Malignant progression of an extraventricular neurocytoma arising from the VIIIth cranial nerve: A case report and literature review.

A rare case of extraventricular neurocytoma (EVN) arising from the VIIIth cranial nerve in a 34-year-old woman is reported. The patient had a 20-year history of hearing loss and facial palsy. Computed tomography showed a 3-cm enhancing lesion in the left cerebellopontine angle (CPA). At operation, the tumor was seen to originate from the cochlear and vestibular nerves. The tumor was subtotally resected. Histologically, the tumor consisted of uniform cells with oval to round nuclei and scant cytoplasm. Immunohistochemically, the tumor cells were positive for synaptophysin, but negative for glial fibrillary acid protein and S-100 protein. The Ki-67 labeling index was 0%. Twelve years after the operation, magnetic resonance imaging (MRI) showed tumor recurrence at the left CPA. The tumor was subtotally resected, and radiation therapy was given. Histologically, the tumor consisted of round cells with mild atypia and one mitosis/20 high-power fields (HPF). Immunohistochemically, tumor cells showed the same findings as the first operation sample, except for the Ki-67 labeling index (3%). Twelve years after the second operation, MRI showed a second tumor recurrence at the left CPA and surroundings of the brain stem. The tumor was subtotally resected. Histologically, the tumor consisted of anaplastic short spindle cells and five mitoses/10 HPF. The immunohistochemical findings were almost the same as the earlier operation samples. However, the Ki-67 labeling index was 20%. In addition, tumor cells from the third specimen were more strongly and more diffusely positive for GAB1 (growth factor receptor-bound protein 2-associated binding protein 1) compared to those of the earlier specimens. Electron microscopy showed the presence of numerous cell processes with a dense core and clear vesicles and microtubules. GAB1 immunostaining also indicated that malignant progression might be associated with the sonic hedgehog signaling pathways. To the best of our knowledge, this is the first report of an EVN arising from the VIIIth cranial nerve with malignant progression.

Transmission electron microscopy studies of the vestibulocochlear nerve in chronic diabetic rats / Estudios de microscopía electrónica de transmisión del nervio vestibulococlear en ratas diabéticas crónicas

It is widely described in the literature that diabetic patients present hearing impairment. Despite the histological alterations of the internal ear structures in these patients as well as in experimental models of diabetes, to the best of our knowledge, an histological evaluation of the vestibulocochlear nerve have not been performed. In the present study, ultrastructural alterations are described and compared between a spinal nerves and a cranial nerve in rats with chronic induced diabetes. Male Wistar rats (n = 12), fed with standard diet from the animal care facility at 42 days of age were used. Induced diabetic animals (n=6) were fasted for 12 hours prior to being injected intraperitoneally with streptozotocin (STZ - 60mg/kg) in a single dose. Control animals (n=6) received (0.01 mol/l citrate buffer, pH 4.5) vehicle alone. Ten weeks after STZ injection the animals were perfused intracardially with Karnovsky solution. Right and left vestibulocochlear nerves were dissected and histologically processed for epoxy resin embedding. Samples were imaged with the transmission electron microscope. Large myelinated fibers with morphological signs of axonal atrophy in the vestibulocochlear nerves were readily observed. These results suggest that chronic STZ-induced diabetes in rats caused alterations in the myelinated fibers and Schwann cells, compatible to the classic diabetes signs and symptoms. Morphological alterations of the vestibulocochlear nerve in diabetes is described for the first time and contributes information for a better understanding of why there are changes in hearing observed in diabetic patients.

Se ha descrito ampliamente en la literatura que los pacientes diabéticos presentan discapacidad auditiva. En estos pacientes, a pesar de las alteraciones histológicas de las estructuras del oído interno, así como en modelos experimentales de diabetes, que mejoran nuestro conocimiento, la evaluación histológica del nervio vestibulococlear no ha sido realizada. Se describen y comparan las alteraciones ultraestructurales entre un nervio espinal y uno craneal en ratas con diabetes crónica inducida. Fueron utilizadas 12 ratas Wistar machos, de 42 días de edad, alimentadas con dieta estándar. Los animales diabéticos inducidos (n = 6) se mantuvieron en ayuno por 12 horas antes de ser inyectados por vía intraperitoneal con estreptozotocina (STZ - 60mg/kg) en una sola dosis. Los animales control (n = 6) sólo recibieron inyección de 0.01 mol/l buffer, citrato pH 4,5. Diez semanas después de la inyección de STZ, los animales fueron perfundidos intracardiacamente con solución de Karnovsky. Los nervios vestibulococlear derecho e izquierdo fueron disecados y procesados histológicamente para ser incluidos en resina epoxy. Las muestras fueron estudiadas con microscopio electrónico de transmisión. Fueron observadas fácilmente, grandes fibras mielinizadas con signos morfológicos de atrofia axonal en los nervios vestibulococlear. Estos resultados sugieren que la diabetes crónica inducida por STZ en ratas causó alteraciones en las fibras mielínicas y células del neurilema, compatible, con los signos y síntomas clásicos de la diabetes. Alteraciones morfológicas del nervio vestibulococlear en la diabetes son descritas por primera vez, lo que aporta información para una mejor comprensión de por qué hay cambios en la audición en los pacientes diabéticos.

The vasculature of the peripheral portion of the human eighth cranial nerve.

The vasculature of the peripheral portion of the human eighth cranial nerve (VIIIN) was investigated by light and transmission electron microscopy. Arterioles and venules running longitudinally around the VIIIN formed the extrinsic vascular system. The anatomical relationship between these extrinsic vessels and the VIIIN sheath was similar to that between blood vessels on the surface of the brain and the pia mater. In the endoneurium, postcapillary venules and large capillaries were sparsely distributed and longitudinally arranged, and these microvessels formed the intrinsic microvascular system, which was supported by the extrinsic vascular system via anastomosing vessels. The ultrastructural features of the internal auditory artery and its main branches were the same as those of other intracranial arteries. Ultrastructural study also revealed myo-endothelial junctions in anastomosing arterioles, and endothelio-pericytic junctions in extrinsic and anastomosing venules. Microvascular endothelial cells were connected by tight junctions in both the vestibular ganglion and the rest of the VIIIN. These features of the vasculature were considered to be effective for maintenance of the endoneurial fluid and regulation of the circulation in the peripheral portion of the human VIIIN.

Normal evoked otoacoustic emissions with a profound hearing loss due to a juvenile pilocytic astrocytoma.

An interesting case is reported of an 11-year-old girl who experienced a sudden, profound right-sided hearing loss at the age of 5 years after hearing a "pop" and the sound of rushing water in her right ear. At that time the patient was thought to have Mondini's deformity, and a perilymphatic fistula of the oval window in the right ear. Six years later she was diagnosed with a juvenile pilocytic astrocytoma of the pons with an exophytic component extending into the cerebellopontine angle. Of particular interest in this case is the presence of evoked otoacoustic emissions in the right ear with a profound neural hearing loss. The presence of transient evoked and distortion product otoacoustic emissions confirmed normal sensory outer hair cell function and an intact peripheral auditory system in a clinically deaf ear, thus indicating hearing loss due to a neural component instead of a sensory component, which was previously assumed.

Angiogenesis from the eighth cranial nerve to vestibular schwannomas.

Vascularization between vestibular schwannomas and the adjacent eighth cranial nerve was examined in order to elucidate the angiogenic effect of these tumours. Specimens from 12 patients were examined by light microscopy and immunohistochemistry (series 1), while specimens from another 17 patients were examined by light and transmission electron microscopy (series 2). Slight to marked angiogenesis was found in 5 patients from series 1 and 7 patients from series 2. Ultrastructural examination indicated that these blood vessels were more fragile than those in the normal eighth cranial nerve. These findings suggested that sudden hearing loss in vestibular schwannoma patients may be related to the disruption of such blood vessels. In addition, surgical injury to these blood vessels may cause postoperative hearing loss despite preservation of the cochlear nerve.

Nerve growth factor receptor expression in heterotransplanted vestibular schwannoma in athymic nude mice.

Nerve growth factor (NGF) has the potential to induce cellular differentiation in various neoplastic and non-neoplastic cell lines. The purpose of the present study was to determine by immunohistochemistry: the presence/distribution of nerve growth factor receptor (NGFr), cellular proliferation expressed by Ki-67, and intratumoral vascularization visualized by the endothelial marker CD 31, in a series of 61 human vestibular schwannoma heterotransplants in athymic nude mice. The immunohistochemical results were correlated to the observed macroscopic growth in 22 heterotransplants (36%) with obvious macroscopic growth, versus 39 heterotransplants (64%), that were stationary or regressed. The positive immunoreactivity to NGFr, number of Ki-67 positive nuclei and number of intratumoral vessels were significantly higher in the 22 (36%) growing heterotransplants than in the 39 heterotransplants (64%), which were stationary or regressed (p < 0.00005, p = 0.046, p < 0.00001). NGFr was statistically related to the vascularity of the heterotransplants expressed by CD 31 (p<0.00001). No significant relation was observed between NGFr and the proliferation, as estimated by Ki-67. The results revealed that the macroscopic growth of VS in athymic nude mice was associated with strong positive expression of NGFr, high cellular proliferation expressed by Ki-67 and vivid neovascularization expressed by CD 31. The possible clinical applicability of the achieved results is discussed.

Laminin promotes differentiation, adhesion and proliferation of cell cultures derived from human acoustic nerve schwannoma.

The influence of laminin on cell cultures derived from unilateral acoustic nerve schwannomas was investigated. Cell cultures were initiated from 12 schwannomas, removed via the enlarged middle cranial fossa approach. Tumor tissue was dispersed by collagenase treatment and cells seeded in uncoated or laminin-coated culture dishes. Confluent cultures were immunocytochemically characterized with antibodies against S-100, CD 68, factor VIII-related antigen and type IV collagen. Cell adhesion in response to different doses of laminin was evaluated with an electronic cell counter. The effect of laminin on cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxy-uridine (BRDU) into cellular DNA. Cells cultured on laminin as substrate appeared more differentiated with long, fusiform, cytoplasmic processes. Cultured cells stained positive for S-100, not for factor VIII-related antigen or CD 68. Only cells cultured on laminin deposited a dense extracellular network of type IV collagen. When laminin was added to the culture medium, cell attachment and proliferation was stimulated in a dose dependent manner. Maximal stimulation of both was observed with a laminin concentration of 50 micrograms/ml, which induced a nearly 2-fold increase in cell attachment and an approximately 66% increase in DNA content. Since laminin is a major component of the extracellular matrix in schwannomas, the possibility exists that laminin is also mitogenic for human neoplastic Schwann cells in situ.

The limitations of hearing preservation in acoustic neuroma surgery: histological study of the interface between the eighth cranial nerve and the tumor.

The interface between the eighth cranial nerve and acoustic neuroma was investigated by light microscopy and immunohistochemistry in paraffin sections in 13 patients, and in Epon sections in 19 patients. The cochlear nerve was severely invaded by tumor cells in two of six specimens examined, moderately invaded in two specimens, and not invaded in two specimens. Gliosis was frequently found within the cochlear and vestibular nerve. Hemangioma-like tissue was occasionally found attached to the cochlear and vestibular nerve adjacent to the tumor. These findings were considered to be related to difficulty in hearing preservation in some patients although acoustic neuroma surgery was successful.

Normal and metastatic melanin in the temporal bone.

PURPOSE: Malignant melanoma is known to metastasize to the temporal bone. However, melanocytes exist in the normal inner ear and may be difficult to distinguish from metastatic melanotic cells. This study describes distribution of normal melanin in the ear and metastatic melanoma to the temporal bone. MATERIALS AND METHODS: Normal melanin distribution is described in 48 temporal bones from White (18), Native-American (19), and African-American (11) individuals and metastatic melanoma to the temporal bone is described in four cases (seven temporal bones). Temporal bones were removed at autopsy, fixed in 10% buffered formalin, and processed for routine celloidin embedding. Sections were cut at a thickness of 20 microns and every tenth section was stained with hematoxylin-eosin for light microscopic evaluation. RESULTS: Normal melanin was found in the inner ear, mainly around terminal neural structures and blood vessels, and occurred in greater quantities in African-American individuals. Metastatic melanotic cells reached the temporal bone by hematological dissemination, and by neural invasion from the central nervous system. No correlation was found between histopathological findings and clinical symptoms of patients. CONCLUSIONS: Metastatic melanoma to the temporal bone may be seen in the same areas as normal melanin. They may also be observed in bone marrow cells of the petrous bone and along the course of nerves of the internal auditory canal and cochlear vestibular labyrinth, either by following neural sheaths or blood vessels that run along the nerve. Metastatic disease to the temporal bone is often asymptomatic, or it may present with uncharacteristic symptoms that may delay diagnosis.

Ultrastructure of astrocytes in the transitional region of the human eighth cranial nerve.

The nerve root segment where the transition from central to peripheral nervous tissue occurs is referred to as the transitional region (TR). Part of the TR is a continuation of the subpial glial limiting membrane (SGLM) which covers the surface of the brain. To assess the physiological and pathophysiological roles of astrocytes in the TR of the human eighth cranial nerve, electron microscopy was performed on surgically resected specimens of the eight cranial nerve root obtained from patients with cerebellopontine angle tumors. The astrocytic glial dome was sharply bounded by a basement membrane and was mainly composed of the bodies and processes of fibrous astrocytes. Desmosomes and gap junctions were found between these astrocytic processes. Half-desmosomes were found on the edge of the astrocytic glial dome and at the luminal surface of the perivascular glial limiting membrane. These ultrastructural features indicate that the astrocytes of the TR might have some motility capacity that allows adjustment to changes in the pressure exerted by the vessels, the peripheral nervous tissue, and the cerebrospinal fluid. In addition, it is also suggested that lack of structures linking the central and peripheral portions of the nerve and the abrupt change of nerve composition at the TR might predispose this area to injury by tractional forces or pathologic conditions such as tumor or arterial compression.

[A case of acoustic neurinoma in a girl aged 13]. / Przypadek nerwiaka nerwu sluchowego u 13-letniej dziewczynki.

A 13-year-old girl with large richly vascularized acoustic neurinoma is reported. The family history and clinical evidence failed to suggest neurofibromatosis in the family. The clinical syndrome included paroxysmal headaches, vertigo, loss of consciousness and left ear hearing loss. The application of Nd-YAG laser during the operation reduced bleeding and enabled radical removal of the tumour.

Further observations in the eighth nerve in Menière's disease.

Forty patients with advanced Menière's disease were operated upon by vestibular or eighth nerve neurectomy. The biopsied nerve specimens were studed by light and electron microscopy. Round areas containing no or very few axons and bundles of proliferated processes of fibrous astrocytes were found in six cases. A combination of clinical and histopathologic findings suggests that some patients with symptoms identical to Menière's disease might have a primary neuronal disease leading to nonspecific reparative response by fibrous astrocytes.

Eighth nerve lipoma. Case report.

A case of lipoma of the right eighth cranial nerve in the cerebellopontine angle (CPA) is presented. The patient had a clinical, diagnostic, surgical, and postoperative course similar to that of patients with other small CPA tumors. The literature on this rare CPA tumor is reviewed and discussed.

Neuroglial tissue in human eighth nerve specimens.

One hundred eighty nerve biopsy specimens from patients with eighth nerve tumors or other vertiginous diseases requiring vestibular neurectomy were studied. In many specimens light microscopy revealed pale areas among the myelinated nerve fibers in the neurolemmal portion of the eighth nerve. Electron microscopy showed that these were ectopic areas of glial tissue consisting of bundles of numerous cytoplasmic processes of fibrous astrocytes. The abundance of filaments within each process and the occurrence of microtubuli suggest that these processes are reactive astrocytes and accordingly are present as a consequence of the reparative potential of the astroglial tissue after a neuronal lesion. The possible functional significance of the findings is discussed.

Artifacts in eighth cranial nerve biopsy.

The occurrence of artifactual morphological changes was investigated in human eighth nerve biopsies and corresponding changes were brought about in biopsies from rats by mechanical handling before fixation. At the very site of compression by a pair of forceps the biopsy stained lighter than in its immediate surroundings. Electron microscopy showed denuded and fragmented axons among vesicular debris in the area. Further away the myelin coats were greatly thickened, often to the degree that the axonal canal could no longer be identified. The myelin lamellae showed separation and were occasionally seen in convoluted forms. Also variations in the diameters of the nerve fibres and ruptures of the meylin coats could be produced after mechanical handling.