Parasagittal ependymoma resembling falcine meningioma.

Presentation, diagnosis, and management of an unusual parasagittal ependymoma, radiographically resembling a falcine meningioma, are described. Despite its radiographic appearance, pathologic evaluation revealed classic features of an ependymoma. The radiographic and pathologic characteristics of this unusual lesion are briefly examined, and the literature is reviewed. Although extraaxial ependymomas are rare, they should be considered in the radiographic differential diagnosis of dural-based lesions, especially for patients within the first 3 decades of life.

Proliferation index is related to patient age in glioblastoma.

Younger patients with glioblastomas have a significantly better prognosis than do older patients. To determine whether patient age might be related to proliferation of glioblastoma cells, glioblastomas from patients of different ages were stained with the Molecular Immunology Borstel number 1 antibody to detect proliferating cells. Younger patient age was a significant predictor of a low Molecular Immunology Borstel number 1 proliferation index (p = 0.0001). This previously unreported association favors an intrinsic difference in the type of glioblastomas that afflict younger patients.

Somatic von Hippel-Lindau gene mutations detected in sporadic endolymphatic sac tumors.

Endolymphatic sac tumors (ELSTs) occur sporadically or in association with an autosomal dominantly inherited tumor syndrome, von Hippel-Lindau (VHL) disease. In VHL disease, a germline mutation of the VHL tumor suppressor gene is inherited, and loss of function of the wild-type allele occurs through genetic deletion with subsequent development of neoplastic growth. Genetic alterations associated with sporadic ELSTs are less well understood. In this study, we used tissue microdissection to selectively analyze neoplastic cells from four sporadic ELSTs. In two cases, we detected somatic mutations involving VHL gene exons 1 and 2, respectively. Additionally, one of these cases revealed deletion of the VHL gene locus. Two cases did not reveal VHL gene mutation; one of these two cases showed VHL gene deletion. These results suggest that mutations and allelic deletions of the VHL tumor suppressor gene play a role in the tumorigenesis of sporadic ELSTs.

Extracranial metastatic meningioma.

Meningiomas rarely metastasize outside the intracranial compartment. We report a case of disseminated metastases from a recurrent intracranial meningioma and review the imaging and pathological literature on metastatic meningioma.

MIB-1 proliferation index predicts survival among patients with grade II astrocytoma.

The purpose of this study was to determine whether a relationship existed between MIB-1 labeling index (LI) percentages and survival in patients with grade II astrocytomas. From archival paraffin-embedded surgical specimens of 50 patients of the University of Michigan Medical Center with World Health Organization grade II astrocytomas, 22 patients had a Ki-67 LI of less than or equal to 2.0; and 28 patients had a MIB-1 LI of more than 2.0. Over a median follow-up interval of 10 years, ranging up to 16 years, 23% (n = 5) died of tumor in the first group while 82% (n = 23) died in the second group, a distinct difference in survival between these groups. Univariate analysis showed that a high MIB-1 predicted shorter survival (p < 0.0001), and that increased age was associated with shorter survival (p = 0.007). Gender, tumor location and radiotherapy had no significant association with survival. When adjusting for these (excluding tumor location) in the Cox proportional hazards model simultaneously, MIB-1 and age were independently prognostic. The hazard ratios were 1.301 per 1% MIB-1 LI (p = 0.0001), and 1.045 per year of age (p = 0.0028). From other studies, we know that histopathologic grade and age predict survival for glioma patients. However, even within grade II astrocytomas there is still a wide heterogeneity in how long a patient survives. We conclude that among grade II astrocytomas older patients and, independently, patients with higher MIB-1 labeling index have shorter survival.

Correlation of intraluminal thrombosis in brain tumor vessels with postoperative thrombotic complications: a preliminary report.

OBJECT: Thrombotic complications (deep vein thrombosis and/or pulmonary embolization [DVT/PE]) occur in 18 to 50% of patients harboring brain tumors who undergo neurosurgical procedures. Such patients are at risk for DVT/PE because of immobility, paresis, hypovolemia, and lengthy surgery. The present study was undertaken to see whether tumor patients at highest risk for DVT/PE could be identified so that augmentation of prophylactic measures might be used to reduce the incidence of thrombotic complications. METHODS: The authors conducted a retrospective analysis of 488 patients enrolled in their brain tumor registries between 1988 and 1995, identifying 57 patients (12%) with recorded symptomatic DVT, PE, or both postoperatively. In 24 of these 57 cases histological specimens were retrievable for review, allowing an in-depth analysis. Forty-five patients were lost to follow-up review, and the remaining 386 patients had no record of systemic thrombosis. Slides of pathological specimens were retrievable in 50 cases in which there was no DVT/PE. From these 50 cases, 25 were selected at random to represent the control group by a blinded observer. Seventeen (71%) of the 24 brain tumor specimens obtained in patients with DVT/PE stained positively for intraluminal thrombosis (ILT) after hematoxylin and eosin had been applied. The odds ratio associated with the presence of ILT was 17.8, with a confidence interval ranging from 4 to 79.3. No evidence of ILT was found in 22 patients (88%) within the control group (p < 0.0001, Fisher's exact test). Other factors that may predispose patients with brain tumors to DVT/PE-limb paresis, extent of tumor removal, and duration of the surgery-were also analyzed and found not to be statistically significant. Therefore, these factors were not the basis for differences seen between the study and control groups. CONCLUSIONS: These preliminary observations suggest that the presence of ILT within malignant glioma or glioblastoma tumor vessels may represent a marker of tumor-induced hypercoagulability.

Insights about brain tumors gained through immunohistochemistry and in situ hybridization of nuclear and phenotypic markers.

Immunohistochemistry (IHC) has provided major insights about the classification of brain tumors by identifying cellular markers of phenotype and about tumor growth potential with nuclear markers of proliferation. In situ hybridization (ISH) research shows promise for diagnostic applications in tumor classification. The avidin-biotin conjugate IHC procedure is highlighted for diagnostic use on routinely processed clinical specimens. The immunophenotypes of brain tumors are tabulated in reference to their common IHC markers. Tumors that have been correctly classified by their IHC phenotypes include the giant-cell glioblastoma, primary brain lymphoma, and central neurocytoma. Phenotypes that may be more definitively detected by ISH, such as pituitary hormone, immunoglobulin light chain, and collagen messages are described. IHC of nuclear proliferation markers correlates with grade of malignancy, predicts tumor growth potential, and is prognostic for patient survival. The incorporation of bromodeoxyuridine, the expression of proliferating cell nuclear antigen, and the expression of Ki-67 antigen detected by MIB-1 antibody are compared in regard to their cell cycle activity and labeling index determinations. Fluorescence in situ hybridization (FISH) of brain tumor interphase nuclei and chromosomes is described. Abnormal FISH signals of specific chromosomes are associated with different types of brain tumors, with different grades of malignancy, and with mesenchymal drift of glioma cells in culture.

Chromosomal characteristics of childhood brain tumors.

In the present cytogenetic analysis of 116 pediatric brain tumors, chromosomal abnormalities were demonstrated in 44 cases, 48 cases revealed only 46,XX or 46,XY cells, and 24 cases were nonproductive. In contrast to studies of adult brain tumors in which isolated loss of one X or the Y chromosome is often encountered, 45,X,-X and 45,X-Y stemlines or sidelines were not observed in this series of childhood tumors. Among the 17 medulloblastomas with cytogenetic abnormalities, chromosome 1 was most frequently affected by structural deviations; the most prevalent specific alteration (7 of 17 tumors) was loss of 17p, through i(17)(q10) or unbalanced translocation. The majority of low grade astrocytomas had normal stemlines, although one pilocytic astrocytoma and one cerebellar astrocytoma had frequent telomeric associations and a second pilocytic astrocytoma had a clone with trisomy 11. Thirteen of 19 high-grade and recurrent astrocytic tumors had abnormal stemlines that were approximately equally divided among cases with chromosomal counts in the near-diploid, hyperdiploid, and near-triploid-tetraploid ranges. Although no consistent abnormalities were observed, subsets of cases had structural abnormalities of chromosome 3, 7q, 9q, or 17p. The cases of childhood brain tumors described here demonstrate that 45,X,-X, and 45,X,-Y stemlines or sidelines are rare in these tumors and confirm frequent loss of 17p in medulloblastomas. High-grade astrocytic tumors in children frequently have abnormal stemlines, often in the hyperdiploid and polyploid ranges, and they differ from high-grade gliomas in the adult by lacking consistent numerical and structural deviations.

A comparison of the predictive power for survival in gliomas provided by MIB-1, bromodeoxyuridine and proliferating cell nuclear antigen with histopathologic and clinical parameters.

The purpose of this prospective study of 65 patients was to compare side-by-side the predictive power for survival of (a) MIB-1, (b) bromodeoxyuridine (BUDR), and (c) proliferating cell nuclear antigen (PCNA). They were compared (a) with each other, (b) with several clinical predictors, and (c) with histopathologic grade under actual clinical biopsy conditions in a study of 1993 World Health Organization (WHO) grade II to IV adult supratentorial gliomas. There was a strong positive relationship between MIB-1 and BUDR by Spearman Rank correlation. In univariate analysis, MIB-1 (logrank p = 0.06) was more predictive of survival than BUDR or PCNA. Longer survivors were distinguished from others by the lowest MIB-1 labeling indices (LI < or = 2.5%) better than by the lowest histopathologic grade. However, histopathologic grades were highly predictive among the entire group (logrank p < 0.0001). Young age (p < 0.0001) and high Karnofsky performance status (p < 0.0001) were the clinical factors most predictive of longer survival. Female gender correlated with longer survival (logrank p = 0.02). In multivariate Cox proportional hazards models, age, Karnofsky performance status, and histopathologic grading remained statistically significant after full reduction of the model. We conclude that Ki-67 measured by MIB-1 monoclonal antibody was superior to other markers of proliferation. When all factors are considered simultaneously over all 3 grades of malignancy, greatest predictive power resides in histopathologic grade and clinical variables. MIB-1 is expected to be most important in cases where clinical or histopathologic factors are ambiguous or where they cannot be fully assessed.

Monitoring early response of experimental brain tumors to therapy using diffusion magnetic resonance imaging.

Quantitative magnetic resonance imaging was performed to evaluate water diffusion and relaxation times, T1 and T2, as potential therapeutic response indicators for brain tumors using the intracranial 9L brain tumor model. Measurements were localized to a column that intersected tumor and contralateral brain and were repeated at 2-day intervals before and following a single injection of 1,3-bis(2-chloroethyl)-1-nitrosourea (13.3 mg/kg). Tumor growth was measured using T2-weighted magnetic resonance imaging to determine the volumetric tumor doubling time (Td) before (Td = 64 +/- 13 h, mean +/- SD, n = 16) and after (Td = 75 +/- 9 h, n = 4) treatment during exponential regrowth. Apparent diffusion coefficient of untreated tumors was independent of tumor volume or growth time, whereas relaxation times increased during early tumor growth. Diffusion displayed the strongest treatment effect and increased before tumor regression by 55% 6-8 days following treatment. Changes in relaxation times were also significant with increases of 16% for T1 and 27% for T2. Diffusion and relaxation times returned to pretreatment levels by 12 days after treatment. Histological examination supports the model that the observed increase in diffusion reflects an increase of extracellular space following treatment. Furthermore, the subsequent apparent diffusion coefficient decrease is a result of viable tumor cells that repopulate this space at a rate dependent on the surviving tumor cell fraction and recurrent tumor doubling time. Serial tumor volume measurements allowed determination of log cell kill of 1.0 +/- 0.3 (n = 4). These results suggest that diffusion measurements are sensitive to therapy-induced changes in cellular structure and may provide an early noninvasive indicator of treatment efficacy.

Chromosome breakpoint at 17q11.2 and insertion of DNA from three different chromosomes in a glioblastoma with exceptional glial fibrillary acidic protein expression.

A glioblastoma that retained glial fibrillary acidic protein (GFAP) in culture has a break in the long arm of chromosome 17 at band 17q11.2. DNA inserted at this breakpoint came from chromosome bands 3p21, 3q23, 16q11.2, and 22q11.2. These chromosome fragments were inserted in band 17q11.2 proximal to the neurofibromatosis-1 (NF-1) gene and neu (HER2; erbB2) oncogene loci. The glioblastoma also contained a reciprocal translocation between 16p12 and 20p12. These structural abnormalities, previously undescribed in gliomas, were demonstrated by high-resolution chromosome banding, microdissection, and fluorescence in situ hybridization (FISH). Numerical changes typical of glioblastoma were present: gain of chromosome 7 and losses of chromosomes 10, 13, and 22. The complex chromosome origin of DNA inserted in this glioma chromosome is described. The association of two infrequent events in this single glioblastoma line, this complex insertion and retention of GFAP expression, is not likely to be a chance occurrence. It raises the possibility of an association between the two events.

Foramen magnum neurenteric cyst causing mollaret meningitis: MR findings.

MR showed a neurenteric cyst posterior to the cervicomedullary junction in a man with chronic recurrent aseptic meningitis. On T1-weighted MR, the cyst was of high intensity in relation to the brain, and on T2-weighted MR it was of less intensity than cerebrospinal fluid.

Immune brachial plexus neuropathy: suggestive evidence for an inflammatory-immune pathogenesis.

We report brachial plexus biopsy findings from two Australian and two American patients with brachial plexus neuropathy. There were florid multifocal mononuclear inflammatory cell infiltrates. Present evidence suggests that these brachial neuropathies have an immune basis.

In vivo MR determination of water diffusion coefficients and diffusion anisotropy: correlation with structural alteration in gliomas of the cerebral hemispheres.

PURPOSE: To determine whether a relationship exists between water diffusion coefficients or diffusion anisotropy and MR-defined regions of normal or abnormal brain parenchyma in patients with cerebral gliomas. METHODS: In 40 patients with cerebral gliomas, diffusion was characterized in a single column of interest using a motion-insensitive spin-echo sequence that was applied sequentially at two gradient strength settings in three orthogonal directions. Apparent diffusion coefficients (ADCs) were derived for the three orthogonal axes at 128 points along the column. An average ADC and an index of diffusion anisotropy (IDA = diffusion coefficientmax-min/diffusionmean) was than calculated for any of nine MR-determined regions of interest within the tumor or adjacent parenchyma. RESULTS: In cerebral edema, mean ADC (all ADCs as 10(-7) cm2/s) was 138 +/- 24 (versus 83 +/- 6 for normal white matter) with mean IDA of 0.26 +/- 0.14 (versus 0.45 +/- 0.17 for normal white matter). Solid enhancing central tumor mean ADC was 131 +/- 25 with mean IDA of 0.15 +/- 0.10. Solid enhancing tumor margin mean ADC was 131 +/- 25, with IDA of 0.25 +/- 0.20. Cyst or necrosis mean ADC was 235 +/- 35 with IDA of 0.07 +/- 0.04. CONCLUSION: In cerebral gliomas ADC and IDA determinations provide information not available from routine MR imaging. ADC and IDA determinations allow distinction between normal white matter, areas of necrosis or cyst formation, regions of edema, and solid enhancing tumor. ADCs can be quickly and reliably characterized within a motion-insensitive column of interest with standard MR hardware.

Products of cells from gliomas: IX. Evidence that two fundamentally different mechanisms change extracellular matrix expression by gliomas.

Four human astrocytic gliomas of high grade of malignancy were each evaluated in tissue and in vitro for percentages of cells expressing glial fibrillary acidic protein (GFAP), collagen type IV, laminin and fibronectin assessed by immunofluorescence with counterstaining of nuclear DNA. Percentages of cells with reticulin and cells binding fluorescein-labeled Ulex europaeus agglutinin were also assessed. In tissue, each extracellular matrix (ECM) component was associated with cells in the walls of abnormal proliferations of glioma vessels, and all four tumors had the same staining pattern. Two strikingly different patterns of conversion of gene product expression emerged during in vitro cultivation. (1). In the most common pattern, percentages of all six markers consistently shifted toward the exact phenotype of mesenchymal cells in abnormal vascular proliferations: increased reticulin, collagen type IV, laminin and fibronectin; markedly decreased glial marker GFAP and absent endothelial marker Ulex europaeus agglutinin. The simplest explanation of this constellation of changes coordinated toward expression of vascular ECM markers is that primary glioma cell cultures are overgrown by mesenchymal cells from the abnormal vascular proliferations of the original glioma. These cell cultures were tested for in situ hybridization (ISH) signals of chromosomes 7 and 10. Cells from one glioma had diploid signals. Cells from the other glioma had aneuploid signals indicating they were neoplastic; however, their signals reflected different numerical chromosomal aberrations than those common to neoplastic glia. (2). The second pattern was different. Cells with ISH chromosomal signals of neoplastic glia retained GFAP, and gained collagen type IV. Their laminin and fibronectin diminished, but persisted among a lower percentage of cells. Cloning and double immunofluorescence confirmed the presence of individual cells with glial and mesenchymal markers. A cell expressing GFAP in addition to either fibronectin, reticulin or collagen type IV is not a known constituent of glioblastoma tissue. This provides evidence of a second mechanism of conversion of gene expression in gliomas.

Aggressive papillary middle ear tumors: a report of two cases with review of the literature.

Adenomatous tumors of the middle ear are rare, with only approximately 100 cases reported. A distinct subclass of this tumor demonstrates microscopic papillary architecture and has a propensity to erode the petrous bone and extend intracranially. The term "aggressive papillary middle ear tumor" has recently been proposed to describe this more invasive type of middle ear tumor. Thirty-seven cases of aggressive papillary middle ear tumors have been reported. We present two additional cases and discuss the clinical, radiologic, histologic, and operative features of this locally aggressive neoplasm. The tumor affects adults of both sexes. The clinical prodrome is prolonged. Presenting signs and symptoms most often relate to the involvement of cranial nerves V-VIII. Imaging studies reveal large, enhancing, destructive tumors with a generous vascular supply. Intraoperatively, the tumors are bloody, fibrous, and adherent to surrounding structures. Various surgical approaches in combination or in series may be used. Preoperative embolization may be helpful. The role of adjunctive radiation is unclear. Aggressive papillary middle ear tumors are histologically benign tumors with clinically destructive behavior. However, it appears that aggressive surgical management affords prolonged survival with minimal worsening of cranial nerve deficits.

Cystic cervical intramedullary ependymoma with previous intracyst hemorrhage. Magnetic resonance imaging at 1.5 T.

A patient with a cystic cervical ependymoma is described. Magnetic resonance imaging identified evidence of previous intratumor hemorrhage, which was confirmed at surgery. The images, operative findings, and pathology are reviewed.

Giant Rathke cleft cyst.

The preoperative diagnosis for an unusual skull base lesion was chordoma. The combination of imaging, pathologic, and surgical findings suggests the diagnosis of Rathke cyst.

Focal cerebral magnetic resonance changes associated with partial status epilepticus.

We report 2 patients with transient abnormalities on magnetic resonance imaging (MRI) associated with partial status epilepticus (SE). A man with a 4-month history of partial seizures had complex partial SE for 9 days, with left temporal maximum on ictal EEG. Left temporal lobe T2 signal was increased on MRI during SE, but cerebral MRI was normal 9 weeks later. A woman with "cryptogenic" temporal lobe epilepsy for 16 years had complex partial SE for 1 week, with right temporal maximum on ictal EEG. T2 Signal was increased over the entire right temporal lobe, extending into the insula, without mass effect, on MRI 1 month after SE ended. Repeat MRI 1 month later showed marked decrease in volume of increased T2 intensity, without gadolinium enhancement, but with mild mass effect over the right anterioinferomesial temporal areas. A gemistocytic astrocytoma was resected. Focal cerebral MRI abnormalities consistent with cerebral edema may be due to partial SE but also may indicate underlying glioma, even in long-standing partial epilepsy. Focal structural imaging changes consistent with neoplasm should be followed to full resolution after partial SE.

Plasminogen activators and inhibitors in gliomas: an immunohistochemical study.

The tissue (tPA) and urokinase (uPA) types of plasminogen activator and the plasminogen activator inhibitor 1 (PAI-1) are enzymatic proteins that may play an important role in the degradation of the extracellular matrix in physiologic and neoplastic conditions. In particular, urokinase may underlie key properties of malignant cells, such as invasiveness and dissemination. We have studied the immunohistochemical distribution of tPA, uPA, and PAI-1 in 24 human gliomas, including seven well-differentiated astrocytomas, three oligodendrogliomas, six anaplastic astrocytomas, and eight glioblastomas multiforme. All anaplastic astrocytomas and glioblastomas showed numerous neoplastic cells immunoreactive for uPA, but not for tPA. In contrast, low-grade gliomas were negative for uPA, but contained some tPA-immunoreactive cells. Endothelial cells of vessels in non-neoplastic and neoplastic brain were immunoreactive for tPA, but not for uPA or PAI-1. Non-neoplastic glia were unreactive for tPA, uPA, and PAI-1. Small anaplastic cells present in three glioblastomas showed immunoreactivity for PAI-1. The presence of a large number of uPA-immunoreactive neoplastic cells in high-grade gliomas suggest that this fibrinolytic protein plays a significant role in the invasive properties of these neoplasms.