High-grade Oligodendroglioma Research Articles

The relationships of platelet-derived growth factor, microvascular proliferation, and tumor cell proliferation in canine high-grade oligodendrogliomas: Immunohistochemistry of 45 tumors and an AFOB-01 xenograft mouse model.

High-grade oligodendroglioma (HGOG) is the most common type of glioma in dogs and expresses platelet-derived growth factor receptor-α (PDGFR-α). Microvascular proliferation is often observed in HGOG. Therefore, the present study investigated the functional relationships between PDGFR-α, microvascular proliferation, and tumor cell proliferation in canine HGOG. The expression of PDGFR-α and PDGF-subunit A (PDGF-A) in tumor cells, as well as endothelial cells and pericytes of tumor-associated microvascular proliferations, in 45 canine HGOGs were examined immunohistochemically. Microvascular proliferation was observed in 24/45 cases (53%). PDGFR-α expression in tumor cells and microvascular proliferations was observed in 45/45 (100%) and 2/24 cases (8%), respectively. Furthermore, PDGF-A expression in tumor cells and microvascular proliferations was detected in 13/45 (29%) and 24/24 cases (100%), respectively. In vitro, stimulation of the canine HGOG cell line AOFB-01 with PDGF-A showed that the doubling time of AOFB-01 cells was significantly shorter with PDGF-A than without PDGF-A. Crenolanib (a PDGFR inhibitor) inhibited AOFB-01 cell proliferation. In vivo, the AOFB-01 xenograft mouse model was treated with crenolanib. Tumor xenografts were smaller in crenolanib-treated mice than in untreated control mice. PDGFR-α expression in tumor cells and PDGF-A expression in microvascular proliferations and tumor cells suggest autocrine and paracrine effects of PDGF-A in canine HGOG. The results of in vitro assays indicate that canine HGOG expresses functional PDGFR-α, which responds to PDGF-A. Therefore, PDGF-A produced by microvascular proliferations and tumor cells may promote the proliferation of PDGFR-α-expressing tumor cells in canine HGOG. PDGFR-α signaling has potential as a therapeutic target.

Consecutive Development of Ependymoma and Glioblastoma in a Single Patient: A Case Report

Introduction: The simultaneous occurrence of ependymoma and glioblastoma in a single patient is an exceptionally rare phenomenon, with limited documented cases in the medical literature.Case Report: This article presents a compelling case study of a 53-yearold female who sequentially developed these two distinct primary brain tumors. The patient initially underwent neurosurgery for a subependymoma in 2010 and later presented with motor and sensory symptoms, leading to the diagnosis of glioblastoma. A diagnostic stereotactic brain biopsy confirmed the presence of a high-grade oligodendroglioma. Despite postoperative complications, the patient’s recovery has been favorable with no epileptic recurrence. The discussion highlights the distinct molecular and clinical heterogeneity of ependymoma and glioblastoma and the lack of reported cases featuring their consecutive occurrence. The underlying mechanisms behind such occurrences remain poorly understood and warrant further investigation.Conclusion: This case underscores the importance of deepening our comprehension of consecutive primary brain tumors to optimize diagnosis, treatment planning, and patient outcomes.

Intra- and Intertumoral Microglia/Macrophage Infiltration and Their Associated Molecular Signature Is Highly Variable in Canine Oligodendroglioma: A Preliminary Evaluation.

The goal of this study was to define the glioma-associated microglia/macrophage (GAM) response and associated molecular landscape in canine oligodendrogliomas. Here, we quantified the intratumoral GAM density of low- and high-grade oligodendrogliomas compared to that of a normal brain, as well as the intratumoral concentration of several known GAM-derived pro-tumorigenic molecules in high-grade oligodendrogliomas compared to that in a normal brain. Our analysis demonstrated marked intra- and intertumoral heterogeneity of GAM infiltration. Correspondingly, we observed significant variability in the intratumoral concentrations of several GAM-associated molecules, unlike what we previously observed in high-grade astrocytomas. However, high-grade oligodendroglioma tumor homogenates (n = 6) exhibited an increase in the pro-tumorigenic molecules hepatocyte growth factor receptor (HGFR) and vascular endothelial growth factor (VEGF), as we observed in high-grade astrocytomas. Moreover, neoplastic oligodendrocytes displayed robust expression of GAL-3, a chimeric galectin implicated in driving immunosuppression in human glioblastoma. While this work identifies shared putative therapeutic targets across canine glioma subtypes (HGFR, GAL-3), it highlights several key differences in the immune landscape. Therefore, a continued effort to develop a comprehensive understanding of the immune microenvironment within each subtype is necessary to inform therapeutic strategies going forward.

Establishment and characterization of two novel patient-derived lines from canine high-grade glioma.

High-grade glioma is an aggressive cancer that occurs naturally in pet dogs. Canine high-grade glioma (cHGG) is treated with radiation, chemotherapy or surgery, but has no curative treatment. Within the past eight years, there have been advances in our imaging and histopathology standards as well as genetic charactereization of cHGG. However, there are only three cHGG cell lines publicly available, all of which were derived from astrocytoma and established using methods involving expansion of tumour cells in vitro on plastic dishes. In order to provide more clinically relevant cell lines for studying cHGG in vitro, the goal of this study was to establish cHGG patient-derived lines, whereby cancer cells are expanded in vivo by injecting cells into immunocompromized laboratory mice. The cells are then harvested from mice and used for in vitro studies. This method is the standard in the human field and has been shown to minimize the acquisition of genetic alterations and gene expression changes from the original tumour. Through a multi-institutional collaboration, we describe our methods for establishing two novel cHGG patient-derived lines, Boo-HA and Mo-HO, from a high-grade astrocytoma and a high-grade oligodendroglioma, respectively. We compare our novel lines to G06-A, J3T-Bg, and SDT-3G (traditional cHGG cell lines) in terms of proliferation and sensitivity to radiation. We also perform whole genome sequencing and identify an NF1 truncating mutation in Mo-HO. We report the characterization and availability of these novel patient-derived lines for use by the veterinary community.

Imaging of midline crossing IDH mutant 1p19q co-deleted high-grade oligodendroglioma: role of ASL perfusion and spectroscopy.

Imaging of midline crossing IDH mutant 1p19q co-deleted high-grade oligodendroglioma: role of ASL perfusion and spectroscopy.

Unique cytologic and imaging features of a lumbosacral oligodendroglioma in a cat.

A 12-y-old castrated male domestic longhaired cat had progressive paraparesis and neurolocalization of L4-S3. MRI revealed a circumscribed intradural-extraparenchymal mass from L5 to S1 that was T2 and short tau inversion recovery hyperintense and strongly contrast-enhancing. Cytologic interpretation of a blind fine-needle aspirate obtained through the L5-L6 space was a tumor of probable mesenchymal origin. A pair of suspect neoplastic cells was seen on a cytocentrifuged preparation of the atlanto-occipital CSF sample, despite a normal nucleated cell count (0 × 106/L) and total protein (0.11 g/L) with only 3 RBCs × 106/L. Clinical signs progressed despite increasing doses of prednisolone and cytarabine arabinoside. Repeat MRI on day 162 demonstrated tumor progression from L4 to Cd2 vertebral segments with intraparenchymal extension. Surgical tumor debulking was attempted, but an L4-S1 dorsal laminectomy revealed diffusely abnormal neuroparenchyma. Intraoperative cryosection favored lymphoma, and the cat was euthanized intraoperatively 163 d following presentation. Postmortem examination was performed, and the final diagnosis was a high-grade oligodendroglioma. This case illustrates the cytologic, cryosection, and MRI features of a unique clinical presentation of oligodendroglioma.

Accuracy of Machine Learning Algorithms for the Classification of Molecular Features of Gliomas on MRI: A Systematic Literature Review and Meta-Analysis.

Simple SummaryGlioma prognosis and treatment are based on histopathological characteristics and molecular profile. Following the World Health Organization (WHO) guidelines (2016), the most important molecular diagnostic markers include IDH1/2-genotype and 1p/19q codeletion status, although more recent publications also include ARTX genotype and TERT- and MGMT promoter methylation. Machine learning algorithms (MLAs), however, were described to successfully determine these molecular characteristics non-invasively by using magnetic resonance imaging (MRI) data. The aim of this review and meta-analysis was to define the diagnostic accuracy of MLAs with regard to these different molecular markers. We found high accuracies of MLAs to predict each individual molecular marker, with IDH1/2-genotype being the most investigated and the most accurate. Radiogenomics could therefore be a promising tool for discriminating genetically determined gliomas in a non-invasive fashion. Although encouraging results are presented here, large-scale, prospective trials with external validation groups are warranted.Treatment planning and prognosis in glioma treatment are based on the classification into low- and high-grade oligodendroglioma or astrocytoma, which is mainly based on molecular characteristics (IDH1/2- and 1p/19q codeletion status). It would be of great value if this classification could be made reliably before surgery, without biopsy. Machine learning algorithms (MLAs) could play a role in achieving this by enabling glioma characterization on magnetic resonance imaging (MRI) data without invasive tissue sampling. The aim of this study is to provide a performance evaluation and meta-analysis of various MLAs for glioma characterization. Systematic literature search and meta-analysis were performed on the aggregated data, after which subgroup analyses for several target conditions were conducted. This study is registered with PROSPERO, CRD42020191033. We identified 724 studies; 60 and 17 studies were eligible to be included in the systematic review and meta-analysis, respectively. Meta-analysis showed excellent accuracy for all subgroups, with the classification of 1p/19q codeletion status scoring significantly poorer than other subgroups (AUC: 0.748, p = 0.132). There was considerable heterogeneity among some of the included studies. Although promising results were found with regard to the ability of MLA-tools to be used for the non-invasive classification of gliomas, large-scale, prospective trials with external validation are warranted in the future.

Neuro-Oncology Clinical Debate: PCV or temozolomide in combination with radiation for newly diagnosed high-grade oligodendroglioma.

The treatment of newly diagnosed oligodendroglioma has been revolutionized in the past decade by multiple studies demonstrating that the addition of chemotherapy to radiation therapy results in a significant survival benefit. While the most direct evidence comes from clinical trials that utilized PCV, a chemotherapy regimen consisting of procarbazine, CCNU (lomustine), and vincristine, there is circumstantial evidence suggesting that the oral agent temozolomide (TMZ), which is both better tolerated and logistically simpler than PCV, may also be effective. The lack of currently available direct comparative data for PCV vs TMZ results in a diversity of practice. In this article, Ruff and Buckner argue for PCV as part of the standard-of-care regimen for newly diagnosed anaplastic oligodendroglioma, while Geurts and van den Bent defend the use of TMZ.

IMAGING DIAGNOSIS-MAGNETIC RESONANCE IMAGING FEATURES OF A MULTIFOCAL OLIGODENDROGLIOMA IN THE SPINAL CORD AND BRAIN OF A DOG.

An 8-year-old neutered male Toy Poodle was presented with chronic, progressive tetraparesis, and possible seizures. Magnetic resonance images demonstrated an extensive, T1 and T2 hyperintense contrast enhancing mass in the cervical spinal cord. Three nodules were present on the surface of the thalamus, with enhancement most evident on delayed images. A diagnosis of high-grade oligodendroglioma was confirmed with postmortem histopathology and immunohistochemical labeling. Oligodendroglioma should be considered as a differential for T1 hyperintense intraaxial or intramedullary lesions with contrast enhancement. If enhancement is not visualized on postcontrast images, delayed images may be beneficial.

Imaging of oligodendroglioma.

Oligodendroglioma are glial tumours, predominantly occurring in adults. Their hallmark molecular feature is codeletion of the 1p and 19q chromosome arms, which is not only of diagnostic but also of prognostic and predictive relevance. On imaging, these tumours characteristically show calcification, and they have a cortical–subcortical location, most commonly in the frontal lobe. Owing to their superficial location, there may be focal thinning or remodelling of the overlying skull. In contrast to other low-grade gliomas, minimal to moderate enhancement is commonly seen and perfusion may be moderately increased. This complicates differentiation from high-grade, anaplastic oligodendroglioma, in which enhancement and increased perfusion are also common. New enhancement in a previously non-enhancing, untreated tumour, however, is suggestive of malignant transformation, as is high growth rate. MR spectroscopy may further aid in the differentiation between low- and high-grade oligodendroglioma. A relatively common feature of recurrent disease is leptomeningeal dissemination, but extraneural spread is rare. Tumours with the 1p/19q codeletion more commonly show heterogeneous signal intensity, particularly on T2 weighted imaging; calcifications; an indistinct margin; and mildly increased perfusion and metabolism than 1p/19q intact tumours. For the initial diagnosis of oligodendroglioma, MRI and CT are complementary; MRI is superior to CT in assessing tumour extent and cortical involvement, whereas CT is most sensitive to calcification. Advanced and functional imaging techniques may aid in grading and assessing the molecular genotype as well as in differentiating between tumour recurrence and radiation necrosis, but so far no unequivocal method or combination of methods is available.

PO30INTRA-OPERATIVE SEIZURES IN AWAKE CRANIOTOMY

INTRODUCTION: Intra-operative seizure is a recognised complication of awake craniotomy (AC) to resect/debulk intracerebral tumour. If not adequately controlled, it may lead to abandonment of the procedure. Here we reviewed the incidence of intra-operative seizure in all AC patients at a regional neurosurgical centre, and examined its association with tumour type and pre-operative use of anti-epileptic drugs (AEDs). METHOD: Review of patients' medical notes. RESULTS: In total, 42 AC were performed on 38 patients. 33.3% (14/42) AC were complicated by intra-operative seizures, resulting in 3 procedures being abandoned. Out of seven patients with low-grade glioma in this series, 71.4% (5/7) had intra-operative seizures. The incidence of intra-operative seizure was 40.0% for high-grade oligodendroglioma, 33.3% for anaplastic astrocytoma and 20.0% for glioblastoma multiforme. Out of all 38 patients, 33 had seizures as a presenting symptom. Of these, 36.4% (12/33) developed intra-operative seizures, while 20.0% (1/5) of those who did not present with a seizure developed intra-operative seizures. 30.6% (11/36) patients who received pre-operative AED developed seizures intra-operatively, compared to 100% (2/2) of those without pre-operative AED. CONCLUSION: 33.3% of patients who underwent AC developed intra-operative seizures. Patients with low-grade glioma were most at risk in our limited series. Pre-operative use of AEDs appeared to reduce the risk of intra-operative seizures. Larger studies are warranted.

Conventional and advanced (DTI/SWI) neuroimaging findings in pediatric oligodendroglioma

Oligodendroglioma are rare pediatric brain tumors. The literature about neuroimaging findings is scant. A correct presurgical diagnosis is important to plan the therapeutic approach. Here, we evaluated the conventional and advanced neuroimaging features in our cohort of pediatric oligodendrogliomas and discuss our findings in the context of the current literature. Clinical histories were reviewed for tumor grading, neurologic manifestation, treatment, and clinical status at the last follow-up. Neuroimaging studies were retrospectively evaluated for tumor morphology and characteristics on conventional and advanced magnetic resonance imaging (MRI). Five children with oligodendroglioma were included in this study. Four children were diagnosed with a low-grade oligodendroglioma. The location of the tumors included the frontal and temporal lobe in two cases each and the fronto-parietal lobe in one. In all oligodendrogliomas, tumor margins appeared sharp. In the high-grade oligodendroglioma, a cystic and partially hemorrhagic component was seen. In all children, the tumor showed a T1-hypointense and T2-hyperintense signal. The signal intensity on fluid attenuation inversion recovery (FLAIR) images was hyperintense in four and mixed hypo-hyperintense in one child. The anaplastic oligodendroglioma showed postcontrast enhancement and decreased diffusion while the low-grade oligodendrogliomas showed increased diffusion. One low-grade oligodendroglioma showed calcifications on susceptibility weighted imaging. Conventional MRI findings of pediatric oligodendrogliomas are nonspecific. Advanced MRI sequences may differentiate (1) low-grade and high-grade pediatric oligodendrogliomas and (2) pediatric oligodendrogliomas and other brain tumors.

Lhx3 is required to maintain cancer cell development of high-grade oligodendroglioma

The LHX genes play a substantial role in an amount of adorning processes. Potential roles of LHXs have been accepted and approved in an assortment of neoplastic tissues as bump suppressors or promoters depending on bump cachet and types. The aim of this abstraction was to investigate the action role of LHXs in the animal High-grade Oligodendroglioma (HG-OT). The gene announcement changes of LHXs in HG-OT tissues compared with non-cancerous colorectal tissues were detected using application real-time quantitative about-face transcriptase-polymerase alternation acknowledgment (QRT-PCR) assay and immunohistochemistry. And we articulate the gene LHX3 that was decidedly up-regulated in HG-OT by QRT-PCR assay and immunohistochemistry. Furthermore, it was obvious that LHX3 responds to blight corpuscle admeasurement in vitro and LHX3 announcement activated with animated β-catenin levels in HG-OT and β-catenin action was appropriate for LHX3's oncogenic effects. Mechanistically, LHX3 facilitates TCF4 to bind to β-catenin and facilitates LHX3/TCF4/β-catenin circuitous and trans-active it's after ambition gene. LHX3 mutations that agitate the LHX3-β-catenin alternation partially anticipate its action in bump cells. All in all, LHX3 is a frequently activated bump apostle that actuates Wnt/β-catenin signaling in blight beef of HG-OT.

Sox2 Is Required to Maintain Cancer Stem Cells in a Mouse Model of High-Grade Oligodendroglioma

The stem cell-determining transcription factor Sox2 is required for the maintenance of normal neural stem cells. In this study, we investigated the requirement for Sox2 in neural cancer stem-like cells using a conditional genetic deletion mutant in a mouse model of platelet-derived growth factor-induced malignant oligodendroglioma. Transplanting wild-type oligodendroglioma cells into the brain generated lethal tumors, but mice transplanted with Sox2-deleted cells remained free of tumors. Loss of the tumor-initiating ability of Sox2-deleted cells was reversed by lentiviral-mediated expression of Sox2. In cell culture, Sox2-deleted tumor cells were highly sensitive to differentiation stimuli, displaying impaired proliferation, increased cell death, and aberrant differentiation. Gene expression analysis revealed an early transcriptional response to Sox2 loss. The observed requirement of oligodendroglioma stem cells for Sox2 suggested its relevance as a target for therapy. In support of this possibility, an immunotherapeutic approach based on immunization of mice with SOX2 peptides delayed tumor development and prolonged survival. Taken together, our results showed that Sox2 is essential for tumor initiation by mouse oligodendroglioma cells, and they illustrated a Sox2-directed strategy of immunotherapy to eradicate tumor-initiating cells.

Increased mitochondrial activity in a novel IDH1-R132H mutant human oligodendroglioma xenograft model: in situ detection of 2-HG and α-KG

BackgroundPoint mutations in genes encoding NADP+-dependent isocitrate dehydrogenases (especially IDH1) are common in lower grade diffuse gliomas and secondary glioblastomas and occur early during tumor development. The contribution of these mutations to gliomagenesis is not completely understood and research is hampered by the lack of relevant tumor models. We previously described the development of the patient-derived high-grade oligodendroglioma xenograft model E478 that carries the commonly occurring IDH1-R132H mutation. We here report on the analyses of E478 xenografts at the genetic, histologic and metabolic level.ResultsLC-MS and in situ mass spectrometric imaging by LESA-nano ESI-FTICR revealed high levels of the proposed oncometabolite D-2-hydroxyglutarate (D-2HG), the product of enzymatic conversion of α-ketoglutarate (α-KG) by IDH1-R132H, in the tumor but not in surrounding brain parenchyma. α-KG levels and total NADP+-dependent IDH activity were similar in IDH1-mutant and -wildtype xenografts, demonstrating that IDH1-mutated cancer cells maintain α-KG levels. Interestingly, IDH1-mutant tumor cells in vivo present with high densities of mitochondria and increased levels of mitochondrial activity as compared to IDH1-wildtype xenografts. It is not yet clear whether this altered mitochondrial activity is a driver or a consequence of tumorigenesis.ConclusionsThe oligodendroglioma model presented here is a valuable model for further functional elucidation of the effects of IDH1 mutations on tumor metabolism and may aid in the rational development of novel therapeutic strategies for the large subgroup of gliomas carrying IDH1 mutations.

Abstract 3663: Characterization of aspartoacylase in oligodendroglioma

Abstract Aspartoacylase (ASPA, ACY2) is an oligodendrocyte-derived amino acid deacetylase (aminoacylase) responsible for supplying acetate for myelin lipid synthesis via the cleavage of N-acetyl-L-aspartate (NAA) into free acetate and aspartate. Our unpublished observations showed ASPA to be significantly down-regulated at the transcriptional and translational level in high-grade oligodendroglioma tumor samples relative to normal brain tissue. Additionally, in silico data indicates that low ASPA expression in oligodendroglioma correlates with increased mortality. While aminoacylase 1 (ACY1) serves as a putative tumor suppressor in small cell lung and renal cell carcinoma, the role of ASPA in oligodendroglioma is previously unexplored. We therefore endeavored to characterize the expression of ASPA in two oligodendroglioma cell lines, Hs683 and HOG cells, and in a murine oligodendrocyte precursor cell line immortalized via stable transfection with the constitutively active ErbB2 receptor (Oli-neu cells). In contrast to our in vivo data, Oli-neu cells displayed lower ASPA expression relative to Hs683 and HOG cells. Nonetheless, ASPA expression increased with time in culture. Unlike Hs683 and HOG cells, which were recalcitrant to differentiation, Oli-neu cells were responsive to cAMP-induced differentiation, as revealed by CNPase up-regulation and a concordant increase in ASPA expression. Interestingly, treatment with ASPA's only known substrate, NAA, significantly inhibited the temporal increase in both CNPase and ASPA expression within Oli-neu cells. Conversely, NAA treatment had no effect on CNPase or ASPA expression in either Hs683 or HOG cells. To address whether the cAMP-mediated ASPA up-regulation in Oli-neu cells was related to differentiation or activation of cAMP signal transduction, Oli-neu cells were treated with an ErbB2 antagonist. In contrast to cAMP, ErbB2-mediated differentiation was associated with down-regulation of ASPA expression. Immunocytochemically, ASPA appears to be diffusely distributed throughout the cytosol in Oli-neu cells. Although ASPA has been previous characterized as a predominantly cytosolic/nuclear protein, in Hs683 and HOG cells ASPA exhibits a highly punctate membrane-associated pattern of expression. Collectively, our results reveal distinct patterns of ASPA regulation and subcellular localization in two oligodendroglioma cell lines compared to a representative oligodendrocyte precursor cell line. More importantly, we reveal distinct in vitro and in vivo ASPA regulation in oligodendroglioma, thus suggesting a possible role of the tumor microenvironment in regulating ASPA expression. This work was supported by a LCCRO/VCC Pilot Project grant, a UVM Internal Grants Program Pilot Project Award, and NIH/NCRR R01NS045225 (DMJ), Neuroscience COBRE (NIH NCRR P20 RR016435), and P30 CA22435 support of the VCC DNA Analysis facility. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3663. doi:10.1158/1538-7445.AM2011-3663

803 PI3K signalling pathway is activated by PIK3CA gain and overexpression in prostate tumours, but PI3KCA, BRAF, KRAS AND AKT1 mutations are an infrequent event

This study assessed the efficacy of FISH for detecting 1p/19q deletion in gliomas on 77 paraffin-embedded tissue samples, of which 42 cases (55%) were positive for 1p/19q codeletion; 7 of the 42 had a previous history of glioma. In one case, analysis failed. The remaining 34 cases were negative; of these, three had a previous history of glioma and one had the reverse 1q/19p deletion. A majority of the 10 recurrent gliomas had progressed, and 70% had a 1p/19q deletion. The signal pattern in a majority of 1p/19q codeletion cases was a single red marker signal and two green reference signals (1R2G) for both probe sets. One case had a different signal pattern for chromosomes 1 and 19 (1R2G and 2R4G), as seen in polysomy cells. Three cases had two target and four control signals (2R4G), as seen in tetraploid cells. Eleven had complex signal patterns seen in diploid and polyploid cells (1R2G/<nRnG). A majority of these complex cases (8 of 11, or 73%) had high-grade oligodendroglioma (n = 4) or oligoastrocytoma (n = 4). The frequency of 1p/19q combined deletion in oligodendroglioma (n = 40), oligoastrocytoma (n = 21), and astrocytoma (n = 8) was 65, 60, and 25%, respectively. Elucidated in this paper are the various FISH signal patterns observed in gliomas and a need for a uniform nomenclature for improved diagnosis.

Advances in Treatment Options for High-grade Glioma - Current Status and Future Perspectives

High-grade gliomas, including glioblastoma, anaplastic astrocytoma, anaplatic oligodendroglioma and anaplastic oligoastrocytoma, account for the majority of malignant primary brain tumours diagnosed in adults. The prognosis for these tumours is poor despite multimodality therapy with surgery, radiation and/or chemotherapy. This review summarises treatment options for high-grade glioma, including standard regimens, targeted agents and novel therapies.

Assessment of 1p/19q deletions by fluorescence in situ hybridization in gliomas

This study assessed the efficacy of FISH for detecting 1p/19q deletion in gliomas on 77 paraffin-embedded tissue samples, of which 42 cases (55%) were positive for 1p/19q codeletion; 7 of the 42 had a previous history of glioma. In one case, analysis failed. The remaining 34 cases were negative; of these, three had a previous history of glioma and one had the reverse 1q/19p deletion. A majority of the 10 recurrent gliomas had progressed, and 70% had a 1p/19q deletion. The signal pattern in a majority of 1p/19q codeletion cases was a single red marker signal and two green reference signals (1R2G) for both probe sets. One case had a different signal pattern for chromosomes 1 and 19 (1R2G and 2R4G), as seen in polysomy cells. Three cases had two target and four control signals (2R4G), as seen in tetraploid cells. Eleven had complex signal patterns seen in diploid and polyploid cells (1R2G/< nR nG). A majority of these complex cases (8 of 11, or 73%) had high-grade oligodendroglioma ( n = 4) or oligoastrocytoma ( n = 4). The frequency of 1p/19q combined deletion in oligodendroglioma ( n = 40), oligoastrocytoma ( n = 21), and astrocytoma ( n = 8) was 65, 60, and 25%, respectively. Elucidated in this paper are the various FISH signal patterns observed in gliomas and a need for a uniform nomenclature for improved diagnosis.

Metastatic oligodendrogliomas: a review of the literature and case report

Oligodendroglioma cells are detectable in the cerebro-spinal fluid in up to 14% of patients [10] and cerebellar and/or spinal cord involvement is a well known phenomenon [3]. Distant spread of oligodendroglioma is exceptional, probably due to the presence of the blood-brain barrier, the absence of lymphatic vessels and the short survival of patients. A review of the worldwide literature yielded 32 previously reported examples since 1951 to the present (Tab1e 1). This review was performed using NCBI-PubMed and "oligodendroglioma, oligodendrogliomas, metastatic, metastasis, metastases, extraneural", in different combinations, as key words and reviewing the bibliography of the consequent selected articles. New therapeutic approaches are prolonging the overall survival of patients with primitive brain tumours and in particular of those with high grade oligodendroglioma which is a chemo-sensitive disease. A longer overall survival could increase the risk of extracranial dissemination of gliomas that in the future might become a less rare clinical complication.