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Major discoveries in the biology of nervous system tumors have raised the question of how non-histological data such as molecular information can be incorporated into the next World Health Organization (WHO) classification of central nervous system tumors. To address this question, a meeting of neuropathologists with expertise in molecular diagnosis was held in Haarlem, the Netherlands, under the sponsorship of the International Society of Neuropathology (ISN). Prior to the meeting, participants solicited input from clinical colleagues in diverse neuro-oncological specialties. The present "white paper" catalogs the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification should follow a set of provided "ISN-Haarlem" guidelines. Salient recommendations include that (i) diagnostic entities should be defined as narrowly as possible to optimize interobserver reproducibility, clinicopathological predictions and therapeutic planning; (ii) diagnoses should be "layered" with histologic classification, WHO grade and molecular information listed below an "integrated diagnosis"; (iii) determinations should be made for each tumor entity as to whether molecular information is required, suggested or not needed for its definition; (iv) some pediatric entities should be separated from their adult counterparts; (v) input for guiding decisions regarding tumor classification should be solicited from experts in complementary disciplines of neuro-oncology; and (iv) entity-specific molecular testing and reporting formats should be followed in diagnostic reports. It is hoped that these guidelines will facilitate the forthcoming update of the fourth edition of the WHO classification of central nervous system tumors. [ABSTRACT FROM AUTHOR]

IDH1/2 mutations occur at high frequency in diffusely infiltrating gliomas of the WHO grades II and III and were identified as a strong prognostic marker in all WHO grades of gliomas. Mutated IDH1 or IDH2 protein leads to the generation of excessive amounts of the metabolite 2-hydroxyglutarate (2HG) in tumor cells. Here, we evaluated whether 2HG levels in preoperative serum samples from patients with gliomas correlate with the IDH1/2 mutation status and whether there is an association between 2HG levels and glioma size. In contrast to the strong accumulation of 2HG in the serum of patients with IDH1/2 mutated acute myeloid leukaemia, no accumulation was observed in this series of IDH1/2 mutated gliomas. Furthermore, we found no association between glioma size measured by magnetic resonance imaging and 2HG levels. We conclude that 2HG levels in preoperative sera from patients with diffusely infiltrating gliomas of the WHO grades II and III cannot be used as a marker to differentiate between tumors with versus without IDH1/2 mutation. Furthermore, the observation that there is no correlation between 2HG levels and tumor volume may indicate that 2HG cannot be utilized as marker to monitor tumor growth in gliomas. [ABSTRACT FROM AUTHOR]

Abstract: Invasion of tumor cells into adjacent brain areas is one of the major problems in treatment of glioma patients. To identify genes that might contribute to invasion, fluorescent F98 glioma cells were allowed to invade an organotypic brain slice. Gene expression analysis revealed 5 up-regulated and 14 down-regulated genes in invasive glioma cells as compared to non-invasive glioma cells. Two gene products, ferritin and cyclin B1, were verified in human gliomas by immunohistochemistry. Ferritin exhibited high mRNA levels in migratory F98 cells and also showed higher protein expression in the infiltrating edge of human gliomas. Cyclin B1 with high mRNA expression levels in stationary F98 cells showed marked protein expression in the central portions of gliomas. These findings are compatible with the concept of tumor cells either proliferating or migrating. Our study is the first to apply brain slice cultures for the identification of differentially regulated genes in glioma invasion. [Copyright &y& Elsevier]