Tumors of glial origin consist of a core mass and a penumbra of invasive, single cells, decreasing in numbers towards the periphery and still detectable several centimeters away from the core lesion. Several decades ago, the diffuse nature of malignant gliomas was recognized by neurosurgeons when super-radical resections using hemispherectomies failed to eradicate these tumors. Local invasiveness eventually leads to regrowth of a recurrent tumor predominantly adjacent to the resection cavity, which is not significantly altered by radiation or chemotherapy. This raises the question of whether invasive glioma cells activate cellular programs that render these cells resistant to conventional treatments. Clinical and experimental data demonstrate that glioma invasion is determined by several independent mechanisms that facilitate the spread of these tumors along different anatomic and molecular structures. A common denominator of this cellular behavior may be cell motility. Gene-expression profiling showed upregulation of genes related to motility, and functional studies demonstrated that cell motility contributes to the invasive phenotype of malignant gliomas. There is accumulating evidence that invasive glioma cells show a decreased proliferation rate and a relative resistance to apoptosis, which may contribute to chemotherapy and radiation resistance. Interestingly, interference with cell motility by different strategies results in increased susceptibility to apoptosis, indicating that this dynamic relationship can potentially be exploited as an anti-invasive treatment paradigm. In this review, we discuss mechanisms of glioma invasion, characteristics of the invasive cell, and consequences of this cellular phenotype for surgical resection, oncologic treatments, and future perspectives for anti-invasive strategies.

Cost of Migration: Invasion of Malignant Gliomas and Implications for Treatment

Hemangiopericytoma. An analysis of 106 cases.

A consecutive series of 23 patients underwent operative removal of an intramedullary spinal cord ependymoma between January, 1976, and September, 1988. Thirteen women and 10 men between the age of 19 and 70 years experienced symptoms for a mean of 34 months preceding initial diagnosis. Eight patients had undergone treatment prior to tumor recurrence and referral. Mild neurological deficits were present in 22 patients on initial examination. The location of the tumors was predominantly cervical or cervicothoracic. Radiological evaluation revealed a wide spinal cord in all cases. Magnetic resonance (MR) imaging was the single most important radiological procedure. At operation, a complete removal was achieved in all patients. No patient received postoperative radiation therapy. Histological examination revealed a benign ependymoma in all cases. The follow-up period ranged from 6 to 159 months (mean 62 months) with seven patients followed for a minimum of 10 years after surgery. Fourteen patients underwent postoperative MR imaging at intervals ranging from 8 months to 10 years postoperatively. No patient has been lost to follow-up review and there were no deaths. No patient showed definite clinical or radiological evidence of tumor recurrence during the follow-up period. Recent neurological evaluation revealed functional improvement from initial preoperative clinical status in eight patients, no significant change in 12 patients, and deterioration in three patients. The data support the belief that long-term disease-free control of intramedullary spinal ependymomas with acceptable morbidity may be achieved utilizing microsurgical removal alone.

Intramedullary ependymoma of the spinal cord

Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease

The effectiveness and complications of radiation therapy for brain neoplasms are reviewed. While the available data suggest a favorable influence and outcome, randomized studies are needed to further optimize radiation therapy techniques and to integrate new therapeutic modalities.

Radiation therapy for neoplasms of the brain

E XTRACRANIAL METASTASIS Of central nervous system gliomas occurs rarely following surgical intervention, 1,12,1s but spontaneous metastasis has been reported only once? ~ Earlier reports emphasize this rarity of metastasis outside the neuraxis by gliomas, and most examples have entered the literature as single case reports. 4,~'s'13'~'21'2-~''~~176 Since many such cases have been seen at the Armed Forces Institute of Pathology ( A F I P ) , a clinicopathologic review was made of the 35 well-documented examples in the files. Only three of these cases have been previously reported. 19,27'3~

Metastasizing neuroectodermal tumors of the central nervous system.

HE propriety of grading ependymomas by a system based upon histological anaplasia, and the effectiveness of irradiation as an adjunctive measure in treatment, are two of the more controversial topics related to this tumor. Utilizing material from the Armed Forces Institute of Pathology (AFIP) supplemented by cases from the Medical College of Georgia (MCG), we will discuss certain aspects of the classification, pathology, diagnosis, and therapy of ependymomas. Source of Material One hundred and eighty cases were available for study: 167 from the AFIP; 13 from the MCG. The AFIP material consisted of histologicM slides and in many cases gross material from which additional slides could be made along with a clinical summary. The patient population from which this material was taken consisted primarily of military personnel and their dependents, veterans, and occasional civilians where slides had been sent to AFIP for consultation. Talmadge Memorial Hospital at the MCG, on the other hand, is a general referral hospital for the State of Georgia. Cases Excluded. Of the 180 cases, 47 were excluded for one or more of the following reasons: 1. Inadequate pathological material to permit accurate diagnosis. 2. Disagreement with the original diagnosis. Most of these cases were seen before 1940 and originally classified as "spongioblastoma ependymale," they are now considered "glioblastoma multiforme" and so have been omitted. All cases in which the degree of anaplasia was such that the basic ependymal origins were not recognizable were also excluded.

Ependymomas: clinical and pathological aspects.

Angioblastic meningiomas; clinicopathologic study of 81 cases.

IN THE ADULT, motor neuron disease or amyotrophic lateral sclerosis can be subdivided into several groups on the basis of clinical, pathologic, and epidemiologic features. 1 The histologic changes observed in the classic sporadic cases include nonspecific degeneration and loss of motor neurons in the spinal cord, brain stem, and cerebral cortex. Demyelination of the pyramidal tracts often accompanies the neuronal losses. 2 A familial variant further characterized by demyelination of the posterior columns and spinocerebellar tracts has been reported. 3 In a few residual motor neurons from these cases, Hirano et al 4 described accumulations of hyalinized material, occasionally with acidophilic cores that resemble Lewy bodies. In still another variant, the amyotrophic lateral sclerosis and Parkinsonism-dementia complex on Guam, neurofibrillary tangles have been observed in the anterior horn cells. 5 This report presents light and electron microscopic observations from an unusual sporadic case of motor neuron disease characterized by

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Intraneuronal Conglomerates in Sporadic Motor Neuron Disease: A Light and Electron Microscopic Study

✓ The vein of Galen was ligated in 16 Rhesus monkeys and six mongrel dogs, and the animals followed for periods up to six months. Ventricular size was determined preoperatively by pneumoencephalography. Angiography was performed prior to surgery and at intervals from the immediate postoperative period to 6 months following vein ligation. After sacrifice, all brains were serially sectioned and examined by light microscopy. In no case was hydrocephalus found to follow vein of Galen ligation. Consequences were limited to angiographic dilatation of major draining sinuses and cortical veins and microscopic dilatation of diencephalic and choroidal vessels. These changes were evident in the immediate postoperative period and persisted for as long as the animals were followed.

Kenneth M. Earle

Papers

Metastasizing neuroectodermal tumors of the central nervous system.

Ependymomas: clinical and pathological aspects.

Angioblastic meningiomas; clinicopathologic study of 81 cases.

Intraneuronal Conglomerates in Sporadic Motor Neuron Disease: A Light and Electron Microscopic Study

Vein of Galen ligation in the primate. Angiographic, gross, and light microscopic evaluation.