Loss of DAL-1, a protein 4.1-related tumor suppressor, is an important early event in the pathogenesis of meningiomas.
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Meningiomas are common nervous system tumors, whose molecular pathogenesis is poorly understood. To date, the most frequent genetic alteration detected in these tumors is loss of heterozygosity (LOH) on chromosome 22q. This finding led to the identification of the neurofibromatosis 2 (NF2) tumor suppressor gene on 22q12, which is inactivated in 40% of sporadic meningiomas. The NF2 gene product, merlin (or schwannomin), is a member of the protein 4.1 family of membrane-associated proteins, which also includes ezrin, radixin and moesin. Recently, we identified another protein 4.1 gene, DAL-1 (differentially expressed in adenocarcinoma of the lung) located on chromosome 18p11.3, which is lost in approximately 60% of non-small cell lung carcinomas, and exhibits growth-suppressing properties in lung cancer cell lines. Given the homology between DAL-1 and NF2 and the identification of significant LOH in the region of DAL-1 in lung, breast and brain tumors, we investigated the possibility that loss of expression of DAL-1 was important for meningioma development. In this report, we demonstrate DAL-1 loss in 60% of sporadic meningiomas using LOH, RT-PCR, western blot and immunohistochemistry analyses. Analogous to merlin, we show that DAL-1 loss is an early event in meningioma tumorigenesis, suggesting that these two protein 4.1 family members are critical growth regulators in the pathogenesis of meningiomas. Furthermore, our work supports the emerging notion that membrane-associated alterations are important in the early stages of neoplastic transformation and the study of such alterations may elucidate the mechanism of tumorigenesis shared by other tumor types. (+info)
Myelomatous involvement of the dura mater: a rare complication of multiple myeloma.
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A case of myelomatous involvement of the dura mater is reported. The patient presented with blurring of vision in the right visual field and left sided facial numbness. A magnetic resonance imaging scan of the head revealed extensive infiltration of the dura mater. Cerebrospinal fluid (CSF) analysis showed no plasmacytosis and although there was a raised CSF protein concentration, no paraprotein band was detected, despite the presence of serum paraprotein. The infiltration of the dura mater is likely to have arisen by spread from contiguous bone lesions, contrasting with the pattern of spread seen in myelomatous involvement of the leptomeninges, which probably occurs through haematogenous seeding of the meninges. Leptomeningeal involvement is associated with a very poor prognosis; however, this patient had a favourable response to combined chemotherapy and cranial radiotherapy, suggesting that myelomatous involvement of the dura mater should be considered as a distinct complication of myeloma. (+info)
Regulation of secretion of PTHrP by Ca(2+)-sensing receptor in human astrocytes, astrocytomas, and meningiomas.
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Parathyroid hormone-related protein (PTHrP) is the major mediator of the humoral hypercalcemia of malignancy and of malignant osteolysis associated with skeletal metastases of common epithelial cancers. PTHrP secretion is regulated by the extracellular calcium concentration ([Ca(2+)](o)) in several types of normal and malignant cells. Because the [Ca(2+)](o)-sensing receptor (CaR) is a key mediator of [Ca(2+)](o)-regulated hormone secretion [e.g., of parathyroid hormone (PTH) by parathyroid chief cells], we investigated the expression of the CaR and PTHrP in normal and neoplastic glial cells and studied the effects of [Ca(2+)](o) on PTHrP secretion. Our results show that primary embryonic human astrocytes (HPA) express CaR mRNA and protein as detected by RT-PCR and Western analysis, respectively. Furthermore, astrocytomas and meningiomas also express the CaR at similar levels as assessed by RT-PCR and Northern and Western blot analyses. HPA and astrocytomas express transcripts encoding all three known isoforms of PTHrP [PTHrP(139), PTHrP(141), and PTHrP(173), comprising 139, 141, and 173 predicted amino acid residues, respectively] as assessed by RT-PCR, whereas meningiomas express only the first two of these. Finally, elevated levels of [Ca(2+)](o) and other polycationic CaR agonists dose dependently stimulate PTHrP secretion from HPA, astrocytomas, and meningiomas, although both basal and high [Ca(2+)](o)-stimulated rates of PTHrP secretion are approximately 2. 5-fold higher in HPA than in the glial tumors studied here. Therefore, our results show that HPA, astrocytomas, and meningiomas express both the CaR and PTHrP and that CaR agonists stimulate PTHrP secretion. (+info)
Primary diffuse leptomeningeal gliomatosis: unusual MRI with non-enhancing nodular lesions on the cerebellar surface and spinal leptomeningeal enhancement.
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A 28 year old man presented with a 1 month history of symptoms of intracranial hypertension. Examination showed bilateral papilloedema and meningeal signs. Magnetic resonance imaging showed nodular lesions on the cerebellar and pontine surface and thickening of the thoracic spinal leptomeninges. Throughout the course of the disease, contrast enhancement was detected in the spinal leptomeninges but not intracranially. Primary diffuse leptomeningeal gliomatosis (PDLG) was diagnosed by biopsy and later confirmed on necropsy. The present case is remarkable for the nodular superficial cerebellar lesions and the absence of intracranial contrast enhancement of the leptomeninges. (+info)
Intracranial and intraspinal meningeal melanocytosis.
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We describe a 35-year-old man with a history of remote closed head injury who presented with new neurologic deficits. A noncontrast head CT scan showed hyperattenuation involving both temporal lobes, frontal lobes, basal meninges, and cerebellum. A subsequent contrast-enhanced MR examination of the brain showed enhancement in the basal cisterns extending into the upper cervical spine and throughout the spinal canal. Gross, histologic, and immunohistochemical analysis revealed meningeal melanocytoma. (+info)
Necrotizing sarcoid granulomatosis mimicking an intracranial neoplasm: clinicopathologic features and review of the literature.
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We present a unique case of biopsy-proven necrotizing sarcoidosis involving the central nervous system (CNS) in a 52-year-old woman. The patient presented with a 3-month history of left-sided headache and sharp, shooting pains on the left side of her face. She also has a previous history of sarcoidosis, histopathologically confirmed on parotid gland biopsy 24 years before. Imaging studies of the present lesion revealed a 1.8 x 1.4-cm mass in the left temporal lobe with signal intensity suggestive of meningioma or low-grade glial neoplasm. Surgical resection was initiated, and intraoperative consultation with frozen sections revealed granulomata. The lesion was biopsied, and surgical intervention was terminated. Permanent sections failed to reveal bacteria, mycobacteria, fungi, or foreign bodies. A diagnosis of necrotizing neurosarcoidosis was rendered. The patient was administered steroid therapy and clinically responded favorably. At the most recent follow-up almost 2 years later, there was no evidence of recurrence or progression. Necrotizing sarcoidosis has been reported most commonly in the lungs and rarely in other organ systems. We report the first histologically proven case involving the CNS as well as a rare example of sarcoidosis and necrotizing sarcoid granulomatosis in the same patient. Sarcoidosis and its necrotizing variant should be considered in the differential diagnosis of a granulomatous mass lesion involving the CNS, particularly in the context of a history of systemic disease. (+info)
Solitary fibrous tumor of the meninges in the posterior cranial fossa: magnetic resonance imaging and histological correlation--case report.
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A 58-year-old female presented with a rare case of intracranial solitary fibrous tumor (SFT) manifesting as progressive ataxic gait and hearing loss on the left persisting for 6 months with recent symptoms of increased intracranial pressure. Computed tomography demonstrated a large isodense irregular-shaped mass in the left posterior cranial fossa. T2-weighted magnetic resonance imaging showed two components appearing as very low intensity and high intensity. Extreme-lateral suboccipital craniotomy was performed. Gross total resection was achieved except for some dural attachment in the jugular foramen. All symptoms and signs subsided after surgery. Histological, immunohistochemical, and electron microscopic examinations led to a diagnosis of SFT. The strongly hypointense areas on the T2-weighted images were hypocellular region characterized by disorganized spindle cells and thick bands of collagen. The hyperintense areas on the T2-weighted images were hypercellular region mimicking hemangiopericytoma. Strong immunoreactivity for CD34 was also helpful in the diagnosis. Electron microscopy revealed absence of pinocytic vesicles and dense laminae which are characteristic of hemangiopericytoma. The magnetic resonance imaging appearance of SFT seems to be pathognomonic. (+info)
The effect of brain tumors on BOLD functional MR imaging activation in the adjacent motor cortex: implications for image-guided neurosurgery.
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BACKGROUND AND PURPOSE: Functional MR (fMR) imaging data coregistered to a neurosurgical navigation system have been proposed as guides for the resection of brain tumor in or adjacent to eloquent cortices. The purpose of this study was to compare data obtained from the side of the brain affected by tumor with the contralateral side and to determine if there are physiological limitations of fMR imaging in accurately determining the location of the primary motor cortex. METHODS: Ten patients with tumors in or directly adjacent to the motor cortex were studied with fMR imaging (finger-tapping paradigm). fMR imaging data were analyzed using multiple R values. These data were coregistered to a real-time intraoperative neurosurgical navigation system. RESULTS: Significant variability of motor cortex activation patterns was noted among individual patients. The activation volumes on the side of the tumor were significantly smaller compared with the contralateral side for all tumors not previously resected (0.66+/-0.47). This was most pronounced in glioblastomas (0.27+/-0.21). We propose that these differences were caused by a loss of autoregulation in the tumor vasculature of glioblastomas and venous effects. CONCLUSION: Notwithstanding the differences noted, the motor cortex was identified successfully in all patients. This was confirmed by intraoperative physiological identification of the motor cortex and a lack of postoperative neurologic deficit. (+info)