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Hypothesis: We sought to determine whether vestibular schwannomas are capable of producing and responding to the glial growth factor neuregulin., Background: Neuregulin is a neuronally derived trophic factor that interacts with erbB2 and erbB3 receptors on Schwann cells and is required for normal Schwann cell proliferation, survival, and development. Vestibular schwannomas grow several millimeters or even centimeters away from adjacent axons, suggesting that vestibular schwannomas do not depend critically on axons for their proliferation or survival. This raises the possibility that vestibular schwannomas themselves produce and respond to trophic factors in an autocrine fashion., Methods: Pathologic specimens from eight patients undergoing microsurgical removal of vestibular schwannomas and one patient undergoing vestibular nerve section were immunostained with anti-neuregulin, anti-erbB2, anti-erbB3, and anti-phosphorylated-erbB2 antibodies. Three patients had received previous gamma knife radiation therapy and two patients had neurofibromatosis Type 2., Results: The Scarpa ganglion neurons express neuregulin, and normal vestibular Schwann cells express erbB2 and erbB3. Vestibular schwannomas from all eight patients demonstrated neuregulin, erbB2, and erbB3 immunoreactivity. In addition, all vestibular schwannomas demonstrated immunoreactivity to anti-phosphorylated-erbB2 antibody that only recognizes erbB2 when it is phosphorylated, or activated., Conclusion: These results demonstrate that vestibular schwannomas express neuregulin and its receptors, erbB2 and erbB3. Because erbB2 exists in an activated state, as evidenced by phosphorylated-erbB2 immunoreactivity, it likely responds to the locally produced neuregulin. This suggests the possibility that vestibular schwannomas produce and respond to neuregulin in an autocrine fashion.

"Primary" ear and temporal bone meningiomas are tumors that are frequently misdiagnosed and unrecognized, resulting in inappropriate clinical management. To date, a large clinicopathologic study of meningiomas in this anatomic site has not been reported. Thirty-six cases of ear and temporal bone meningiomas diagnosed between 1970 and 1996 were retrieved from our files. Histologic features were reviewed, immunohistochemical analysis was performed (n = 19), and patient follow-up was obtained (n = 35). The patients included 24 females and 12 males, aged 10-80 years (mean, 49.6 years), with female patients presenting at an older age (mean, 52.0 years) than male patients (mean, 44.8 years). Patients presented clinically with hearing changes (n = 20), otitis (n = 7), pain (n = 5), and/or dizziness/vertigo (n = 3). Symptoms were present for an average of 24.6 months. The tumors affected the middle ear (n = 25), external auditory canal (n = 4), or a combination of temporal bone and middle ear (n = 7). The tumors ranged in size from 0.5 to 4.5 cm in greatest dimension (mean, 1.2 cm). Radiographic studies demonstrated a central nervous system connection in 2 patients. Histologically, the tumors demonstrated features similar to those of intracranial meningiomas, including meningothelial (n = 33), psammomatous (n = 2), and atypical (n = 1). An associated cholesteatoma was identified in 9 cases. Immunohistochemical studies confirmed the diagnosis of meningioma with positive reactions for epithelial membrane antigen (79%) and vimentin (100%). The differential diagnosis includes paraganglioma, schwannoma, carcinoma, melanoma, and middle ear adenoma. Surgical excision was used in all patients. Ten patients developed a recurrence from 5 months to 2 years later. Five patients died with recurrent disease (mean, 3.5 years), and the remaining 30 patients were alive (n = 25, mean: 19.0 years) or had died (n = 5, mean: 9.5 years) of unrelated causes without evidence of disease. We conclude that extracranial ear and temporal bone meningiomas are rare tumors histologically similar to their intracranial counterparts. They behave as slow-growing neoplasms with a good overall prognosis (raw 5-y survival, 83%). Extent of surgical excision is probably the most important factor in determining outlook because recurrences develop in 28% of cases.

Background: Squamous cell carcinomas of the head and neck region (HNSCC) are among the most common malignancies in this area. The VX2 carcinoma of the New Zealand white rabbit metastasizes lymphatically as is the case in HNSCC and therefore, potentially, could be used as a model for HNSCC. Since the family of matrix-metalloproteinases (MMPs) is involved in the process of HNSCC invasion, the aim of this study was to investigate the expression level of MMPs and their specific inhibitors (TIMPs) in the VX2 carcinoma to evaluate if they also play a role in VX2 tumor invasion as observed in human HNSCC., Materials and Methods: The VX2 carcinoma was generated by tumor implantation in the rabbit's ear as previously described. Western blots were performed under standard conditions, utilizing antibodies against MMP-3, MMP-13, TIMP-2 and TIMP-3. Immunohistochemical staining was performed with the ABC-complex method., Results: A positive immunohistochemical signal could be detected for MMP-3, TIMP-2 and TIMP-3 with no significant signal for MMP-13. In the Western blots immunoreactive bands could be observed for MMP-3, MMP-13, TIMP-2 and TIMP-3., Conclusion: MMP-3, MMP-13, TIMP-2 and TIMP-3 were found to be expressed in VX2 carcinomas of the New Zealand white rabbits. The VX2 carcinoma therefore resembles HNSCC tumors not only in its metastatic behavior, but also regarding the expression of MMPs and TIMPs, which are the probable keyplayers during the event of invasion. These observations further underline the significance of the VX2 carcinoma as a model tumor of human HNSCC.

Aims: To investigate the role of the tumour suppressor gene PTEN in the tumorigenesis and growth of sporadic vestibular schwannomas, and to characterize the cellular distribution of the PTEN protein in relation to the MIB-1 proliferation index in these tumour., Methods and Results: Immunoexpression of the PTEN protein was observed within the neoplastic Schwann cells in 21 out of 30 sporadic schwannomas examined (70%). PTEN expression was consistently stronger in Antoni A areas than in Antoni B areas. High levels of PTEN immmunoexpression in schwannomas were associated with an increased MIB-1 labelling index. Occasionally, vascular endothelial cells also showed PTEN immunoreaction. By polymerase chain reaction-single strand conformation polymorphism screening, no mutations were found in the complete protein coding region of the PTEN gene., Conclusions: The PTEN tumour suppressor gene is expressed in the majority of sporadic schwannomas. The maintained expression of the PTEN protein, together with the lack of detectable mutations in this gene, suggests that the function of the PTEN tumour suppressor gene is not altered in sporadic vestibular schwannomas.

Background: Kaposiform hemangioendothelioma is an uncommon vascular tumor initially reported to occur exclusively in children., Methods: The presentation, pathologic evaluation, and management of an unusual case of kaposiform hemangioendothelioma is presented and discussed., Results: A 27-year-old HIV-negative man was initially seen with a reddish nodule located in the outer third of the external auditory canal. Histologically, the tumor was composed of spindle-shaped cells arranged in short fascicles associated with small endothelial-like vascular spaces, similar in appearance to Kaposi's sarcoma. The lesion was locally excised but recurred 1 month later; then radiation therapy was performed. The patient remains well at 5-year follow-up., Conclusions: Recognition of kaposiform hemangioendothelioma is important to avoid possible confusion with a variety of vascular neoplasms with different biologic potential. This case presented some diagnostic difficulty because of the age of the patient and the unusual location of the lesion and had to be mainly distinguished from Kaposi's sarcoma., (Copyright 2002 Wiley Periodicals, Inc.)

Carcinoid tumors and adenomas of the middle ear are rare neoplasms of indeterminate relationship to one another. Indeed, the literature is devoid of a large comprehensive series that evaluates the clinical, histologic, and immunophenotypic features of these tumors and their potential relationship. Forty-eight cases of middle ear adenoma between 1970 and 1995 were identified in the files of the Armed Forces Institute of Pathology. All cases were evaluated for cytomorphology and architectural pattern, in addition to their reactivity with various immunohistochemical reagents. Clinical follow-up was also obtained. A comprehensive review of the literature was performed with an eye toward correlating any distinct differences or similarities between carcinoid tumors and adenomas of the middle ear. The patients included 21 women and 27 men, aged 20 to 80 years (mean, 45.0 y). Patients experienced hearing loss, mass, and/or pain for a mean duration of 1.7 years. The mean tumor size was 0.8 cm, with six tumors extending beyond the middle ear. Histologically, the tumors were moderately cellular and unencapsulated, arranged in glandular, trabecular, and solid patterns composed of small cells with "salt and pepper" nuclear chromatin distribution. The tumor cells were immunoreactive with keratin, keratin 7, chromogranin, and human pancreatic polypeptide. All patients had surgery. No patients died with their disease (mean follow-up, 15.7 y). Eight patients developed recurrences that were treated surgically and were without evidence of disease at last follow-up (mean, 15.1 y). Our study and the review of the literature showed adenomas and carcinoid tumors of the middle ear to be essentially indistinguishable benign tumors. Middle ear adenoma most correctly describes their morphologic features and clinical behavior, although neuroendocrine adenoma of the middle ear may be a more accurate designation.

Low-grade adenocarcinoma arising from the endolymphatic sac is an uncommon tumor that is characterized clinically by hearing loss and radiologically by temporal bone destruction. The authors report a case of low-grade adenocarcinoma of endolymphatic sac origin that mimicked a posterior fossa meningioma in both clinical and neuroimaging examinations. In this case, the most unusual and interesting feature was the lack of auditory symptoms and temporal bone destruction. The lesion occurred in a 21-year-old man who presented with headaches that had been increasing in frequency for 6 months and was associated with blurring of vision, diplopia, occasional nausea and vomiting, and gait disturbance. On examination, this patient exhibited bilateral papilledema, left sixth cranial nerve palsy, and gait ataxia. Neuroimaging studies revealed a large right posterior fossa tumor. At surgery, a hemorrhagic papillary adenocarcinoma of endolymphatic sac origin was found.

The authors report a case of endolymphatic sac tumor (ELST) associated with Von Hippel-Lindau disease (VHL). A 20-year-old female VHL patient received a resection of a cerebellar hemangioblastoma 3 years ago and she had a co-existing of left petrous tumor. The petrous tumor showed a remarkable progression in 3 years and was resected subtotally. Histologically, the resected petrous tumor showed a papillary structure containing cuboidal or columnar cells with fibrous stroma and numerous microvessels and destructed temporal bone, all of which are consistent with ELST. We studied the expression of various kinds of cytokeratins (CKs) immunohistochemically and found distinct expression of CKs (CAM 5.2, 34betaE-12, CK7, CK8 and CK19), but not for CK10/13 or CK20. Vascular endothelial growth factor and neuron specific enolase showed strong immunoreactivity in the tumor cells. CD34 also had weak expression. Ki-67 antigen (MIB-1) immunoreactivity was found in focal areas, and the labeling index in the highest-density area was 48.9%. These findings suggest that vascular endothelial growth factor overexpression is an important factor for angiogenesis in ELST, much like other VHL-associated tumors, and that ELST may have a more highly aggressive component than the low-grade malignancy noted in previous reports.

We have previously described a line of transgenic mice (TG3) that spontaneously develops heritable malignant melanoma. Histological analysis of these animals during the first postnatal month is described here. In the TG3 line, the number of melanocytes is increased at all anatomical sites to which neural-crest-derived melanocytes normally migrate. Clonal expansion and morphological changes of these melanocytes can be detected as early as postnatal day (PND) 15. By PND 30, cells morphologically indistinguishable from the tumor cells of adult transgenic mice were detected in the ear, eye lid and perianal region. These cells are believed to be the precursors of the primary tumors in adult mice. The stepwise development of melanoma in the TG3 line is similar to the stepwise development of melanoma in humans.

The lining of the middle ear cleft is normally a thin modified respiratory type mucosa. Normal mucosa of the middle ear is devoid of salivary type seromucous glands. Middle ear adenoma is a rare tumor that seems to be derived from the middle ear mucosa. This tumor has been previously described under a variety of names because of its different nature and biological behavior. We herein report a case of middle ear tumor that shows adenomatous and neuroendocrine features. A 64-year-old woman presented with a history of hearing loss, tinnitus and stuffy feeling of the right ear. The patient was treated two times for ear polyp. She finally underwent a tympanomastoidectomy and there was no evidence of recurrence 18 months after the procedure. Histopathological examination displayed cuboidal and columnar cells, arranged as glands, trabeculae and solid sheets. Neuroendocrine differentiation was revealed by immunohistochemical staining with polyclonal antibodies against neuron specific enolase and chromogranin antigens.

A case of pigmented squamous cell carcinoma (SCC) with dendritic melanocyte colonization in the external auditory canal is reported and the previous cases are reviewed. A 65-year-old Japanese female was referred with a 7-year history of otitis. The patient also had a darkly pigmented 9 x 8 mm nodule in the external auditory canal. Microscopically, the tumor was SCC, but in some areas melanin pigments were found in the cytoplasm of the tumor cells. The tumor was thus diagnosed as pigmented SCC. As well as the tumor cells, dendritic-shaped cells colonized the tumor parenchyma and were immunohistochemically defined as melanocytes. The authors believe this is the first case of pigmented SCC with dendritic melanocyte colonization in the external auditory canal.

A primary adenomatous tumor of the middle ear was examined by light microscopy, ultrastructural and immunohistochemical techniques. In support of its extensive neuroendocrine differentiation, was the diffuse detection of neuron-specific enolase (NSE) and positive immunoreaction with antibodies to chromogranin and synaptophysin. The great majority of tumor cells contained neurosecretory granules and intraluminal mucin production could be focally detected. These characteristics confirm the diagnosis of a middle ear adenomatous tumor (MEAT) of a biphasic nature and with a prominent neuroendocrine component.

Primary cultures were established from vestibular schwannomas of NF2 patients. The cultured tumor cells were selectively amplified by growth factor supplemented medium and characterized by immunocytochemistry. NF2 cDNA was amplified by RT-PCR and mutations were detected by both the non-isotopic RNase cleavage assay and direct DNA sequencing, no detectable wild-type NF2 transcript was found in cDNA from the cultured cells. Distinguishable morphology and growth rate differences have been observed in different passages of the primary cells. The data suggest that a pure schwannoma primary culture can be established and could be very useful in vitro model for further understanding the NF2 gene function in Schwann cells.

Hypothesis/background: The mucoperiosteal lining of the middle ear cavity is subject to radical changes during and after acute infection. Among these is the formation of mucosal polyps. Previous studies on experimental acute otitis media have shown a marked impact of penicillin on mucosal histomorphology. This study reports on the effect of penicillin administration on polyp formation., Methods: The mucosa of 75 rat middle ears in a model of acute otitis media was examined. Whole-mount and section preparations from 25 normal ears, 25 ears inoculated with Streptococcus pneumoniae, and 25 inoculated, penicillin-treated ears were inspected for number, size, anatomic localization, and histopathologic morphology of occurring polyps., Results: The total number of polyps was unaffected by penicillin administration, although polyps occurred in fewer ears. The polyps from treated ears tended to be smaller and stalky, appeared later in the timespan covered, and often were located around the tubal orifice. Histopathologic morphology of polyp base, core, and epithelial covering was otherwise unaffected by penicillin., Conclusions: Administration of penicillin has inconspicuous effect on the formation of polyps in experimental otitis media caused by S. pneumoniae in contrast to a marked impact on mucosal goblet cell density and other histopathologic features reported in previous studies.

We report the case of a 41-yr-old woman who presented with arterial hypertension and tinnitus in the right ear synchronous with pulse. She had previously undergone surgery for suspected pheochromocytoma without positive therapeutic effect. CT and MRI revealed a homogenous tumor with contrast enhancement in the right hypotympanon and foramen jugulare, and [123I]metaiodobenzylguanidine (MIBG) scintigraphy demonstrated strong tracer uptake in the same area. Selective venous sampling of catecholamines in the ipsilateral jugular vein confirmed the tumor to have originated from hormone production.

Increased levels of 5-hydroxyindole acetic acid (5-HIAA) were found in a patient with a tumor arising in the middle ear. Iodine-123-metaiodobenzylguanidine ([123I]MIBG) scintigraphy and biochemical analysis showed evidence of serotonin production by the tumor. Immunohistochemistry of the tumor showed reactivity with antibodies directed against serotonin, chromogranin, leu-7 and neuron-specific enolase; S-100, met-enkephalin, leu-enkephalin and glial fibrillary acid protein were negative. This case suggests a close relationship between functioning paragangliomas and carcinoid tumors because a strong clinical and endocrinological resemblance exists. The hormonal activity found is discussed in relation to extra-adrenal paragangliomas. We recommend urinary screening not only for detection of increased levels of catecholamines, but also of 5-HIAA in all patients with paragangliomas of the head and neck. When elevated levels are found, [123I]MIBG scintigraphy should be performed to localize the areas of increased uptake in or outside the head and neck region.

The immunocytochemical analysis of two cases of well-differentiated endocrine tumours (carcinoids) of the middle ear revealed predominant cell populations producing pancreatic polypeptide (PP)-related peptides, glucagon-related peptides, and serotonin (the latter only in one case). In consecutive sections PP- and glucagon-related immunoreactivities mainly colocalized in the same tumour cells. Ultrastructurally tumour cells were characterized by medium-sized to large granules of moderate to high density, on which PP and glicentin were localized by the immunogold technique. No amphicrine cells were found. These features are consistent with those of similar tumours in the rectal mucosa that are mainly composed of L cells coexpressing both PP-related and glucagon-related peptides. Additional tumour antigens of hindgut type detected immunohistochemically were prostatic acid phosphatase and CAR-5 mucin. Expression of the CAR-5 antigen was also found in samples of normal middle ear mucosa, in which endocrine cells have not been identified. In case 1 peritumoral mucosal invaginations showed a proliferation of endocrine cells identical immunophenotypically to tumour cells, possibly representing a precursor lesion. It is concluded that well-differentiated endocrine tumours of the middle ear are a distinct pathological entity characterized by multiple hormone production, typically involving three classes of hormones (pancreatic polypeptide-related peptides, glucagon-related peptides, and serotonin) of the hindgut endocrine system.

A 69-year-old man complaining of longstanding hearing loss and mild otorrhea was found to have a mass obliterating the external auditory canal and polypous tympanic mucosa with accompanying absence of the tympanic membrane and ossicular chain. Tumors excised from the external auditory canal and tympanum showed histologic features essentially characteristic of a carcinoid tumor: a ribbon or festoon arrangement of tumor cells, formation of anastomosing cords and glandular spaces, presence of numerous argyrophilic as well as argentaffin secretory granules within many of the tumor cells, and ultrastructural evidence of neurosecretory granules in the tumor cell cytoplasm. Immunohistochemically, the tumor was found to contain not only neuronal marker substances such as neuron-specific enolase, S-100 protein and chromogranin A, but also serotonin and multiple peptide hormones such as pancreatic polypeptide, glucagon, cholecystokinin and leucine-enkephalin. A review of the pathology of 17 previous cases of carcinoid of the middle ear suggested that this type of carcinoid may have a variegated hormone profile among carcinoids of foregut origin, and hormonally may resemble ileal carcinoid arising from the midgut, although their histogenetic origins may differ, because of frequent production of serotonin.

The peroxidase-antiperoxidase method was used to quantify immunoglobulin (Ig)-containing cells at the host-tumour interface in ovine aural squamous cell carcinoma lesions at various stages of development. IgM-containing cells were never observed; only scattered, but strongly staining, IgA-containing cells were present. IgG-containing cells predominated; their prevalence increased from 0.17 +/- 0.34 cells per high power field (hpf; mean +/- standard deviation) in precursor lesions to a maximum of 13.6 +/- 2.6 cells per hpf in overt tumours which had not metastasized. Their prevalence in overt tumours which had metastasized was 4.6 +/- 3.9 cells per hpf. Quantitation of pyroninophils in sections stained by the methyl green-pyronin method showed a greater prevalence of plasma cells than IgG-containing cells, but a similar pattern of change was apparent. Mast cells were most prevalent in early stages, but no significant change in eosinophil numbers was observed.

We report 6th case of carcinoid tumor of the middle ear in a 16-year-old man. The clinical, histologic, immunohistochemical and ultrastructural features are discussed. The tumor in the attic and the tympanic cavity was successfully excised by radical mastoidectomy. Microscopically, the argyrophilic property and neurosecretory granules which are characteristic of carcinoid tumor were found in the cytoplasm of tumor cells. Furthermore, peptide hormones were confirmed immunohistochemically in this case. This tumor should be considered in the differential diagnosis when biologically lowgrade tumor with glandular and trabecular architectures are encountered in the middle ear.

Seven patients with middle ear adenomas (MEA) are presented. MEA are cytologically stereotyped neoplasms with a spectrum of architectural patterns. All tumors were composed of uniform, round, or ovoid cells that resembled normal middle ear epithelium. The histologic patterns varied from tumor to tumor and within a single lesion. Broad sheets of tightly packed cells were commonly present, but glandular and cribriform areas were also frequent. Complex, interdigitating trabeculae, rows of individual cells, and dissociated cells were sometimes seen. Grimelius argyrophil stains were focally positive in three of five stained tumors, but Churukian-Schenk argyrophil preparations demonstrated only rare positive cells in two of these cases. Lysozyme was demonstrable immunohistochemically in each tumor. Lysozyme is present in normal middle ear epithelium and may be a useful marker for MEA, since the tumor is apparently derived from these cells. The clinical features of the seven cases that we report are combined with 44 MEA from the literature. MEA seldom recurs after excision and very rarely invades bone. No patient died of disease. The clinical and histologic distinction of these tumors from plasmacytoma, paraganglioma, ceruminoma, carcinoid tumor, and papillary carcinoma is discussed.

Primary carcinoid tumours of the middle ear are extremely rare, only nine cases having been reported. However, their true incidence is probably greater, since they are very difficult or impossible to distinguish from adenomas and adenocarcinomas with conventional histological stains. We describe the clinical, histological, immunohistochemical and ultrastructural findings in a carcinoid tumour of the middle ear in a 50-year-old woman. Immunohistochemical studies on non-neoplastic middle ear mucosa undertaken to investigate the histogenesis of such tumours are also reported. Histologically, the tumour consisted of both solid areas and areas of tubular structures containing intraluminal mucus. All the tumour cells reacted with the anti-keratin antibody KL 1; some were argyrophil and reacted with antibodies against neuron-specific enolase, chromogranin A, Leu-7, serotonin, pancreatic polypeptide, glucagon and lysozyme. Electron microscopy revealed dense core granules in the tumour cells. Endocrine cells could not be detected in non-neoplastic middle ear mucosa. Pancreatic-polypeptide-like immunoreactivity was demonstrated immunohistochemically in all three other published cases of carcinoid tumour of the middle ear investigated for this peptide, and glucagon-like immunoreactivity was also exhibited by one of these. Since carcinoid tumours of the middle ear often, as in this case, exhibit some degree of glandular differentiation, immunohistochemical or electron-microscopic investigation to detect neuroendocrine differentiation is of particular importance in adenomatous middle ear neoplasms.

A primary tumor of the middle ear was examined histologically, histochemically, immunohistochemically and ultrastructurally. Neuroendocrine cell differentiation, a carcinoid feature, was demonstrated by the presence of numerous argyrophil granules, as well as positive serotonin, glicentin, glucagon, and human pancreatic polypeptide (hPP) granules in some of the Grimelium-positive cells. Chromogranin A was also detected in the cells, but much less frequently than Grimelius-positive staining. Neither neuron-specific enolase (NSE) nor epithelial membrane antigen (EMA) was demonstrated in the tumor. Mucin was demonstrated only intraluminally. Electron microscopy revealed many typical neurosecretory granules in tumor cells, but no apical mucin granules. The tumor appeared to be benign, and there has been no sign of recurrence during a postoperative period of one year.

The aim of this study was to culture keratinocytes from migratory skin and from cholesteatomatous matrix. At operation, cholesteatomatous matrix, normal drumhead and non-migratory stratifying skin from the extrameatal incision were obtained. Successful cultures of keratinocytes were produced in 4 out of 5 attempts. The cholesteatomatous keratinocytes produced slower growing colonies with an abnormal pattern of keratinization, whereas the drumhead produced rapidly growing colonies with a more regular pattern of keratinization, similar to those obtained from a vertically stratifying epidermis. This method may offer new fields of study in the investigation of cholesteatoma.

In order to study the manifestation and genesis of cholesterol deposits in the temporal bone and the paranasal sinuses, 137 temporal bones and 3 paranasal sinuses with deposits were examined. For histological study, 1036 specimens were obtained from temporal bones, and 16 specimens were obtained from paranasal sinuses. Several stages of a progressive foreign body reaction, including the appearance of histiocytes, granuloma formation and the development of granulation into scar tissue, were observed depending on the size and form of the crystals. Many large deposits were found in the temporal bones of patients with chronic non-suppurative lesions. Blue eardrum and hemotympanum were seen in the last stage of this foreign body reaction in these patients. Small deposits were found in the temporal bones and the paranasal sinuses of patients with chronic suppurative lesions. Most of these deposits were found in the obstructed parts. The pathogenesis of the cholesterol deposits is suspected to be fatty degeneration of the connective tissue.