Clear cell pleomorphic xanthoastrocytoma: case report.

Pleomorphic xanthoastrocytoma (PXA) is a well-described astrocytic neoplasm with distinctive clinical and pathological features. Although most patients with PXAs are cured by surgical excision, other patients experience malignant progression and tumor recurrence. We describe a 47-year-old woman with a left temporal lobe PXA that had classic histopathological characteristics as well as extensive clear cell and focal papillary changes, and some anaplastic findings. The patient has now suffered two recurrences after complete resection. The case illustrates a rare, previously undescribed histological variant of PXA, with a prominent clear cell and focal papillary morphology. The study of histologically similar cases is needed to determine whether this variant is always associated with a greater likelihood of recurrence.

Alpha(v)beta3 and alpha(v)beta5 integrin expression in glioma periphery.

OBJECTIVE: This study analyzed the expression of integrins alpha(v)beta3 and alpha(v)beta5 in glioma tissue and focused on the periphery of high-grade gliomas. METHODS: The analysis was performed with Western blot, immunohistochemistry, and immunofluorescence, by use of two monoclonal antibodies able to recognize the functional integrin heterodimer. The expression of integrin-related ligands and growth factors also was studied. Sections from the tumor periphery were classified as either tumor periphery (light tumor infiltrate or scant visible cells) or peritumor (heavy tumor infiltration). RESULTS: Our data on glioma tissues demonstrated that both integrins were expressed in glioma cells and vasculature and their expression correlated with the histological grade. Alpha(v)beta3 expression was prominent in astrocytic tumors. Both integrins were markers of tumor vasculature, particularly of endothelial proliferation. A high-grade glioma periphery demonstrated a prominent expression of integrin alpha(v)beta3. Cells demonstrating alpha(v)beta3 positivity were identified as tumor astrocytes and endothelial cells by double imaging. The same cells were surrounded by some alpha(v)beta3 ligands and co-localized fibroblast growth factor 2. Matrix metalloproteinase 2 also was found to be co-localized with alpha(v)beta3 in the same cells. Alpha(v)beta3 expression was more relevant in tumor astrocytes. Alpha(v)beta3 integrin and vascular endothelial growth factor expression increased from the periphery to the tumor center. CONCLUSION: Our data support the role of integrins alpha(v)beta3 and alpha(v)beta5 in glioma-associated angiogenesis. In addition, they suggest a role for integrin alpha(v)beta3 in neoangiogenesis and cell migration in high-grade glioma periphery.

Fluorescent imaging in a glioma model in vivo.

BACKGROUND AND OBJECTIVE: Nile blue dyes have been shown to have affinity for tumor tissue as compared to surrounding normal tissue and to be relatively non-toxic. We have employed EtNBA, a lipophilic, fluorescent benzophenoxazine dye, in a murine model to image subcutaneous and intracranial U-87 glioma implants. STUDY DESIGN/MATERIALS AND METHODS: The imaging system used to detect fluorescence consists of a SIT video camera fitted with a zoom microscope-magnifying lens. The tumor was illuminated with a 632.8-nm diffuse beam from a helium-neon laser. The video image was processed using a Sony image processor to give real-time pseudocolor and enhanced black and white images. RESULTS: Following subcutaneous injection of the dye at doses of 2.5-5.0 mg/kg bw, we observed a gradual increase of the fluorescent signal from the tumor which peaked 1-3 hours post-injection with variable selectivity (typically 4:1) for tumor to normal surrounding tissues permitting the clear demarcation of the tumor. CONCLUSIONS: The present in vivo study demonstrates that EtNBA is a safe and effective photodiagnostic agent, able to demarcate U87-MG solid tumors in mice on a real-time basis at a concentration of 2.5-5.0 mg/kg 1-3 hours after administration.

Alpha(v)beta3 and alpha(v)beta5 integrin expression in meningiomas.

OBJECTIVE: Integrins are emerging as alternative receptors capable of mediating several biological functions, such as cell-matrix and cell-cell adhesion, cell migration, signal transduction, and angiogenesis. Two alpha(v) integrins, i.e., alpha(v)beta3 and alpha(v)beta5, play critical roles in mediating these activities, particularly in tumors. No data are available on the expression of these integrins in meningiomas. METHODS: Using Western blot and immunohistochemical analyses with LM609 and PG32, two monoclonal antibodies capable of recognizing the functional integrin heterodimer, we evaluated the expression of alpha(v)beta3 and alpha(v)beta5 integrins in a series of 34 meningiomas of different histological subtypes and grades. We studied their expression in tumor cells and vasculature, as well as the expression of their related angiogenic factors (fibroblast growth factor 2 and vascular endothelial growth factor) and the alpha(v)beta3 ligand vitronectin. RESULTS: Alpha(v)beta3 and alpha(v)beta5 integrins were expressed by neoplastic vasculature and cells. Alpha(v)beta3 and alpha(v)beta5 expression was associated and correlated with that of their respective growth factors (fibroblast growth factor 2 and vascular endothelial growth factor) and microvessel counts and densities. Alpha(v)beta3 was more strongly expressed than alpha(v)beta5 in two cases of histologically benign meningiomas with aggressive clinical behavior. Alpha(v)beta3 expression was associated with that of its related ligand vitronectin and was also evident in small vessels of brain tissue closely surrounding meningiomas. CONCLUSION: Our data demonstrate the expression of alpha(v)beta3 and alpha(v)beta5 integrins in meningioma cells and vasculature. Our findings suggest a role for both of these integrins, and particularly alpha(v)beta3, in meningioma angiogenesis.

Expression of cyclooxygenase 2 (COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor, NS-398.

The up-regulation of cyclooxygenase 2 (COX-2) expression is a frequent occurrence in a variety of different tumors. In this study, COX-2 protein expression was investigated in 50 glioma and 3 normal brain specimens by immunohistochemistry. Expression of COX-2 protein was observed in all normal brain and glioma specimens by immunohistochemistry, regardless of histological grade. The immunoreactive score was significantly higher in high-grade glioma than low-grade glioma and normal brain specimens. For a subset of these tumors (nine gliomas and three normal brain), Western blot analysis was also performed. COX-2 protein was detected in all specimens by Western blot analysis. The effect of the specific COX-2 inhibitor NS-398 on monolayer cell cultures and three-dimensional glioma spheroids was investigated using U-87MG and U-251MG human glioblastoma cell lines. The proliferation rate was assessed in monolayer cultures. In addition, a growth assay, a migration assay, an apoptosis assay, and a tumor invasion assay were performed in a three-dimensional spheroid culture system. NS-398 was able to reduce the proliferation of monolayer cell cultures, as well as the growth of spheroids and tumor cell migration, in a dose-dependent manner. There was also a moderate increase in the number of apoptotic cells in the treated spheroids. NS-398 did not have an inhibitory effect on tumor invasion in the coculture spheroid system. Our study provides evidence that COX-2 is up-regulated in the majority of high-grade gliomas and that a potential role of COX-2 inhibitors as an adjuvant therapy for brain tumors may exist.

Molecular analysis of alterations of the p18INK4c gene in human meningiomas.

Meningiomas are common primary brain tumours frequently presenting with deleted and/or mutated NF2 gene located on 22q.1p has been reported as the second most commonly deleted chromosomal region in these neoplasms. A new member of the INK4 family of CDK inhibitors, the p18INK4c gene, has recently been mapped to this chromosomal arm. By virtue of its structural and functional similarities with the p16 gene, p18 has been implicated as a tumour suppressor gene in a variety of cancers. In this paper 40 human meningiomas were analysed for loss of heterozygosity (LOH) at the p18 locus, mutations and inactivating methylation of the p18 gene. LOH at D1S193, D1S463 and D1S211 microsatellite marker loci mapped to 1p32 was detected in 13 of 35 (37%), four of 20 (20%), and six of 24 (25%) tumour samples, respectively. One sample presented with homozygous deletion at D1S193. Mutational analysis using single stranded conformational polymorphism (SSCP) and direct sequencing did not detect any missense mutation but revealed a novel silent mutation, G to T, at coding nucleotide 435. Analysis of HgaI, BsaHI, ScrFI and Eco0109I restriction sites of p18 exon 1 revealed absence of inactivating methylation. Immunohistochemistry with p18 monoclonal antibody detected presence of cytoplasmic p18 staining in 21 of 22 examined samples. One sample did not stain and was shown to carry homozygous deletion at D1S193. Despite the high frequency of LOH at 1p32 microsatellite markers, the lack of genetic and epigenetic aberrations in the p18 gene together with the presence of p18 protein in all but one meningioma samples argues against the role of p18 as a tumour suppressor gene important for meningioma development.

Spontaneous thrombosis of vein of Galen aneurysmal malformation.

Two cases of aneurysmal malformations of the vein of Galen (AVG) with spontaneous thrombosis are reported. Angiogram and MRI before thrombosis demonstrated AVGs with slow arteriovenous shunts and associated stagnation of contrast in the venous sac secondary to severe outflow restriction. Based on these findings, one patient was managed conservatively, and the other underwent placement of a ventriculoperitoneal shunt. Surveillance of the lesions with subsequent MRIs revealed spontaneous thrombosis of the AVGs with excellent clinical outcomes. Proposed mechanisms of spontaneous thrombosis include slow flow shunts, obstruction of the venous outflow or obstruction of the feeding artery. Similar cases in the literature are reviewed with special emphasis on diagnostic tests, symptomatology, mechanisms of thrombosis and therapeutic options.

Idiopathic pinealitis. Case report.

This 63-year-old man presented with complaints of "having a feeling of falling backward" over a 3-month period. Results of his general physical examination, laboratory studies, and neurological examination were unremarkable. A magnetic resonance image revealed a 1.8 x 1.4 x 1.2-cm enhancing mass in the posterior third ventricle just above the corpora quadrigemina. The pineal gland was found to be diffusely enlarged at operation and separable from the posterior thalamus and was totally resected. The patient had an uneventful postoperative course but continues to be somewhat confused. The lesion consisted of a remarkable chronic inflammatory cell infiltrate permeating the pineal lobules and was composed of T and B lymphocytes, macrophages, eosinophils, and mast cells. Immunoperoxidase studies did not demonstrate Langerhans cells, and a search for microorganisms was unrevealing. There was no evidence of neoplasia; results of immunostaining for germ cell markers and other tumor-associated antigens were negative.

Parasagittal solitary fibrous tumor of the meninges. Case report and review of the literature.

The clinical, radiologic and pathologic features of a case of parasagittal solitary fibrous tumor of the meninges are reported. The patient was a 44 year-old male who presented with a complex partial seizure and a history of headaches and confusion. Radiological studies showed a large extra-axial dural-based mass in the right parietal region, predominantly isointense with gray matter and hypointense with respect to white matter on T1-weighted images, and hypointense with respect to gray matter on T2-weighted images. At surgery, the mass was very vascular, quite firm and very adherent to the convexity. Histologically the tumor was composed of spindle-shaped cells growing in fascicles within a collagenous matrix. Solitary fibrous tumor of the meninges is a newly described entity, which should be kept in mind in the clinical and radiological differential diagnosis of extra-axial brain tumors.

Neurosurgical considerations in supratentorial low-grade gliomas: experience with 175 patients.

The authors reviewed 175 low-grade hemispheric gliomas surgically treated by one surgeon (P.B.) between 1987 and 1996: 74 astrocytomas (42%), 35 oligodendrogliomas (20%), 52 mixed gliomas (30%), 12 gangliogliomas (7%), and two ependymomas (1%). Patient age ranged from 7.5 to 81.9 years (mean 39.2 years); 84 patients (48%) were males and 91 (52%) females. Postsurgical follow-up review ranged from 0.1 to 225.2 months (mean 36.2 months, median 24.9 months). Either T(2)-weighted or contrast-enhanced T(1)-weighted magnetic resonance (MR) images were used to evaluate the percentage of resection achieved and volume of residual disease postoperatively. The majority of patients (55%) had seizures as the presenting symptom, and 45% experienced preoperative symptoms for more than 12 months. Tumor enhancement was present in 21% of cases. In 66% of surgical procedures at least one of the following technical adjuncts was used: monitored local anesthesia, real-time MR imaging, stereotactic guidance with computerized tomography, three dimensional reconstruction, cortical mapping with cortical stimulation, somatosensory or visual evoked potential recording, corticography, or intraoperative ultrasound. Intraoperative MR imaging was used for 40 (22.9%) of the craniotomies and nine (5.14%) biopsies. There were no surgery-related deaths. Complications appeared in 6% of the patients. Progression to a higher-grade tumor occurred in 9.2% of patients within the 3-year follow-up period.