Keratinocyte growth factor and its receptor expression in chronic otitis media with and without cholesteatoma.

INTRODUCTION: Chronic suppurative otitis media (CSOM) with and without cholesteatoma is regarded as chronic inflammation of the middle ear and mastoid mucosa that can be associated with the presence of granulation tissue and infection, which can lead to ossicular damage and hearing loss, but it is commonly known that cholesteatoma behaves aggressively. Both lesions appear to contain a predominant population of inflammatory cells, among which proinflammatory cytokines secreting keratinocyte growth factor (KGF) and its receptor (KGFR). No clear difference was demonstrated between these entities. The purpose of this study was to investigate the potential influence of KGF and KGFR in increased epithelial-cell proliferation of chronic otitis media (COM) with cholesteatoma in contrast to COM without cholesteatoma (CSOM), particularly in the granulative form, and to compare the rate of proliferation activity of epithelial cells using the Ki-67 epithelial proliferation marker expression. PATIENTS, MATERIALS AND METHODS: We analyzed 105 ears with cholesteatoma vs. 53 ears with CSOM without cholesteatoma using our KGF and KGFR variables, and the ratio of proliferating epithelial cells using Ki-67. The percentage of the specimens expressing KGF and KGFR was compared between the two groups for statistical significance using the Pearson's chi-square test. Immunohistochemical staining was conducted and the proportion of the cells staining positive for the nuclear antigen Ki-67 was evaluated in a quantitative and visual way, using light microscopes. RESULTS: KGF was positive in 88.57% of cholesteatoma and was positive in 41.51% CSOM without cholesteatoma specimens (cholesteatoma vs. CSOM, p=0.001). The positive rate of KGFR in the CSOM group was 33.96% compared to those in cholesteatoma, which was 60.95%. Compared to the cholesteatoma specimens, a significantly smaller number of Ki-67 labeling index was detected in CSOM specimens. CONCLUSIONS: Our results indicated that the abnormal behavior of the cholesteatoma epithelium seems to be induced by the paracrine interaction between KGF and KGFR. Furthermore, we found that cholesteatoma expressing both KGF and KGFR had high Ki-67 index, which correlated with its aggressiveness. These findings suggest that excessive KGF and KGFR synthesis may contribute to the hyperproliferative state in cholesteatoma and could explain the pathological difference between cholesteatoma and CSOM.

Mastoiditis and facial paralysis as initial manifestations of temporal bone systemic diseases - the significance of the histopathological examination.

UNLABELLED: Several systemic diseases, including granulomatous and infectious processes, tumors, bone disorders, collagen-vascular and other autoimmune diseases may involve the middle ear and temporal bone. These diseases are difficult to diagnose when symptoms mimic acute otomastoiditis. CASE REPORTS: The present report describes our experience with three such cases initially misdiagnosed. Their predominating symptoms were otological with mastoiditis, hearing loss, and subsequently facial nerve palsy. The cases were considered an emergency and the patients underwent tympanomastoidectomy, under the suspicion of otitis media with cholesteatoma, in order to remove a possible abscess and to decompress the facial nerve. The common features were the presence of severe granulation tissue filling the mastoid cavity and middle ear during surgery, without cholesteatoma. The definitive diagnoses was made by means of biopsy of the granulation tissue from the middle ear, revealing granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) in one case, middle ear tuberculosis and diffuse large B-cell lymphoma respectively. After specific associated therapy facial nerve functions improved, and atypical inflammatory states of the ear resolved. CONCLUSIONS: As a group, systemic diseases of the middle ear and temporal bone are uncommon, but aggressive lesions. After analyzing these cases and reviewing the literature, we would like to stress upon the importance of microscopic examination of the affected tissue, required for an accurate diagnosis and effective treatment.

Molecular biology of cholesteatoma.

Cholesteatoma is a non-neoplastic, keratinizing lesion, characterized by the proliferation of epithelium with aberrant micro-architecture into the middle ear and mastoid cavity. The exact pathogenic molecular mechanisms behind the formation and propagation of cholesteatoma remain unclear. Immunohistochemical examinations of the matrix and perimatrix have considerably improved the knowledge of cholesteatoma pathogenesis. In this review, the current concepts of cholesteatoma pathogenesis are discussed. Currently, the most widely acknowledged pathogenesis of acquired cholesteatoma is the theory that negative pressure, dysfunction of the Eustachian tube, causes a deepening retraction pocket that, when obstructed, desquamated keratin cannot be cleared from the recess, and a cholesteatoma results. Local infection leads to a disturbance of self-cleaning mechanisms, with cell debris and keratinocytes accumulate inside the retraction pocket, and this is followed by an immigration of immune cells, i.e., Langerhans' cells, T-cells, macrophages. There is an imbalance and a vicious circle of epithelial proliferation, keratinocyte differentiation and maturation, prolonged apoptosis, and disturbance of self-cleaning mechanisms. The inflammatory stimulus will induce an epithelial proliferation along with expression of lytic enzymes and cytokines. Bacteria inside the retraction pocket produce some antigens, which will activate different cytokines and lytic enzymes. These cytokines lead to activation and maturing of osteoclasts with the consequence of degradation of extracellular bone matrix and hyperproliferation, bone erosion and finally progression of the disease. Further research is necessary for a better understanding of the pathogenetic mechanisms and to expand the spectrum of therapeutic options.

Anatomical variants of tympanic compartments and their aeration pathways involved in the pathogenesis of middle ear inflammatory disease.

AIM: The aim of this article is to review the anatomy of middle ear compartments and folds and to demonstrate through anatomical evidence their presence at birth. Additionally, their role in the obstructions of middle ear ventilatory pathway is highlighted. METHODS: Ninety-eight adult temporal bones, with no history of auricular disease and fifteen newborn temporal bones were studied by micro dissection. Documentation was done by color photography using the operation microscope. RESULTS: Our micro-dissections have showed that mucosal folds from the middle ear are steadily present since birth, given that they were found in all newborn temporal bones. The mucosal folds in our normal adult material, showed some variations including membrane defects but they were constantly present. Our micro dissections showed that the epitympanic diaphragm consisted, in addition to malleal ligamental folds and ossicles, of only two constantly present folds: the tensor tympani fold and the incudomalleal fold. When the tensor fold is complete the only ventilation pathway to the anterior epitympanic space is through the isthmus, whereas its absence creates an efficient additional aeration route from the Eustachian tube to the epitympanum. CONCLUSIONS: The goal of surgery in the chronic pathology of the middle ear should be restoration of normal ventilation of the attical-mastoid area. This is possible by removing the tensor fold and restoring the functionality of the isthmus tympani.