diagnosed as having chronic otitis media with acquired cholesteatoma and were divided into primary and secondary acquired cholesteatoma groups. Cholesteatoma tissue and normal tissue specimens from the external ear canal skin were taken from the patients during surgical operations. MN frequencies of cholesteatoma and control samples were determined according to standard criteria.

Results—The MN frequencies of the cholesteatoma and control tissues were 0.54%±0.31% and 0.24%±0.11%, respectively (p<0.01). MN frequencies for the primary and secondary acquired cholesteatoma groups were 0.63%±0.36% and 0.46%±0.26%, respectively (p>0.05). MN frequencies in cholesteatoma patients without and with complications were 0.42%±0.19% and 0.85%±0.37%, respectively (p<0.05).

Conclusion—MN frequencies were found to be increased in cholesteatoma tissues when compared with external ear canal skin. The MN frequency in five cases with complications was higher than in cases without complications. These results indicate that there could be associations between MN frequency and acquired cholesteatoma and between MN frequency and complications.     

Mode of growth of acquired cholesteatoma

A histopathological study of acquired cholesteatoma in four temporal bones from two adults and one child is presented. The findings suggest that the cholesteatoma originated from the retraction pockets of the tympanic membrane and there was active growth of the squamous epithelium of the retraction pockets, which may be enhanced in the presence of otitis media.     

Clinical analysis of secondary acquired cholesteatoma

Objective

This study aimed to analyze the clinical features of patients who underwent surgery for secondary acquired cholesteatoma (SAC).

Materials and methods

The subjects were 30 patients who underwent surgery for SAC in 30 ears. We investigated the age distribution, sex, tympanic membrane (TM) findings, temporal bone pneumatization, morphology of TM epidermis invasion, extent of cholesteatoma invasion, ossicular erosion, surgical methods and surgical results.

Results

There were 10 males (33.3%) and 20 females (66.6%), with a mean age 54.9 years. The TM perforation was medium-sized or larger in 27 ears (90%). Temporal bone pneumatization was poor or bad in 90% (18/20) of the evaluated ears. The cholesteatoma invaded from the malleus manubrium to the promontory in 23 ears (76.7%). There were no patients in whom the cholesteatoma invaded the antrum or mastoid. The ossicles were affected in 19 ears (63.3%). Ossiculoplasty with a columella on the stapes was the most frequent procedure, performed for 16 ears (53.3%). There were no hearing results with a postoperative air-bone gap of more than 31 dB.

Conclusions

Although SAC is rare, it is important for the clinician to keep this type of cholesteatoma in mind.     

TNF-R2 expression in acquired middle ear cholesteatoma

Acquired middle ear cholesteatoma is a disease which promotes bone erosion resulting in potentially serious complications. The tumor necrosis factor alpha (TNF-α) is present in cholesteatoma and it is related to bone erosion, as shown by different authors. To understand the aggressiveness characteristics of cholesteatoma is necessary, however, to better address the presence and distribution of their receptors.ObjectiveTo evaluate the expression of type 2 TNF-α receptor (TNF-R2) in fragments of cholesteatoma and correlate it to the degree of inflammation present.Material and methodsobservational cross-sectional study, which analyzed 33 fragments of cholesteatomas through histological analysis and immunohistochemistry (using as primary antibody to TNF-R2 LabVision ® brand). The evaluation was performed by means of a qualitative and semi-quantitative agreement with the observed intensity. For statistical analysis we used the Fisher exact test and Spearman's correlation coefficient (considered statistically significant when p ≤ 0.05).ResultsThe expression of TNF-R2 was present in all fragments, however a statistical analysis showed no correlation or association between inflammation and the expression of TNF-R2.ConclusionsTNF-R2 is present in cholesteatoma of the middle ear, however, its expression is not directly related to the degree of inflammation observed in patients with this disease.     

The nature of the epithelium in acquired cholesteatoma

The nature of the epithelium in acquired cholesteatoma Monoclonal antibodies with defined specifications for individual cytokeratins were used to stain the epithelia of the external auditory meatus, the middle ear and cholesteatoma. The observed staining indicated that the epithelium of the external auditory meatus has a pattern of keratin expression typical of epidermis in general and the epithelium of the middle ear resembles simple columnar epithelia. The pattern of staining of cholesteatoma closely resembled that of the skin of the external auditory meatus.     

Congenital and acquired cholesteatoma middle ear in children

Cholesteatoma of the middle ear in children may cause hypoacusis. Early diagnosis and optimal treatment is neccessary for good functional effect. We present 57 children (58 ears) with cholesteatoma treated in ENT Department of Medical University in Gdańsk in 1991-2002. The age of patients ranged between 3 and 16 years, the most common 11-15 years. In 52 (89.6%) cases acquired cholesteatoma and in 6 (10.4%) congenital cholesteatoma was diagnosed. Epitympanal cholesteatoma was found in 32 children (55.1%) whereas in posterior part of tympanic cavity--in 20 children (34.5%). In 6 cases (10.4%) intact tympanic membrane was found. Mean air-bone gap in acquired cholesteatoma before treatment was 18.7 dB, after treatment 15.7 dB. In congenital cholesteatoma mean air-bone gap before treatment was 13.6 dB, after treatment 14 dB. The most frequent symptom was hearing loss (98.3%) and purulent otorrhea (85.4%). Positive bacteriological culture was obtained in 43.1% of the cases. X-ray revealed sclero-pneumatic mastoid in 26 (34.5%) cases, sclerotic in 25 (43.1%) and pneumatic mastoid in 7 (12.1%) cases. Intracranial complications were found in 2 cases, intratemporal in 2 cases and extracranial complication in 1 case. Radical surgery was performed in 23 cases (39.7%) and in each case, which required reoperation, modified radical mastoidectomy in 20 cases (34.4%), in another 15 children (25.9%) tympanoplasty was done. The most frequent failure was purulent otorrhea in 21 (36.2%) cases. Reoperation in cholesteatoma recurrence was performed in 17 children (29.3%). Improvement or the same as preoperatively hearing level was obtained in 35 (60.3%) ears, hearing loss was revealed in 23 (39.7%) ears. Treatment of temporal bone cholesteatoma in children is difficult due to silent beginning, aggressive growth and frequent recurrence. The best treatment results in children cholesteatoma are obtained in early clinical stage and with open tympanoplasty procedure.     

Mucosubstance histochemistry and pathogenesis of acquired cholesteatoma

Mucosubstance histochemical study of 33 cholesteatoma tissues was performed to clarify the distribution and character of mucin in the perimatrix. Mean density of glandular cysts was 0.18 per mm². Mean frequency of ruptured cysts was 0.16 per cyst. Glandular cysts as well as hallow spaces in the perimatrix were filled with sulfomucin and sialomucin. Fragments of mucin were found in some macrophages and multinucleated giant cells. Since phagocytosis is host defenses attempt, the process indicates that mucin in the perimatrix is a cause of inflammation. Sialomucin infiltrated in the subepidermis where the epidermis formed papillary proliferation without an apparent sign of inflammation. Six glandular cysts were found in the matrix and the debris. They may have been eliminated from the perimatrix as a sequel to cholesteatoma growth. These findings suggest that embedded mucosa in the perimatrix may play a crucial role in pathogenesis of acquired cholesteatoma.     

A new experimental model of acquired cholesteatoma

OBJECTIVE: Cholesteatoma is a recurrent disease that is difficult control by otologists. This study aims to develop an experimental model of cholesteatoma that is easy to reproduce, using latex to induce the inflammatory reaction and propylene glycol as the foreign body in the middle ear. STUDY DESIGN: We used a new experimental model in which an intentional perforation was performed on the tympanic membrane of rats, followed by the introduction of a latex biomembrane. METHODS: A control group was submitted only to perforation of the tympanic membrane. Propylene glycol with latex was used in experimental group 1 and latex alone in experimental group 2. The rats were killed during the eighth week and their tympanic bullae were stained with hematoxylin and eosin. RESULTS: Eighty percent of the animals in group 1 and 90% in group 2 developed a cholesteatoma. No formation of cholesteatomas or inflammatory tissue occurred in the control group. CONCLUSION: The presence of inflammatory cells may provoke the production of cytokines (IL-1, IL-2, IL-6, IL-8) and growth factors, which, together with the latex biomembrane, which is known to contain a protein that favors vascular growth, may cause chemotactic migration of the squamous epithelium from the external auditory meatus to the middle year of the rat, causing a cholesteatoma. The induction of an experimental cholesteatoma in rats with latex and latex plus 50% propylene glycol was effective, representing an excellent experimental model. The theory of epithelial migration in the genesis of cholesteatomas was confirmed by our observations in rats. The latex induced an acute and chronic inflammatory reaction when in contact with the mucosa of the middle ear.     

Hearing loss assessment in primary and secondary acquired cholesteatoma

IntroductionAcquired middle ear cholesteatoma can be classified as primary or secondary. Although both can result in hearing loss, it is still controversial whether there is an association between the type of cholesteatoma and the degree of hearing loss.ObjectiveTo analyze the association between hearing loss and the type of acquired cholesteatoma, and the status of the ossicular chain.MethodsThis was a cross-sectional historical cohort study involving patients diagnosed with acquired cholesteatoma who were surgically treated. Air and bone conduction thresholds, air–bone gaps and the status of the ossicular chain were analyzed for both types of cholesteatoma.ResultsEighty patients aged 5–57 were included in the study. Fifty-one patients had primary cholesteatoma and 29 had secondary cholesteatoma. Both types of cholesteatoma determined greater air–bone gaps at 0.5 kHz. Secondary cholesteatoma determined greater hearing loss in all analyzed frequencies and higher air conduction and air–bone gap means.ConclusionThere was association between hearing loss and the type of cholesteatoma. Secondary cholesteatoma resulted in greater hearing impairment.     

Cytokeratin expression pattern in congenital and acquired pediatric cholesteatoma

Pediatric cholesteatoma can be classified as congenital or acquired based on clinical criteria. We studied the expression patterns of five distinctive cytokeratins in both types of cholesteatoma in order to improve understanding of their pathogenesis and origin. A comparable expression pattern for CK10, CK14, CK18, CK19 and 34E12 antigens was found in the matrix of congenital and acquired pediatric cholesteatoma. Our results demonstrate that congenital and acquired pediatric cholesteatoma exhibit an identical cytokeratin distribution pattern, suggesting that they share a common origin. Therefore, it seems possible that a portion of the so-called acquired cholesteatoma may actually originate from advanced congenital cholesteatoma with secondary destruction of the tympanic membrane in the pediatric patient population.     

Confirmation of mucin in lymphatic vessels of acquired cholesteatoma

Abundant inflammatory cells infiltrate in the advancing front of the cholesteatoma perimatrix towards the middle ear mucosa. However, the cause of inflammation is not yet clear. The middle ear mucosa is often embedded in the cholesteatoma perimatrix. We hypothesized that the embedded mucosa is the cause of inflammation. Surgical specimens obtained from 20 cases of acquired cholesteatoma were used for the study. Lymphatic vessels were stained by the immunohistochemical method using the antibody against podoplanin. Mucin was simultaneously stained by alcian blue. The results of our examination were the following: (1) the presence of infiltrating mucin in the perimatrix; (2) the degeneration and reduction of lymphatic vessels; (3) the accumulation of inflammatory cells around morbid lymphatic vessels. Based on our findings, cholesteatoma can be defined as an inflammation affected by infiltrating mucin that escaped from embedded mucosa in the perimatrix.     

The nature of the epithelium in acquired cholesteatoma.

Monoclonal antibodies with defined specifications for individual cytokeratins were used to stain the epithelia of the external auditory meatus, the middle ear and cholesteatoma. The observed staining indicated that the epithelium of the external auditory meatus has a pattern of keratin expression typical of epidermis in general and the epithelium of the middle ear resembles simple columnar epithelia. The pattern of staining of cholesteatoma closely resembled that of the skin of the external auditory meatus.     

周期蛋白D1在先天性与后天性胆脂瘤中的表达

目的通过研究周期蛋白D1(CyclinD1)在先天性胆脂瘤和后天性胆脂瘤的表达,探讨其表达差异的意义。方法选取我院就诊的60例中耳胆脂瘤患者,其中先天性胆脂瘤25例,后天性胆脂瘤35例;同时选取同期3例慢性中耳炎手术患者正常耳廓后皮肤组织作为对照组。采用免疫组化方法检测胆脂瘤组织中CyclinD1的表达。结果 CyclinD1免疫组化染色在先天性胆脂瘤和后天性胆脂瘤中均为阳性表达,但后天性胆脂瘤中阳性表达率高于先天性胆脂瘤,其差异具有统计学意义(P<0.01);CyclinD1在正常皮肤中不表达。结论 CyclinD1在后天性胆脂瘤上皮表达增强,可能是炎症刺激所致。     

Identification of Id1 in acquired middle ear cholesteatoma

OBJECTIVES: To determine (1) the relationship between chronic inflammatory changes in the ossicular chain area (OCA) and the formation of cholesteatoma and (2) the correlates between aberrant gene expression and abnormal proliferation of cholesteatoma. METHODS: Two hundred sixty-four ears with chronic otitis media that had undergone ear surgery were included in this study for statistical analysis of the relationship between abnormalities in the OCA and cholesteatoma. Fourteen middle ear cholesteatoma specimens were collected for immunohistochemical analysis of candidate molecules involved in the abnormal proliferation of keratinocytes. A cell model was used for verification of candidate molecule involvement. RESULTS: The formation of cholesteatoma was accompanied by chronic inflammatory changes in the OCA, including granulated tissue, adhesion, and stagnating effusion. The inhibitor of the DNA-binding (Id1) gene, which is involved in controlling cell cycle progression, was abundantly expressed in cholesteatoma epithelium. In vitro studies indicate that Id1 regulated the expression of nuclear factor kappaB, cyclin D1, proliferating cell nuclear antigen, and cell cycle progression of keratinocytes, CONCLUSIONS: Chronic inflammation in the OCA is closely related to the formation of cholesteatoma. The Id1/nuclear factor kappaB/cyclin D1/proliferating cell nuclear antigen signaling pathway is involved in the abnormal proliferation of keratinocytes in acquired cholesteatoma.     

Primary acquired and recurrent cholesteatoma versus residual cholesteatoma. A light- and electron-microscopical study

A comparative morphological study was performed between the primary acquired and recurrent cholesteatoma on the one hand and the residual type on the other. Between these two groups of cholesteatomas, one can distinguish differences in the pathogenesis and clinical features which may have therapeutic implications. This study, based on light- and electron microscopy, revealed no essential differences in morphology between the two groups of cholesteatoma. In particular, infiltration of matrix into subepithelial tissues could be found in cholesteatoma both with and without signs of inflammation or infection in the perimatrix, and this phenomenon could be applied to both types of cholesteatoma. This morphological uniformity suggests that the differences in clinical features and pathogenesis should not influence the otologist's choice of therapeutic approach. The results of this study emphasize the importance of removing as much as possible of the adjacent subepithelial tissue during eradication of the cholesteatoma, regardless of clinical type of cholesteatoma or signs of infection.