Cochlear bone erosion: effects on cochlear hair cells. A scanning electron microscopy study.

Cochleae from gerbils with normal middle ears were compared with cochleae from gerbils with experimentally induced cholesteatomas that were in contact with the cochlear wall (stage III cholesteatomas). Cochleae from gerbils with stage III cholesteatomas were further divided into two groups: one without erosion of cochlear bone, and one with cholesteatoma-induced bone erosion but without cochlear fistulae. The cochleae with bone erosion showed significant loss of outer hair cells in the middle and apical turns, but not in the basal turn. The cochleae with stage III cholesteatomas but without bone erosion did not differ from normal controls. These results suggest that an ototoxic agent, involved in the process of bone erosion, acts through the bony cochlear wall.

The motility of keratinocytes in cholesteatoma: an ultrastructural approach to epithelial migration.

Eight cases of attico-antral cholesteatoma were studied by transmission electron microscopy concentrating on the mechanisms involved in intercellular adhesion. Desmosomes were found in large numbers throughout the epidermis and were arranged in various orientations around the keratinocytes. Those desmosomes found in the stratum corneum were significantly less dense than those in deeper layers and were associated with a large number of intercellular spaces, which would reduce the cohesive strength of this layer. The tortuous basement membrane features numerous hemidesmosomes along its length. The findings of this study were compared with previous ultrastructural observations made on the pars flaccida and pars tensa of the tympanic membrane and external canal skin. This revealed that the morphological characteristics of cholesteatoma resemble pars flaccida and external canal skin rather than pars tensa. The implications of these findings are discussed.

[Anatomo-pathology of cholesteatoma]. / Anatomo-pathologie du cholestéatome.

The authors, from their own histopathological studies and from an overview of otological literature focus the controversial problems about the so-called disease cholesteatoma. The history of cholesteatoma has been marked out by pathologic data which, initially caused the cholesteatoma to be identified as a keratinized squamous tumor. This misnomer will however be retained because of it long-established usage. "Skin in the wrong place" in the middle ear summarizes this clinical entity. Electron microscopic observations provide arguments in favour of the migratory theory and the invasion of the epidermis from the bottom of the external ear canal into the middle ear cavity (identical fine morphology between skin and cholesteatoma, presence of Langerhans and Merkel cells, sharp junction between the advancing front of the cholesteatoma and the middle ear mucosa). Recent immunohistological techniques allow consideration of cholesteatoma as a self-induced inflammatory process in response to tissular and cellular conflicts. A cholesteatoma could be merely a non-healing wound process and a disease of epidermal growth control occurring in the middle ear space. The logical principles governing cholesteatoma surgery, suggested by these biological considerations, are: total removal of cholesteatoma matrix, prevention of cholesteatoma recurrence by a careful respect of the barrier separating the middle ear mucosa from the skin-lined bony external ear canal, maintenance of good healing conditions for both mucosa in a closed well-ventilated middle ear and epidermis in a harmonious anatomical external canal.

Tympanic membrane microstructure in experimental cholesteatoma.

This study assessed changes in tympanic membrane microstructure associated with cholesteatoma development following middle ear application of 50% propylene glycol in chinchillas. Although the epidermal layer of the tympanic membrane (TM) was destroyed immediately after propylene glycol application, the epidermal basal lamina remained intact and appeared to serve as a substrate for regrowth of epidermis over the TM. During the initial phase of epidermal repair (4 to 7 days after propylene glycol administration), pseudopodial processes from the epidermal cells occasionally penetrated the basal lamina; however, no migration of epidermis into the lamina propria occurred at that time. The basal lamina remained largely intact until about 2 weeks, when it became fragmented in some areas, so that sizable gaps appeared. Hyperplastic epidermal cells then migrated through the gaps into the rapidly proliferating connective tissue of the lamina propria. At 2 to 4 weeks, degenerative changes were observed in portions of the fibrous layer, which underwent phagocytosis by foreign body giant cells. This process created defects in the fibrous layer which permitted invasion of epidermis to the medial portion of the lamina propria. The epidermis subsequently reached the medial side of the TM in areas where there was incomplete repair of the mucosal layer.

Diagnóstico de los tumores endocraneales: tomografía computada, resonancia nuclear magnética, anatomía patológica

Clasificación histológica de los tumores del sistema nervioso central, de acuerdo con la OMS. Nuevos criterios sobre tumores del sistema nervioso en niños. Descripción anatomopatológica de los tumores del sistema nervioso central. Ordenamiento de los tumores endocraneales por frecuencia e incidencia, de acuerdo a edad, sexo y localización. Consideraciones generales sobre el diagnóstico por imágenes de los tumores endocraneales. Estadística de los 765 tumores endocraneales estudiados por tomografía computada, resonancia nuclear magnética, cirugía y anatomía patológica. Descripción de las imágenes de los principales tumores del sistema nervioso central. Biopsia cerebral, guiada por tomografía computada

Diagnóstico de los tumores endocraneales: tomografía computada, resonancia nuclear magnética, anatomía patológica

Clasificación histológica de los tumores del sistema nervioso central, de acuerdo con la OMS. Nuevos criterios sobre tumores del sistema nervioso en niños. Descripción anatomopatológica de los tumores del sistema nervioso central. Ordenamiento de los tumores endocraneales por frecuencia e incidencia, de acuerdo a edad, sexo y localización. Consideraciones generales sobre el diagnóstico por imágenes de los tumores endocraneales. Estadística de los 765 tumores endocraneales estudiados por tomografía computada, resonancia nuclear magnética, cirugía y anatomía patológica. Descripción de las imágenes de los principales tumores del sistema nervioso central. Biopsia cerebral, guiada por tomografía computada

[Ultrastructural aspects of cholesteatoma of the middle ear]. / Contributo allo studio degli aspetti ultrastrutturali del colesteatoma dell'orecchio medio.

Middle ear cholesteatomas were intraoperatively obtained from 6 male patients and studied under light (L.M.), transmission (T.E.M.) and scanning (S.E.M.) electron microscopy. Cholesteatoma proved to be formed by keratinizing squamous epithelium, or matrix, and by connective tissue, chorion or perimatrix. With regard to the matrix, a progressive differentiation of cells belonging to the stratum germinativum could be observed towards spinosum, granulosum and corneum cells with formation of keratinized lamellae. Moreover, keratinocytes and Langerhans cells were found in the stratum spinosum. The perimatrix consisted of granulation tissue, or inflamed subepithelial connective tissue displaying inflammatory cells. Furthermore, the advancing front of cholesteatoma proved to be formed by lymphocytes and plasma cells, partially covered by respiratory type epithelium.

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.

Cochlear hair cell loss in ears with cholesteatomas. Scanning electron microscopy study.

Cochleas from 16 Mongolian gerbils with spontaneous aural cholesteatomas, and four of similar age without cholesteatomas, were examined by scanning electron microscopy to quantify cochlear hair cell loss. Loss of hair cell stereocilia was found in all ears with cholesteatomas and was significantly increased when compared with uninvolved ears from animals of similar age. The hair cell loss associated with gerbilline cholesteatomas appeared to be most marked in the middle turn of the cochlea and increased in severity with increasing size of the cholesteatomas. Outer hair cells were affected more than inner hair cells. Inner and outer hair cell loss was not significantly different in infected cholesteatomas versus sterile cholesteatomas. The greater damage to hair cells at the middle turn compared to the basal turn suggests that these losses may be the result of some agent acting through the cochlear wall rather than through the round window.

Differentiation of nuclei during keratinization in middle ear cholesteatoma. DNA cytophotometry completed by computerized image analysis.

Quantitative DNA cytophotometric techniques were applied to judge the alteration (differentiation) and ultimate fate of nuclei during keratinization in human middle ear cholesteatoma. Compared with a healthy epidermis, a tendency towards postponed nuclear degradation was noticed. Two patterns governing the loss of DNA are recognized. In one group, the mean nuclear DNA content declines continuously, starting in the nearest suprabasal layers and continuing throughout the prickle and granular cell stages, where the ultimate degeneration of nuclei takes place. This pathway corresponds to that observed in epidermis, but evolves more slowly. In another group of samples, the onset of the DNA decline is delayed to the upper prickle cells, exceptionally to more terminal stages of keratinization. During matrix keratinization, a profound nuclear remodelling takes place, similar to that in epidermal tissues, as far as eu- and heterchromatin DNA and area data are concerned. However, euchromatinization of nuclei in matrix prickle cells is more pronounced than in epidermal tissues. The topography of residual heterochromatic clumps does not reflect a persistent margination as in epidermal nuclei, but is the result of more individualized rearrangements. The changes in karyotype are less elaborate when the complete decline of the nuclear DNA content only occurs during terminal keratinization.

[Conditions necessary for a cure of cholesteatomatous chronic otitis]. / Les conditions de guérison de l'otite chronique cholestéatomateuse.

The authors present a homogeneous series of 750 cholesteatomas treated surgically between 1973 and 1984, 710 cases by a closed technique (94%) and 40 by an open technique. After dealing with the false problem of the choice between open technique and closed technique, the authors attempt to define the conditions required for successful treatment of cholesteatomatous chronic otitis, and on that basis justify their own therapeutic attitude. Excision of the cholesteatoma must be complete and as a single block, from the periphery to the point of origin of the epidermal matrix. Such excision is possible in the majority of cases without damage to the bony canal walls. The risk of residual cholesteatoma fell from 19% in 1978 to 8% in 1984. The prevention of cholesteatoma is based upon our basic knowledge of the disease. It requires avoiding damage to or repair of the osteo-membranous anatomical barrier which separate the two compartments, outer and middle, of the ear. This aim can now be better achieved by the use of tympanic homografts and recent techniques for repair of the bony external auditory canal. Recurrences (13%) are due to the ability of progression of the cholesteatoma but also, and above all, the imperfect surgery. Whilst it was long believed that complete eradication of cholesteatoma was impossible without destruction of part of the architecture of the ear, it is now known to be possible, and even represents one of the best methods for the prevention of recurrences.

Cholesterol metabolism in cholesteatoma and cholesterol granuloma.

Based on biochemical and morphological studies, the significance of cholesterol in cholesteatoma and cholesterol granuloma is discussed. In cholesteatoma, cholesterol is synthesized through desmosterol and delta 7-cholestenol (lathosterol), possibly in the matrix. Cholesterol crystal might have educed from keratin layers or a cell-disintegrated layer adjacent to the matrix by a physicochemical rather than by a biochemical process. Production of cholesterol in the matrix may differ depending on the cell cycle. In cholesterol granuloma, cholesterol may be derived from blood with some other compositions such as albumin and cholestanol, although other sources cannot be denied. Crystallized cholesterol is treated by the surrounding tissue as a foreign body; this results in formation of granuloma. The delta 7-cholestenol is not involved in the biosynthesis of cholesterol in cholesterol granuloma.

Tissue culture of migratory skin of the external ear and cholesteatoma: a new research tool.

There has been considerable research interest in cholesteatoma in recent years but an understanding of the pathology has been handicapped by the lack of a suitable research model. Animal experiments are unsatisfactory as they may not fully represent the human pathology. In 1975 Rheinwald and Green devised a method of growing skin in tissue culture, using a feeder layer of lethally irradiated fetal mouse fibroblasts. This technique has been adapted for use with otological surgical specimens so that a comparison can be made between skin colonies derived from cholesteatoma matrix, migratory epithelium of the external ear, and normal skin from an extraconchal incision, as well as foreskin from neonatal circumcision as a control. The colonies so produced are then available for study by phase contrast microscopy, conventional light microscopy, and scanning and transmission electron microscopy. Differences in behavior and morphology between the various colonies grown in tissue culture have been demonstrated.

Sem studies of the inflammatory changes of the middle ear mucosa.

Mucosal specimens of the middle ear from patients who had chronic otitis media were studied and compared with normal middle ear specimens using a scanning electron microscope. The epithelia in chronic otitis media were usually thick and those surface structures varied depending on the area in which the biopsy was taken. Moreover, the structure was not uniform even in the same specimen. Some areas showed a great number of secretory cells, while others demonstrated high population of ciliated cells. Areas with loss of the superficial layer were also observed in a few cases. There were less ciliated cells than we expected. They were not evenly distributed, except for the eustachian tube region. Morphologically, most of these ciliated cells seemed to be normal, and a few isolated atrophic ones were also observed. In cholesteatoma cases, squamous epithelia with desquamating, flat and keratinized cells were observed.

Cholesteatoma. A clinical and morphological analysis.

A total of 33 consecutively operated aural cholesteatomas were analysed with regard to preoperative findings and correlated with the morphology of the cholesteatoma tissue. Patients were found in all age groups, 9/33 of the patients were operated at an age below 15 years. A persistent ear discharge had occurred in all patients but in 9 cases the patient history was of less than one year. Impaired hearing was found in 29/33. A demineralization of ossicles was observed at X-ray also in cases in which the ossicular chain appeared normal at operation. In only 5/33 cases was there a retraction of the tympanic membrane without a perforation. The morphological features were the same in both very rapidly and very slowly growing cholesteatomas.

A contribution to the pathogenesis of cholesteatoma. A histochemical and ultrastructural study.

In a histochemical and ultrastructural study the pathogenesis of cholesteatoma ostitis is analysed on human tissue. In the subepithelial layer there is evidence of an inflammatory reaction leading to proliferation of granulation tissue with bony invasion. Bony destruction is initiated by osteocytic osteolysis. In the case of cholesteatoma there is a combined action of extraosseous and osseous lysosomal enzymes. The pathological changes of the fibrillar elements suggest that the self-perpetuation of degeneration is maintained by a disturbance of fibrillogenesis. The causal pathogenesis of cholesteatoma formation is discussed as a function of a disturbance between cellular activity, extracellular matrix, and cellular surface.