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.

[Infraorbital schwannoma. Case report]. / Schwannoma infraorbitario. Informe de un caso.

BACKGROUND: Infraorbital schwannoma is a benign tumor of the peripheral nerve seath composed of Schwann cells. Usually occurs between 20 and 70 years of age, are usually asymptomatic and can cause progressive, painless proptosis during growth. CLINICAL CASE: A 32-year-old male admitted to ophthalmologic hospital with a painless, slowly progressive mass above the left lacrimal sac. At the ophthalmologic examination the tumor had a rubbery consistency and was firmly attached to the surrounding structures. The transillumination was negative. The B mode ultrasound disclosed a phakic eye as well as an infraorbital well-circumscribed homogeneous mass with a largest diameter of 19.7 mm, without involvement of the lacrimal pathway. The A mode ultrasound showed medium-high reflectivity with small internal vascularity. The computed tomography showed a homogeneous wellcircumscribed solid mass anterior and inferior to the left globe without bony erosion. Through subdermic incision the mass was excised. The histopathological diagnosis was "Infraorbital schwannoma". CONCLUSIONS: The schwannoma is a rare benign tumor in the orbit, few cases have been reported. The definitive diagnosis is made by histopathologic findings as the presence of a true capsule, hyper-and hypocellular areas, thickening and hyalinization of the vessel walls. When these findings are not be confused with benign fusocellular tumors. We report a new case of infraorbital schwannoma and compared it with those cases previously reported.

Antecedentes: el schwannoma infraorbitario es un tumor benigno de la vaina nerviosa periférica compuesto por células de Schwann. Suele aparecer entre los 20 y 70 años de edad, asintomático y producir proptosis progresiva e indolora durante su crecimiento. Caso clínico: paciente masculino de 32 años de edad que ingresó al hospital debido a un tumor no doloroso de crecimiento lentamente progresivo sobre el saco lagrimal izquierdo. A la exploración oftalmológica el tumor era de consistencia ahulada y estaba firmemente adherido a las estructuras vecinas. La transiluminación resultó negativa. El ultrasonido modo B mostró un ojo fáquico y un tumor infraorbitario homogéneo, bien circunstrito, con diámetro mayor de 19.7 mm, sin afectación de la vía lagrimal. El ultrasonido modo A mostró una reflectividad media-alta, con escasa vascularidad interna. La tomografía computada mostró un tumor de densidad homogénea, bien circunscrito a la región anterior y por debajo del globo ocular, sin erosión ósea. El tumor se extirpó mediante una incisión subdérmica. El diagnóstico histopatológico fue: schwannoma infraorbitario. Conclusiones: el schwannoma es un tumor benigno, poco frecuente en la órbita. Su diagnóstico definitivo se establece con base en los hallazgos histopatológicos, como: cápsula verdadera, áreas hiper e hipocelulares, engrosamiento y hialinización de las paredes vasculares. Sin esos hallazgos puede confundirse con tumores fusocelulares benignos. Se informa un nuevo caso de schwannoma infraorbitario y se compara con los casos previamente reportados.

[Differential diagnosis between melanotic schwannoma of gasserian ganglion and metastatic melanoma of middle cranial fossa].

We present a case of a rare tumor--melanotic schwannoma of trigeminal nerve root and gasserian ganglion. Differential diagnosis between metastatic melanoma and melanotic schwannoma (MS) is associated with serious difficulties and high responsibility. Metastatic melanoma is a high grade tumor while most MS are benign lesions with good outcome. By the date 105 cases of these tumors are described in the world literature, 3 of them originated from trigeminal nerve root and gasserian ganglion. MS predominantly occur in relatively young patients, they are characterized by presence of Carney's complex and psammomatous bodies and absence of primary focus. MS and metastatic melanoma have similar appearance on MRI due to presence of melanin granules. Indirect signs evident for MS include cystic structure and dumbbell-shaped growth. Metastatic melanoma of cranial nerves is more typical in people older than 40, primary focus in the face in the zone of innervation of affected nerve is common. In case of absence of the listed features differential diagnosis is based on immunohistochemical analysis and electron microscopy of tissue samples.

Ultrastructural characteristics of axons in traumatic neuromas of the human lingual nerve.

AIMS: To determine the ultrastructural characteristics of axons in traumatic neuromas of the human lingual nerve during the surgical removal of lower third molar teeth and to establish whether any characteristics were different between patients with dysesthesia and patients without dysesthesia. METHODS: Transmission electron microscopy was used to determine the ultrastructural morphological characteristics of human lingual nerve neuromas (n = 34) removed at the time of microsurgical nerve repair. From a sample population of myelinated and nonmyelinated fibers within the neuromas, fiber diameter, myelin thickness, g-ratio, and the number of mitochondria per axon were quantified. Comparisons were made with normal control lingual nerve specimens (n = 8) removed at the time of organ donor retrieval. RESULTS: Significant differences in ultrastructural morphology were found between the neuromas and control nerves. The neuromas contained a higher proportion of small (2- to 8-microm diameter) myelinated nerve fibers than controls, and the mean myelinated fiber diameter was significantly lower in neuromas than in controls. Mean myelin sheath thickness was significantly thinner in neuromas (0.6 +/- 0.1 microm) than in controls. However, the g-ratio, which is a measure of the myelination status of the nerve fibers in relation to their diameter, was found to be similar in each group, suggesting a normal process of myelination in the damaged axons. Nonmyelinated axon diameter was also significantly smaller in the neuromas than in the controls, and Schwann cells were found to sheathe more nonmyelinated axons in neuromas than in controls. The ratio of nonmyelinated to myelinated axons was significantly higher in neuromas than in controls. However, no significant differences were found between patients with dysesthesia and those without dysesthesia. CONCLUSION: Damage to the lingual nerve results in marked changes to axon diameter, myelin sheath thickness, and Schwann cell-axon relationships. These ultrastructural changes could contribute to the altered electrophysiological properties of axons trapped within neuromas. However, no significant differences in the ultrastructural characteristics studied were found between specimens from patients with or without symptoms of dysesthesia.

De novo desmoplastic neurotropic melanoma of the lower lip: a neoplasm with ominous behavior.

Desmoplastic neurotropic melanoma represents a rare histologic variant of malignant melanoma that is characterized by a proliferation of spindle cells in a densely collagenous stroma with pronounced neurotropism. A 60-year-old man appeared for evaluation of a mass in the lower lip. The labial mucosa was intact, and the lesion had been present for 2 months. The tumor was surgically removed, and after immunohistochemical and ultrastructural analysis it was diagnosed as desmoplastic neurotropic melanoma. The tumor recurred 6 months later, with involvement of the inferior alveolar nerve.

Optic nerve glioma mimicking an optic nerve meningioma.

The case is described of an optic nerve glioma, mimicking an optic nerve meningioma in a man aged 41 years. CT, MRI and DSA revealed an enhancing tumor surrounding the optic nerve. Histopathologic examination of the removed optic nerve revealed a centrally located glioma surrounded by normal optic nerve fibres.

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.

Acoustic neurinoma with a large organized hematoma--case report.

A 66-year-old female presented with a large organized hematoma within an acoustic neurinoma. She had suffered from diminished hearing for 20 years and had headache 1 week before presentation. Computed tomography demonstrated an inhomogeneously high density cerebellopontine angle mass, and magnetic resonance imaging showed a mass with heterogeneous intensity and gadolinium-diethylenetriaminepenta-acetic acid enhancement of only the peripheral surface of the mass and the inner parts of the internal auditory meatus. At operation the majority of the mass was soft and feature-less with a firm capsule, and a yellowish soft tumor was removed from the perimeatal area. Histological examination showed the mass was an acoustic neurinoma with a large organized hematoma. Extensive hemorrhage from an abnormal vascularity in the tumor had repeated followed by granulomatous organization.

Intracranial hypoglossal neurinoma without preoperative hypoglossal nerve paresis--case report.

A 46-year-old female presented with an intracranial hypoglossal neurinoma manifesting only as spasticity in the lower extremities without hypoglossal nerve paresis. Magnetic resonance imaging greatly aided in the early detection of the tumor with this atypical presentation. Unilateral suboccipital craniotomy with resection of the occipital condyle allowed us to approach the tumor in front of the medulla from an inferolateral direction and to remove it successfully. We emphasize the need to pack dead space with fatty tissue to prevent cerebrospinal fluid leakage.

Histopathology of the peripheral vestibular system in small vestibular schwannomas.

Gadolinium-enhanced magnetic resonance imaging can be used to detect small vestibular schwannomas/acoustic neuromas. Early detection raises the question of the necessity of their surgical removal. Do all tumors induce lesions in the vestibule and to what extent? We thus investigated the ultrastructure of peripheral vestibular systems in grades I and II schwannomas. Vestibular tissues were fixed as soon as they were removed during the resection of tumors, by the translabyrinthine approach, and then processed for transmission electron microscope observations. In neurosensory epithelia, hair cells lost stereocilia, whereas cuticular plates disaggregated. The cytoplasm of hair cells degenerated in either a dense or vacuolated manner, and cytoplasmic blisters extended into the endolymph. In some cases, supporting cells extended processes covering the apical surface of hair cells. Nerve fibers massively disappeared from epithelia, only few nerve fibers contacted type I and type II hair cells, and both afferent and efferent terminals were abnormal. In vestibular nerves, axons degenerated, and myelin sheaths disaggregated. Glycogen was present in both intracellular and extracellular spaces. Luse bodies associated with collagen bundles were found between fibers. Scarpa ganglion neurons contained lysosomes/lipofuscin granules and vacuoles. Tumor cells were found in both the ganglion and the vestibular nerve. Thus small tumors induce extensive degeneration of vestibular tissues. The various hallmarks of schwannomas are already present in small acoustic neuromas. Moreover, different types of degeneration of hair cells and neurons were observed, together with the covering of hair cells by supporting cells and the accumulation of glycogen in the vestibular nerve.

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.

Magnetic resonance imaging and intraoperative frozen sections in intratemporal facial schwannomas.

Seven cases of intratemporal facial schwannoma were assessed by preoperative magnetic resonance imaging (MRI) and intraoperative frozen sections to determine tumor boundaries. These results were then analyzed with respect to gross tumor appearance, under the operating microscope, and final histopathologic diagnosis, with immunostains. Gadolinium-enhanced MRI was helpful in planning the surgical and approach and in defining the extent of tumor involvement relative to the facial nerve. Frozen sections on the other hand were often unreliable in confirming the completeness of resection, frequently overestimating tumor infiltration. Ultimately, tumor-nerve interface, especially in the proximal facial segments, is best judged by its gross intraoperative appearance under high magnification, with the aid of MRI. The difficulty in establishing tumor infiltration in the presence of organized neutral fibers and artifacts is emphasized. Immunohistochemical assays are essential in this regard. Complete tumor removal was achieved in all seven cases, with acceptable functional outcome in those with sufficiently long follow-up.

[Electron microscopic observation on benign tumors of the facial nerve].

Two cases of benign tumors of the facial nerve were examined. One was neurilemmoma and the other neurofibroma. The histopathological diagnoses of the tumors are difficult to make with light microscope. However, electron microscopy may be helpful. Under transmission electron microscope, the difference of two kinds of tumors is obvious. The main pathological features had been discussed.

Histiocytic tumor of Meckel's cave. An intracranial equivalent of juvenile xanthogranuloma of the skin.

We present the case of a 7-year-old boy who had a solitary mass within Meckel's cave that recurred 6 weeks after the initial resection. The histological, immunohistochemical, electron-microscopical, and molecular genetical features established the lesion's histiocytic nature. Our findings showed that it was closely related to juvenile xanthogranuloma, a benign lesion that usually occurs in the skin but has not yet been histologically confirmed in the brain. The present tumor is different from other intracranial histiocytic and xanthogranulomatous lesions.

Benign nerve sheath tumors: a light microscopic, electron microscopic and immunohistochemical study of 102 cases.

One hundred and two cases of benign nerve sheath tumors (NSTs) were studied with a combined approach using routine light microscopy (LM), immunohistochemistry (IH) for myelin basic protein (MBP) and S-100 protein as well as transmission electron microscopy (TEM) with the aim of obtaining greater insight into the true nature of these neoplasms, and also to establish the importance of IH and TEM in their diagnosis. Myelin basic protein was not identified in any of these tumors, whereas S-100 protein was positive to a variable degree in both schwannomas and neurofibromas. TEM revealed that Schwann cells predominated in tumors which were strongly positive for S-100 protein and appeared as schwannomas by LM. However, neurofibromas showing a variable patchy positivity for S-100 were composed of an admixture of Schwann cells, fibroblast-like cells and intermediate cells considered to be modified Schwann cells. Perineurial cells in typical form were not seen. It is concluded that all NSTs are basically of Schwann cell origin and that the intermediate cells and fibroblast-like cells are variants of Schwann cells. The different morphological appearances and biological behaviour of schwannomas and neurofibromas may be related to some other factors like micro-environment or genetic predisposition. Further, both IH, especially for S-100 protein, and TEM play an important role in establishing their diagnosis.

[Clinicopathologic and ultrastructural studies of olfactory neuroblastoma].

The clinicopathologic and ultrastructural studies of 12 cases of olfactory neuroblastoma were made. The ages of patients ranged from 2 to 58 years with a mean of 32. Eleven cases occurred in men and 1 case in woman. An acidophilic fibrillary intercytoplasmic background was present in every case. Its amount varied focally. Ultrastructurally, the acidophilic fibrillary background was composed of neuronal cell processes. Homer-Wright rosettes were found in 7 cases, Flexner type rosettes in 4 cases, 3 of which shared both Homer-Wright and Flexner type rosettes. Almost all cases with rosettes also had apparent acidophilic fibrillary intercytoplasmic background. So, we think that acidophilic fibrillary intercytoplasmic background was the most useful diagnostic feature by light microscopic observation. The diagnosis of olfactory neuroblastoma by electron microscopy was mainly based on neuronal processes, neurosecretory granules, microtubules, neurofilaments, synaptic-like junctions and occasionally both microvilli and olfactory vesicles at the luminal borders of Flexner type rosettes.