oligoastrocytomas. Lower grade tumors tend to be well differentiated, have increased cell density and some cellular anomalies. Lower grade tumors already contain specific genetic alterations and may progressively accumulate more gene alterations that correlate with their tumor lineage, malignancy and progression to a higher grade. Higher grade tumors are anaplastic, show signs of increased vessel density, elevated mitotic activity, and higher cellular density. Glioblastoma is a specific grade IV astrocytoma, showing vascular endothelial proliferation necrosis and very high cell density and atypias. Genetic markers Genetic markers allow subclasses of glioma to be identified based on a molecular signature or gene expression patterns. Genetic markers contribute to more detailed elucidation of components of molecular pathways, such as, which oncogenes are activated and which cell cycle control elements are lost. The most common elements lost are tumor suppressor genes like p53, the retinoblastoma gene or phosphatase and tensin homologue. Clinical applications Gliomas harboring gemistocytic cells are known to have a more aggressive clinical behavior due to the high proliferation rates of the non-gemistocytic cells which compete for nutrients and induce the gemistocytic morphology in other cells. Gemistocytes are suggested to be entrapped non-neoplastic glial cells that can be transformed into their specific phenotype due to the deprivation of nutrients when there is competition and increasing demand for surrounding tumor cells. Rapid progression of neoplastic glial cells are able to outgrow the vascular supply of the tumor which results in a metabolic disadvantage for the neoplastic cells causing metamorphosis to occur in the gemistocytic phenotype. Aside from the lack of proliferating activity of gemistocytic cells, their presence in gliomas appears to be a poor indication, and most tumors will rapidly become anaplastic astrocytomas. Disease Gemistocytes are also found in some chronic diseases and within certain brain tumors, which suggests the presence of a long-lasting pathological reaction. Gemistocytic astrocytes can be observed in tissue damage, particularly Creutzefldt-Jakob disease and progressive multifocal leukoencephalopathy, which can be characterized by very large gemistocytic astrocytes. In the context of cancer (gemistocytic astrocytomas), gemistocytes are known to de-differentiate to a high grade (III or IV) glioma (i.e. glioblastoma multiforme) at a rapid pace, usually indicative of a poor prognosis. References Cytopathology