The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Petra Schmalbrock - One of the best experts on this subject based on the ideXlab platform.
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Submillimeter Magnetic Resonance Imaging of the Temporal Bone in Meniere's Disease†‡
Laryngoscope, 1996Co-Authors: D. Bradley Welling, Petra Schmalbrock, Donald W Chakeres, Mark W. Clarkson, Beth A. Miles, Philip M. Williams, M C OehlerAbstract:The pathoetiology of Meniere's disease remains elusive. Histopathologic and imaging studies have implicated congenital or developmental abnormality of the Endolymphatic Duct as a likely predisposing factor to the development of Endolymphatic hydrops and clinical Meniere's disease. Recently, improved high-resolution magnetic resonance imaging (MRI) protocols have allowed better demonstration of the soft tissues of the Endolymphatic Duct and sac. This study is a prospective evaluation of the ability of submillimeter MRI to detect the Endolymphatic Duct in Meniere's disease patients and control subjects. In addition, the development of the temporal bone in the region of the Endolymphatic sac and Duct is evaluated by measurements of the distance from the posterior semicircular canal to the subarachnoid space and the distance from the vestibule to the subarachnoid space. Visualization of the Endolymphatic Duct was found to be significantly less frequent in the Meniere's disease patients (29%) than in the control subjects (91%). Temporal bone measurements in the region of the Endolymphatic Duct showed patients with Meniere's disease to have smaller dimensions than control subjects.
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High-resolution 3DFT MR imaging of the Endolymphatic Duct and soft tissues of the otic capsule
American Journal of Neuroradiology, 1991Co-Authors: Michael Brogan, Donald W Chakeres, Petra SchmalbrockAbstract:This study compares the visualization of otic capsule anatomy by thin-section three-dimensional Fourier transformation (3DFT) MR imaging with that by high-resolution CT. The osseous margins of the otic capsule are delineated by high-resolution CT, while MR displays the soft-tissue structures. Routine two-dimensional Fourier transformation (2DFT) spin-echo MR techniques have been limited by slice thickness and signal to noise. Previous longer TE 3DFT gradient-echo MR images of the otic structures have been degraded by magnetic susceptibility effects, which limit spatial resolution and decrease signal to noise. These effects are especially prevalent in the otic capsule, where small soft-tissue structures interface with surrounding air and bone. We developed a high-resolution 3DFT MR technique to image five normal subjects. MR images were compared with high-resolution CT images of the same subjects. Axial, sagittal, and coronal 3DFT gradient-echo MR images with a short TR/TE and 15° flip angle were acquired on a General Electric 1.5-T Signa unit using a 3-in. circular, receive-only surface coil. Axial, sagittal, and coronal 1.5-mm-thick contiguous high-resolution CT bone-algorithm images were obtained also. There was a high correlation between the MR and CT findings. The 3DFT MR images demonstrated significantly higher spatial resolution and soft-tissue detail than the high-resolution CT images did. For example, the Endolymphatic Duct was seen on twice the number of consecutive sagittal and axial MR slices. Other soft-tissue otic capsule structures routinely seen on the 3DFT MR images included the entire facial nerve, membranous labyrinth including cochlea, and tensor tympani muscle. This study demonstrates a new high-resolution 3DFT MR technique for visualizing the soft-tissue microstructures of the otic capsule and achieves a level of spatial resolution beyond that possible with high-resolution CT.
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high resolution 3dft mr imaging of the Endolymphatic Duct and soft tissues of the otic capsule
American Journal of Neuroradiology, 1991Co-Authors: Michael Brogan, Donald W Chakeres, Petra SchmalbrockAbstract:This study compares the visualization of otic capsule anatomy by thin-section three-dimensional Fourier transformation (3DFT) MR imaging with that by high-resolution CT. The osseous margins of the otic capsule are delineated by high-resolution CT, while MR displays the soft-tissue structures. Routine two-dimensional Fourier transformation (2DFT) spin-echo MR techniques have been limited by slice thickness and signal to noise. Previous longer TE 3DFT gradient-echo MR images of the otic structures have been degraded by magnetic susceptibility effects, which limit spatial resolution and decrease signal to noise. These effects are especially prevalent in the otic capsule, where small soft-tissue structures interface with surrounding air and bone. We developed a high-resolution 3DFT MR technique to image five normal subjects. MR images were compared with high-resolution CT images of the same subjects. Axial, sagittal, and coronal 3DFT gradient-echo MR images with a short TR/TE and 15 degrees flip angle were acquired on a General Electric 1.5-T Signa unit using a 3-in. circular, receive-only surface coil. Axial, sagittal, and coronal 1.5-mm-thick contiguous high-resolution CT bone-algorithm images were obtained also. There was a high correlation between the MR and CT findings. The 3DFT MR images demonstrated significantly higher spatial resolution and soft-tissue detail than the high-resolution CT images did. For example, the Endolymphatic Duct was seen on twice the number of consecutive sagittal and axial MR slices. Other soft-tissue otic capsule structures routinely seen on the 3DFT MR images included the entire facial nerve, membranous labyrinth including cochlea, and tensor tympani muscle. This study demonstrates a new high-resolution 3DFT MR technique for visualizing the soft-tissue microstructures of the otic capsule and achieves a level of spatial resolution beyond that possible with high-resolution CT.
Shinji Naganawa - One of the best experts on this subject based on the ideXlab platform.
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Significance of high signal intensity in the Endolymphatic Duct on magnetic resonance imaging in ears with otological disorders
Acta Oto-laryngologica, 2020Co-Authors: Kyoko Morimoto, Shinji Naganawa, Tadao Yoshida, Masumi Kobayashi, Satofumi Sugimoto, Naoki Nishio, Masaaki Teranishi, Michihiko SoneAbstract:BACKGROUND High signal intensity in the Endolymphatic Duct (ED) is occasionally observed on magnetic resonance imaging (MRI) in ears that have otological disorders. OBJECTIVE The signal intensity (SI) in the ED on post-contrast MRI was investigated in subjects with various otological disorders, and the meaning of high SI in the ED was evaluated. MATERIAL AND METHODS 392 patients with otological disorders and 21 controls without otological symptoms underwent 3 T MRI. The SIs of the ED and the cerebellum were measured, the SI ratio (SIR) was calculated, and ears with SIR ≥4 were identified. RESULTS A high SIR was identified in the ED of 3.7% of ears affected by definite Meniere's disease (dMD), 100% of ears affected by large vestibular aqueDuct syndrome (LVAS), and 7.1% of ears with no otological symptoms. On the whole, a significant relationship was found between the existence of vestibular or cochlear EH and the SIR in the ED. CONCLUSION The MRI finding of high SI in the ED may indicate the mechanism of inner ear disturbances in ears with otological disorders, especially in those with LVAS, and it may suggest an underlying disorder in some ears in which otological symptoms are not apparent.
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significance of high signal intensity in the Endolymphatic Duct on magnetic resonance imaging in ears with otological disorders
Acta Oto-laryngologica, 2020Co-Authors: Kyoko Morimoto, Shinji Naganawa, Tadao Yoshida, Masumi Kobayashi, Satofumi Sugimoto, Naoki Nishio, Masaaki Teranishi, Michihiko SoneAbstract:High signal intensity in the Endolymphatic Duct (ED) is occasionally observed on magnetic resonance imaging (MRI) in ears that have otological disorders. The signal intensity (SI) in the ED on post...
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effect of an enlarged Endolymphatic Duct on bone conDuction threshold
Acta Oto-laryngologica, 2008Co-Authors: Eisuke Sato, Terukazu Mizuno, Hironao Otake, Ieda Maria Ishida, Takahiko Yoshino, Shinji Naganawa, Makoto Sugiura, Tsutomu NakashimaAbstract:Conclusion. An enlarged Endolymphatic Duct and sac (EDS) that makes contact with the cerebrospinal fluid–dural interface plays an important role in the pathway of bone conDuction and enhances bone conDuction at lower frequencies. Objectives. We investigated whether the bone conDuction threshold was improved when the EDS was enlarged. Subjects and methods. Twenty-three patients (46 ears) with large vestibular aqueDucts underwent standard pure tone audiometry (PTA) and magnetic resonance imaging (MRI) to investigate the relation between the diameter of the Endolymphatic Duct (ED) and the air or bone conDuction threshold. We also investigated the relation between the volume of the EDS and the air or bone conDuction threshold. Results. All ears had a mixed type hearing loss. The air–bone gaps were significantly larger at 250 and 500 Hz than at higher frequencies. The bone conDuction thresholds were significantly lower at 250 Hz and 1000 Hz when the diameter of the ED was large, whereas there was no relation b...
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Effect of an enlarged Endolymphatic Duct on bone conDuction threshold
Acta Oto-Laryngologica, 2008Co-Authors: Eisuke Sato, Terukazu Mizuno, Hironao Otake, Ieda Maria Ishida, Takahiko Yoshino, Shinji Naganawa, Makoto Sugiura, Tsutomu NakashimaAbstract:Conclusion. An enlarged Endolymphatic Duct and sac (EDS) that makes contact with the cerebrospinal fluid-dural interface plays an important role in the pathway of bone conDuction and enhances bone conDuction at lower frequencies. Objectives. We investigated whether the bone conDuction threshold was improved when the EDS was enlarged. Subjects and methods. Twenty-three patients (46 ears) with large vestibular aqueDucts underwent standard pure tone audiometry (PTA) and magnetic resonance imaging (MRI) to investigate the relation between the diameter of the Endolymphatic Duct (ED) and the air or bone conDuction threshold. We also investigated the relation between the volume of the EDS and the air or bone conDuction threshold. Results. All ears had a mixed type hearing loss. The air-bone gaps were significantly larger at 250 and 500 Hz than at higher frequencies. The bone conDuction thresholds were significantly lower at 250 Hz and 1000 Hz when the diameter of the ED was large, whereas there was no relation between the diameter of the ED and the air conDuction threshold. In addition, there was no correlation between the volume of the EDS and air or bone conDuction thresholds. © 2008 Taylor & Francis.
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visualization of a high protein concentration in the cochlea of a patient with a large Endolymphatic Duct and sac using three dimensional fluid attenuated inversion recovery magnetic resonance imaging
Journal of Laryngology and Otology, 2006Co-Authors: Makoto Sugiura, Eisuke Sato, Shinji Naganawa, Tsutomu NakashimaAbstract:Objective: To evaluate the inner ear of a patient with an enlarged vestibular aqueDuct and acute hearing deterioration, using three-dimensional fluid-attenuated inversion recovery (3D FLAIR) magnetic resonance imaging (MRI). Background: Three-dimensional fluid-attenuated inversion recovery MRI has been recently developed to detect haemorrhage and high concentrations of protein. Application of this method to inner-ear diseases has not been fully described. Method: We used 3D FLAIR MRI to evaluate a patient with an enlarged vestibular aqueDuct and acute hearing deterioration. Results: On 3D FLAIR MRI, this patient had high signals in the Endolymphatic Duct and sac, the vestibule and the cochlea and was diagnosed as having a high protein concentration in the inner ear. These high signal areas were not detected by T1- and T2-weighted MRI. Conclusion: This is the first published case in which a high protein concentration in the cochlea of a patient with an enlarged vestibular aqueDuct was detected by 3D FLAIR MRI. These findings strongly supported the theory of the pathophysiology of hearing deterioration in patients with an enlarged vestibular aqueDuct, which states that hyperosmolar fluid in the enlarged Endolymphatic sac refluxes into the cochlea, resulting in damage to the hair cells. Thus, these finding may help clarify the cause of hearing deterioration in the presence of a large Endolymphatic Duct and sac.
Tsutomu Nakashima - One of the best experts on this subject based on the ideXlab platform.
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effect of an enlarged Endolymphatic Duct on bone conDuction threshold
Acta Oto-laryngologica, 2008Co-Authors: Eisuke Sato, Terukazu Mizuno, Hironao Otake, Ieda Maria Ishida, Takahiko Yoshino, Shinji Naganawa, Makoto Sugiura, Tsutomu NakashimaAbstract:Conclusion. An enlarged Endolymphatic Duct and sac (EDS) that makes contact with the cerebrospinal fluid–dural interface plays an important role in the pathway of bone conDuction and enhances bone conDuction at lower frequencies. Objectives. We investigated whether the bone conDuction threshold was improved when the EDS was enlarged. Subjects and methods. Twenty-three patients (46 ears) with large vestibular aqueDucts underwent standard pure tone audiometry (PTA) and magnetic resonance imaging (MRI) to investigate the relation between the diameter of the Endolymphatic Duct (ED) and the air or bone conDuction threshold. We also investigated the relation between the volume of the EDS and the air or bone conDuction threshold. Results. All ears had a mixed type hearing loss. The air–bone gaps were significantly larger at 250 and 500 Hz than at higher frequencies. The bone conDuction thresholds were significantly lower at 250 Hz and 1000 Hz when the diameter of the ED was large, whereas there was no relation b...
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Effect of an enlarged Endolymphatic Duct on bone conDuction threshold
Acta Oto-Laryngologica, 2008Co-Authors: Eisuke Sato, Terukazu Mizuno, Hironao Otake, Ieda Maria Ishida, Takahiko Yoshino, Shinji Naganawa, Makoto Sugiura, Tsutomu NakashimaAbstract:Conclusion. An enlarged Endolymphatic Duct and sac (EDS) that makes contact with the cerebrospinal fluid-dural interface plays an important role in the pathway of bone conDuction and enhances bone conDuction at lower frequencies. Objectives. We investigated whether the bone conDuction threshold was improved when the EDS was enlarged. Subjects and methods. Twenty-three patients (46 ears) with large vestibular aqueDucts underwent standard pure tone audiometry (PTA) and magnetic resonance imaging (MRI) to investigate the relation between the diameter of the Endolymphatic Duct (ED) and the air or bone conDuction threshold. We also investigated the relation between the volume of the EDS and the air or bone conDuction threshold. Results. All ears had a mixed type hearing loss. The air-bone gaps were significantly larger at 250 and 500 Hz than at higher frequencies. The bone conDuction thresholds were significantly lower at 250 Hz and 1000 Hz when the diameter of the ED was large, whereas there was no relation between the diameter of the ED and the air conDuction threshold. In addition, there was no correlation between the volume of the EDS and air or bone conDuction thresholds. © 2008 Taylor & Francis.
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visualization of a high protein concentration in the cochlea of a patient with a large Endolymphatic Duct and sac using three dimensional fluid attenuated inversion recovery magnetic resonance imaging
Journal of Laryngology and Otology, 2006Co-Authors: Makoto Sugiura, Eisuke Sato, Shinji Naganawa, Tsutomu NakashimaAbstract:Objective: To evaluate the inner ear of a patient with an enlarged vestibular aqueDuct and acute hearing deterioration, using three-dimensional fluid-attenuated inversion recovery (3D FLAIR) magnetic resonance imaging (MRI). Background: Three-dimensional fluid-attenuated inversion recovery MRI has been recently developed to detect haemorrhage and high concentrations of protein. Application of this method to inner-ear diseases has not been fully described. Method: We used 3D FLAIR MRI to evaluate a patient with an enlarged vestibular aqueDuct and acute hearing deterioration. Results: On 3D FLAIR MRI, this patient had high signals in the Endolymphatic Duct and sac, the vestibule and the cochlea and was diagnosed as having a high protein concentration in the inner ear. These high signal areas were not detected by T1- and T2-weighted MRI. Conclusion: This is the first published case in which a high protein concentration in the cochlea of a patient with an enlarged vestibular aqueDuct was detected by 3D FLAIR MRI. These findings strongly supported the theory of the pathophysiology of hearing deterioration in patients with an enlarged vestibular aqueDuct, which states that hyperosmolar fluid in the enlarged Endolymphatic sac refluxes into the cochlea, resulting in damage to the hair cells. Thus, these finding may help clarify the cause of hearing deterioration in the presence of a large Endolymphatic Duct and sac.
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enlarged Endolymphatic Duct and sac syndrome relationship between mr findings and genotype of mutation in pendred syndrome gene
Magnetic Resonance Imaging, 2004Co-Authors: Shinji Naganawa, Takahiko Yoshino, Eisuke Sato, Makoto Sugiura, Hiroshi Fukatsu, Tokiko Koshikawa, Taekeo Ishigaki, Tsutomu NakashimaAbstract:Abstract Pendred syndrome (PDS) is characterized by profound deafness in childhood, positive perchlorate challenge, and goiter. PDS is often associated with enlarged Endolymphatic Duct and sac (EEDS), and recently, PDS gene mutations have been reported even in those patients with EEDS without classic Pendred syndrome. In a previous report, the number of mutant alleles was correlated with the degree of subclinical thyroid abnormality, but not with hearing loss, in patients with missense mutation H723R. It also has been reported that the hearing loss in EEDS was not correlated with the EEDS volume, cochlear modiolar area, or signal intensity of the Endolymphatic sac. We evaluated the correlations between the number of mutant alleles and these parameters in patients with EEDS to investigate the mechanisms underlying this condition. The study group was comprised of 16 Japanese patients with EEDS diagnosed by MR imaging. The H723R mutation was homozygous in six patients and heterozygous in six patients, with no mutation found in four patients. The modiolar area, EEDS volume, and signal intensity ratio (sac signal/cerebrospinal fluid signal) were not significantly correlated with the number of mutant alleles. PDS gene mutations may not be the only cause of EEDS, and the mechanisms underlying EEDS remain unclear.
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mr imaging of the enlarged Endolymphatic Duct and sac syndrome by use of a 3d fast asymmetric spin echo sequence volume and signal intensity measurement of the Endolymphatic Duct and sac and area measurement of the cochlear modiolus
American Journal of Neuroradiology, 2000Co-Authors: Shinji Naganawa, Tsutomu Nakashima, Eriko Iwayama, Hiroshi Fukatsu, Takeo Ishigaki, Tokiko Koshikawa, Tsuneo Ishiguchi, Mitsuru Ikeda, Nobuyasu IchinoseAbstract:BACKGROUND AND PURPOSE: In enlarged Endolymphatic Duct (EED) and sac (EES) syndrome, deformity of the EED and EES is congenital; however, hearing loss is acquired. To investigate the pathophysiology of progressive sensorineural hearing loss in EED and EES syndrome, we measured the volume of the EED and EES, the diameter of the EED and EES, the area of the cochlear modiolus, and the signal intensity of the EES and compared our findings against degree of hearing loss. METHODS: Thin-section MR images of 33 ears in 17 patients with EED and EES syndrome were studied. All studies were obtained on a 1.5-T MR unit using a quadrature surface phased-array coil. Heavily T2-weighted 3D fast asymmetric spin-echo images were obtained with a voxel size of 0.3 x 0.3 x 0.8 mm without zero-fill interpolation. Two radiologists traced the areas of the EED and EES manually, and the volume was calculated. The area of the cochlear modiolus, diameter of the EED and EES, and signal intensity of the EES were also measured by drawing regions of interest manually. The signal intensity ratio of EES/CSF was calculated. These measured values were compared against audiographic data, and the degree of linear correlation was determined. RESULTS: The volume of the EED and EES, the area of the modiolus, the diameter of the EED and EES, and the signal intensity of the EES did not show significant correlation with degree of hearing loss. CONCLUSION: These findings suggest that there is a microscopic area of damage or fragility in the inner ear not visible even with thin-section heavily T2-weighted MR imaging.
Cliff A Megerian - One of the best experts on this subject based on the ideXlab platform.
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surgical inDuction of Endolymphatic hydrops by obliteration of the Endolymphatic Duct
Journal of Visualized Experiments, 2010Co-Authors: Cliff A Megerian, Chris Heddon, Sami Melki, Suhael R Momin, Janis Paulsey, Joy Obokhare, Kumar N AlagramamAbstract:Surgical inDuction of Endolymphatic hydrops (ELH) in the guinea pig by obliteration and obstruction of the Endolymphatic Duct is a well-accepted animal model of the condition and an important correlate for human Meniere's disease. In 1965, Robert Kimura and Harold Schuknecht first described an intradural approach for obstruction of the Endolymphatic Duct (Kimura 1965). Although effective, this technique, which requires penetration of the brain's protective covering, incurred an undesirable level of morbidity and mortality in the animal subjects. Consequently, Andrews and Bohmer developed an extradural approach, which predictably produces fewer of the complications associated with central nervous system (CNS) penetration.(Andrews and Bohmer 1989) The extradural approach described here first requires a midline incision in the region of the occiput to expose the underlying muscular layer. We operate only on the right side. After appropriate retraction of the overlying tissue, a horizontal incision is made into the musculature of the right occiput to expose the right temporo-occipital suture line. The bone immediately inferio-lateral the suture line (Fig 1) is then drilled with an otologic drill until the sigmoid sinus becomes visible. Medial retraction of the sigmoid sinus reveals the operculum of the Endolymphatic Duct, which houses the Endolymphatic sac. Drilling medial to the operculum into the area of the Endolymphatic sac reveals the Endolymphatic Duct, which is then packed with bone wax to produce obstruction and ultimately ELH. In the following weeks, the animal will demonstrate the progressive, fluctuating hearing loss and histologic evidence of ELH.
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Endolymphatic Duct status during middle fossa dissection of the internal auditory canal a human temporal bone radiographic study
Laryngoscope, 2006Co-Authors: Brian R Drew, Maroun T Semaan, Cliff A MegerianAbstract:Objective: Successful hearing preservation after acoustic neuroma resection is sometimes complicated by delayed hearing deterioration. The middle fossa approach appears to offer superior long-term hearing results when compared to the retrosigmoid surgical approach. The goal of this study is to investigate the hypothesis that internal auditory canal (IAC) drilling during middle fossa acoustic neuroma removal is associated with a lower incidence of Endolymphatic Duct (ELD) injury, a potential cause of delayed hearing loss (HL) known to accompany retrosigmoid hearing preservation dissection techniques. Study Design: A human temporal bone anatomic and radiographic study complemented with a literature review. Methods: Twenty human temporal bones were analyzed with high-resolution multislice computed tomography (HRMCT) and subjected to standard extended middle fossa IAC dissection with labyrinthine preservation and follow-up HRMCT for analyses of the ELD. Results: Zero of 20 (0%) temporal bones were found to have violation of the ELD with preservation of the labyrinthine structures and the Endolymphatic sac. Reviews of human and animal studies indicate that injury to the ELD may create Endolymphatic hydrops, a known cause of hearing deterioration. Conclusion: The ELD is not vulnerable to injury during IAC dissection using the middle fossa approach. A previous radiographic study has shown that the ELD is violated in 24% of temporal bones during retrosigmoid dissection of the IAC. These findings support and may help explain other outcome studies that show that long-term hearing results are superior with the use of the middle fossa approach when compared to results following retrosigmoid dissection.
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Endolymphatic Duct violation during retrosigmoid dissection of the internal auditory canal a human temporal bone radiographic study
Laryngoscope, 2004Co-Authors: Cecille G Sulman, Mark A Vecchiotti, Maroun T Semaan, Jonathan S Lewin, Cliff A MegerianAbstract:Objective/Hypothesis: Successful hearing preservation after acoustic neuroma resection is sometimes complicated by delayed hearing deterioration. The goal of this study was to investigate the hypothesis that internal auditory canal (IAC) drilling during retrosigmoid acoustic neuroma removal may result in Endolymphatic Duct (ELD) injury, a potential cause of delayed hearing loss (HL) after hearing preservation surgery. Study Design: Temporal bone anatomic and radiographic study and literature review. Methods: Twenty-one human temporal bones were analyzed with high-resolution multislice computed tomography (HRMCT) and subjected to standard retrosigmoid IAC dissection with labyrinthine preservation and follow-up HRMCT for analyses of the ELD. A MEDLINE search was performed of studies documenting long-term hearing preservation outcomes after retrosigmoid dissection. Results: Five of 21 (24%) bones were found to have violation of the ELD despite preservation of labyrinthine structures and the Endolymphatic sac. These results correlate with the mean incidence of long-term hearing decline (26.6%). Reviews of human and animal studies indicate that injury to the ELD may create Endolymphatic hydrops. Conclusions: The ELD is vulnerable to injury during IAC dissection even if labyrinthine structures at the lateral aspect of the IAC are preserved. These findings may be helpful in explaining and potentially preventing some cases of long-term hearing deterioration that may be a result of Endolymphatic hydrops after ELD injury during acoustic tumor removal. Careful preoperative review of imaging studies using HRMCT may prove useful before retrosigmoid dissection.
AO Vortmeyer - One of the best experts on this subject based on the ideXlab platform.
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effects of vhl deficiency on Endolymphatic Duct and sac
Cancer Research, 2005Co-Authors: Sven Glasker, Russell R Lonser, Maxine G B Tran, Barbara Ikejiri, John A Butman, Weifen Zeng, Patrick H Maxwell, Zhengping Zhuang, Edward H Oldfield, AO VortmeyerAbstract:The von Hippel-Lindau (VHL) disease is caused by VHL germ line mutation. Inactivation of the wild-type copy of the VHL gene leads to up-regulation of hypoxic response and tumor formation within central nervous system (CNS), kidneys, pancreas, adrenal glands, epididymis, broad ligament, and the Endolymphatic sac/petrous bone. Endolymphatic sac tumors (ELST) have been proposed to be derived from Endolymphatic sac epithelium, but other possible structures of origin have been implicated. To clarify the anatomic and cellular origin of ELSTs, we did a morphologic and molecular pathologic analysis of 16 tumors. In addition, we investigated effects of VHL deficiency on “tumor-free” Endolymphatic Duct and sac of VHL patients. Several tumors included in this study were VHL -deficient microscopic abnormalities with morphologic similarities to ELSTs. We conclude that most, if not all, ELSTs arise within the intraosseous portion of the Endolymphatic Duct/sac, the vestibular aqueDuct. In analogy to renal parenchyma and selected topographical sites within the CNS, Endolymphatic Duct/sac epithelia are preferentially and multifocally targeted in VHL disease. The primary effect of VHL deficiency on human Endolymphatic Duct/sac epithelium seems to be the generation of multifocal sites of VHL-deficient cell proliferations from which tumorigenesis may or may not occur. Therefore, inactivation of the VHL wild-type allele seems necessary but not sufficient for the formation of tumor.
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Effects of VHL deficiency on Endolymphatic Duct and sac
CANCER RES, 2005Co-Authors: AO VortmeyerAbstract:The von Hippel-Lindau (VHL) disease is caused by VHL germ line mutation. Inactivation of the wild-type copy of the VHL gene leads to up-regulation of hypoxic response and tumor formation within central nervous system (CNS), kidneys, pancreas, adrenal glands, epididymis, broad ligament, and the Endolymphatic sac/petrous bone. Endolymphatic sac tumors (ELST) have been proposed to be derived from Endolymphatic sac epithelium, but other possible structures of origin have been implicated. To clarify the anatomic and cellular origin of ELSTs, we did a morphologic and molecular pathologic analysis of 16 tumors. In addition, we investigated effects of VHL deficiency on "tumor-free" Endolymphatic Duct and sac of VHL patients. Several tumors included in this study were