'Pseudopalisading' necrosis in glioblastoma: A familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis

摘要: Glioblastoma (GBM) is a highly malignant, rapidly progressive astrocytoma that distinguished pathologically from lower grade tumors by necrosis and microvascular hyperplasia. Necrotic foci are typically surrounded "pseudopalisading" cells-a configuration relatively unique to malignant gliomas has long been recognized as an ominous prognostic feature. Precise mechanisms relate morphology biologic behavior have not described. Recent investigations demonstrated pseudopalisades severely hypoxic, overexpress hypoxia-inducible factor (HIF-1), secrete proangiogenic factors such VEGF IL-8. Thus, the hyperplasia in GBM provides new vasculature promotes peripheral tumor expansion tightly linked with emergence of pseudopalisades. Both pathologic observations experimental evidence indicated development hypoxia within astrocytomas could arise secondary vaso-occlusion intravascular thrombosis. This emerging model suggests represent wave cells actively migrating away central arises after vascular insult. Experimental glioma models shown endothelial apoptosis, perhaps resulting angiopoetin-2, initiates pathology, whereas human clearly thrombosis develops high frequency transition GBM. Tissue factor, main cellular initiator thrombosis, dramatically upregulated response PTEN loss promote prothrombotic environment precipitates these events. A also activates family protease activated receptors (PARs) on cells, which G-protein-coupled enhance invasive properties. Vaso-occlusive readily explain presence pseudopalisading tissue sections, rapid neuroimaging, dramatic shift accelerated rate clinical progression hypoxia-induced angiogenesis.