Oligodendroglioma overview: Difference between revisions

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==Overview==
==Overview==
Oligodendrogliomas are a type of [[glioma]] that are believed to originate from the tripotential [[glial cell|glial precursor cells]]. The term "oligodendroglioma" was first coined by Bailey and Cushing in 1926 following the observation that the tumor cells are morphologically similar to [[oligodendrocyte]]s. According to the new 2016 edition of WHO classification of gliomas based on histopathologic appearance and well-established molecular parameters, oligodendrogliomas are subclassified into grade II tumors including oligodendroglioma IDH-mutant and 1p/19q-codeleted, oligodendroglioma NOS, oligoastrocytoma NOS, and grade III tumors including anaplastic oligodendroglioma IDH-mutant and 1p/19q-codeleted, anaplastic oligodendroglioma NOS, and anaplastic oligoastrocytoma NOS. Genes associated with the pathogenesis of oligodendroglioma include [[Translocation|t[1;19][q10;p10]]], ATRX, ''[[Mutation|NJDS]]'', ''[[Isocitrate dehydrogenase|IDH1]]'', ''[[IDH2]]'', TERT promoter, H3 K27M (''H3F3A, HIST1H3B/C),'' ''CIC'', ''[[Far upstream element-binding protein 1|FUBP1]]'', ''[[p53]]'', ''[[CD57|Leu-7]]'', ''[[TCF12|TCF-12]]'', ''TP53,[[Ogt|MGMT]]'', ''[[P73|TP73]]'', BRAF, ''[[EGFR]]'', and ''[[PTEN]].'' Common intracranial sites involved by oligodendroglioma include [[Cerebral hemisphere|cerebral hemispheres]], [[posterior fossa]], and [[Spinal cord|intramedullary spinal cord]]. On gross pathology, oligodendroglioma is characterized by a well-circumscribed, gelatinous, calcified, cystic, gray mass with focal hemorrhage which may expand a [[gyrus]] and remodel the [[skull]]. On microscopy, it shows a diffuse growth pattern of highly cellular lesion of monomorphic cells having rounded nucleus with [[atypia]], speckled "''salt-and-pepper''" chromatin pattern and perinuclear halo resembling ''fried eggs'', distinct cell borders, clear cytoplasm, abundant [[calcification]] and "''chicken-wire''" like vascularity pattern. Common causes of oligodendroglioma include [[mutation|genetic mutations]], some viral cause or irradiation of pituitary adenoma. On the basis of [[seizure]], [[visual disturbance]], and constitutional symptoms, oligodendroglioma must be differentiated from [[astrocytoma]], [[meningioma]], [[hemangioblastoma]], [[pituitary adenoma]], [[schwannoma]], [[Primary central nervous system lymphoma|primary CNS lymphoma]], [[medulloblastoma]], [[ependymoma]], [[craniopharyngioma]], [[pinealoma]], [[Arteriovenous malformation|AV malformation]], [[brain aneurysm]], [[bacterial]] [[brain]] [[abscess]], [[tuberculosis]], [[toxoplasmosis]], [[hydatid cyst]], [[CNS]] [[cryptococcosis]], [[CNS]] [[aspergillosis]], and [[brain metastasis]]. It constitutes about 9.4% of all CNS tumors and 5%–18% of all [[Glioma|glial neoplasms]] with incidence of oligodendroglioma and [[Anaplastic|anaplastic oligodendroglioma]] to be 0.32 and 0.17 cases per 100,000 individuals in the United States, respectively. Oligodendroglioma is a disease that tends to affect the middle-aged adult population mainly occurring in the 4th and 5th decade of life with median age at the time of diagnosis to be 35-47 years. Males are more commonly affected than females with the male to female ratio of approximately 1.3:1. Oligodendroglioma usually affects individuals of the Caucasian race and African American, Latin American, and Asian individuals are less likely to develop oligodendroglioma. The most potent risk factor in the development of oligodendroglioma is [[family history]] of [[brain tumors]]. If left untreated, patients with oligodendroglioma may progress to develop [[seizures]], focal neurological deficits, [[hydrocephalus]], [[brain herniation]], [[intracranial hemorrhage]], and ultimately death. Common complications associated with oligodendroglioma include [[hydrocephalus]], [[intracranial hemorrhage]], [[coma]], [[Metastasis|bone marrow metastasis]], recurrence, [[venous thromboembolism]], [[parkinsonism]], and side effects of [[chemotherapy]] and [[radiotherapy]]. The overall prognosis is good but prognosis may vary depending upon various prognostic factors such as population based estimates, clinical factors, tumor grade (II versus III), mechanism of chemosensitivity, and molecular markers such as 1p/19q-codeletion, IDH1/2 mutation, and TERT promoter mutations. Symptoms associated with oligodendroglioma include [[seizure]], [[headache]], [[nausea]], [[vomiting]], [[vertigo]], [[visual loss]], [[diplopia]], [[strabismus]], [[Hemiparesis|muscle weakness]], [[numbness]], speech difficulties, mood disturbances, personality changes, memory problems, low energy, fatigue, urge to sleep, loss of interest in daily activities, abulia, lack of spontaneity, loss of consciousness with syncope (few tonic-clonic jerks), and classic triad of headache, nausea, and papilledema due to raised intracranial pressure. Findings on CT scan suggestive of oligodendroglioma are round or oval, marginated, hypo- to isodense mass with [[hemorrhage]], ribbon-like [[calcification]], ill-defined enhancement following intravenous contrast administration, pressure erosion/remodelling of overlying skull, and marked ventricular enlargement suggestive of [[hydrocephalus]]. On brain MRI, oligodendroglioma is characterized by a mass which is typically hypointense on T1-weighted images and hyperintense on T2-weighted images. [[Calcification]] is observed as areas of "blooming" on T2 decay component of MRI. Other imaging studies for oligodendroglioma include MR spectroscopy (dominant [[N-acetyl aspartate]] peak, increased [[choline]] levels and decreased [[N-acetyl aspartate|NAA]] levels with a [[myo-inositol]] peak), MR perfusion (increased "''chicken wire''" network of vascularity, which results in elevated relative cerebral blood volume), PET scan (to differentiate between oligodendroglioma from anaplastic oligodendroglioma and tumor recurrence from tumor necrosis), and bone scan (bone metastasis). Other diagnostic studies for oligodendroglioma include [[biopsy]] (homogeneous, compact, rounded cells with distinct borders and clear cytoplasm surrounding a dense central nucleus and perinuclear halo) and [[Fish|fluorescent in-situ hybridization (FISH) technique]] (deletions of [[Chromosome 1|chromosome 1p]] and [[Chromosome 19|19q]]). The predominant therapy for oligodendroglioma is surgical resection. Adjunctive chemotherapy and radiation are required. Supportive therapy for oligodendroglioma includes [[anticonvulsants]] and [[corticosteroids]].
[[Oligodendrogliomas]] are a type of [[glioma]] that are believed to originate from the tripotential [[glial cell|glial precursor cells]]. The term "[[oligodendroglioma]]" was first coined by Bailey and Cushing in 1926 following the [[observation]] that the [[Tumor cell|tumor cells]] are [[Morphological computation|morphologically]] [[Similarity matrix|similar]] to [[oligodendrocyte]]s. According to the [[new]] 2016 edition of [[World Health Organization|WHO]] [[classification]] of [[gliomas]] based on [[histopathologic]] [[appearance]] and well-established [[molecular]] [[Parameter|parameters]], [[oligodendrogliomas]] are subclassified into [[Grading (tumors)|grade]] II [[tumors]] including [[oligodendroglioma]] [[IDH1|IDH]]-[[mutant]] and [[1p36 deletion syndrome|1p]]/19q-codeleted, [[oligodendroglioma]] NOS, [[oligoastrocytoma]] NOS, and grade III [[tumors]] including [[anaplastic]] [[oligodendroglioma]] [[IDH1|IDH]]-[[mutant]] and [[1p36 deletion syndrome|1p]]/19q-codeleted, [[anaplastic]] [[oligodendroglioma]] NOS, and [[anaplastic oligoastrocytoma]] NOS. [[Genes]] [[Association (statistics)|associated]] with the [[pathogenesis]] of [[oligodendroglioma]] include [[Translocation|t[1;19][q10;p10]]], [[ATRX]], ''[[Mutation|NJDS]]'', ''[[Isocitrate dehydrogenase|IDH1]]'', ''[[IDH2]]'', [[TERT]] [[promoter]], [[H3F3A|H3]] K27M (''[[H3F3A]], [[HIST1H3B]]/[[HIST1H3C|C]]),'' ''[[CIC (gene)|CIC]]'', ''[[Far upstream element-binding protein 1|FUBP1]]'', ''[[p53]]'', ''[[CD57|Leu-7]]'', ''[[TCF12|TCF-12]]'', ''[[TP53]], [[Ogt|MGMT]]'', ''[[P73|TP73]]'', [[BRAF]], ''[[EGFR]]'', and ''[[PTEN]].'' Common intracranial sites involved by [[oligodendroglioma]] include [[Cerebral hemisphere|cerebral hemispheres]], [[posterior fossa]], and [[Spinal cord|intramedullary spinal cord]]. On [[gross pathology]], [[oligodendroglioma]] is characterized by a well-circumscribed, gelatinous, [[Calcification|calcified]], [[cystic]], [[gray]] [[mass]] with focal [[hemorrhage]] which may [[Expanded access|expand]] a [[gyrus]] and remodel the [[skull]]. On [[microscopy]], it shows a [[diffuse]] [[growth]] [[pattern]] of highly [[cellular]] [[lesion]] of monomorphic [[Cells (biology)|cells]] having rounded [[nucleus]] with [[atypia]], [[Speckle pattern|speckled]] "''[[salt]]-and-[[Pepper spray|pepper]]''" [[chromatin]] [[pattern]] and [[Perinuclear space|perinuclear]] [[Halo (medicine)|halo]] resembling ''fried [[Egg (biology)|eggs]]'', [[Distinctive feature|distinct]] [[Cell (biology)|cell]] borders, clear [[cytoplasm]], abundant [[calcification]] and "''chicken-wire''" like [[vascularity]] [[pattern]]. Common [[causes]] of [[oligodendroglioma]] include [[mutation|genetic mutations]], some [[viral]] [[Causes|cause]] or [[irradiation]] of [[pituitary adenoma]]. On the basis of [[seizure]], [[visual disturbance]], and constitutional [[symptoms]], [[oligodendroglioma]] must be [[Differentiate|differentiated]] from [[astrocytoma]], [[meningioma]], [[hemangioblastoma]], [[pituitary adenoma]], [[schwannoma]], [[Primary central nervous system lymphoma|primary CNS lymphoma]], [[medulloblastoma]], [[ependymoma]], [[craniopharyngioma]], [[pinealoma]], [[Arteriovenous malformation|AV malformation]], [[brain aneurysm]], [[bacterial]] [[brain]] [[abscess]], [[tuberculosis]], [[toxoplasmosis]], [[hydatid cyst]], [[CNS]] [[cryptococcosis]], [[CNS]] [[aspergillosis]], and [[brain metastasis]]. It constitutes about 9.4% of all [[CNS]] [[tumors]] and 5%–18% of all [[Glioma|glial neoplasms]] with [[Incidence (epidemiology)|incidence]] of [[oligodendroglioma]] and [[Anaplastic|anaplastic oligodendroglioma]] to be 0.32 and 0.17 cases per 100,000 [[Individual growth|individuals]] in the [[United States]], respectively. [[Oligodendroglioma]] is a [[disease]] that tends to [[affect]] the [[Middle age|middle-aged]] [[adult]] [[population]] mainly occurring in the 4th and 5th decade of [[life]] with [[median]] [[age]] at the [[Time series|time]] of [[diagnosis]] to be 35-47 [[Year|years]]. [[Males]] are more commonly [[Affect (psychology)|affected]] than [[females]] with the [[male]] to [[female]] [[ratio]] of approximately 1.3:1. [[Oligodendroglioma]] usually [[Affect (psychology)|affects]] [[Individual growth|individuals]] of the [[Caucasian honey bee|Caucasian]] [[race]] and African American, [[Latin Americans|Latin American]], and Asian [[Individual growth|individuals]] are less likely to [[Development|develop]] [[oligodendroglioma]]. The most [[Potential|potent]] [[risk factor]] for the [[development]] of [[oligodendroglioma]] is [[family history]] of [[brain tumors]]. If left untreated, [[patients]] with [[oligodendroglioma]] may progress to [[Development|develop]] [[seizures]], focal [[neurological]] deficits, [[hydrocephalus]], [[brain herniation]], [[intracranial hemorrhage]], and ultimately [[Death Cap|death]]. Common [[complications]] [[Association (statistics)|associated]] with [[oligodendroglioma]] include [[hydrocephalus]], [[intracranial hemorrhage]], [[coma]], [[Metastasis|bone marrow metastasis]], [[Recurrence plot|recurrence]], [[venous thromboembolism]], [[parkinsonism]], and [[side effects]] of [[chemotherapy]] and [[radiotherapy]]. The overall [[prognosis]] is good but the [[prognosis]] may vary [[Dependent variable|depending]] upon various [[prognostic]] factors such as [[population]] based [[Estimate|estimates]], [[clinical]] factors, [[tumor]] [[Grading (tumors)|grade]] (II versus III), [[Mechanism (biology)|mechanism]] of [[chemosensitivity]], and [[Molecular marker|molecular markers]] such as [[1p36 deletion syndrome|1p]]/19q-codeletion, [[IDH1]]/[[IDH2|2]] [[mutation]], and [[TERT]] [[promoter]] [[mutations]]. [[Symptoms]] [[Association (statistics)|associated]] with [[oligodendroglioma]] include [[seizure]], [[headache]], [[nausea]], [[vomiting]], [[vertigo]], [[visual loss]], [[diplopia]], [[strabismus]], [[Hemiparesis|muscle weakness]], [[numbness]], [[speech difficulties]], [[mood disturbances]], [[personality changes]], [[memory]] [[Problem Solved|problems]], low [[energy]], [[fatigue]], [[Urgency|urge]] to [[sleep]], [[Loss function|loss]] of [[Interest (emotion)|interest]] in [[Activities of daily living|daily activities]], [[abulia]], [[Lack (manque)|lack]] of spontaneity, [[loss of consciousness]] with [[syncope]] (few [[tonic-clonic]] [[Jerking|jerks]]), and classic [[Triad (anatomy)|triad]] of [[headache]], [[nausea]], and [[papilledema]] due to [[raised intracranial pressure]]. Findings on [[CT scan]] [[Suggestion|suggestive]] of [[oligodendroglioma]] are round or [[oval]], marginated, hypo- to isodense [[mass]] with [[hemorrhage]], ribbon-like [[calcification]], ill-defined enhancement following [[intravenous]] [[contrast]] administration, [[pressure]] [[Erosion (dental)|erosion]]/remodelling of overlying [[skull]], and marked [[ventricular]] enlargement [[Suggestion|suggestive]] of [[hydrocephalus]]. On [[brain]] [[Magnetic resonance imaging|MRI]], [[oligodendroglioma]] is characterized by a [[mass]] which is typically hypointense on [[T1]]-[[Weighted mean|weighted]] [[images]] and hyperintense on T2-[[Weighted mean|weighted]] [[images]]. [[Calcification]] is [[Observation|observed]] as [[Area|areas]] of "blooming" on T2 [[Decay mode|decay]] component of [[Magnetic resonance imaging|MRI]]. Other [[imaging studies]] for [[oligodendroglioma]] include [[MR]] [[spectroscopy]] (dominant [[N-acetyl aspartate]] peak, increased [[choline]] levels and decreased [[N-acetyl aspartate|NAA]] levels with a [[myo-inositol]] peak), [[MR]] [[perfusion]] (increased "''chicken wire''" [[Network effect|network]] of [[vascularity]], which [[Result|results]] in elevated relative [[cerebral]] [[blood volume]]), [[Positron emission tomography|PET scan]] (to [[differentiate]] between [[oligodendroglioma]] from [[anaplastic]] [[oligodendroglioma]] and [[tumor]] [[Recurrence plot|recurrence]] from [[tumor]] [[necrosis]]), and [[bone scan]] ([[bone metastasis]]). Other [[diagnostic]] [[Study design|studies]] for [[oligodendroglioma]] include [[biopsy]] ([[homogeneous]], [[Compact tissue|compact]], rounded [[cells]] with [[Distinctive feature|distinct]] borders and clear [[cytoplasm]] surrounding a [[dense]] [[central]] [[nucleus]] and [[Perinuclear space|perinuclear]] [[Halo (medicine)|halo]]) and [[Fish|fluorescent in-situ hybridization (FISH) technique]] ([[Deletion (genetics)|deletions]] of [[Chromosome 1|chromosome 1p]] and [[Chromosome 19|19q]]). The predominant [[therapy]] for [[oligodendroglioma]] is [[surgical resection]]. [[Adjuvant chemotherapy|Adjunctive chemotherapy]] and [[radiation]] are required. [[Support|Supportive]] [[therapy]] for [[oligodendroglioma]] includes [[anticonvulsants]] and [[corticosteroids]].


==Historical Perspective==
==Historical Perspective==
In 1926, the term "[[oligodendroglioma]]" was first coined by Bailey and Cushing, and was first described and published by W. E. Carnegie Dickson. [[Oligodendrogliomas]] were first [[Classification|classified]] and [[Grading (tumors)|graded]] in a [[system]] devised by Bailey and Cushing, and later revised by Kernohan, Ringertz, and others, and since then, [[classification]] and [[Grading (tumors)|grading]] of [[gliomas]] have [[evolved]] over the time. Modern [[World Health Organization|WHO]] [[classification]] of [[oligodendrogliomas]] was first published in 1979 and revised four times since then, with the most recent published in 2016. In 1997, a Westergaard's [[Study design|study]] showed that [[patients]] younger than 20 years had a [[median]] [[Survival rate|survival]] of 17.5 years. In 2001, a [[Study design|study]] at [[Mayo Clinic]] was conducted to [[Assessment and Plan|assess]] the [[prognostic]] [[Value (mathematics)|value]] of [[histological]] [[Grading (tumors)|grading]] of [[Oligodendroglial tumor|oligodendroglial tumors]] in [[Grading (tumors)|tumor grading]] and [[Significant figure|significant]] [[Association (statistics)|association]] with [[Survival analysis|survival]] was found for [[age]], high [[Cellular|cellularity]], presence of [[mitoses]], [[endothelial]] [[hypertrophy]] and [[proliferation]] and [[necrosis]] on [[univariate]] [[analysis]], but only [[age]] and presence of [[endothelial]] [[proliferation]] were found to be [[Independent assortment|independently]] [[Association (statistics)|associated]] with [[Survival rate|survival]] on a multivariable [[analysis]]. In 2009, ''[[Mutation|NJDS]]'' [[mutation]] was first identified in the [[pathogenesis]] of [[oligodendroglioma]] by Kevin Smith. It was suggested in 2009 ASCO Annual Meeting that [[PCV regimen|PCV]] [[therapy]] may be [[superior]] in [[efficacy]] to the [[New|newer]] [[temozolomide]] [[therapy]]. [[Radiation|Irradiation]] of [[pituitary adenoma]] was also [[Discovery system|discovered]] to be associated with [[oligodendroglioma]] by Kevin Smith et al.
In 1926, the term "[[oligodendroglioma]]" was first coined by Bailey and Cushing, and was first described and published by W. E. Carnegie Dickson. [[Oligodendrogliomas]] were first [[Classification|classified]] and [[Grading (tumors)|graded]] in a [[system]] devised by Bailey and Cushing, and later revised by Kernohan, Ringertz, and others, and since then, [[classification]] and [[Grading (tumors)|grading]] of [[gliomas]] have [[evolved]] over the time. Modern [[World Health Organization|WHO]] [[classification]] of [[oligodendrogliomas]] was first published in 1979 and revised four times since then, with the most recent published in 2016. In 1997, a Westergaard's [[Study design|study]] showed that [[patients]] younger than 20 [[Year|years]] had a [[median]] [[Survival rate|survival]] of 17.5 years. In 2001, a [[Study design|study]] at [[Mayo Clinic]] was conducted to [[Assessment and Plan|assess]] the [[prognostic]] [[Value (mathematics)|value]] of [[histological]] [[Grading (tumors)|grading]] of [[Oligodendroglial tumor|oligodendroglial tumors]] in [[Grading (tumors)|tumor grading]] and [[Significant figure|significant]] [[Association (statistics)|association]] with [[Survival analysis|survival]] was found for [[age]], high [[Cellular|cellularity]], presence of [[mitoses]], [[endothelial]] [[hypertrophy]] and [[proliferation]] and [[necrosis]] on [[univariate]] [[analysis]], but only [[age]] and presence of [[endothelial]] [[proliferation]] were found to be [[Independent assortment|independently]] [[Association (statistics)|associated]] with [[Survival rate|survival]] on a multivariable [[analysis]]. In 2009, ''[[Mutation|NJDS]]'' [[mutation]] was first identified in the [[pathogenesis]] of [[oligodendroglioma]] by Kevin Smith. It was suggested in 2009 ASCO Annual Meeting that [[PCV regimen|PCV]] [[therapy]] may be [[superior]] in [[efficacy]] to the [[New|newer]] [[temozolomide]] [[therapy]]. [[Radiation|Irradiation]] of [[pituitary adenoma]] was also [[Discovery system|discovered]] to be [[Association (statistics)|associated]] with [[oligodendroglioma]] by Kevin Smith et al.


==Classification==
==Classification==
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==Pathophysiology==
==Pathophysiology==
Oligodendroglioma arises from the tripotential [[Glial cell|glial precursor cells]] and ''not'' from the bipotential [[Oligodendrocyte|oligodendrocytes]]. Genes associated with the pathogenesis of oligodendroglioma include [[Translocation|t[1;19][q10;p10]]], ATRX, ''[[Mutation|NJDS]]'', ''[[Isocitrate dehydrogenase|IDH1]]'', ''[[IDH2]]'', TERT promoter, H3 K27M (''H3F3A, HIST1H3B/C),'' ''CIC'', ''[[Far upstream element-binding protein 1|FUBP1]]'', ''[[p53]]'', ''[[CD57|Leu-7]]'', ''[[TCF12|TCF-12]]'', ''TP53,[[Ogt|MGMT]]'', ''[[P73|TP73]]'', BRAF, ''[[EGFR]]'', and ''[[PTEN]]''. Common intracranial sites involved by oligodendroglioma include [[Cerebral hemisphere|cerebral hemispheres]], [[posterior fossa]], and [[Spinal cord|intramedullary spinal cord]]. On gross pathology, oligodendroglioma is characterized by a well-circumscribed, gelatinous, calcified, cystic, gray mass with focal hemorrhage which may expand a [[gyrus]] and remodel the [[skull]]. On microscopic histopathological analysis, oligodendroglioma is characterized by diffuse growth pattern of highly cellular lesion of monomorphic cells having rounded nucleus with [[atypia]], speckled "''salt-and-pepper''" chromatin pattern and perinuclear halo resembling ''fried eggs'', distinct cell borders, clear cytoplasm, abundant [[calcification]] and "''chicken-wire''" like vascularity pattern. Oligodendroglioma is demonstrated by positivity to tumor markers such as [[Isocitrate dehydrogenase|IDH1-R132H]], [[Microtubule-associated protein|MAP2]], [[GFAP]], [[S100 calcium binding protein A8|S-100]], SOX10, EMA, ATRX, [[Ki-67 (Biology)|Ki-67]], [[Neuron-Specific Enolase (NSE)|NSE]], [[synaptophysin]], [[OLIG1]], and [[OLIG2]].
[[Oligodendroglioma]] arises from the tripotential [[Glial cell|glial precursor cells]] and ''not'' from the [[bipotential]] [[Oligodendrocyte|oligodendrocytes]]. [[Genes]] [[Association (statistics)|associated]] with the [[pathogenesis]] of [[oligodendroglioma]] include [[Translocation|t[1;19][q10;p10]]], [[ATRX]], ''[[Mutation|NJDS]]'', ''[[Isocitrate dehydrogenase|IDH1]]'', ''[[IDH2]]'', [[TERT]] [[promoter]], [[H3F3A|H3]] K27M (''[[H3F3A]], [[HIST1H3B]]/[[HIST1H3C|C]]),'' ''[[CIC (gene)|CIC]]'', ''[[Far upstream element-binding protein 1|FUBP1]]'', ''[[p53]]'', ''[[CD57|Leu-7]]'', ''[[TCF12|TCF-12]]'', ''[[TP53]],[[Ogt|MGMT]]'', ''[[P73|TP73]]'', [[BRAF]], ''[[EGFR]]'', and ''[[PTEN]]''. Common intracranial sites involved by [[oligodendroglioma]] include [[Cerebral hemisphere|cerebral hemispheres]], [[posterior fossa]], and [[Spinal cord|intramedullary spinal cord]]. On [[gross pathology]], [[oligodendroglioma]] is characterized by a well-circumscribed, gelatinous, [[Calcified lesion|calcified]], [[cystic]], [[gray]] [[mass]] with focal [[hemorrhage]] which may expand a [[gyrus]] and remodel the [[skull]]. On [[microscopic]] [[histopathological]] [[analysis]], [[oligodendroglioma]] is characterized by [[diffuse]] [[growth]] [[pattern]] of highly [[cellular]] [[lesion]] of monomorphic [[Cells (biology)|cells]] having rounded [[nucleus]] with [[atypia]], speckled "''[[salt]]-and-[[Pepper spray|pepper]]''" [[chromatin]] [[pattern]] and [[Perinuclear space|perinuclear]] [[Halo (medicine)|halo]] resembling ''fried [[Egg (biology)|eggs]]'', [[Distinctive feature|distinct]] [[Cell (biology)|cell]] borders, clear [[cytoplasm]], abundant [[calcification]] and "''chicken-wire''" like [[vascularity]] [[pattern]]. [[Oligodendroglioma]] is demonstrated by [[Positivity effect|positivity]] to [[tumor markers]] such as [[Isocitrate dehydrogenase|IDH1-R132H]], [[Microtubule-associated protein|MAP2]], [[GFAP]], [[S100 calcium binding protein A8|S-100]], [[SOX10]], EMA, [[ATRX]], [[Ki-67 (Biology)|Ki-67]], [[Neuron-Specific Enolase (NSE)|NSE]], [[synaptophysin]], [[OLIG1]], and [[OLIG2]].


==Causes==
==Causes==
The most common [[etiology]] of [[oligodendroglioma]] includes [[Mutation|genetic mutations]] such as [[Translocation|t(1;19)(q10;p10)]], ''[[Mutation|NJDS]],'' ''[[Isocitrate dehydrogenase|IDH1]],'' ''[[IDH2]],'' ''CIC,'' ''[[Far upstream element-binding protein 1|FUBP1]],'' ''[[p53]],'' ''[[CD57|Leu-7]],'' ''[[TCF12|TCF-12]],[[Ogt|MGMT]],'' ''[[P73|TP73]],'' ''[[EGFR]]'' and ''[[PTEN]].'' It may be [[Association (statistics)|associated]] with some [[viral]] [[Causes|cause]] or [[irradiation]] of [[pituitary adenoma]].
The most common [[etiology]] of [[oligodendroglioma]] includes [[Mutation|genetic mutations]] such as [[Translocation|t(1;19)(q10;p10)]], ''[[Mutation|NJDS]],'' ''[[Isocitrate dehydrogenase|IDH1]],'' ''[[IDH2]],'' ''[[CIC (gene)|CIC]],'' ''[[Far upstream element-binding protein 1|FUBP1]],'' ''[[p53]],'' ''[[CD57|Leu-7]],'' ''[[TCF12|TCF-12]],[[Ogt|MGMT]],'' ''[[P73|TP73]],'' ''[[EGFR]]'' and ''[[PTEN]].'' It may be [[Association (statistics)|associated]] with some [[viral]] [[Causes|cause]] or [[irradiation]] of [[pituitary adenoma]].


==Differentiating Oligodendroglioma from other diseases==
==Differentiating Oligodendroglioma from other diseases==
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==Epidemiology and Demographics==
==Epidemiology and Demographics==
Oligodendroglioma, although rare, is the third most common [[glioma]]. In adults, it constitutes about 9.4% of all primary brain and central nervous system tumors and 5%–18% of all [[Glioma|glial neoplasms]]. The incidence of oligodendroglioma and [[Anaplastic|anaplastic oligodendroglioma]] is estimated to be 0.32 and 0.17 cases per 100,000 individuals in the United States, respectively. Oligodendroglioma tends to affect the middle-aged adult population, most commonly occurring in the 4th and 5th decade of life. Median age at diagnosis of oligodendroglioma is 35-47 years. Males are more commonly affected with oligodendroglioma than females with male to female ratio being approximately 1.3:1. Oligodendroglioma usually affects individuals of the Caucasian race. African American, Latin American, and Asian individuals are less likely to develop oligodendroglioma.
[[Oligodendroglioma]], although rare, is the third most common [[glioma]]. In [[Adult|adults]], it constitutes about 9.4% of all primary [[brain]] and [[central nervous system]] [[tumors]] and 5%–18% of all [[Glioma|glial neoplasms]]. The [[Incidence (epidemiology)|incidence]] of [[oligodendroglioma]] and [[Anaplastic|anaplastic oligodendroglioma]] is estimated to be 0.32 and 0.17 cases per 100,000 [[Individual growth|individuals]] in the [[United States]], respectively. [[Oligodendroglioma]] tends to [[affect]] the [[Middle age|middle-aged]] [[adult]] [[population]], most commonly occurring in the 4th and 5th decade of [[life]]. [[Median]] [[age]] at the [[Time series|time]] of [[diagnosis]] of [[oligodendroglioma]] is 35-47 [[Years of potential life lost|years]]. [[Males]] are more commonly [[Affect (psychology)|affected]] with [[oligodendroglioma]] than [[females]] with [[male]] to [[female]] [[ratio]] being approximately 1.3:1. [[Oligodendroglioma]] usually [[Affect|affects]] [[Individual growth|individuals]] of the [[Caucasian honey bee|Caucasian]] [[race]]. African American, [[Latin Americans|Latin American]], and Asian [[Individual growth|individuals]] are less likely to [[Development|develop]] [[oligodendroglioma]].


==Risk factors==
==Risk factors==
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==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==
If left untreated, patients with oligodendroglioma may progress to develop [[seizures]], focal neurological deficits, [[hydrocephalus]], [[brain herniation]], [[intracranial hemorrhage]], and ultimately death.Common complications associated with oligodendroglioma include [[hydrocephalus]], [[intracranial hemorrhage]], [[coma]], [[Metastasis|bone marrow metastasis]], recurrence, [[venous thromboembolism]], [[parkinsonism]], and side effects of [[chemotherapy]] and [[radiotherapy]]. Oligodendroglioma is a slow growing tumor having a good prognosis overall with prolonged survival. But the prognosis of oligodendroglioma may vary depending upon various prognostic factors such as population based estimates, clinical factors, tumor grade (II versus III), mechanism of chemosensitivity, and molecular markers such as 1p/19q-codeletion, IDH1/2 mutation, and TERT promoter mutations. The [[median]] survival time for oligodendroglioma is 11.6 years for grade II and 3.5 years for grade III.
If left untreated, [[patients]] with [[oligodendroglioma]] may progress to [[Development|develop]] [[seizures]], focal [[neurological]] deficits, [[hydrocephalus]], [[brain herniation]], [[intracranial hemorrhage]], and ultimately [[Death Cap|death]].Common [[complications]] [[Association (statistics)|associated]] with [[oligodendroglioma]] include [[hydrocephalus]], [[intracranial hemorrhage]], [[coma]], [[Metastasis|bone marrow metastasis]], [[Recurrence plot|recurrence]], [[venous thromboembolism]], [[parkinsonism]], and [[side effects]] of [[chemotherapy]] and [[radiotherapy]]. [[Oligodendroglioma]] is a [[slow]] [[Growth|growing]] [[tumor]] having a good [[prognosis]] overall with prolonged [[Survival function|survival]]. But the [[prognosis]] of [[oligodendroglioma]] may vary depending upon various [[prognostic]] factors such as [[population]] based [[Estimate|estimates]], [[clinical]] factors, [[tumor]] grade (II versus III), [[Mechanism (biology)|mechanism]] of chemosensitivity, and [[Molecular marker|molecular markers]] such as [[1p36 deletion syndrome|1p]]/19q-codeletion, [[IDH1]]/[[IDH2|2]] [[mutation]], and [[TERT]] [[promoter]] [[mutations]]. The [[median]] [[Survival analysis|survival]] [[Time series|time]] for [[oligodendroglioma]] is 11.6 [[Year|years]] for [[Grading (tumors)|grade]] II and 3.5 [[Year|years]] for [[Grading (tumors)|grade]] III.


==Diagnosis==
==Diagnosis==
Line 38: Line 38:
**[[Tumor]] [[Location parameter|location]]
**[[Tumor]] [[Location parameter|location]]
**[[Heterogeneity|Hetero]]/[[homogeneity]]
**[[Heterogeneity|Hetero]]/[[homogeneity]]
*However, the [[Confirmatory factor analysis|confirmation]] of final [[diagnosis]] is [[Dependent variable|dependent]] on [[histopathologic]] [[examination]] of the [[biopsy]] specimen
*However, the [[Confirmatory factor analysis|confirmation]] of final [[diagnosis]] is [[Dependent variable|dependent]] on [[histopathologic]] [[examination]] of the [[biopsy]] specimen.


==Staging==
==Staging==
Line 44: Line 44:


==History and Symptoms==
==History and Symptoms==
When evaluating a patient for oligodendroglioma, a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, a thorough past medical history review, and review of common risk factors such as [[family history]] of [[brain tumors]]. Oligodendroglioma is a slow-growing, infiltrative tumor that may be clinically silent for many years. With tumor progression, symptoms may vary depending upon the location, size, and rate of tumor growth. Oligodendroglioma mainly involves the frontal lobe. Symptoms associated with oligodendroglioma include [[seizure]], [[headache]], [[nausea]], [[vomiting]], [[vertigo]], [[visual loss]], [[diplopia]], [[strabismus]], [[Hemiparesis|muscle weakness]], [[numbness]], speech difficulties, mood disturbances, personality changes, memory problems, low energy, fatigue, urge to sleep, loss of interest in daily activities, abulia, lack of spontaneity, loss of consciousness with syncope (few tonic-clonic jerks), and classic triad of headache, nausea, and papilledema due to raised intracranial pressure.
When evaluating a [[patient]] for [[oligodendroglioma]], a [[Detailed balance|detailed]] [[History and Physical examination|history]] of the [[presenting symptom]] (onset, duration, and progression), other [[Association (statistics)|associated]] [[symptoms]], a thorough past [[medical history]] [[review]], and [[review]] of common [[risk factors]] such as [[family history]] of [[brain tumors]]. [[Oligodendroglioma]] is a [[slow]]-[[Growth|growing]], [[Infiltration (medical)|infiltrative]] [[tumor]] that may be [[Clinical|clinically]] silent for many [[Year|years]]. With [[tumor]] progression, [[symptoms]] may vary depending upon the [[Location parameter|location]], [[Size consistency|size]], and [[rate]] of [[tumor]] [[growth]]. [[Oligodendroglioma]] mainly involves the [[frontal lobe]]. [[Symptoms]] [[Association (statistics)|associated]] with [[oligodendroglioma]] include [[seizure]], [[headache]], [[nausea]], [[vomiting]], [[vertigo]], [[visual loss]], [[diplopia]], [[strabismus]], [[Hemiparesis|muscle weakness]], [[numbness]], [[speech difficulties]], [[mood disturbances]], [[personality changes]], [[memory]] [[Problem Solved|problems]], low [[energy]], [[fatigue]], [[Urgency|urge]] to [[sleep]], [[Loss function|loss]] of [[Interest (emotion)|interest]] in [[Activities of daily living|daily activities]], [[abulia]], [[Lack (manque)|lack]] of spontaneity, [[loss of consciousness]] with [[syncope]] (few [[tonic-clonic]] [[Jerking|jerks]]), and classic [[Triad (anatomy)|triad]] of [[headache]], [[nausea]], and [[papilledema]] due to [[raised intracranial pressure]].


==Physical examination==
==Physical examination==
Common physical examination findings of oligodendroglioma include [[nystagmus]], [[papilledema]], [[esotropia]], [[Vision loss|visual field loss]], [[altered mental status]], [[aphasia]], [[Ataxia|ataxia,]][[hemiparesis]], [[tremor]], and focal neurological deficits including cranioneuropathies, corticospinal and spinocerebellar defects.
Common [[physical examination]] findings of [[oligodendroglioma]] include [[nystagmus]], [[papilledema]], [[esotropia]], [[Vision loss|visual field loss]], [[altered mental status]], [[aphasia]], [[Ataxia|ataxia,]][[hemiparesis]], [[tremor]], and focal [[neurological]] deficits including cranioneuropathies, [[Corticospinal tract|corticospinal]] and [[Spinocerebellar tract|spinocerebellar]] [[Defect|defects]].


==Laboratory Findings==
==Laboratory Findings==
Some patients with oligodendroglioma may have elevated [[protein]] and cell count with normal [[glucose]] and [[lactate]] on [[Lumbar puncture|CSF analysis]], which is usually suggestive of [[hydrocephalus]]. Immunohistochemistry of oligodendrgliomas shows positive staining for [[Isocitrate dehydrogenase|IDH1-R132H]], ATRX, [[GFAP]], SOX10, [[Microtubule-associated protein|MAP2]], [[S100 calcium binding protein A8|S-100]], EMA, [[Ki-67 (Biology)|Ki-67]], [[Neuron-Specific Enolase (NSE)|NSE]], [[synaptophysin]], [[OLIG1|OLIG1,]] and [[OLIG2]], and negative staining for p53, and keratins.
Some [[patients]] with [[oligodendroglioma]] may have elevated [[protein]] and [[cell]] count with normal [[glucose]] and [[lactate]] on [[Lumbar puncture|CSF analysis]], which is usually [[Suggestion|suggestive]] of [[hydrocephalus]]. [[Immunohistochemistry]] of [[oligodendrogliomas]] shows positive [[staining]] for [[Isocitrate dehydrogenase|IDH1-R132H]], [[ATRX]], [[GFAP]], [[SOX10]], [[Microtubule-associated protein|MAP2]], [[S100 calcium binding protein A8|S-100]], EMA, [[Ki-67 (Biology)|Ki-67]], [[Neuron-Specific Enolase (NSE)|NSE]], [[synaptophysin]], [[OLIG1|OLIG1,]] and [[OLIG2]], and [[Negative-sense|negative]] [[staining]] for [[p53]], and [[keratins]].


==Chest X Ray==
==Chest X Ray==
Chest x-ray may be performed to detect the [[metastases]] of [[anaplastic|anaplastic oligodendroglioma]] to lungs.
[[Chest X-ray|Chest x-ray]] may be performed to [[Detection theory|detect]] the [[metastases]] of [[anaplastic|anaplastic oligodendroglioma]] to [[lungs]].


==CT==
==CT==
Head CT scan may be helpful in the diagnosis of oligodendroglioma. Findings on CT scan suggestive of oligodendroglioma are round or oval, marginated, hypo- to isodense mass with [[hemorrhage]], ribbon-like [[calcification]], ill-defined enhancement following intravenous contrast administration, pressure erosion/remodelling of overlying skull, and marked ventricular enlargement suggestive of [[hydrocephalus]].
[[Head]] [[CT scan]] may be helpful in the [[diagnosis]] of [[oligodendroglioma]]. Findings on [[Computed tomography|CT scan]] [[Suggestion|suggestive]] of [[oligodendroglioma]] are round or [[oval]], marginated, hypo- to isodense [[mass]] with [[hemorrhage]], ribbon-like [[calcification]], ill-defined enhancement following [[intravenous]] [[contrast]] administration, [[pressure]] [[Erosion (dental)|erosion]]/remodelling of overlying [[skull]], and marked [[ventricular]] enlargement [[Suggestion|suggestive]] of [[hydrocephalus]].


==MRI==
==MRI==
Brain MRI is helpful in the diagnosis of oligodendroglioma. On brain MRI, oligodendroglioma is characterized by a mass which is typically hypointense on T1-weighted images and hyperintense on T2-weighted images. [[Calcification]] is observed as areas of "blooming" on T2 decay component of MRI. T1 C + gadolinium shows heterogeneous contrast enhancement and diffusion weighted images help differentiate lower grade oligodendrogliomas from higher grade astrocytomas which have higher ADC values because of lower cellularity and greater hyaluronan proportion. MR perfusion (PWI) is 95% sensitive for diagnosis of oligodendrogliomas and 87% sensitive for distinguishing grade II from grade III oligodendrogliomas. On PWI, "chicken wire" network of vascularity results in elevated relative cerebral blood volume (rCBV) of grade II vs grade III and rCBV above the threshold of 1.75 demonstrates more rapid tumor progression.
[[Brain]] [[Magnetic resonance imaging|MRI]] is helpful in the [[diagnosis]] of [[oligodendroglioma]]. On [[brain]] [[Magnetic resonance imaging|MRI]], [[oligodendroglioma]] is characterized by a [[mass]] which is typically hypointense on [[T1]]-[[Weighted mean|weighted]] [[images]] and hyperintense on T2-[[Weighted mean|weighted]] [[images]]. [[Calcification]] is observed as [[Area|areas]] of "blooming" on T2 decay component of [[Magnetic resonance imaging|MRI]]. [[T1]] C + [[gadolinium]] shows [[heterogeneous]] [[contrast]] [[Enhancer|enhancement]] and [[Diffusion-weighted imaging|diffusion weighted images]] help [[differentiate]] lower grade [[oligodendrogliomas]] from higher grade [[astrocytomas]] which have higher [[ADCC|ADC]] values because of lower [[Cellular|cellularity]] and greater [[hyaluronan]] [[Proportionality (mathematics)|proportion]]. [[MR]] [[perfusion]] (PWI) is 95% [[Sensitivity (test)|sensitive]] for [[diagnosis]] of [[oligodendrogliomas]] and 87% [[Sensitivity|sensitive]] for distinguishing [[Grading (tumors)|grade]] II from [[Grading (tumors)|grade]] III [[oligodendrogliomas]]. On PWI, "chicken wire" [[Network effect|network]] of [[vascularity]] [[Result|results]] in elevated relative [[cerebral]] [[blood volume]] (rCBV) of [[Grading (tumors)|grade]] II vs [[Grading (tumors)|grade]] III and rCBV above the [[Threshold potential|threshold]] of 1.75 demonstrates more rapid [[tumor]] progression.


==Ultrasound==
==Ultrasound==
There are no ultrasound findings associated with oligodendroglioma.
There are no [[ultrasound]] findings associated with [[oligodendroglioma]].


==Other Imaging Findings==
==Other Imaging Findings==
Other imaging studies for oligodendroglioma include MR spectroscopy (dominant [[N-acetyl aspartate]] peak, increased [[choline]] levels and decreased [[N-acetyl aspartate|NAA]] levels with a [[myo-inositol]] peak), MR perfusion (increased "''chicken wire''" network of vascularity, which results in elevated relative cerebral blood volume), PET scan (to differentiate between oligodendroglioma from anaplastic oligodendroglioma and tumor recurrence from tumor necrosis), and bone scan (bone metastasis).
Other [[imaging studies]] for [[oligodendroglioma]] include [[MR]] [[spectroscopy]] ([[dominant]] [[N-acetyl aspartate]] peak, increased [[choline]] levels and decreased [[N-acetyl aspartate|NAA]] levels with a [[myo-inositol]] peak), [[MR]] [[perfusion]] (increased "''chicken wire''" [[Network effect|network]] of [[vascularity]], which results in elevated relative [[cerebral]] [[blood volume]]), [[PET scan]] (to [[differentiate]] between [[oligodendroglioma]] from [[anaplastic]] [[oligodendroglioma]] and [[tumor]] [[Recurrence plot|recurrence]] from [[tumor]] [[necrosis]]), and [[bone scan]] ([[bone metastasis]]).


==Other Diagnostic Studies==
==Other Diagnostic Studies==
Other diagnostic studies for oligodendroglioma include [[biopsy]] (homogeneous, compact, rounded cells with distinct borders and clear cytoplasm surrounding a dense central nucleus and perinuclear halo) and [[fish|fluorescent in-situ hybridization (FISH) technique]] (deletions of [[chromosome 1|chromosome 1p]] and [[chromosome 19|19q]]).
Other [[Diagnostic study of choice|diagnostic studies]] for [[oligodendroglioma]] include [[biopsy]] ([[homogeneous]], [[Compact tissue|compact]], rounded [[Cells (biology)|cells]] with [[Distinctive feature|distinct]] [[Borderline|borders]] and clear [[cytoplasm]] surrounding a [[dense]] [[central]] [[nucleus]] and [[Perinuclear space|perinuclear]] [[Halo (medicine)|halo]]) and [[fish|fluorescent in-situ hybridization (FISH) technique]] ([[Deletion (genetics)|deletions]] of [[chromosome 1|chromosome 1p]] and [[chromosome 19|19q]]).


==Treatment==
==Treatment==
'''Innovative treatment options:'''
'''Innovative treatment options:'''
* Brain tumors can be complex and require a combination of treatments for the best outcome
* [[Brain]] [[tumors]] can be [[Complex (chemistry)|complex]] and require a [[Combination therapy|combination of treatments]] for the [[Best practice|best]] [[outcome]].
* There is quite a wide range of treatments to meet the individual needs of each patient which includes standard therapies, precision medicine and clinical trials
* There is quite a wide [[Range (statistics)|range]] of [[treatments]] to meet the [[Individual growth|individual]] needs of each [[patient]] which includes [[standard]] [[Therapy|therapies]], [[precision]] [[medicine]] and [[clinical trials]].
* Some of them are listed below:
* Some of them are listed below:
**'''Brachytherapy:'''
**'''[[Brachytherapy]]:'''
*** Destroys tumors by implanting radioactive medicine directly to or near the treatment site
*** Destroys [[tumors]] by [[Implant|implanting]] [[radioactive]] [[medicine]] [[Directly observed treatment|directly]] to or near the [[Treatments|treatment]] site.
**'''Chemotherapy:'''
**'''[[Chemotherapy]]:'''
*** Reaches cancer that may have spread, even microscopically, throughout the body
*** [[Reachback|Reaches]] [[cancer]] that may have [[Spreading activation|spread]], even [[Microscopic|microscopically]], throughout the [[Human body|body.]]
**'''Craniotomy:'''
**'''[[Craniotomy]]:'''
*** Surgical procedure that removes a bone flap, a section of the skull, to access the brain
*** [[Surgical procedure]] that removes a [[bone]] flap, a [[section]] of the [[skull]], to [[Accessibility|access]] the [[brain]].
**'''Intensity-modulated radiation therapy:'''  
**'''Intensity-modulated [[radiation therapy]]:'''  
***Uses computer technology to deliver radiation treatment that precisely fits the size and shape of the tumor
***Uses [[Computer-assisted|computer]] technology to [[Delivery|deliver]] [[radiation treatment]] that precisely [[fits]] the [[Size consistency|size]] and [[Shape parameter|shape]] of the [[tumor]].
**'''Minimally invasive cranial base surgery:'''
**'''Minimally invasive cranial base surgery:'''
*** Uses smaller incisions and specially designed instruments to eliminate a tumor while saving the surrounding tissue from damage
*** Uses smaller [[Incision|incisions]] and specially [[Design matrix|designed]] [[Instrumental variable|instruments]] to eliminate a [[tumor]] while saving the surrounding [[tissue]] from damage.
**'''Stereotactic radiosurgery & radiotherapy:'''
**'''[[Stereotactic radiosurgery]] & [[radiotherapy]]:'''
*** A noninvasive procedure that applies large doses of radiation directly to a tumor
*** A [[noninvasive]] [[procedure]] that applies [[Large-print|large]] [[doses]] of [[radiation]] [[Directly observed treatment|directly]] to a [[tumor]].


==Medical Therapy==
==Medical Therapy==
The predominant therapy for oligodendroglioma is surgical resection. Adjunctive chemotherapy and radiation are required. Supportive therapy for oligodendroglioma includes [[anticonvulsants]] and [[corticosteroids]].
The predominant [[therapy]] for [[oligodendroglioma]] is [[surgical resection]]. [[Adjuvant chemotherapy|Adjunctive chemotherapy]] and [[radiation]] are required. [[Support|Supportive]] [[therapy]] for [[oligodendroglioma]] includes [[anticonvulsants]] and [[corticosteroids]].


==Surgery==
==Surgery==
[[Surgery]] is the first-line treatment option for patients with oligodendroglioma. However, oligodendrogliomas cannot be completely resected because of their diffusely infiltrating nature. The aim of surgery is to make a definitive diagnosis, debulk the [[tumor]] to relieve [[elevated intracranial pressure]] and reduce the [[Tumor|tumor mass]] as a precursor to adjuvant treatment. [[Hydrocephalus surgery|CSF shunting]] is usually reserved for patients with [[hydrocephalus]] and includes two types of shunts: external ventricular drain-temporary shunt and internal drain-permanent shunt.
[[Surgery]] is the first-line [[Treatment IND|treatment]] option for [[patients]] with [[oligodendroglioma]]. However, [[oligodendrogliomas]] cannot be completely [[Resection|resected]] because of their [[Diffuse|diffusely]] [[Infiltration (medical)|infiltrating]] [[nature]]. The aim of [[surgery]] is to make a [[Definitive host|definitive]] [[diagnosis]], [[Debulking|debulk]] the [[tumor]] to relieve [[elevated intracranial pressure]] and [[Reduced|reduce]] the [[Tumor|tumor mass]] as a [[precursor]] to [[Adjuvant treatment|adjuvant treatment.]] [[Hydrocephalus surgery|CSF shunting]] is usually reserved for [[patients]] with [[hydrocephalus]] and includes two types of [[shunts]]: external [[ventricular]] [[Drain (surgery)|drain]]-temporary [[Shunt (medical)|shunt]] and [[internal]] [[Drain (surgery)|drain]]-permanent [[Shunt (medical)|shunt]].


==Primary Prevention==
==Primary Prevention==
There is no established method for prevention of oligodendroglioma.
There is no established [[Method of Levels|method]] for [[primary prevention]] of [[oligodendroglioma]].


==Secondary Prevention==
==Secondary Prevention==
There are no secondary preventive measures available for oligodendroglioma.
There are no [[Secondary prevention|secondary preventive]] [[Measure (mathematics)|measures]] available for [[oligodendroglioma]].


==References==
==References==

Latest revision as of 16:46, 6 June 2019

Oligodendroglioma Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2]Sujit Routray, M.D. [3]

Overview

Oligodendrogliomas are a type of glioma that are believed to originate from the tripotential glial precursor cells. The term "oligodendroglioma" was first coined by Bailey and Cushing in 1926 following the observation that the tumor cells are morphologically similar to oligodendrocytes. According to the new 2016 edition of WHO classification of gliomas based on histopathologic appearance and well-established molecular parameters, oligodendrogliomas are subclassified into grade II tumors including oligodendroglioma IDH-mutant and 1p/19q-codeleted, oligodendroglioma NOS, oligoastrocytoma NOS, and grade III tumors including anaplastic oligodendroglioma IDH-mutant and 1p/19q-codeleted, anaplastic oligodendroglioma NOS, and anaplastic oligoastrocytoma NOS. Genes associated with the pathogenesis of oligodendroglioma include t[1;19][q10;p10], ATRX, NJDS, IDH1, IDH2, TERT promoter, H3 K27M (H3F3A, HIST1H3B/C), CIC, FUBP1, p53, Leu-7, TCF-12, TP53, MGMT, TP73, BRAF, EGFR, and PTEN. Common intracranial sites involved by oligodendroglioma include cerebral hemispheres, posterior fossa, and intramedullary spinal cord. On gross pathology, oligodendroglioma is characterized by a well-circumscribed, gelatinous, calcified, cystic, gray mass with focal hemorrhage which may expand a gyrus and remodel the skull. On microscopy, it shows a diffuse growth pattern of highly cellular lesion of monomorphic cells having rounded nucleus with atypia, speckled "salt-and-pepper" chromatin pattern and perinuclear halo resembling fried eggs, distinct cell borders, clear cytoplasm, abundant calcification and "chicken-wire" like vascularity pattern. Common causes of oligodendroglioma include genetic mutations, some viral cause or irradiation of pituitary adenoma. On the basis of seizure, visual disturbance, and constitutional symptoms, oligodendroglioma must be differentiated from astrocytoma, meningioma, hemangioblastoma, pituitary adenoma, schwannoma, primary CNS lymphoma, medulloblastoma, ependymoma, craniopharyngioma, pinealoma, AV malformation, brain aneurysm, bacterial brain abscess, tuberculosis, toxoplasmosis, hydatid cyst, CNS cryptococcosis, CNS aspergillosis, and brain metastasis. It constitutes about 9.4% of all CNS tumors and 5%–18% of all glial neoplasms with incidence of oligodendroglioma and anaplastic oligodendroglioma to be 0.32 and 0.17 cases per 100,000 individuals in the United States, respectively. Oligodendroglioma is a disease that tends to affect the middle-aged adult population mainly occurring in the 4th and 5th decade of life with median age at the time of diagnosis to be 35-47 years. Males are more commonly affected than females with the male to female ratio of approximately 1.3:1. Oligodendroglioma usually affects individuals of the Caucasian race and African American, Latin American, and Asian individuals are less likely to develop oligodendroglioma. The most potent risk factor for the development of oligodendroglioma is family history of brain tumors. If left untreated, patients with oligodendroglioma may progress to develop seizures, focal neurological deficits, hydrocephalus, brain herniation, intracranial hemorrhage, and ultimately death. Common complications associated with oligodendroglioma include hydrocephalus, intracranial hemorrhage, coma, bone marrow metastasis, recurrence, venous thromboembolism, parkinsonism, and side effects of chemotherapy and radiotherapy. The overall prognosis is good but the prognosis may vary depending upon various prognostic factors such as population based estimates, clinical factors, tumor grade (II versus III), mechanism of chemosensitivity, and molecular markers such as 1p/19q-codeletion, IDH1/2 mutation, and TERT promoter mutations. Symptoms associated with oligodendroglioma include seizure, headache, nausea, vomiting, vertigo, visual loss, diplopia, strabismus, muscle weakness, numbness, speech difficulties, mood disturbances, personality changes, memory problems, low energy, fatigue, urge to sleep, loss of interest in daily activities, abulia, lack of spontaneity, loss of consciousness with syncope (few tonic-clonic jerks), and classic triad of headache, nausea, and papilledema due to raised intracranial pressure. Findings on CT scan suggestive of oligodendroglioma are round or oval, marginated, hypo- to isodense mass with hemorrhage, ribbon-like calcification, ill-defined enhancement following intravenous contrast administration, pressure erosion/remodelling of overlying skull, and marked ventricular enlargement suggestive of hydrocephalus. On brain MRI, oligodendroglioma is characterized by a mass which is typically hypointense on T1-weighted images and hyperintense on T2-weighted images. Calcification is observed as areas of "blooming" on T2 decay component of MRI. Other imaging studies for oligodendroglioma include MR spectroscopy (dominant N-acetyl aspartate peak, increased choline levels and decreased NAA levels with a myo-inositol peak), MR perfusion (increased "chicken wire" network of vascularity, which results in elevated relative cerebral blood volume), PET scan (to differentiate between oligodendroglioma from anaplastic oligodendroglioma and tumor recurrence from tumor necrosis), and bone scan (bone metastasis). Other diagnostic studies for oligodendroglioma include biopsy (homogeneous, compact, rounded cells with distinct borders and clear cytoplasm surrounding a dense central nucleus and perinuclear halo) and fluorescent in-situ hybridization (FISH) technique (deletions of chromosome 1p and 19q). The predominant therapy for oligodendroglioma is surgical resection. Adjunctive chemotherapy and radiation are required. Supportive therapy for oligodendroglioma includes anticonvulsants and corticosteroids.

Historical Perspective

In 1926, the term "oligodendroglioma" was first coined by Bailey and Cushing, and was first described and published by W. E. Carnegie Dickson. Oligodendrogliomas were first classified and graded in a system devised by Bailey and Cushing, and later revised by Kernohan, Ringertz, and others, and since then, classification and grading of gliomas have evolved over the time. Modern WHO classification of oligodendrogliomas was first published in 1979 and revised four times since then, with the most recent published in 2016. In 1997, a Westergaard's study showed that patients younger than 20 years had a median survival of 17.5 years. In 2001, a study at Mayo Clinic was conducted to assess the prognostic value of histological grading of oligodendroglial tumors in tumor grading and significant association with survival was found for age, high cellularity, presence of mitoses, endothelial hypertrophy and proliferation and necrosis on univariate analysis, but only age and presence of endothelial proliferation were found to be independently associated with survival on a multivariable analysis. In 2009, NJDS mutation was first identified in the pathogenesis of oligodendroglioma by Kevin Smith. It was suggested in 2009 ASCO Annual Meeting that PCV therapy may be superior in efficacy to the newer temozolomide therapy. Irradiation of pituitary adenoma was also discovered to be associated with oligodendroglioma by Kevin Smith et al.

Classification

According to the old 2007 WHO classification of the central nervous system tumors, oligodendrogliomas were divided into five subtypes: oligodendroglioma (OII), anaplastic oligodendroglioma (OIII), oligoastrocytoma (OAII), anaplastic oligoastrocytoma (OAIII), and glioblastoma with oligodendroglioma component (GBMo). But the new 2016 edition of WHO classification of gliomas is based not only on histopathologic appearance but also on well-established molecular parameters, and oligodendroglial tumors are now more narrowly defined by molecular diagnostics to include only those diffuse gliomas having both a mutation in isocitrate dehydrogenase type 1 (IDH1) or type 2 (IDH2) and codeletion of chromosomes 1p and 19q. This new pattern of classification divides oligodendrogliomas into grade II tumors including oligodendroglioma IDH-mutant and 1p/19q-codeleted, oligodendroglioma NOS, oligoastrocytoma NOS, and grade III tumors including anaplastic oligodendroglioma IDH-mutant and 1p/19q-codeleted, anaplastic oligodendroglioma NOS, and anaplastic oligoastrocytoma NOS.

Pathophysiology

Oligodendroglioma arises from the tripotential glial precursor cells and not from the bipotential oligodendrocytes. Genes associated with the pathogenesis of oligodendroglioma include t[1;19][q10;p10], ATRX, NJDS, IDH1, IDH2, TERT promoter, H3 K27M (H3F3A, HIST1H3B/C), CIC, FUBP1, p53, Leu-7, TCF-12, TP53,MGMT, TP73, BRAF, EGFR, and PTEN. Common intracranial sites involved by oligodendroglioma include cerebral hemispheres, posterior fossa, and intramedullary spinal cord. On gross pathology, oligodendroglioma is characterized by a well-circumscribed, gelatinous, calcified, cystic, gray mass with focal hemorrhage which may expand a gyrus and remodel the skull. On microscopic histopathological analysis, oligodendroglioma is characterized by diffuse growth pattern of highly cellular lesion of monomorphic cells having rounded nucleus with atypia, speckled "salt-and-pepper" chromatin pattern and perinuclear halo resembling fried eggs, distinct cell borders, clear cytoplasm, abundant calcification and "chicken-wire" like vascularity pattern. Oligodendroglioma is demonstrated by positivity to tumor markers such as IDH1-R132H, MAP2, GFAP, S-100, SOX10, EMA, ATRX, Ki-67, NSE, synaptophysin, OLIG1, and OLIG2.

Causes

The most common etiology of oligodendroglioma includes genetic mutations such as t(1;19)(q10;p10), NJDS, IDH1, IDH2, CIC, FUBP1, p53, Leu-7, TCF-12,MGMT, TP73, EGFR and PTEN. It may be associated with some viral cause or irradiation of pituitary adenoma.

Differentiating Oligodendroglioma from other diseases

On the basis of seizure, visual disturbance, and constitutional symptoms, oligodendroglioma must be differentiated from astrocytoma, meningioma, hemangioblastoma, pituitary adenoma, schwannoma, primary CNS lymphoma, medulloblastoma, ependymoma, craniopharyngioma, pinealoma, AV malformation, brain aneurysm, bacterial brain abscess, tuberculosis, toxoplasmosis, hydatid cyst, CNS cryptococcosis, CNS aspergillosis, and brain metastasis.

Epidemiology and Demographics

Oligodendroglioma, although rare, is the third most common glioma. In adults, it constitutes about 9.4% of all primary brain and central nervous system tumors and 5%–18% of all glial neoplasms. The incidence of oligodendroglioma and anaplastic oligodendroglioma is estimated to be 0.32 and 0.17 cases per 100,000 individuals in the United States, respectively. Oligodendroglioma tends to affect the middle-aged adult population, most commonly occurring in the 4th and 5th decade of life. Median age at the time of diagnosis of oligodendroglioma is 35-47 years. Males are more commonly affected with oligodendroglioma than females with male to female ratio being approximately 1.3:1. Oligodendroglioma usually affects individuals of the Caucasian race. African American, Latin American, and Asian individuals are less likely to develop oligodendroglioma.

Risk factors

The most potent risk factor for the development of oligodendroglioma is a positive family history of brain tumors.

Screening

There is insufficient evidence for recommending routine screening for oligodendroglioma.

Natural History, Complications and Prognosis

If left untreated, patients with oligodendroglioma may progress to develop seizures, focal neurological deficits, hydrocephalus, brain herniation, intracranial hemorrhage, and ultimately death.Common complications associated with oligodendroglioma include hydrocephalus, intracranial hemorrhage, coma, bone marrow metastasis, recurrence, venous thromboembolism, parkinsonism, and side effects of chemotherapy and radiotherapy. Oligodendroglioma is a slow growing tumor having a good prognosis overall with prolonged survival. But the prognosis of oligodendroglioma may vary depending upon various prognostic factors such as population based estimates, clinical factors, tumor grade (II versus III), mechanism of chemosensitivity, and molecular markers such as 1p/19q-codeletion, IDH1/2 mutation, and TERT promoter mutations. The median survival time for oligodendroglioma is 11.6 years for grade II and 3.5 years for grade III.

Diagnosis

Staging

There is no established system for the staging of oligodendroglioma.

History and Symptoms

When evaluating a patient for oligodendroglioma, a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, a thorough past medical history review, and review of common risk factors such as family history of brain tumors. Oligodendroglioma is a slow-growing, infiltrative tumor that may be clinically silent for many years. With tumor progression, symptoms may vary depending upon the location, size, and rate of tumor growth. Oligodendroglioma mainly involves the frontal lobe. Symptoms associated with oligodendroglioma include seizure, headache, nausea, vomiting, vertigo, visual loss, diplopia, strabismus, muscle weakness, numbness, speech difficulties, mood disturbances, personality changes, memory problems, low energy, fatigue, urge to sleep, loss of interest in daily activities, abulia, lack of spontaneity, loss of consciousness with syncope (few tonic-clonic jerks), and classic triad of headache, nausea, and papilledema due to raised intracranial pressure.

Physical examination

Common physical examination findings of oligodendroglioma include nystagmus, papilledema, esotropia, visual field loss, altered mental status, aphasia, ataxia,hemiparesis, tremor, and focal neurological deficits including cranioneuropathies, corticospinal and spinocerebellar defects.

Laboratory Findings

Some patients with oligodendroglioma may have elevated protein and cell count with normal glucose and lactate on CSF analysis, which is usually suggestive of hydrocephalus. Immunohistochemistry of oligodendrogliomas shows positive staining for IDH1-R132H, ATRX, GFAP, SOX10, MAP2, S-100, EMA, Ki-67, NSE, synaptophysin, OLIG1, and OLIG2, and negative staining for p53, and keratins.

Chest X Ray

Chest x-ray may be performed to detect the metastases of anaplastic oligodendroglioma to lungs.

CT

Head CT scan may be helpful in the diagnosis of oligodendroglioma. Findings on CT scan suggestive of oligodendroglioma are round or oval, marginated, hypo- to isodense mass with hemorrhage, ribbon-like calcification, ill-defined enhancement following intravenous contrast administration, pressure erosion/remodelling of overlying skull, and marked ventricular enlargement suggestive of hydrocephalus.

MRI

Brain MRI is helpful in the diagnosis of oligodendroglioma. On brain MRI, oligodendroglioma is characterized by a mass which is typically hypointense on T1-weighted images and hyperintense on T2-weighted images. Calcification is observed as areas of "blooming" on T2 decay component of MRI. T1 C + gadolinium shows heterogeneous contrast enhancement and diffusion weighted images help differentiate lower grade oligodendrogliomas from higher grade astrocytomas which have higher ADC values because of lower cellularity and greater hyaluronan proportion. MR perfusion (PWI) is 95% sensitive for diagnosis of oligodendrogliomas and 87% sensitive for distinguishing grade II from grade III oligodendrogliomas. On PWI, "chicken wire" network of vascularity results in elevated relative cerebral blood volume (rCBV) of grade II vs grade III and rCBV above the threshold of 1.75 demonstrates more rapid tumor progression.

Ultrasound

There are no ultrasound findings associated with oligodendroglioma.

Other Imaging Findings

Other imaging studies for oligodendroglioma include MR spectroscopy (dominant N-acetyl aspartate peak, increased choline levels and decreased NAA levels with a myo-inositol peak), MR perfusion (increased "chicken wire" network of vascularity, which results in elevated relative cerebral blood volume), PET scan (to differentiate between oligodendroglioma from anaplastic oligodendroglioma and tumor recurrence from tumor necrosis), and bone scan (bone metastasis).

Other Diagnostic Studies

Other diagnostic studies for oligodendroglioma include biopsy (homogeneous, compact, rounded cells with distinct borders and clear cytoplasm surrounding a dense central nucleus and perinuclear halo) and fluorescent in-situ hybridization (FISH) technique (deletions of chromosome 1p and 19q).

Treatment

Innovative treatment options:

Medical Therapy

The predominant therapy for oligodendroglioma is surgical resection. Adjunctive chemotherapy and radiation are required. Supportive therapy for oligodendroglioma includes anticonvulsants and corticosteroids.

Surgery

Surgery is the first-line treatment option for patients with oligodendroglioma. However, oligodendrogliomas cannot be completely resected because of their diffusely infiltrating nature. The aim of surgery is to make a definitive diagnosis, debulk the tumor to relieve elevated intracranial pressure and reduce the tumor mass as a precursor to adjuvant treatment. CSF shunting is usually reserved for patients with hydrocephalus and includes two types of shunts: external ventricular drain-temporary shunt and internal drain-permanent shunt.

Primary Prevention

There is no established method for primary prevention of oligodendroglioma.

Secondary Prevention

There are no secondary preventive measures available for oligodendroglioma.

References


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