bromochloroacetic-acid and Ear-Diseases

Topics: Aminolevulinic Acid; Biopsy; Diagnosis, Differential; Ear Diseases; Ear, External; Epithelial Cells; Female; Humans; Keratins; Keratosis; Middle Aged; Miliaria; Photochemotherapy; Photosensitizing Agents

Epidermoid cyst of the external auditory canal (EAC) is rarely encountered in the clinical practice, but when it occurs, it may cause obstruction of the meatus that necessitates surgical excision. The aims of this study were to present 9 pediatric patients with epidermoid cysts of the EAC and to evaluate the outcome of the surgical technique that has been used in excision. Surgical removal of the cyst was carried out through a simple transmeatal approach, a medially based rectangular skin flap was elevated and the cyst was completely removed. No complications or recurrence have been reported. Epidermoid cyst should be listed in the differential diagnosis of EAC masses; it appears on computed tomography as a cystic mass in the outer cartilaginous part of EAC that is usually limited to the soft tissue with no bone erosion. It can be removed easily through simple transmeatal approach with high success rate and no morbidity.

Topics: Child; Child, Preschool; Diagnosis, Differential; Dissection; Ear Canal; Ear Diseases; Epidermal Cyst; Female; Follow-Up Studies; Humans; Keratins; Male; Retrospective Studies; Surgical Flaps; Suture Techniques; Tomography, X-Ray Computed; Treatment Outcome

Topics: Aged; Cholesteatoma, Middle Ear; Diagnosis, Differential; Ear Canal; Ear Diseases; Earache; Female; Hearing Loss, Conductive; Humans; Keratins; Keratosis

Pleomorphic adenoma (PA) is a rare tumor of the skin that may arise from either the apocrine or the eccrine glands. Only 4 cases of PA in the auricle have been reported. We experienced the case of a 40-year-old woman who had a slowly growing, nontender auricle mass for 3 years. Under a clinical diagnosis of an epidermal inclusion cyst, we performed a total excision of the tumor with the skin and with direct closure. No recurrence was found during the 18 months of postoperative follow-up. Histologic examination confirmed a diagnosis of PA. Hematoxylin-eosin stain showed tubules that were lined with 2 layers of epithelial cells. The stroma was composed of the myxoid and chondroid matrices. Immunohistochemical staining was positive for cytokeratin, epithelial membrane antigen, and gross cystic disease fluid protein, whereas it was negative for S-100 and carcinoembryonic antigen. These findings suggested that this tumor originated from the apocrine glands. Only a few cases of PA in the auricle have been reported in the literature, 2 of which occurred in the helical rim. Recurrence is rare if there is complete resection of the tumor along with the surrounding capsule. We report herein a rare case of PA that developed in the auricle.

Topics: Adenoma, Pleomorphic; Adult; Biomarkers, Tumor; Carrier Proteins; Cyst Fluid; Diagnosis, Differential; Ear Auricle; Ear Diseases; Ear Neoplasms; Epidermal Cyst; Epithelial Cells; Female; Follow-Up Studies; Glycoproteins; Humans; Keratins; Membrane Transport Proteins; Mucin-1

S100 proteins were reported to be involved in different biological activities such as transduction of intracellular calcium signalling. It has been reported that each member of the S100 protein family exhibits a distinct tissue-specific pattern of expression. Furthermore, altered S100 protein expression and function correlate with many diseases. The expression of S100A1 was reported to be increased in different tissue with hyperplasia. The external auditory canal cholesteatoma (EACC) is a benign hyperplasia of the auditory meatal skin. However, without treatment, EACC destroys adjacent tissue. Seventeen EACC specimens were collected and investigated immunohistochemically against S100A1. Normal auditory meatal skin served as control. In the EACC, S100A1 showed a more homogeneous staining pattern, positively expressed throughout the epithelial layers. The keratin debris showed no detectable expression of S100A1. In the auditory meatal skin (control), S100A1 was only expressed in the basal layer of the epithelium. We showed that there are different staining patterns in normal auditory meatal skin, middle ear cholesteatoma and external auditory canal cholesteatomas. The immunoreactivity increased with the stage of the disease. Contrary to that reported previously in the middle ear cholesteatomas, the reactivity was strongest in the upper epithelial layers. In our collective, the epithelial matrix of the EACC showed strong reactivity throughout all the layers. Surprisingly, there is no study regarding the connection between growth factors and S100A1. In previous experiments we showed significant increase of growth factors in EACC. This correlates with our new data concerning S100A1. This is the first study to show the different reactivity pattern of S100A1 in the external auditory canal cholesteatoma.

Topics: Adult; Aged; Cholesteatoma; Ear Canal; Ear Diseases; Female; Gene Expression Regulation; Humans; Hyperplasia; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Signal Transduction

Topics: Aged; Aged, 80 and over; Cholesteatoma; Diagnosis, Differential; Ear Canal; Ear Diseases; Epithelium; Female; Humans; Keratins

Topics: Aged; Ear Diseases; Ear, External; Epidermal Cyst; Female; Humans; Keratins; Skin Diseases

Intradermal administration of concanavalin A, a potent T-cell mitogen, into an ear lap resulted in activation of chondrogenesis and stimulation of epidermis proliferation. This proliferation is sometimes invasive in character (pearls and epidermal nests form in the underlying connective tissue) but never turns into true cancerous lesions. This reaction can be delayed, but not prevented, by the prostaglandin inhibitor indomethacin. Stimulation of epidermis proliferation was also caused by administration of other immunomodulators, such as carrageenan type IV, Moloney sarcoma development, and rarely in the course of GvHr, but to much lesser degree than with concanavalin A. It is suggested that the same growth factors, which are mediators of local chondrocyte stimulation, are also mediators of keratinocyte activation.

Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bone Marrow Transplantation; Carrageenan; Chondrocytes; Concanavalin A; Drug Eruptions; Ear Diseases; Ear Neoplasms; Ear, External; Epidermis; Epithelium; Female; Graft vs Host Reaction; Hyperplasia; Hypertrophy; Indomethacin; Keratinocytes; Keratins; Male; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Mice, Inbred DBA; Mice, Inbred ICR; Mice, SCID; Moloney murine sarcoma virus; Precancerous Conditions; Sarcoma, Experimental; Transplantation, Heterotopic

Topics: Aged; Aged, 80 and over; Ear Diseases; Ear, External; Epidermis; Follow-Up Studies; Humans; Keratins; Keratosis; Male

Human neonatal temporal bones frequently show the formation of granulation tissue provoked by amniotic fluid keratin contents, desquamated keratinized epithelial cells and lanugo hair. Similar histopathologic findings have been produced previously in a short-term animal model. To test the hypothesis that those short-term pathologic observations could have theoretical relevance for ear disease in older patients, a longer term animal model study was necessary.. Into the right bulla of 10 chinchilla pups was placed an aliquot of autogenous, nonviable epidermal scrapings and hair. Into the left bulla was placed 1 mm2 viable autogenous epidermal tissue. Animals were killed at intervals up to 11 months and then studied by light microscopy.. Chronic ear histopathologic changes such as granulation tissue, osteoneogenesis, adhesions, and cholesteatoma were present. Over time, these secondary pathologic changes became more obvious than the initial keratin implant.. The authors conclude that chronic pathologic changes resembling human ear disorders persist and that this model further extends the hypothesis that prenatally acquired keratin eventually could account for some cases of human ear disease.

Topics: Animals; Chinchilla; Chronic Disease; Ear Diseases; Ear, Middle; Epidermis; Granulation Tissue; Hair; Keratins; Transplantation, Autologous

The accumulation of keratinizing epithelium in the middle ear cavity is a crucial factor in the pathogenesis of cholesteatoma. We hypothesize that keratinocytes from the skin of the ear canal migrate and hyperproliferate in response to inflammation in the middle ear cavity to cause accumulation of keratin debris. In the present study, we investigated the expression of specific cytokeratins (CKs) in the cholesteatoma matrix to determine whether cholesteatoma is a hyperproliferative disease. Cytokeratin expression was examined in cholesteatoma, meatal skin, and tympanic membrane with two monoclonal antibodies, one for both cytokeratins 13 and 16 (antibody K8.12), and another for cytokeratin 13 only (antibody KS-1A3). CK 13 (MW 51 KD) is a marker of differentiation and CK 16 (MW 48 KD) is a marker of hyperproliferation of keratinocytes. The use of immunoblot probes showed that CKs 13 and 16 were present in cholesteatoma. Immunofluorescent staining showed the presence of CK 16 in the suprabasal layer of cholesteatoma, which was located near the external ear canal. CK 13 was localized in the suprabasal layer of meatal skin and tympanic membrane. CK 13 was localized in the basal layer of the cholesteatoma, distal to the external ear canal, but not in the meatal skin and tympanic membrane. Taken together, the present data suggest that cholesteatoma is a hyperproliferative disease and that cholesteatoma expresses CK 16 near the external ear canal and transforms to express CK 13 during growth distally.

Topics: Cholesteatoma; Ear Canal; Ear Diseases; Ear, Middle; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Gene Expression; Head and Neck Neoplasms; Humans; Immunoblotting; Keratins; Skin; Sodium Dodecyl Sulfate; Tympanic Membrane

A variety of solutions were tested in vitro to find a suitable solvent which could be used in clinical practice for cholesteatoma debris. Though a little weak as a solvent, a liquid soap composed mainly of plant oil did not cause irritation of the middle ear mucosa, and was thought to be a promising solvent with which to rinse away tenacious debris, especially when used in combination with hydrogen peroxide.

Topics: Cholesteatoma; Ear Diseases; Ear, Middle; Humans; Hydrogen Peroxide; Keratins; Soaps; Solubility; Solvents; Therapeutic Irrigation

The expression of epithelial markers (cytokeratins, Filaggrin, BerEp4 and EMA), collagen IV and Ki67 was studied immunohistochemically in cholesteatoma and compared with that in epidermis of meatal skin, squamous epithelium of eardrum and simple epithelium of middle ear mucosa. MNF116 (cytokeratin 10, 17, 18) stained the full layer of normal epithelium and all cholesteatoma specimens. CK10 and Filaggrin were expressed in the upper layer of epidermis but more diffusely in cholesteatoma. BerEp4 was found in the basal layer of normal epithelium but was detected in most epithelial cells in cholesteatoma matrix. Variability was observed in EMA and CK14 immunostaining. Collagen IV was localized in the basement membrane of normal epithelium with a continuously staining pattern, an observation also made in the cholesteatomas studied. However, in one of these small areas the basement membrane was not stained with collagen IV. Ki67 was expressed in nuclei of the cells in the basal layer of normal epithelium but extended to epithelial cells in the upper layers of cholesteatoma matrix. The results of the present study indicate that the expression pattern of epithelial markers in cholesteatoma corresponds to that in normal epidermis. The increasing expression of BerEp4 and Ki67 confirms the hyperproliferative nature of cholesteatoma. Whether or not the lack of expression of collagen IV in one of the cholesteatomas reflects a true degradation of the basement membrane needs further investigation in extended materials.

Topics: Cholesteatoma; Collagen; Ear Diseases; Ear, Middle; Epidermis; Epithelium; Filaggrin Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Ki-67 Antigen; Neoplasm Proteins; Nuclear Proteins

To determine the behavior of epidermal cells after transplantation in the middle ear.. In a rat model, full-thickness meatal skin grafts were transplanted into the middle ear and studied morphologically and immunohistochemically with the use of antibodies directed against different cytokeratin (Ck) polypeptides, which are markers of different types of epithelial cell differentiation.. The grafts had either transformed into epithelial cysts or had become integrated into the middle ear epithelium. The epithelium of the integrated grafts showed gradual transition into the epithelium of the middle ear. A clear distinction between epidermal cells and middle ear epithelium could be made only on the basis of their Ck profiles. The Ck profiles of the grafts revealed a decrease in the expression of epidermal Cks, while nonepidermal Cks became expressed. These changes can be ascribed to replacement of the dermal mesenchyma by mesenchyma from the middle ear. In two ears with superimposed infection, the graft epithelium showed expansive growth.. Meatal epidermis is well tolerated in the middle ear, but superimposed infection can induce expansive growth. These findings favor the concept that the progressive growth of cholesteatoma is related to the presence of inflammatory processes.

Topics: Animals; Antibodies, Monoclonal; Bacterial Infections; Cell Differentiation; Connective Tissue; Dendritic Cells; Ear Canal; Ear Diseases; Ear, Middle; Epidermal Cyst; Epidermis; Epithelium; Keratinocytes; Keratins; Mesoderm; Rats; Rats, Wistar; Skin; Skin Transplantation; Vimentin

Immunohistochemical investigations were carried out to further reveal the pattern of cytokeratin (CK) expression in middle ear cholesteatoma. Using chain-specific monoclonal antibodies and the indirect immunoperoxidase technique, 10 out of 19 CK polypeptides were screened in cryoslices of fresh postmortem eardrums and external ear canal specimens. Our data, combined with those published before, indicate an intimate relationship between middle ear cholesteatoma lesions and epidermal tissues in the immediate vicinity. Our CK data do not favor the metaplastic origin of cholesteatoma, because the CK complement of cholesteatoma lesions does not include major and typical CK constituents of the middle ear mucosa.

Topics: Antibodies, Monoclonal; Biomarkers; Cholesteatoma; Ear Canal; Ear Diseases; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Mucous Membrane; Tympanic Membrane

Cholesteatoma is characterized by the presence of a squamous epithelium invading the middle ear altering its growth properties. This epithelium is believed to have hyperproliferative properties. Keratin 16 is accepted as a molecular marker for hyperproliferative epithelia. Two monoclonal antibodies K8.12 (directed against keratin 13) and KS.1A3 (directed against keratin 13 and 16) were used in an alkaline phosphatase anti-alkaline-phosphatase (APAAP)-technique to compare the expression of both keratin 13 and keratin 16 in normal human skin and aural cholesteatoma. Furthermore, the cytokeratin expression was compared to that of normal skin and palatine tonsil using one-dimensional gel electrophoresis. For both monoclonal antibodies, normal ear skin was stained only in the basal layer. In contrast, in the cholesteatoma samples the immunostaining of the antibody KS-1A3 was done not only in the basal cell layer but also in the suprabasal cells of the stratum spinosum and stratum granulosum. Using gel-electrophoresis, the presence of cytokeratin 16 was demonstrated in the cholesteatoma samples only. These results support the hyperproliferative character of cholesteatoma epithelium.

Topics: Cell Division; Cholesteatoma; Ear Diseases; Ear, Middle; Electrophoresis, Polyacrylamide Gel; Epithelial Cells; Gene Expression; Humans; Immunoenzyme Techniques; Keratins; Palatine Tonsil; Skin

Immunohistochemical investigations were carried out to determine the pattern of cytokeratin (CK) expression in middle ear cholesteatoma and related epithelia. Using monoclonal antibodies specific for CK chains and the indirect immunoperoxidase technique, we examined 10 CK polypeptides for expression. The external stratified squamous epithelium of the tympanic membrane generally expressed CKs 5, 10, and 14. In addition, basal keratinocytes in the annular region of the pars tensa expressed CK 19 (a simple epithelium marker), while suprabasally the hyperproliferative marker CK 16 was expressed. These data reflect the unusual proliferative nature of this region. The unexpected appearance of CK 16 (known to have a limited distribution in healthy epidermis) clearly relates to its expression in the neighboring deep meatus. The medial simple epithelium of the eardrum revealed mucosal CKs 7, 8, 14, 18, and 19. Acquired cholesteatoma lesions, besides CKs 5, 10, and 14, consistently expressed CK 16 in suprabasal layers. These results constitute the first direct molecular evidence for the hyperproliferative nature of the cholesteatoma matrix. Overall, our CK data suggest that aural cholesteatoma lesions and epidermal tissue in this area are related. However, they do not explain the mechanism(s) by which the eardrum or meatal epithelia might invade the middle ear cavity. Congenital cholesteatomas expressed CKs 5, 10, 14, and 16 equally. These CK data do not support the idea of a metaplastic origin from middle ear mucosa; instead, they suggest activation of an ectodermal rest in the middle ear cavity.

Topics: Adult; Cholesteatoma; Ear Diseases; Ear, External; Ear, Middle; Epidermis; Epithelium; Humans; Immunohistochemistry; Keratins; Tympanic Membrane

The position of a cell in a stratified squamous epithelium correlates with its state of differentiation as well as with the expression of certain cytokeratins. By means of both immunohistochemistry using the APAAP method and high resolution one-dimensional gel electrophoresis, specimens of cholesteatoma epithelium and normal ear skin were investigated whether they contain keratin 16 (K 16) which is known to be a marker of hyperproliferation. It could be shown that K 16 is expressed in all layers of cholesteatoma epithelium. Further to prove this fact gel electrophoresis was used showing a protein band at the localization of keratin 16. Hence, cholesteatoma can be seen as a locally hyperproliferative disease.

Topics: Cell Division; Cholesteatoma; Ear Diseases; Ear, Middle; Electrophoresis, Polyacrylamide Gel; Epithelium; Humans; Immunoenzyme Techniques; Keratins

Although cholesteatomas are more commonly found in the middle ear and the mastoid, the disease can occur in the external ear canal. All cases of ear canal cholesteatoma treated by the author were reviewed. There were nine ears in seven patients, who had an average age of 62 years. The lesions ranged in size from a few millimeters to extensive mastoid destruction. Smaller lesions can be managed by frequent cleaning as an office procedure. Larger lesions require surgery, either canaloplasty or mastoidectomy. The otolaryngologist should suspect this disease in the elderly. Microscopic examination of the ear with meticulous cleaning of all wax, especially in elderly patients, is most useful in detecting early disease. Frequent applications of mineral oil to the canal should be used in the management of the disease and to prevent recurrence.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Audiometry; Bone Diseases; Cerumen; Cholesteatoma; Ear Canal; Ear Diseases; Female; Follow-Up Studies; Granulation Tissue; Humans; Keratins; Male; Mastoid; Middle Aged; Mineral Oil

Cholesteatoma of the middle ear is characterized by the presence of hyperproliferative keratinizing squamous epithelium in the middle ear cavity and destruction of adjacent bone. Interleukin 1 (IL-1) is an autocrine growth factor for normal keratinocytes and is capable of inducing bone degradation. The distribution of two molecular species of IL-1, IL-1 alpha and IL-1 beta, was investigated immunohistochemically in the hyperproliferative epithelium of cholesteatoma, in normal epidermis of the auditory canal and of the retroauricular region, and in nonkeratinizing tonsillar epithelium. In all squamous epithelia examined, IL-1 alpha and IL-1 beta were present in comparable amounts. The IL-1 content of cholesteatoma epithelium was clearly increased in relation to normal skin keratinocytes. All cellular layers of cholesteatoma epithelium stained strongly and uniformly for Il-1 alpha and IL-1 beta, whereas the keratin layer was negative for IL-1. No particularly strong reaction with basal cells was detected. In the connective tissue under the squamous epithelium of cholesteatoma, intensely positive cells were scattered between negative stromal cells. Our results suggest that IL-1 could be liberated from disintegrating keratinocytes and cells of the monocyte-macrophage lineage, stimulate the proliferation of the cholesteatoma epithelium in an autocrine manner, and contribute to the enhancement of bone destruction in the presence of cholesteatoma.

Topics: Cholesteatoma; Ear Canal; Ear Diseases; Ear, External; Ear, Middle; Epidermis; Epithelium; Humans; Immunohistochemistry; Interleukin-1; Keratins; Palatine Tonsil

Both the centrifugal keratin dispersion on the pars tensa as well as the centripetal proliferative properties at the inferior annular tympanic region are discussed. There is evidence, histological and clinical, that these features are two distinct and different phenomena which both have clinical implications. While the centrifugal keratin dispersion is a physiological cleaning mechanism, the cytokeratin expression demonstrates the unusual but for years clinically noticed proliferative nature of the lower annular epithelium and provides biochemical evidence for a relationship between this epithelium and cholesteatoma formation.

Topics: Cell Movement; Cholesteatoma; Culture Techniques; Ear Diseases; Epithelial Cells; Humans; Keratins; Rupture; Tympanic Membrane

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.

Topics: Antibodies, Monoclonal; Cholesteatoma; Ear Diseases; Ear, External; Ear, Middle; Epithelium; Humans; Keratins; Staining and Labeling; Tympanic Membrane

The expression of cytokeratins varies with the type of epithelium, the state of differentiation, and pathological conditions. In this study, the differential expression of cytokeratins in external meatal skin and middle ear epithelium was used for a pathogenetic study of cholesteatoma lesions and infection-induced epidermoid formations in the middle ear of the rat. Immunocytochemistry generally revealed an epidermal-type cytokeratin profile in the cholesteatoma matrix, except for the focal expression of nonepidermal cytokeratins at the invasion front. Comparable observations were made in the middle ear of the rat after an infection-induced invasion of epidermal cells from the meatal skin. An infection-induced-cornifying metaplastic lesion of the middle ear epithelium revealed nonepidermal cytokeratin expression. The results of this combined study suggested that the cholesteatoma specimens studied had an epidermal origin. The expression of nonepidermal cytokeratins was considered to result from a state of hyperproliferation rather than from metaplasia.

Topics: Animals; Cholesteatoma; Ear Diseases; Ear, Middle; Epidermis; Epithelium; Eustachian Tube; Humans; Immunoenzyme Techniques; Keratins; Rats; Rats, Inbred Strains

In the majority of individuals, impaction of cerumen in the external auditory canal does not occur, and it is only a fraction of the population who regularly need to consult their physician for aural toilet. In this study we looked at the clinical features associated with recurrent cerumen impaction in 20 individuals. This was complemented by an examination of the cerumen plugs taken from their ears and hydrated to analyze the morphology of the keratin sheets, which had been observed in a previous study to constitute over one-half of the volume of impacted cerumen. In a further eight patients with cerumen, impaction plugs of cerumen were removed and subjected to histological examination. We observed that excessively long sheets of undivided keratin could be isolated from the hydrated cerumen plugs and that these sheets of keratin morphologically resembled the superficial layers of the stratum corneum of normal human deep external auditory canal skin. Based on these observations, we propose that cerumen impaction is the result of a failure in the normal keratinocyte separation which occurs in the superficial external auditory canal.

Topics: Cerumen; Ear Canal; Ear Diseases; Humans; Keratinocytes; Keratins; Recurrence

A histochemical study was performed to determine the involvement of epidermal transglutaminase (ETgase) in the keratinization of middle ear cholesteatomatous lesions, and to compare it with its role in the middle ear mucosa and epidermis. In a first assay, we localized the (E)Tgase activity in situ. A second immunohistochemical assay revealed the distribution of the particulate form of ETgase, which is involved in cross-linked envelope formation. A remarkable difference between strongly keratinized epidermal tissues and the cholesteatoma matrix is the frequent observation in the latter of the remnants of (E)Tgase activity in cytosol, even in advanced stages of differentiation. As a consequence, the cell-membrane-associated ETgase activity, and thus the extent of cross-linking within the envelope, is at a lower level than expected. This aspect is reminiscent of the keratinization phenomenon manifested by thin epidermal tissues. In addition, our findings are the first to show that ETgase is a substantial marker of middle ear mucosa.

Topics: Cholesteatoma; Ear Diseases; Ear, Middle; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Mucous Membrane; Transglutaminases

A histochemical study was performed to clarify further the role played by epidermal transglutaminase (ETgase) in the keratinization of aural cholesteatoma. Weakly and strongly keratinized epidermal tissues and healthy middle ear mucosa were included as references. A first assay revealed the distribution of non-specified acyl donor substrates. In a second assay, the topography of involucrin was assessed immunohistochemically. In both epidermal and cholesteatoma matrix tissues, the presence of acyl donors was not restricted to the sites of (E)Tgase activity, but was almost uniformly extended throughout living layers. In reference tissues, residual acyl donors were poorly detected in horny layers, while they were more abundant in the stratum corneum of the cholesteatomas studied. The presence of involucrin along the cell membrane was observed at varying distances throughout the spinous and granular layers, depending upon the epidermal and matrix configurations. In thick epithelia, involucrin rapidly became concentrated at the cell periphery (in spinous keratinocytes), while in thin epithelia it was usually associated with cell flattening. This latter staining profile was observed more frequently in cholesteatomatous tissues. In addition, we regularly noticed an immediately suprabasal accumulation of involucrin, suggesting a locally hyperproliferative state of the matrix. An insufficient availability of acyl donors, especially involucrin, could not be used to explain the defective ETgase-mediated cross-linking of cholesteatoma cell membranes during terminal stages of differentiation. The present investigation may be the first to demonstrate the presence of involucrin in middle ear mucosa.

Topics: Cholesteatoma; Ear Diseases; Ear, Middle; Humans; Immunoenzyme Techniques; Keratins; Mucous Membrane; Protein Precursors; Transglutaminases

We present a patient with lichen amyloidosus on the ears and macular amyloidosis on the back. These diagnoses were supported by histological, histochemical and immunohistochemical studies. This is to the best of our knowledge the first reported case of a biphasic form of amyloidosis whose lichenoid counterpart consists of papules on the ears. This suggests that primary cutaneous localized amyloidosis may have peculiar clinical manifestations depending on the location of the lesion.

Topics: Amyloidosis; Ear Diseases; Ear, External; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Skin Diseases

An indirect immunofluorescent method with monoclonal anti-cytokeratin antibodies was used to localize various cytokeratins in human middle ear cholesteatoma. The 50 K/58 K and 56.5 K/65-67 K paired cytokeratins are markers of skin type and were found in the specimens of human middle ear cholesteatomas studied. In contrast, the 40 K and 45 K cytokeratins (markers of simple epithelia), the 48 K cytokeratin (marker of hyperproliferative epidermal disease) and the 51 K cytokeratin (marker of internal organ epithelia) were absent in human middle ear cholesteatoma. These findings indicate that the pattern of cytokeratins in human middle ear cholesteatoma is similar to that of skin but is different from those of simple epithelium, internal organ epithelia, and hyperproliferative epidermal disease. These findings also support the skin type epithelial origin of cholesteatoma and strongly favor the migration theory in the genesis of cholesteatomas.

Topics: Antibodies, Monoclonal; Cholesteatoma; Ear Diseases; Ear, Middle; Epithelium; Fluorescent Antibody Technique; Humans; Keratins

Specimens of cholesteatoma matrix, meatal epidermis, and middle ear epithelium were removed during surgery, and immunohistochemical techniques were used to investigate cytokeratin expression. The use of five chain-specific anticytokeratin monoclonal antibodies and one broad specific anticytokeratin monoclonal antibody showed the divergent behavior of middle ear epithelium compared with the cytokeratin expression of the other two types of epithelium. Middle ear epithelium was characterized by the presence of cytokeratins 4, 8, 18, and 19, whereas in both cholesteatoma and meatal epidermis cytokeratin 10 predominated. Furthermore, cholesteatoma showed an infrequent focal presence of cytokeratins 4, 18, and 19. The similarity between cholesteatoma and meatal epidermis with respect to morphology, and the presence of cytokeratin 10 support an epidermal origin of cholesteatoma. However, a metaplastic origin cannot be excluded, because of the infrequent occurrence of a small amount of cytokeratins 4, 18, and 19 in cholesteatoma matrix that was not found in meatal epidermis but was a component of the cytokeratin pattern of middle ear epithelium.

Topics: Antibodies, Monoclonal; Cholesteatoma; Ear Canal; Ear Diseases; Ear, Middle; Epidermis; Epithelium; Humans; Immunohistochemistry; Keratins

The accumulation of desquamated keratinizing squamous epithelial cells appears to be a crucial factor in the pathogenesis of middle ear cholesteatomas. The accumulation of keratin debris is due to the proliferation and the terminal differentiation of basal keratinocytes. Since cholesteatomas are usually associated with inflammatory reactions in the middle ear cavity, we examined the effects of a granulation tissue conditioned medium on the terminal differentiation of basal keratinocytes in vitro. This conditioned medium stimulated the terminal differentiation of basal keratinocytes by showing: (a) increased incorporation of 3H-leucine into cell envelopes; (b) an increased number of SDS-insoluble cell envelopes; and (c) increased transglutaminase activity (as a marker for terminal cellular differentiation). Our present studies further suggest that inflammatory granulation tissue plays an important role in the clinical growth and development of the cholesteatoma.

Topics: Animals; Cell Differentiation; Cholesteatoma; Culture Media; Ear Diseases; Epidermis; Granulation Tissue; Keratins; Rats; Rats, Inbred Lew

Amniotic fluid cellular content (AFCC), especially keratinized, non-nucleated squamous epithelial cells and lanugo hair, have been detected in the fetal and neonatal ear. We wished to evaluate the incidence, amount and histological findings of AFCC in the neonatal and early infant period. Temporal bones (n = 63) from children aged 10 min to 70 days were examined. AFCC was discovered in 39 of 43 bones in neonates. In children of 31-70 days of age, AFCC was present in 11 of 20 bones. A measurement of the amount of AFCC was performed; the maximum was 11.47 mm3 with a mean of 2.40 mm3. Histological findings varied from the mere presence of AFCC to the formation of epithelialized granulation tissue. This granulation tissue was found in 19 of the bones. Theoretical clinical implications are considered for middle ear adhesions, otitis media and cholesteatoma.

Topics: Amniotic Fluid; Child, Preschool; Cholesteatoma; Ear Diseases; Ear, Middle; Epidermal Cells; Epithelium; Foreign-Body Reaction; Granulation Tissue; Hair; Humans; Infant; Infant, Newborn; Keratins; Otitis Media; Skin; Temporal Bone; Tissue Adhesions

Topics: Animals; Chickens; Cholesteatoma; Ear Diseases; Ear, Middle; Germ Cells; Humans; Keratins; Mucous Membrane; Phenotype; Skin; Skin Physiological Phenomena; Vitamin A

Topics: Acetylcysteine; Acid Phosphatase; Alkaline Phosphatase; Cholesteatoma; Ear Diseases; Humans; Keratins; Microbial Collagenase

For the extraction of soft keratins from bovine snout or human epidermis the best results were obtained with a detergent (sodium dodecyl sulphate, SDS) or hydrogen bond breaking agent (urea) in a reducing medium (2-mercaptoethanol, 2-ME). N-acetylcysteine was a little less effective. Keratins from both sources gave typical sets of protein bands with molecular weights between 40.000 and 70.000 daltons. Upon electrofocusing special precautions had to be taken to avoid reoxidation and reaggregation of protein subunits. Keratins from aural cholesteatomas were obtained by extraction with SDA and 2-ME, with N-acetylcysteine alone and to a lesser extent with urea and 2-ME. The pattern of these keratins on SDS-gel is less complicated than that obtained from human skin or bovine snout. Histophotometric results argue for a clear analogy between the nuclear DNA metabolism in normal skin epidermis and cholesteatoma matrix. The only differences of potential relevance are the much wider range of the nuclear DNA amount in cholesteatoma stratum basale cells compared with basal cells in normal epidermis, and the higher persistence of nuclear DNA in cholesteatoma stratum granulosum, indicating postponement of keratinocyte terminal differentiation.

Topics: Animals; Cattle; Cholesteatoma; DNA; Ear Diseases; Epithelium; Humans; Keratins; Nose; Proteins

An attic cholesteatoma is defined as an epidermoid cyst found in the attic. This is differentiated from an infected retraction pocket of the pars tensa or a retraction pocket cholesteatoma. Stratified squamous epithelium may also be present in the middle ear as other clinical or pathological entities, such as metaplastic islands of the mucosa in chronic ears with central perforations. Histological examination of 22 temporal bones with attic cholesteatomas has shown them to reside mainly medial to the ossicular chain. This explains the difficulty they have in self-cleansing, as well as the ensuing secondary infection. When a similar process occurs lateral to the ossicles, a self-cleansing nature's atticotomy may be formed. The aetiology of an attic epidermoid cyst, i.e., an attic cholesteatoma, is usually considered to be an invasive retraction from the external ear. However, it is difficult to accept invasion of external canal skin into the upper medial attic. This is especially so in the face of such biological phenomena as epithelial contact inhibition, or the invariable outward migration of stratified squamous epithelium from the edges of retraction pockets as well as from cholesteatoma perforations. Also, large cholesteatomas usually present themselves from the "beginning" simultaneously with their perforations; no documentation of an evolving process from a pre-existing perforation exists at present. Marginal perforations, which have later evolved into attic cholesteatomas have so far not been documented. On the other hand, retraction pockets of the pars tensa or pars flaccida associated with some middle ear negative pressure do occur, however, it is yet to be shown that such retractions can reach the medial part of the ossicular chain and form epidermoid-like cysts there. Therefore, the possibility that an attic cholesteatoma often arises primarily in the attic and presents itself secondarily in the external canal as a "perforated" epidermoid cyst, is to be considered. The possibility that a congenital rest is responsible for such an epidermoid cyst has often been put forward, but evidence that such rests actually exist has not yet been presented. The frequency with which cholesteatoma sacs found in the attic show mucosal cells as part of their lining, suggests a metaplastic phenomenon. This means that the epithelial cells of the middle ear lining may have changed from mucosal into keratinizing cells (or even vice versa). Metaplastic changes of muco

Topics: Cholesteatoma; Ear Diseases; Epidermal Cyst; Epithelium; Eustachian Tube; Humans; Keratins; Metaplasia; Mucus; Temporal Bone; Tympanic Membrane

In a collection of 1,100 operated ears, 426 of which had cholesteatoma and 674 had not, the various defects of the ossicular chain are described and related to the nature of the disease and the site of perforation. The analysis showed marked differences between the various diseases and in the frequency of the individual ossicular defects or combinations of defects. Defects of the head of the malleus and of the body of the incus were found exclusively in chiolesteatomas, most often those affecting the attic. Isolated defects of the malleus handle were most common in cholesteatoma of the parts tensa and in total perforations. Defects of the long process of the incus occurred in 74--88 per cent of cholesteatomatous diseases, defects of the stapedial arch in 47 per cent of ears with sinus cholesteatoma. In granulating otitis without cholesteatoma and in sequelae to otitis there was less ossicular pathology, and 57 per cent of these ears had an intact ossicular chain. Total or posterior perforations were associated with pathology of the ossicles more often than inferior or anterior perforations. All cases with destruction of the body of the incus and the head of the malleus showed squamous epithelium in close relation to the ossicular defect, indicating a marked--presumably enzymatic--influence by the squamous epithelium upon the bone resorption.

Topics: Bone Resorption; Cholesteatoma; Chronic Disease; Ear Diseases; Ear Ossicles; Ear, Middle; Epithelium; Humans; Keratins

Two patients who had undergone radical mastoid surgery developed an isolated focus of cholesteatoma embedded in the sternomastoid muscle just below the mastoid tip. In one instance the etiology was felt to be iatrogenic implantation of squamous epithelium. In the second, unrecognized extension from the mastoid tip probably occurred. The purpose of this paper is to describe and discuss in detail the clinical and pathological features of these two cases.

Topics: Adolescent; Aged; Cholesteatoma; Connective Tissue; Ear Diseases; Epithelium; Female; Humans; Keratins; Male; Mastoid

In a study of the behavior of the keratin layer of the drumhead epidermis in some otologic conditions, a marker dye was applied to the tympanic membrane, and migration and/or desquamation of the dotted spots observed. Decelerated migration with desquamation in situ was observed during the quiescent phase of recurrent otitis externa, with or without myringitis. The same findings were observed in most cases of chronic secretory otitis media and its sequelas (retraction pockets, atrophic membranes, and scarring). The remnants of drumhead with keratotic and hyperplastic changes in the middle ear cleared themselves of the dye very slowly.

Topics: Adolescent; Adult; Aged; Child; Ear Diseases; Humans; Inflammation; Keratins; Middle Aged; Otitis Externa; Otitis Media; Skin; Tympanic Membrane

The structure of middle ear cholesteatoma obtained at surgical interventions in 12 patients was investigated by light and electron microscopy. Keratinizing squamous epithelium with underlying granulomatous, partly necrotic tissue showing signs of an acute or chronic inflammatory reaction was observed. Cholesterol clefts were only observed in two specimens in which a chronic hemorrhage was present. It is proposed that a cholesteatoma starts by immigration of epidermal tissue from the tympanic membrane. Destruction of the middle ear components and of the neighboring osseous walls results from invasion of squamous epithelium, underlying necrotizing connective tissue, and keratin.

Topics: Cholesteatoma; Ear Diseases; Ear, Middle; Epithelial Cells; Epithelium; Humans; Keratins

Topics: Administration, Topical; Anti-Inflammatory Agents; Colistin; Ear Canal; Ear Diseases; Ear Neoplasms; Granuloma; Hydrocortisone; Keratins; Neomycin; Otitis Externa; Polyps; Quaternary Ammonium Compounds

Topics: Alkaline Phosphatase; Cholesteatoma; Cysteine; Ear Diseases; Epithelium; Glycerophosphates; Histocytochemistry; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Iodoacetates; Keratins; Phosphatidylcholines; Skin Diseases; Sulfhydryl Compounds

Topics: Bone and Bones; Cholesteatoma; Chronic Disease; Ear Diseases; Ear Ossicles; Epithelium; Granulation Tissue; Humans; Keratins; Mucus; Otitis Media

Topics: Adolescent; Child; Chronic Disease; Ear Diseases; Female; Humans; Keratins; Male; Middle Aged; Otitis