Gliomas - ReadingSample

The term oligodendroglioma was created by Bailey, Cushing, and Bucy based on the observation that these tumors share morphological similarities with oligodendrocytes (Bailey and Cushing 1926; Bailey and Bucy 1929). However, a convincing link between oligodendrocytes and oligodendrogliomas still needs to be shown. Oligoastrocytomas or mixed gliomas are histologically defined by the presence of oligodendroglial and astrocytic components. According to the WHO classification of brain tumors, oligodendroglial tumors are separated into oligodendrogliomas WHO grade II (OII), anaplastic oligodendrogliomas WHO grade III (OIII), oligoastrocytomas WHO grade II (OAII), anaplastic oligoastrocytomas WHO grade III (OAIII), and glioblastomas with oligodendroglioma component WHO grade IV (GBMo) (Louis et al. 2007).The perception of oligodendroglial tumors has changed in recent years. The diagnosis of oligodendroglioma or oligoastrocytomas is made much more frequently than 10 years ago. Treatment modalities have been advanced and novel concepts regarding the origin of oligodendroglial tumors have been developed. This review focuses on recent developments with impact on the diagnosis and understanding of molecular mechanisms in oligodendroglial tumors. 2.1 Epidemiological, Neuroradiological, and Clinical Features Oligodendrogliomas occur 1.5–2.1 times more frequently in men than in women (Mork et al. 1986; Zulch 1986). The average age of onset of oligodendrogliomas is between 35 and 55 years with a peak incidence around 45 years (Mork et al. 1986; Zulch 1986). Often OII occur in patients under 40 years of age and OIII arise in patients over 40 years of age (Ludwig et al. 1986). The incidence of oligodendrogliomas has risen over the last few years, reaching levels of 25% of primary brain tumors. This rise is most likely due to the improvement in the therapy of oligodendroglial tumors and the feeling of the diagnostician not to withhold potentially effective treatment for patients with glioma containing any feature reminiscent of Molecular Pathology of Oligodendroglial Tumors Christian Hartmann and Andreas von Deimling 2 Christian Hartmann ( ) Universitätsklinikum Heidelberg Pathologisches Institut Abt. Neuropathologie und Klinische Kooperationseinheit Neuropathologie Deutsches Krebsforschungszentrum Im Neuenheimer Feld 220/221 69120 Heidelberg Germany E-mail: [email protected] Andreas von Deimling (Ed.), Gliomas, Recent Results in Cancer Research 171, 25 DOI: 10.1007/978-3-540-31206-2_2, © Springer-Verlag Berlin Heidelberg 2009 26 C. Hartmann and A. von Deimling 2 oligodendroglial tumors (Coons et al. 1997; Ironside et al. 2002). The frequency of anaplastic tumors among the oligodendroglial gliomas varies strongly between 3.5% and 50% (Winger et al. 1989; Shaw et al. 1992). The incidence of oligoastrocytomas also ranges from 2% to 19%, which is most likely a consequence of the lack of stringent diagnostic criteria (Jaskolsky et al. 1987; Louis et al. 2007). The etiology of oligodendrogliomas remains unclear with only few studies and some case reports pointing to tumor-initiating factors. None of the hereditary tumor syndromes is associated with oligodendrogliomas. However, familiar oligodendrogliomas were reported in single cases (Ferraresi et al. 1989; Kros et al. 1994). In rabbits, application of N-methyl-N-nitrosourea induced tumors with histological features of oligodendrogliomas (Kleihues et al. 1970). The involvement of SV40 and JS viruses in the induction of oligodendrogliomas is uncertain and conflicting data have been reported (Herbarth et al. 1998; Huang et al. 1999). In one patient an oligodendrogliomas might have been induced by radiation therapy (Huang et al. 1987). In two patients that sustained head injuries, oligodendrogliomas arose at the site of brain damage due to contusion (Perez-Diaz et al. 1985). Furthermore, a few case reports proposed an association between multiple sclerosis and oligodendrogliomas (Giordana et al. 1981; Sega et al. 2006). Within the group of gliomas, epileptic seizures are most frequently encountered in oligodendrogliomas. Often an epileptic seizure is the first symptom of an oligodendroglioma. Other typical clinical symptoms of oligodendrogliomas are headaches in combination with signs of increased intracranial pressure. Depending on the location of the tumor, varying focal neurological symptoms occur. OII are slowly growing tumors. Cases with seizures as a first symptom usually present a clinical history of about 1 year. Intervals of more than 5 years are not uncommon and in children more than 10 years between onset of seizures and diagnosis of oligodendroglioma has been reported (Greenfield et al. 2002). Compared to white matter, oligodendrogliomas usually appear on computed tomography (CT) images as a well-demarcated hypoor isodense lesion. Frequently calcifications can be found, mostly around the periphery of the tumor in a so-called gyriform or ribbon-like pattern. On magnetic resonance imaging (MRI) oligodendrogliomas typically appear as hypointense lesions on T1 and hyperintense on T2 images. The margins are sharply demarcated and perifocal edema is rather small. Varying signal intensities are found in rare cases due to hemorrhages or cystic degeneration. Gadolinium contrast enhancement shows low accuracy in predicting OIII. Enhancement was also found in OII, and on the other hand lack of enhancement was seen in OIII (Ginsberg et al. 1998; Lebrun et al. 2004; White et al. 2005). However, noninvasive grading of oligodendrogliomas appears to be more promising with techniques such as proton magnetic resonance spectroscopic imaging (MRSI) (Rijpkema et al. 2003; Xu et al. 2005). In a small series FDG-PET showed raised glucose utilization within the tumor in six of eight WHO Grade II gliomas with 1p/19q LOH and in none of the WHO Grade II gliomas without this genetic alteration (Stockhammer et al. 2007).