Reversion of phenotype of endothelial cells in brain tissue around glioblastomas

With the aim of studying the putative involvement of peritumoral microvessels in the formation of brain edema, small pieces of peritumoral brain tissue were removed from six patients with glioblastoma multiforme submitted to surgery. All patients had cerebral edema, as shown by preoperative C.T. and N.M.R. Control specimens were obtained from four patients undergoing ventriculo-peritoneal shunt. The tissue fragments were fixed in glutaraldehyde-osmium and embedded in Epon. In semi-thin sections observed under light microscopy peritumoral endothelial cells exhibited voluminous cytoplasm and nucleus. Under the electron microscope, capillary cells from glioblastoma patients differed from controls mainly by showing nuclei rich in euchromatin, cytoplasm rich in pinocytotic vesicles and with occasional fenestrations. All these morphological characteristics are compatible with a process of reversion of phenotype of capillaries around glioblastomas to that of periphery as well as an increase in permeability. Both events may be due to diffusion of a tumoral vascular permeability/endothelial growth factor. This peripheral vessel phenotype of peritumoral microvessels supports their participation in the formation of brain edema and may provide a new clue for therapeutic intervention: for example it fits quite well to the known increase in permeability by leukotrienes and decrease in permeability by corticosteroids in tumoral edema.