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We placed in culture brain tumors from 45 cases (7 cases of astrocytoma, 2 from oligodendrogliomas, 2 glioblastomas, 2 ependymomas, 13 meningiomas, 6 pituitary adenomas, 5 neurinomas, a malignant lymphoma, a choroid plexus papilloma, and 6 metastatic tumors) and succeeded in making a primary culture from 33, and maintained 17 in vitro over a considerable period of time (greater than three months). In the early period of the primary cultures, the astrocytoma cells had cytoplasmic processes which contacted each other, the oligodendroglioma cells were small and spindle-shaped, the glioblastoma cells were neoplastic with pleopmorphic features and possessed cytoplasmic processes, the ependymoma cells formed a rosette-like cell arrangement, the meningioma cells were spindle- or round-shaped cells and characterized as forming psammoma bodies, the pituitary adenoma cells were round- or oval-shaped cells and produced growth hormone (GH), adenocorticoid tropic hormone (ACTH), prolactin, or other hypophyseal hormones, the choroid plexus papilloma cells were round-or polygonal and showed a papillary cell arrangement, the neurinoma cells were spindle- or fibrous-shaped cells, and the malignant lymphoma cells were round and formed cell aggregates floating in the culture medium.

The present study has attempted to demonstrate that the morphological spectrum of oligodendrogliomas includes tumors which are traditionally misinterpreted as 'diffuse fibrillary astrocytoma'. We have shown that these tumors are in fact made of isolated neoplastic oligodendrocytes which are entrapped in a fibrillary background composed of axons and fibrillary reactive gliosis. Analysis in a series of 153 'pure' supratentorial oligodendrogliomas composed of 'classical' or pseudo 'diffuse fibrillary oligodendrogliomas' diagnosed by imaging-based serial stereotactic biopsies showed that 2/3 of the tumors were exclusively made of isolated tumor cells (ITCs) (structure type III) and that only 1/3 of them exhibited both ITCs and solid tumor tissue components (structure type II). The tumor tissue destroys the brain parenchyma and contains new formed microblood vessels whereas ITCs do not destroy the parenchyma and are not associated with microangiogenesis. These fundamentally opposite morphological characteristics were reflected by the following findings: 1) contrast enhancement was observed in 64% of structure type II but was never seen in structure type III oligodendrogliomas. 2) a neurological deficit occurred in 57% of structure type II but in only 8% of structure type III oligodendrogliomas. 3) using the new grading system described in the companion paper to this study, we found that the biological behavior of oligodendrogliomas was also closely related to the patterns of tumor growth. From a synthesis of data gathered in this study it is suggested that emergence of microangiogenesis within a tumor which at first grows slowly with a structure type III pattern is a crucial event toward more aggressive behavior.

In 48 patients with gliomas in whom complete clinical follow-up was obtained, DNA ploidy was evaluated by using formalin-fixed paraffin-embedded tissues and by means of image analysis. The mean DNA indices, determined by averaging DNA indices of all tumor cells in a tumor, were mainly affected by mean DNA indices of the nuclei of SG2M phase tumor cell (including S phase and G2M phase cells) (SG2M DNA indices) and that mean DNA indices correlated with the SG2M phase fraction. The SG2M DNA indices and the percentage of tumor cells with S phase and G2M phase were higher in high grade gliomas including anaplastic glioma and glioblastoma multiforme than in low grade gliomas. Patients with G2M-hypertetraploid tumors demonstrated a shorter time to tumor progression than those with G2M-tetraploid in high grade glioma. Morphometrically, the nuclei of SG2M phase glioma cells were larger and more deformity than those of G0G1 phase (including G0 phase and G1 phase cells) cells. The G2M-hypertetraploid tumors were highly malignant and demonstrated large nuclei, greater nuclear deformity, and a higher proliferative potential. The G2M-tetraploid gliomas demonstrated a shorter time to tumor progression in cases whose the SG2M fraction was large. In contrast, G2M-hypotetraploid gliomas revealed an insignificant trend towards a longer time to tumor progression than those associated with tetraploid and hypertetraploid gliomas. We emphasize herein the prognostic importance of the SG2M phase cell, as well as other proliferation indices.

Intraventricular neurocytoma, a newly identified disease entity with probably not so rare incidence, has several distinctive clinico-pathological characteristics. Four cases are presented. As in the other cases reported in the literature [1-7], the characteristic features are young age, location close to the junction of the septum pellucidum and foramen of Monro, and well-differentiated neuronal origin pathologically.

The expression of epidermal growth factor receptor (EGF-R) was examined in 27 primary human brain tumors (7 glioblastomas, 10 astrocytomas, 5 oligodendrogliomas, 1 schwannoma, 1 ganglioneuroma, 1 medulloblastoma, 1 ependymoma, 1 histiocytic lymphoma), in 6 brain metastases from lung carcinomas and in 20 meningiomas. Peritumoral tissues histologically normal excised surgically along with a large tumor were used as control. All plasma membranes from brain tissues tested showed specific EGF binding. The EGF receptor is expressed at low levels in the control human brain and at very high levels in 60% of the total intracranial tumors studied. When the various histological types of tumors were analyzed, the higher percentage of positive tumors was found with the meningiomas (85%) and the glioblastomas (71%), while the lower percentage of positivity was found with the oligodendrogliomas (40%) and the astrocytomas (30%). A good correlation between binding and total amount of EGF-R protein detected by Western Blot was also observed.