Malignant glioma: neuropathology and neurobiology

Malignant gliomas may manifest at any age including congenital and childhood cases. Peak incidence is, however, in adults older than 40 years. Males are more frequently affected than females. The sole unequivocal risk factor is therapeutic ionizing irradiation. Malignant gliomas comprise a spectrum of different tumor subtypes. Within this spectrum, glioblastoma, anaplastic astrocytoma and anaplastic oligodendroglioma share as basic features preferential location in cerebral hemispheres, diffuse infiltration of brain tissue, fast tumor growth with fatal outcome within months or years. Invasion is regarded as one of the main reasons for poor therapeutic success, because it makes complete surgical removal of gliomas impossible. Invasion of glioma cells requires interaction with the extracellular matrix and with surrounding cells of the healthy brain tissue. Vascular proliferates and tissue necrosis are characteristic features of malignant gliomas, in particular glioblastoma. These features are most likely the consequence of rapidly increasing tumor mass that is inadequately oxygenized by the preexisting vasculature. In malignant glioma, distinct molecular pathways including the p53 pathway, the RB pathway and the EGFR pathway show frequent alterations that seem to be pathogenetically relevant. Methylguanine-methyltransferase (MGMT) promoter methylation status in glioblastoma and 1p19q deletion status in anaplastic oligodendroglioma are associated with response to chemotherapy. The role of neuropathology and neurobiology in neurooncology is 1. to provide a clinically meaningful classification of brain tumors on basis of pathobiological factors, 2. to clarify etiology and pathogenesis of brain tumors as rational basis for development of new diagnostic tests and therapies, and 3. to translate testing for new clinically relevant molecular parameters into clinical application.