Predicting residual cholesteatoma with the Potsic staging system still lacks evidence: a systematic review and meta-analysis.

PURPOSE: To investigate the rate of residual disease in the Potsic staging system for congenital cholesteatomas. METHODS: A protocol registration was published on PROSPERO (CRD42022383932), describing residual disease as a primary outcome and hearing improvement as secondary. A systematic search was performed in four databases (PubMed, Embase, Cochrane Library, Web of Science) on December 14, 2022. Articles were included if cholesteatomas were staged according to the Potsic system and follow-up duration was documented. Risk of bias was evaluated using the Quality In Prognosis Studies (QUIPS) tool. In the statistical synthesis a random effects model was used. Between-study heterogeneity was assessed using I2. RESULTS: Thirteen articles were found to be eligible for systematic review and seven were included in the meta-analysis section. All records were retrospective cohort studies with high risk of bias. Regarding the proportions of residual disease, analysis using the χ2 test showed no statistically significant difference between Potsic stages after a follow-up of minimum one year (stage I 0.06 (confidence interval (CI) 0.01-0.33); stage II 0.20 (CI 0.09-0.38); stage III 0.06 (CI 0.00-0.61); stage IV: 0.17 (CI 0.01-0.81)). Postoperative and preoperative hearing outcomes could not be analyzed due to varied reporting. Results on cholesteatoma location and mean age at staging were consistent with those previously published. CONCLUSION: No statistically significant difference was found in the proportions of residual disease between Potsic stages, thus the staging system's applicability for outcome prediction could not be proven based on the available data. Targeted studies are needed for a higher level of evidence.

[Diagnosis and surgical outcomes in the management of petrous bone cholesteatoma]. / Diagnostika i effektivnost' khirurgicheskogo lecheniya kholesteatomy piramidy visochnoi kosti.

OBJECTIVE: To evaluate the effectiveness of surgical treatment of patients with petrous bone cholesteatoma (PBC) depending on the localization of the pathological process. MATERIAL AND METHODS: The analysis of surgical treatment using various surgical approaches and its results in 32 patients with PBC, depending on the type, localization in petrous bone and intraoperative findings, is presented. Patients with supralabirint PBC underwent extended atticoantromastoidotomy with tympanoplasty and mastoidoplasty with automaterials (n=19), labyrinthectomy (n=4), subtotal petrozectomy with labyrinthectomy and suturing of the external auditory meatus (EAM) (n=2). In infralabirint and infralabirint-apical PBC, a transotic approach was used with Rambo suturing of EAM (n=9). The pre-sigmoid approach was performed in 1 patient. With an extradural subtemporal approach, PBC of apical localization was removed in 1 case. RESULTS: After surgical treatment, hearing remained at the same level in 15 (47%) patients, 14 of them had deafness. In the early postoperative period, a temporary increase in bone conduction hearing thresholds by 10-20 dB was detected in 14 (44%) patients with their gradual recovery over 3 months. Deafness in the postoperative period developed in 3 (9%) patients after removal of supralabirint cholesteatoma. In the early postoperative period, 3 (9%) patients developed systemic dizziness, which was stopped after 3 months. In 25 (78%) patients, the function of the facial nerve in the early postoperative period remained at the same level, of which 14 (44%) were normal, and 11 (34%) had the same degree according to the House-Brackmann (HB) classification. Improvement of function by one degree of HB classification was observed in 4 (12.5%) patients on average 5 months after surgery. CONCLUSION: An adequate personalized choice of surgical treatment methods allowed mainly to preserve the function of hearing and facial nerve. In cases of deterioration of facial nerve function in the postoperative period, gradual improvement was observed for 3-10.5 months with further positive dynamics.

Detection of respiratory viruses in primary cholesteatoma tissues.

Cholesteatomas are frequent middle ear benign tumors of unknown etiology. Infectious agents have been considered as possible contributing factors in the pathogenesis of cholesteatomas. Aiming to investigate the presence of respiratory viruses in primary cholesteatoma tissues, 26 formalin-fixed paraffin-embedded primary cholesteatoma tissues obtained from patients seen at the of the Clinical Hospital of the University of São Paulo School of Medicine, in Ribeirão Preto, Brazil were tested by real-time polymerase chain reaction (PCR). Considering the PCR results, 35% of the tissues were positive for human rhinovirus (HRV), 15.3% for human enterovirus (EV), 3.8% for human metapneumovirus (HMPV), and 3.8% for human bocavirus (HBoV). Serial immunohistochemistry for virus antigens and cell surface markers evidenced that the viruses were associated with fibroblasts, dendritic cells, macrophages, B lymphocytes, CD4+ , and CD8+ T lymphocytes. These findings indicate for the first time the presence of active respiratory virus infection in primary cholesteatoma tissues, suggesting that persisting virus infection in the middle could play a role in the pathogenesis and evolution of cholesteatomas.

Impact of the demographic and aetiological factors and intraoperative findings on postoperative outcomes in chronic otitis media surgery

Background/aim: Surgical success is related with many factors belonging to both the patient and the disease. This study aims to analyse the preoperative and intraoperative characteristics, the postoperative results, and the factors affecting the surgical success in different types of chronic otitis media (COM). Materials and methods: A total of 1510 ears of 1398 patients who underwent COM surgery were included in the study. Postoperative results were obtained from 376 ears of 356 patients who had been followed after surgery. The demographic characteristics of the patients, such as age and sex, operative findings, preoperative audiological examination results, and final audiometric and otoscopic examination findings, were retrospectively obtained from the archives of the department. Results: The most frequent diagnosis was simple COM (39.9%), and the most frequently performed surgery was tympanoplasty without mastoidectomy (46.6%). The overall hearing success rate was found to be 75.8%. Postoperative hearing success was significantly associated with the chronic otitis subgroup, ossicular pathologies, and the condition of the middle ear mucosa. Postoperative graft take rate was found to be 78.6%. Graft success was statistically significantly higher in patients with normal middle ear mucosa. Performing mastoidectomy, the presence of patency in aditus ad antrum, and being a paediatric case had no impact on graft success. Conclusion: Factors affecting the success of COM surgery include age, chronic otitis subgroup, location and size of perforation, the condition of the middle ear mucosa, and the level of the ossicular disease. These factors should be known and an appropriate treatment plan should be prepared.

Down-regulation of exosomal miR-106b-5p derived from cholesteatoma perimatrix fibroblasts promotes angiogenesis in endothelial cells by overexpression of Angiopoietin 2.

Human cholesteatoma perimatrix fibroblasts (hCPFs) can stimulate the endothelial cells of nearby microvessels to proliferate and migrate in a paracrine manner. Exosomes, secreted from various cell types, are one of the most important paracrine factors and play critical roles in intercellular communication. However, whether exosomes derived from human cholesteatoma perimatrix fibroblasts (hCPFs-Exo) can promote angiogenesis has not been reported. In this study, we isolated exosomes secreted by hCPFs and observed that hCPFs-Exo was able to promote migration and tube formation in human umbilical vein endothelial cells (HUVECs). Advanced studies revealed hCPFs-Exo with low expression of miR-106b-5p was transferred into HUVECs, and decreased expression of miR-106b-5p could promote angiogenesis by targeting Angiopoietin 2 (Angpt2) via binding to its 3'-UTR. Furthermore, low levels of miR-106b-5p triggered overexpression of Angpt2, and significantly increased HUVEC migration and tube formation. Taken together, our results suggest that hCPFs-Exo transports low expressed exosomal miR-106b-5p to endothelial cells and promotes angiogenesis by overexpression of Angpt2.

Downregulation of MiR-203a Disinhibits Bmi1 and Promotes Growth and Proliferation of Keratinocytes in Cholesteatoma.

Background: Keratinocytes are the predominant cell type in a cholesteatoma, and microRNA (miR)-203a has been shown to be essential for the growth and differentiation of keratinocytes. The regulatory mechanisms of miR-203a and Bmi1-the predicted target of miR-203a that is associated with cholesteatoma-have not been clarified. Methods: Real-time PCR and western blot were carried out for the detection of miRNAs, mRNAs, and proteins, including miR-203a, Bmi1, and phosphorylated (p-)Akt. Immunohistochemical staining was applied to observe the expression and distribution of Bmi1 and of p-Akt in cholesteatoma and in control retroauricular skin. The dual luciferase reporter assay was used to analyze the relationship between miR-203a and Bmi1. Ectopic miR-203a and Bmi1 were transfected into an immortalized line of human keratinocytes (HaCaT cells), and the roles of these molecules in cell proliferation, apoptosis, and migration were explored. Results: Cholesteatoma tissues were characterized by downregulation of miR-203a and concomitant upregulation of Bmi1. Results of the dual-luciferase reporter assay indicated that Bmi1 was a direct target gene of miR-203a. Silencing of miR-203a increased Bmi1 expression; promoted proliferation, colony formation, and migration of HaCaT cells; and inhibited apoptosis. Moreover, p-Akt was significantly increased in cholesteatoma tissues and was positively correlated with Bmi1. Suppression of Bmi1 reduced p-Akt expression in HaCaT cells; subsequent inhibition of miR-203a reversed this phenomenon. Conclusions: Our results reveal that miR-203a may regulate cholesteatoma growth and proliferation by targeting Bmi1. These findings provide insight for the development of novel nonsurgical options for cholesteatoma.

[Sanation of petrous bone cholesteatoma in the otosurgical practice]. / Sanatsiia kholesteatomy piramidy visochnoi kosti v otokhirurgicheskoi praktike.

The present article reports the clinical cases of the surgical intervention on 20 patients presenting with petrous bone cholesteatoma. We have identified several clinical variants of petrous bone cholesteatoma based on the results of multispiral computed tomography (MSCT) of the temporal bones and categorized them into the following types in accordance with the classification proposed by Moffat-Smith an M. Sanna for this pathological condition: supralabyrinthine (n=8), supralabyrinthine-apical (n=2), infralabyrinthine (n=3), infralabyrinthine-apical (n=5), massive (n=1), and massive - apical (n=1). The surgical sanation of petrous bone cholesteatoma was performed in all the 20 patients in the absence of the pronounced bone destruction in the walls of the temporal bone pyramid and of the subdural expansion of cholesteatoma. In all the cases, the trepanation cavity remained open till its complete epidermization. The follow up period was around 3 years in duration on the average. The post-surgical analysis of the clinical conditions of each of the 20 patients was performed with special reference to the surgical technique applied for the removal of petrous bone cholesteatoma and the final outcome of the radical treatment.

Pediatric middle ear cholesteatoma: the comparative study of congenital cholesteatoma and acquired cholesteatoma.

This study examined the differences between congenital cholesteatoma (CC) and acquired cholesteatomas (AC) in children by comparing clinical features and treatment courses. This was a retrospective study which retrospectively evaluated 127 children with middle ear cholesteatomas using medical records from January 1999 to December 2012 in the Department of Otolaryngology, Niigata University Hospital. The study comprised 69 and 58 cases of CC and AC, respectively. The main outcome measures include patient backgrounds, the opportunities for consultations, mastoid cell development, intraoperative finding of stapes, surgical procedure and number of surgeries. The average age at operation was 6.4 and 9.8 years in CC and AC, respectively. AC was more prevalent in boys. Mastoid development was better in CC than in AC. We adopted a two-stage operation in 17 cases (25 %) of CC and in 22 cases (38 %) of AC. The repeat surgery rate was 11.6 % in CC and 27.6 % in AC. Three times as many operations were required for three cases (4.3 %) of CC and 10 cases (17.2 %) of AC. The lesions in AC were more difficult to control. In the treatment of pediatric middle ear cholesteatoma, we had to keep the outcome in mind.

Comparative analysis of the expression of E-cadherin, ß-catenin, and ß1 integrin in congenital and acquired cholesteatoma.

E-cadherin, ß-catenin, and ß1 integrin are important cell adhesion molecules to maintain epithelial structure and function. We investigated the expression of these cell adhesion molecules in cholesteatomas to understand the role of cell-cell and cell-extracellular matrix interaction in cholesteatomas. An immunohistochemical investigation was carried out on 35 cholesteatoma tissue samples (14 congenital, 21 acquired cholesteatomas) and 10 normal retroauricular skin (RAS) tissues which are obtained during middle ear surgery. The expression rate was measured to find out differences between retroauricular skin and cholesteatoma, as well as between congenital and acquired cholesteatoma. E-cadherin expression rate was significantly lower in the cholesteatoma (spinous layer 88.7 ± 17.9 %, granular layer 54.6 ± 22.6 %) than in the RAS (100 %, 74.4 ± 7.4 %) and in the acquired (83.3 ± 19.4 %, 48.1 ± 22.9 %) than in the congenital (96.7 ± 12.0 %, 64.4 ± 18.8 %). ß-catenin expression rate was significantly lower in the cholesteatoma (spinous layer 84.1 ± 17.2 %, granular layer 28.7 ± 30.8 %) than in the RAS (100 %, 75.9 ± 6.1 %) and in the acquired (78.1 ± 17.0 %, 17.1 ± 22.3 %) than in the congenital (93.2 ± 13.5 %, 46.1 ± 34.2 %). The expression pattern of ß-catenin is similar to that of E-cadherin. In ß1 integrin, there was no significant difference of the expression rate between RAS and cholesteatoma, as well as between congenital and acquired cholesteatoma. In conclusion, the expression of E-cadherin and ß-catenin is reduced in cholesteatoma, and the reduction is more pronounced in acquired cholesteatoma than in congenital cholesteatoma. Acquired cholesteatomas showed more aggressive characteristics than congenital cholesteatomas in terms of cell-cell adhesion.

Cholesteatoma of Maxillary Sinus: What Is the Best Surgical Approach?

Cholesteatoma is a relatively common disease entity within the middle ear or mastoid cavity but cholesteatoma of the paranasal sinuses is a rare diseases entity, especially in the maxillary sinus. As the authors recently experienced a patient of maxillary sinus cholesteatoma, the authors tried to review all the literatures previously reported on the "Cholesteatoma of the maxillary sinus." The aim of this study was to describe authors' recent experience and review previously reported patients of cholesteatoma of the maxillary sinus. Additionally, it is to describe the clinical features focusing on the computed tomography findings and to elucidate which approach may be best for complete excision. The authors thoroughly reviewed 10 patient reports written in English regarding the cholesteatoma of maxillary sinus which have been published since the 1980s. Based on authors' review, the authors suggest some conclusions. First, the diagnosis of cholesteatoma, although rare, should be considered for any slowly expansile lesion of the maxillary sinus. Second, there was no specific computed tomography finding that was helpful for the diagnosis of maxillary sinus cholesteatoma. Last, the surgical approach to cholesteatoma of the maxillary sinus should be chosen to allow visibility and complete removal according to the size, location, and extent of diseases.

Induction of cytokine production in cholesteatoma keratinocytes by extracellular high-mobility group box chromosomal protein 1 combined with DNA released by apoptotic cholesteatoma keratinocytes.

High-mobility group box chromosomal protein 1 (HMGB-1), a nuclear DNA binding protein, was recently rediscovered as a new proinflammatory cytokine. The purpose of this study was to determine HMGB-1 expression in vivo and to identify the effect of extracellular HMGB-1 in inflammatory process associated with bone destruction in cholesteatoma. We investigated the expression and location of HMGB-1 in the cholesteatoma and healthy skin using an immunofluorescence assay. We also detected apoptosis and DNA fragments in the cholesteatoma by TUNEL staining. HMGB-1 concentration in apoptotic supernatants from UV light-treated cells, culture supernatants and its translocation in cholesteatoma keratinocytes stimulated by supernatants from UV light-treated cells were measured by immunoblot analysis and immunofluorescence assay. Cultures of human cholesteatoma keratinocytes were exposed to CpG-DNA, HMGB-1, or CpG-DNA complexed to HMGB-1 for 24 h. Cytokines in the culture supernatant were measured by ELISA. In addition, levels of proinflammatory cytokines released by cholesteatoma keratinocytes stimulated by supernatants from UV light-treated cells with or without anti-HMGB-1 antibodies and supernatants from UV light-treated cells with DNase 1 were measured by enzyme-linked immunosorbent assay. The expression of HMGB-1 in cholesteatoma increased and it translocated both to the cytoplasm and extracellular space. Furthermore, the HMGB-1 concentration in supernatants increased significantly after addition of supernatants from UV light-treated cells. TNF-α and IL-1ß can be induced by purified HMGB-1 combined with CpG-DNA in the cholesteatoma keratinocytes. In addition, supernatants of apoptotic cells containing HMGB-1-DNA were effective in inducing TNF-α and IL-1ß secretion. This study suggested that persistent expression of extracellular HMGB-1 and DNA fragments in cholesteatoma leads to TNF-α and IL-1ß production, causing bone resorption and destruction. Thus, we have implicated that HMGB-1-DNA complexes might act as a key molecule involved in bone resorption associated with cholesteatoma.

Multi-color reflectance imaging of middle ear pathology in vivo.

Otoscopic examination using white-light illumination has remained virtually unchanged for well over a century. However, the limited contrast of white-light otoscopy constrains the ability to make accurate assessment of middle ear pathology and is subject to significant observer variability. Here, we employ a modified otoscope with multi-color imaging capabilities for superior characterization of the middle ear constituents in vivo and for enhanced diagnosis of acute otitis media and cholesteatoma. In this pilot study, five patients undergoing surgery for tympanostomy tube placement and congenital cholesteatoma excision were imaged using the custom-designed multi-color video-rate reflectance imaging system. We show that the multi-color imaging approach offers an increase in image contrast, thereby enabling clear visualization of the middle ear constituents, especially of the tympanic membrane vascularity. Differential absorption at the multiple wavelengths provides a measure of biochemical and morphological information, and the rapid acquisition and analysis of these images aids in objective evaluation of the middle ear pathology. Our pilot study shows the potential of using label-free narrow-band reflectance imaging to differentiate middle ear pathological conditions from normal middle ear. This technique can aid in obtaining objective and reproducible diagnoses as well as provide assistance in guiding excisional procedures.

[Cholesteatoma of the external and middle ear in the childhood].

The objective of the present work was to enhance the effectiveness of diagnostics of cholesteatoma of the external and middle ear in the children. The study included 66 patients presenting with chronic suppurative otitis media and one child having cholesteatoma of the external auditory meatus. All the patients were examined with the use of otoendoscopy and CT of the temporal bones. It was shown that the frequent occurrence of acute suppurative otitis media, exudative suppurative otitis media, and adhesive otitis media is the risk factor of the development of cholesteatoma of the external and middle ear in the children. The following CT features of cholesteatoma of the external ear were revealed: the sclerotic or mixed type of the mastoid process, the presence of pathological contents in the epitympanic space, homogeneous character of pathological contents in the antrum, widened aditus, caries of antrum walls, the presence of soft tissues around the auditory ossicles, destruction of the long process of the anval bone, and a soft-tissue structure in the external auditory meatus.

Inflammation-induced miR-802 promotes cell proliferation in cholesteatoma.

Cholesteatoma is a destructive and abnormal skin growth consisting of keratinizing squamous epithelium in the middle ear. Its molecular mechanisms remain poorly understood. Here, we found that the NF-κB inflammatory signaling pathway was highly activated in cholesteatoma. NF-κB activation increased the expression of microRNA-802 (miR-802) and chromatin immunoprecipitation assays showed that P65 could uniquely bind to miR-802 promoter. miR-802 overexpression promoted keratinocyte cell proliferation and cell cycle progression, while inhibition of miR-802 decreased these effects. From computational analysis and luciferase report assays, miR-802 directly repressed PTEN expression by targeting its 3'-UTR. Our results demonstrate that the NF-κb/miR-802/PTEN signaling pathway plays an important role in the development of cholesteatoma.

Fallopian canal dehiscence at pediatric cholesteatoma surgery.

The objectives of the study were to investigate the characteristics of ears with dehiscence of the fallopian canal at the time of cholesteatoma surgery and the relationship between dehiscence and age, and to consider the reasons why the fallopian canal tends to be preserved in pediatric patients. This study included 37 ears with cholesteatoma in pediatric patients (mean age 9.2 years, age range 4-14 years) and 273 ears with cholesteatoma in non-pediatric patients (mean age 45 years, age range 15-84 years). Patients were treated between January 2006 and April 2012. All patients had undergone prior tympanoplasty under general anesthesia at our institution. Facial canal dehiscence was evaluated by inspection and through palpation by blunt picking after the pathological tissues had been removed. The size of fallopian canal dehiscence was not investigated in this study. The frequency of dehiscence of the fallopian canal according to the type of cholesteatoma and coexisting pathological conditions, including destruction of the stapes, presence of a labyrinthine fistula, and dural exposure, were compared between the pediatric and non-pediatric groups. The frequency of dehiscence in cases with destruction of the stapes was also compared between the pediatric and non-pediatric groups. Dehiscence of the fallopian canal occurred in 6 of 37 ears (16.8 %) in the pediatric group and 91 of 273 ears (33.3 %) in the non-pediatric group (p < 0.05). In congenital cholesteatoma, the frequency of dehiscence was lower in the pediatric group than in the non-pediatric group (p < 0.05). However, in other types of cholesteatoma there was no statistically difference between the two types of cholesteatoma. The frequency of the destruction of the stapes was higher in the pediatric group than in the non-pediatric group (43.2 vs. 16.5 %, p < 0.001). In patients with severe destruction of the stapes, the fallopian canal was preserved more frequently in the pediatric group than in the non-pediatric group (p < 0.05). The frequency of dehiscence of the fallopian canal at the time of cholesteatoma surgery was lower in the ears of pediatric patients than in the ears of non-pediatric patients. This is probably due to the difference in types of cholesteatoma between the two groups and other unknown mechanisms.

[The hearing function in the patients presenting with the intralabyrinthine distribution of giant cholesteatoma].

The objective of the present study was to evaluate the state of the hearing function in the patients presenting with the intralabyrinthine distribution of giant cholesteatoma before and after the surgical treatment based on the results of examination by the subjective and objective methods. The possibility of preservation of the hearing function after the surgical intervention has been demonstrated.

Evaluation of Eustachian tube dimensions by temporal bone computed tomography in patients with chronic otitis media.

OBJECTIVE: To clarify the relationship between Eustachian tube dimensions and chronic otitis media aetiology using temporal bone computed tomography. METHODS: The data of 231 adults who had undergone surgery for unilateral chronic otitis media were reviewed retrospectively. Diseased and healthy ears were enrolled in groups 1 and 2, respectively. Group 1A included chronic otitis media with cholesteatoma (n = 28) and group 1B included chronic otitis media without cholesteatoma (n = 203). The Eustachian tube dimensions of groups 1 and 2 were compared, to clarify the relationship between the Eustachian tube dimensions and chronic otitis media aetiology. Groups 1A and 1B were compared to assess the effect of Eustachian tube dimensions on cholesteatoma development. RESULTS: The Eustachian tube was shorter, narrower and located more horizontally in ears with chronic otitis media. No significant difference was found between groups 1A and 1B. CONCLUSION: Eustachian tube dimensions are closely related to chronic otitis media aetiopathology, but are not related to cholesteatoma development.

Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction.

Cholesteatoma, which potentially results from tympanic membrane retraction, is characterized by intractable local bone erosion and subsequent hearing loss and brain abscess formation. However, the pathophysiological mechanisms underlying bone destruction remain elusive. Here, we performed a single-cell RNA sequencing analysis on human cholesteatoma samples and identify a pathogenic fibroblast subset characterized by abundant expression of inhibin ßA. We demonstrate that activin A, a homodimer of inhibin ßA, promotes osteoclast differentiation. Furthermore, the deletion of inhibin ßA /activin A in these fibroblasts results in decreased osteoclast differentiation in a murine model of cholesteatoma. Moreover, follistatin, an antagonist of activin A, reduces osteoclastogenesis and resultant bone erosion in cholesteatoma. Collectively, these findings indicate that unique activin A-producing fibroblasts present in human cholesteatoma tissues are accountable for bone destruction via the induction of local osteoclastogenesis, suggesting a potential therapeutic target.

Higher degree of keratinization correlated with severe bone destruction in acquired Cholesteatoma.

BACKGROUND: Acquired cholesteatoma is characterized by hyper-keratinized squamous epithelium and bone destruction. However, direct evidence for hyper-keratinized epidermis promoting bone destruction is lacking. AIMS/OBJECTIVES: To determine whether higher degree of keratinization correlated with severe bone destruction and further offer direct evidence for keratinocyte-inducing osteoclastogenesis. MATERIALS AND METHODS: Histological changes and clinical relevance were analyzed in human-acquired cholesteatoma. Animal models were established by implanting autologous epidermis with different degrees of keratinization. The severity of bone resorption and the number of osteoclasts were compared in different keratinized groups. An in vitro coculture system was developed to mimic the progress of keratinocyte-inducing osteoclastogenesis. RESULTS: The matrix of cholesteatoma was composed of a thicker stratum corneum than normal skin. The stratum corneum thickness and the expression of Keratin 10 positively correlated to the severity of bone destruction. Animal models revealed that the bone destruction induced by a higher keratinized epidermis was more severe. Osteoclasts were detected in bone erosion areas, and the number of osteoclasts increased with the keratinization degrees of the graft. In vitro studies showed that keratinocytes directly promoted monocytes differentiating into osteoclasts. CONCLUSIONS AND SIGNIFICANCE: In acquired cholesteatoma, the degree of keratinization correlated with disease severity, and keratinocytes directly promote osteoclastogenesis.