Faculty Bibliography

Two cases of cystic brainstem schwannomas protruding into the fourth ventricle are described. Both patients presented with hemifacial spasm. While there is only one previous case report of an intraventricular brainstem schwannoma, there has been no prior description in the literature of hemifacial spasm associated with such a tumor. The clinical, radiographic, surgical, and histopathological features of these tumors are elaborated. The relationship of hemifacial spasm to the various putative theories of origin proposed for intraparenchymal schwannomas is discussed

A 13-year-old boy with Down syndrome (DS) had a brainstem glioma confirmed at autopsy, 10 years after receiving prophylactic cranial irradiation for acute myeloblastic leukemia. There is no clear association of brain tumors with DS; despite a reported link between leukemia and glioma, a causal association with radiation therapy is more likely

Because of the prominent neovascularization observed in the growth of brain tumors, we studied the occurrence of basic fibroblast growth factor (bFGF), a potent angiogenic factor in astrocytomas, the most aggressive of which often have marked vascular hyperplasia. Using immunohistochemical methods, we examined 21 examples of such tumors, 7 glioblastomas multiforme, 7 anaplastic astrocytomas, and 7 low grade astrocytomas. Using polyclonal and affinity-purified rabbit antisera to human bFGF, we detected immunoreactive bFGF in all cases of glioblastoma multiforme. bFGF was present in both endothelial cells and neoplastic astrocytes. In 4 of 7 anaplastic astrocytomas, the tumor astrocytes had bFGF immunoreactivity and, in 5 of 7 cases, endothelial cells were also immunopositive. In glioblastomas multiforme and anaplastic astrocytomas, capillaries adjacent to tumor showed bFGF immunoreactivity, whereas capillaries distant from the tumors were not immunostained. In low grade astrocytomas, astrocytic cells were weakly immunoreactive in 2 of 7 cases, and in only 1 of the 7 cases capillaries were immunostained. In each grade, reactive astroglial cells showed variable bFGF immunoreactivity. The immunostaining was not seen with the flow-through fraction obtained after affinity purification of the bFGF antiserum with pure recombinant bFGF. These results suggest a possible role for bFGF in tumor growth and in angiogenesis in astrocytomas

Microvascular proliferation, a hallmark of malignant brain tumors, represents an attractive target of anticancer research, especially because of the quiescent nonproliferative endothelium of the normal brain. Cerebral neoplasms sequester copper, a trace metal that modulates angiogenesis. Using a rabbit brain tumor model, normocupremic animals developed large vascularized VX2 carcinomas. By contrast, small, circumscribed, relatively avascular tumors were found in the brains of rabbits copper-depleted by diet and penicillamine treatment (CDPT). The CDPT rabbits showed a significant decrease in serum copper, copper staining of tumor cell nuclei, microvascular density, the tumor volume, endothelial cell turnover, and an increase in the vascular permeability (breakdown of the blood-brain barrier), as well as peritumoral brain edema. In non-tumor-bearing animals, CDPT did not alter the vascular permeability or the brain water content. CDPT also inhibited the intracerebral growth of the 9L gliosarcoma in F-344 rats, with a similar increase of the peritumoral vascular permeability and the brain water content. CDPT failed to inhibit tumor growth and the vascularization of the VX2 carcinoma in the thigh muscle or the metastases to the lung, findings that may reflect regional differences in the responsiveness of the endothelium, the distribution of copper, or the activity of cuproenzymes. Metabolic and pharmacologic withdrawal of copper suppresses intracerebral tumor angiogenesis; angiosuppression is a novel biologic response modifier for the in situ control of tumor growth in the brain

The copper ion, a cofactor of angiogenesis, is sequestered in human brain tumors and the adjacent brain. The invasive spread of neoplastic cells has been linked to angiogenesis and involves similar mechanisms of migration and tumor-matrix interaction. In this report, copper depletion inhibited the infiltrative spread of the normally invasive 9L gliosarcoma. Twenty made Fischer 344 rats were each injected with 1 X 10(5) 9L cells; 10 rats were treated with a low-copper diet and penicillamine. In the normocupremic control rats, a 'diffuse' invasive pattern was observed in all 10 animals. In the hypocupremic group, a 'nodular' pattern, with a discrete border between tumor and brain, was found in 7 of 10 rats (P less than 0.01). In a second experiment, the brains of 16 tumor-bearing rats were studied by electron microscopy. In the 8 normocupremic control rats, cytoplasmic extensions and pseudopodial protrusions, cytological markers of invasive cells, were prominent at the tumor-brain interface. In striking contrast, pseudopodia were absent along the border of the tumors in the 8 hypocupremic rats. These findings suggest a biological role of copper in the neoplastic spread of brain tumor cells. Pharmacological and metabolic alteration of the cellular microenvironment to inhibit invasiveness represents a novel therapeutic approach, especially for tumors of the brain in which malignancy is a function of regional invasiveness