‘Pseudopalisading’ Necrosis in Glioblastoma: A Familiar Morphologic Feature That Links Vascular Pathology, Hypoxia, and Angiogenesis
Open Access
- 1 June 2006
- journal article
- review article
- Published by Oxford University Press (OUP) in Journal of Neuropathology and Experimental Neurology
- Vol. 65 (6), 529-539
- https://doi.org/10.1097/00005072-200606000-00001
Abstract
Glioblastoma (GBM) is a highly malignant, rapidly progressive astrocytoma that is distinguished pathologically from lower grade tumors by necrosis and microvascular hyperplasia. Necrotic foci are typically surrounded by “pseudopalisading” cells—a configuration that is relatively unique to malignant gliomas and has long been recognized as an ominous prognostic feature. Precise mechanisms that relate morphology to biologic behavior have not been described. Recent investigations have demonstrated that pseudopalisades are severely hypoxic, overexpress hypoxia-inducible factor (HIF-1), and secrete proangiogenic factors such as VEGF and IL-8. Thus, the microvascular hyperplasia in GBM that provides a new vasculature and promotes peripheral tumor expansion is tightly linked with the emergence of pseudopalisades. Both pathologic observations and experimental evidence have indicated that the development of hypoxia and necrosis within astrocytomas could arise secondary to vaso-occlusion and intravascular thrombosis. This emerging model suggests that pseudopalisades represent a wave of tumor cells actively migrating away from central hypoxia that arises after a vascular insult. Experimental glioma models have shown that endothelial apoptosis, perhaps resulting from angiopoetin-2, initiates vascular pathology, whereas observations in human tumors have clearly demonstrated that intravascular thrombosis develops with high frequency in the transition to GBM. Tissue factor, the main cellular initiator of thrombosis, is dramatically upregulated in response to PTEN loss and hypoxia in human GBM and could promote a prothrombotic environment that precipitates these events. A prothrombotic environment also activates the family of protease activated receptors (PARs) on tumor cells, which are G-protein-coupled and enhance invasive and proangiogenic properties. Vaso-occlusive and prothrombotic mechanisms in GBM could readily explain the presence of pseudopalisading necrosis in tissue sections, the rapid peripheral expansion on neuroimaging, and the dramatic shift to an accelerated rate of clinical progression resulting from hypoxia-induced angiogenesis.Keywords
This publication has 84 references indexed in Scilit:
- Clarifying the Diffuse GliomasAmerican Journal of Clinical Pathology, 2005
- Radiotherapy plus Concomitant and Adjuvant Temozolomide for GlioblastomaNew England Journal of Medicine, 2005
- MRI in treatment of adult gliomasThe Lancet Oncology, 2005
- Epidemiology and etiology of gliomasActa Neuropathologica, 2005
- Microregional extracellular matrix heterogeneity in brain modulates glioma cell invasionThe International Journal of Biochemistry & Cell Biology, 2004
- Virtual and real brain tumors: using mathematical modeling to quantify glioma growth and invasionJournal of the Neurological Sciences, 2003
- Continuous growth of mean tumor diameter in a subset of grade II gliomasAnnals of Neurology, 2003
- Genetic and Biologic Progression in Astrocytomas and Their Relation to Angiogenic DysregulationAdvances in Anatomic Pathology, 2002
- Quantification of endothelial permeability, leakage space, and blood volume in brain tumors using combined T1 and T2* contrast-enhanced dynamic MR imagingJournal of Magnetic Resonance Imaging, 2000
- Treatment of Malignant GliomaArchives of Neurology, 1976