oligodendroglioma pathology outlines

Copyright 1999 2023 GoDaddy Operating Company, LLC. They can rarely arise infratentorially or in the spinal cord. Pathophysiology Cell (or cells) of origin for oligodendroglioma remains unknown IDH mutation is likely the initiating event (driver mutation), which precedes 1p / 19q codeletion ( Adv Anat Pathol 2015;22:50, Biomed Res Int 2014;2014:540236 ) IDH mutations give rise to metabolic alterations, with increased production of 2-hydroxyglutarate (2HG) A rare, giant, anaplastic oligodendroglioma. 8th ed. JmjC demethylases are one of the many dioxygenases regulated by -KG and inhibited by 2-HG. 97, 23812386. In 8 recurring oligodendrogliomas, the number of GFAP positive tumour cells was the same in the primary tumour and in its recurrence. 112, 801809. IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. It can also stimulate the activity of EGLN leading to decreased HIF levels. For instance it needs to be sorted out how (histopathological) criteria for grading of 'canonical oligodendrogliomas' should be adapted, how pediatric oligodendrogliomas (known to lack codeletions) should be defined, which platforms and cut-off levels should ideally be used for demonstration of particular molecular aberrations, and how the diagnosis of oligodendroglioma should be made in centers/countries where molecular diagnostics is not available. Oligodendroglioma is a primary central nervous system (CNS) tumor. Jorge C Kattah, MD Head, Associate Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria Seizure characteristics and control following resection in 332 patients with low-grade gliomas. IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system. (2012) reported the survival benefit of immunotherapy in patients with relapsed AO enrolled in the HGG-IMMUNO-2003 trial. TERT mutations in glioma are often found within the promoter region. Neuro Oncol. About 1,000 oligodendrogliomas are diagnosed per year in the United States. Temozolomide for low-grade gliomas: predictive impact of 1p/19q loss on response and outcome. Salvage chemotherapy with paclitaxel for recurrent primary brain tumors. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. This transition to an integrated morphological and molecular diagnosis may result in the disappearance of oligoastrocytoma as an entity, but brings new challenges as well. 479-91. Grade II and grade III tumors can be differentiated most of the times by the presence of anaplastic features. Patients with low-grade gliomas can be conventionally stratified into high risk and low risk categories, with risk referring to risk of tumor progression or recurrence. 24, 27072714. [1] . Clinical trials, with new chemotherapy, targeted therapy, or immunotherapy drugs, may also be available and can be a possible treatment option. (2006). New York: Oxford University Press; 2000. First, like most primary brain neoplasms in adults, this neoplasm is usually in the supratentorial brain, most commonly in the frontal lobes. 0000126977 00000 n Accessed Dec. 20, 2022. Re-analysis of some trials prior to the 2016 WHO brain tumor classification has given further insight into some molecular pathways that were previously poorly defined or investigated. May have neuronal "islands" (Synapto +ve, NeuN +ve). Here are some possible symptoms that can occur. This content does not have an English version. Elsewhere, another phase 1 study (NCT02644291) is assessing the use of mebendazole in recurrent/progressive pediatric brain tumors of 21 participants. Meanwhile, smart integration of morphological and molecular information will lead to recognition of biologically much more uniform groups within the spectrum of diffuse gliomas and thereby facilitate tailored treatments for individual patients. ; Hartmann, C.; Felsberg, J.; Platten, M. et al. Winn HR, ed. Radiation therapy. (2021). (2017). TCF12 protein functions as transcriptional repressor of E-cadherin, and its overexpression is correlated with metastasis of colorectal cancer. It was found that CIMP + or MGMT-STP27 methylated tumors had a superior OS 1.05 vs. 6.46 years and 1.06 vs. 3.8 years (both P < 0.0001) for CIMP and MGMT-STP27 status, respectively. This highlights the importance in incorporating novel techniques to better understand the tumor microenvironment (Yu et al., 2021). As for the clinical relevance of these molecular markers, inactivating mutations affecting FUBP1 have correlated with a shorter time to recurrence and CIC mutations have been associated with worse prognosis, especially in those patients with 1p/19q co-deleted oligodendrogliomas (Chan et al., 2014; Michaud et al., 2018). They're the third most-common glioma, accounting for 2-5% of all primary brain tumours and 5-18% of gliomas. doi: 10.1046/j.1460-9568.2003.02639.x, Lee, C.-C., Chen, W.-S., Chen, C.-C., Chen, L.-L., Lin, Y.-S., Fan, C.-S., et al. This results in the opening of a binding site for the E26 transformation-specific transcription factors (Killela et al., 2013). Mur, P.; Mollejo, M.; Ruano, Y.; de Lope, R. Additionally, hypermethylation caused by IDH1 mutations was shown to occur at CTCF-binding sites that normally insulate and prevent the interaction between different parts of the genome (Flavahan et al., 2016). These tumors are genetically defined according to the mutations they harbor. (2013). 61(9):1862-6. (WC/jensflorian), Demonstration of IDH1 R132H mutation in oligodendroglioma. Oligodendrogliomas are tumors that develop from a certain type of cell called oligodendroglial progenitor cells. Case Report: Single-Cell Transcriptomic Analysis of an Anaplastic Oligodendroglioma Post Immunotherapy. A neuropathologist should then review the tumor tissue. 0000018446 00000 n Yu, G., Butler, M. K., Abdelmaksoud, A., Pang, Y., Su, Y.-T., Rae, Z., et al. Sometimes surgery can't be done if the tumor is in a part of the brain that makes it hard to access with surgical tools. Subsequently, this codeletion appeared to not only carry diagnostic, but also prognostic and predictive information, the latter aspect only recently resolved after carefully constructed clinical trials with very long follow-up times. (2001). Concurrent inactivation of RB1 and TP53 pathways in anaplastic oligodendrogliomas. 0000014853 00000 n Their predictive value stems from their close relationship to human gliomas. 12, 20132021. Diffuse gliomas histopathologically form a spectrum, both with regard to cell type (astrocytic, oligodendroglial, mixed) and malignancy grade. Few calcifications are present. The brain surgeon, who is also called a neurosurgeon, works to remove the tumor without harming healthy brain tissue. Englot, D. J., Berger, M. S., Barbaro, N. M., and Chang, E. F. (2011). Megyesi JF, Kachur E, Lee DH, et al. Survival outcome and prognostic factors in anaplastic oligodendroglioma: a single-institution study of 95 cases. Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, Phi Beta KappaDisclosure: Nothing to disclose. 0000230615 00000 n J Clin Oncol. 57(2):172-5. Ajuria, L., Nieva, C., Winkler, C., Kuo, D., Samper, N., Andreu, M. J., et al. 0000277542 00000 n Of all brain tumors in the United States: Peak incidence in fourth and fifth decades of life (, Infiltrative neoplasm involving the white and gray matter, Can occur anywhere in the neuraxis; most common locations (, Rarely observed in midline structures, brainstem, cerebellum or spinal cord, Leptomeningeal spread occasionally observed, particularly at recurrence (, Cell (or cells) of origin for oligodendroglioma remains unknown, Increased 2HG inhibits histone demethylation, causing a hypermethylation phenotype in neoplastic cells: glioma CpG island methylated phenotype (GCIMP) (, Generally sporadic without significant known risk factors, Rare instances of familial oligodendroglioma and genetic alterations with associated increased risk of developing oligodendroglioma (, About 67% of patients present with seizure (, Other common presenting symptoms: headache, focal neurologic deficits or cognitive / mental status change, depending on anatomic location, Well differentiated tumor lacking anaplastic features (brisk mitotic activity, microvascular proliferation, necrosis). These cells make a substance that protects nerve cells and helps with the flow of electrical signals in the brain and spinal cord. Alattar et al. As a result of the disruption of IDHs enzymatic function, 2-HG tilts off the NADP/NADPH balance thereby increasing the production of ROS and leading to DNA damage and tumor formation (Latini et al., 2003; Rinaldi et al., 2016). It was shown by Uhm (2010) that IDH mutations lead to the acquisition of a new enzymatic function that catalyzes the formation of D-2HG from alpha-KG. Classification and Diagnosis of Adult Glioma: A Scoping Review. J. Clin. 0000255382 00000 n (2017). 0000245854 00000 n Investigat. Li S, Yan C, Huang L, Qiu X, Wang Z, Jiang T. Molecular prognostic factors of anaplastic oligodendroglial tumors and its relationship: a single institutional review of 77 patients from China. Oncol. Oligodendrogliomas. Lower grade gliomas. Roughly 20 years ago, the first glioma-associated molecular signature was found with complete chromosome 1p and 19q codeletion being particularly common in histologically classic oligodendrogliomas. doi: 10.1126/science.1170944, Zou, P., Xu, H., Chen, P., Yan, Q., Zhao, L., Zhao, P., et al. Imaging correlates of molecular signatures in oligodendrogliomas. Oligodendroglioma with ganglioglioma-like maturation: the histopathological diagnostic challenge of a brain neoplasm with aberrant neuronal component - A case report and review of the literature. doi: 10.1016/S0002-9440(10)61702-6, Shaw, E. G., Berkey, B., Coons, S. W., Bullard, D., Brachman, D., Buckner, J. C., et al. 17, 12481260. 374 (14):1344-55. [QxMD MEDLINE Link]. 6, 2127. Tambi Jarmi, MD Resident Physician, Department of Internal Medicine, Carraway Methodist Medical Center The retinoblastoma protein and cell cycle control. Elens, I., De Vleeschouwer, S., Pauwels, F., and Van Gool, S. (2012). Following the stratification of AO according to 1p/19q co-deletion status, an in-depth genetic analysis of 1p/19q co-deleted tumors revealed inactivating mutations affecting the FUBP1 gene on chromosome 1p and the CIC gene on chromosome 19 (Bettegowda, 2000; Sahm et al., 2012; Yip et al., 2012). Mol. Neuro Oncol. "[Diagnostic and prognostic values of 1p and 19q deletions in adult gliomas: critical review of the literature and implications in daily clinical practice]" (in French). Therefore, PTEN is a target of 10q loss, and PTEN alterations are associated with aggressive tumor phenotypes regardless of chemosensitivity (Sasaki et al., 2001). (2013). Commun. In practice, (neuro)pathologists who readily accept the existence of mixed gliomas will more liberally diagnose oligoastrocytomas, while those who are skeptical that this entity exists will designate the vast majority of diffuse gliomas as either astrocytic or oligodendroglial (, Example of how molecular reclassification may affect tumor grade. 0000013354 00000 n For patients with WHO grade 2 and KPS 60, the majority (90.5% . Tumour cells may be plasmacytoid, i.e. 0000225852 00000 n Neurosurgery. Commun. Boston: Butterworth Heinemann; 1997. Brain Pathol. HA conceived the idea for the manuscript. Oligodendrogliomas with vascular proliferation and significant mitotic activity are best considered to be anaplastic oligodendrogliomas (World Health Organization [WHO] grade III). (2003). CDKN2A inhibits the interaction between the cyclin dependent-kinases CDK4 or CDK6 and D-type cyclins, preventing both the phosphorylation of the retinoblastoma (RB1) protein and the release of the elongation factor (EF2) (Weinberg, 1995; Sherr and Roberts, 1999). doi: 10.1007/s11095-013-1264-4, Amankulor, N. M., Kim, Y., Arora, S., Kargl, J., Szulzewsky, F., Hanke, M., et al. Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. Genes Dev. Pediatric oligodendroglioma is a low-grade glioma that remains relatively rare when compared to adults. Newly diagnosed oligodendroglioma, IDH-mutant and 1p19q codeleted. Oligodendroglioma of the posterior fossa in childhood. Prior to the WHO 2016 classification of CNS tumors, grades 2 and 3 gliomas were not molecularly distinguished by 1p/19q codeletion status. Oncol. Recently, immunotherapy has been explored as a potential treatment modality. This comes with a risk of sacrificing important brain centers and hence compromising functionality and quality of life. Zou et al. 13, 15011512. 0000003153 00000 n 0000247714 00000 n Two main alterations affecting the TCF12 protein have been reported in AO: absence of bHLH DNA-binding domain and single amino acid substitutions such as R602M within the bHLH domain. doi: 10.1016/s1470-2045(16)30122-x, Batchelor, T. T., Gilbert, M. R., Supko, J. G., Carson, K. A., Nabors, L. B., Grossman, S. A., et al. Genes Dev. Douglas E Ney, MD Associate Professor of Neurology and Neurosurgery, Director of Neurology Residency Program, University of Colorado School of Medicine (Mar 2001). Cerebral oligodendroglioma: prognostic factors and life history. Oncometabolite D-2-hydroxyglutarate inhibits ALKBH DNA repair enzymes and sensitizes IDH mutant cells to alkylating agents. doi: 10.1016/j.ccr.2010.12.014, Yip, S., Butterfield, Y. S., Morozova, O., Chittaranjan, S., Blough, M. D., An, J., et al. Wiestler, B.; Capper, D.; Hovestadt, V.; Sill, M.; Jones, DT. With approximately 108 participants included in this study, the estimated completion date is July 2022. J. Neurosci. ; Tihan, T.; Lin, D.; McDonald, W.; Nigro, J.; Feuerstein, B.; Jackson, S.; Cohen, K. et al. doi: 10.1007/BF00177439, Mason, W. P., Krol, G. S., and DeAngelis, L. M. (1996). doi: 10.1215/15228517-2008-073, Wang, P., Wu, J., Ma, S., Zhang, L., Yao, J., Hoadley, K. A., et al. 0000277188 00000 n The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Kang SG, Kim JH, Nam do H, Park K. Clinical and radiological prognostic factors of anaplastic oligodendroglioma treated by combined therapy. 2023 Feb 28;13(5):914. doi: 10.3390/diagnostics13050914. Buckner JC, Shaw EG, Pugh SL, Chakravarti A, Gilbert MR, Barger GR, et al. J. Neuropathol. 20 (8):2076-84. (1999). With almost 12 years of follow-up, patients harboring tumors with 1p19q co-deletions showed an improved survival when treated with PCV and RT as compared to RT alone (EORTC26951: 157 vs. 50 months; RTOG9402: 14.7 vs. 7.3 years). 79, 153157. Neurol Sci. Tests can show what types of cells are involved. Both types of alterations have been shown to drastically impact the ability of TCF12 to function as a transcription factor and interact with other bHLH proteins, eventually leading to mutant protein accumulation (Labreche et al., 2015). Contrast-enhanced computed tomography scan in a 44-year-old man with a 3-year history of epileptic seizures. In patients with astrocytic tumors, only PFS was prolonged in patients treated with XRT who received up-front PCV vs. PCV at the time of recurrence (Pan-Weisz, 2019; Tork and Atkinson, 2020). doi: 10.1038/nature10860, Luyken, C., Blmcke, I., Fimmers, R., Urbach, H., Elger, C. E., Wiestler, O. D., et al. PFA ependymoma-associated protein EZHIP inhibits PRC2 activity through a H3 K27M-like mechanism. 9, 860864. This review assesses the latest management modalities along with the pathways involved in the pathogenesis of this malignancies. 0000000016 00000 n While IDH-WT tumors retained a poor prognosis and showed no benefit from PCV treatment, improved OS was seen in IDH mutant non-co-deleted tumors, and astrocytic tumors when treated with PCV plus RT. Salvage chemotherapy with taxol for recurrent anaplastic astrocytomas. Few neural tumours have round nuclei - DDx in intraoperative specimen: High mitotic rate (6 or more mitoses/10 HPF of 0.55mm). Seizure characteristics and outcomes in 508 Chinese adult patients undergoing primary resection of low-grade gliomas: a clinicopathological study. Health-Related Quality of Life and Executive Functioning among Primary Brain Tumor Patients: Associations and Causal Pathways: University of California, San Diego; 2019. [QxMD MEDLINE Link]. Cell Rep. 13, 23532361. Oligodendrogliomas are primary glial brain tumors that are divided into grade 2 and grade 3 tumors, with grade 3 tumors showing anaplastic features such as microvascular proliferation, necrosis,. Interestingly, an in vitro treatment of cells with D-2HG also induced a similar methylation pattern (Lu et al., 2012) which further supports the vital role of this metabolite in epigenetic alteration and tumor formation. Biophys. 0000141681 00000 n doi: 10.1212/01.wnl.0000262034.26310.a2, Kaminska, B., Czapski, B., Guzik, R., Krl, S. K., and Gielniewski, B. TERT reactivation then takes place when GA-binding protein (GABP) transcription factor binds to the mutant TERT promoter (Dahlin et al., 2016). Molecular pathways in gliomagenesis and their relevance to neuropathologic diagnosis. Cancer 94, 26882697. Recurrence following neurosurgeon-determined gross-total resection of adult supratentorial low-grade glioma: results of a prospective clinical trial. Although a mutated IDH1 cannot generate NADPH since it has lost its normal catalytic activity, it gains the function of producing D-(R)-2-hydroxyglutarate. 129, 19. Investigators of this trial will be testing the in vitro sensitivity of individual primary tumors to anti-mir-10b treatment. Pan-Weisz, T. M. (2019). doi: 10.3171/JNS/2008/108/2/0227, Chang, S. M., Kuhn, J. G., Robins, H. I., Schold, S. C. Jr., Spence, A. M., Berger, M. S., et al. The cause of most oligodendrogliomas is not known. Unauthorized use of these marks is strictly prohibited. Oligodendroglial tumors can be divided into two groups based on the classification of the world health organization (WHO): grade II oligodendroglioma and grade III (anaplastic) oligodendroglioma. Classic histologic image of oligodendroglioma. Yip S, Butterfield YS, Morozova O, Chittaranjan S, Blough MD, An J, Birol I, Chesnelong C, Chiu R, Chuah E, Corbett R, Docking R, Firme M, Hirst M, Jackman S, Karsan A, Li H, Louis DN, Maslova A, Moore R, Moradian A, Mungall KL, Perizzolo M, Qian J, Roldan G, Smith EE, Tamura-Wells J, Thiessen N, Varhol R, Weiss S, Wu W, Young S, Zhao Y, Mungall AJ, Jones SJ, Morin GB, Chan JA, Cairncross JG, Marra MA. (2001). 24, 47464753. A feature of oligodendroglioma that can be assessed on CT, as well as on MRI, is the typical location of the lesion. PTEN is a target of chromosome 10q loss in anaplastic oligodendrogliomas and PTEN alterations are associated with poor prognosis. Unable to load your collection due to an error, Unable to load your delegates due to an error. Sci. 0000392498 00000 n (2007). NCT04708548 is an ongoing European cross-sectional study that is looking at health-related quality of parameters and outcomes in survivors after being treated with surgery, chemotherapy and/or RT. Loss of CIC and FUBP1 expressions are potential markers of shorter time to recurrence in oligodendroglial tumors. Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers. Am. B., Raizer, J. J., Mason, W., et al. However, analysis of other trials such as the EORTC 26951 did not reveal a correlation between IDH mutations and survival in patients with astrocytic tumors (grade II) (van den Bent et al., 2010, 2013a). Cyclin D1 expression was also significantly higher in AO and was associated with a shorter EFS (Michaud et al., 2018). Cancer. All rights reserved. Neuropathol. CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated. 2012 Jun;123(6):853-60. doi: 10.1007/s00401-012-0993-5. Hence, cellular proliferation and dysregulation of pro-apoptotic pathways ensues (Ruas and Peters, 1998). 43, 7178. Oligodendroglioma is most common in adults, but it can happen at any age. More recently described biomarkers, including the non-balanced translocation leading to 1p/19q codeletion, promoter hypermethylation of the MGMT gene, mutations of the IDH1 or IDH2 gene, and mutations of FUBP1 (on 1p) or CIC (on 19q), have greatly enhanced our understanding of oligodendroglioma biology, although their diagnostic, prognostic, and predictive roles are less clear. Neurosurgery 68, 13261333. More studies, however, are needed to explore molecular pathways in oligodendroglioma and AO specifically after the 2016 classification. 0000280922 00000 n Even though there wasnt any difference in OS, the PFS remained shorter for patients not receiving any RT; even after adjusting for IDH status and RT treatment status. Epub 2015 Sep 9. In addition to the aforementioned pathways, homozygous and the less common hemizygous losses of 9p21 have been reported with high frequencies in gliomas, and up to 55% in AO (Maruno et al., 1996; Perry et al., 1999; Rasheed et al., 2002; Ohgaki and Kleihues, 2009; Michaud et al., 2018). Oligodendrogliomas instead share an immune phenotype with oligodendrocyte progenitor cells (OPCs). (Dec 2014). Oligodendroglioma. 10, 139144. 6(4):371-4. Two plausible hypotheses to explain treatment resistance in oligodendrogliomas exist. 0000245728 00000 n For example, a test may look at the changes in the tumor cells' genetic material, called DNA. Accounting to up to 5% of all neuroepithelial tumors ( Ostrom et al., 2017 ), oligodendroglial tumors have an incidence rate of around 1,000 new cases per year in the United States. Consequences of IDH1/2 mutations in gliomas and an assessment of inhibitors targeting mutated IDH proteins. Surgery to remove the tumor. On magnetic resonance imaging, he was considered to have disease progression. 0000005169 00000 n Oligodendrogliomas Primary GBMs Alternative lengthening of telomeres (ALT)/ATRX Astrocytomas Secondary GBMs Cohesion between sister chromatids provides a template for recombination and repair during and after DNA replication in S and G 2phases of the cell cycle 11 Mutations of Selected Genes in Glioma Subtypes doi: 10.1227/neu.0b013e31820c3419, Soffietti, R., Rud, R., Bradac, G. B., and Schiffer, D. (1998). Advances in the biology and treatment of oligodendrogliomas. 0000225482 00000 n [QxMD MEDLINE Link]. Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers. Accessed Sept. 26, 2022. Epub 2012 May 17. van den Bent MJ, Dubbink HJ, Marie Y, Brandes AA, Taphoorn MJ, Wesseling P, Frenay M, Tijssen CC, Lacombe D, Idbaih A, van Marion R, Kros JM, Dinjens WN, Gorlia T, Sanson M. Clin Cancer Res. 287, 27982809. Although these tumors were not examined for correspondence between PDGFR expression and PDGFR gene amplification, application of the same methodology on studies involving EGFR indicate that a high level of protein expression is to be expected in the future (Smith et al., 2000b). Neuro Oncol. Consequently, and in terms of improvement in quality of life (QOL), the EORTC study showed no difference between the two groups, and PCV toxicity contributed to a decreased QOL for a prolonged period. Molecular analysis of IDH1/2 hotspots and LOH1p/19q testing is required for diagnosis. Retrospective studies have clearly defined the most common presenting symptoms and tumor locations. (2011). doi: 10.1242/dev.057729, Alattar, A. 0000144370 00000 n 0000004633 00000 n Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma. 2006. doi: 10.1101/gad.13.12.1501. 36:294-295. Pang Y, Zhou S, Zumbo P, Betel D, Cisse B. 0000015277 00000 n This suggests that TCF12 alterations play a role in dictating an aggressive phenotype in AO. (2017). Oligodendrogliomas are primary brain tumours that are a type of glioma.

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