Oligodendroglioma overview
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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
- CT or MRI scan is necessary to characterize the anatomy of oligodendroglial tumors such as:
- However, the confirmation of final diagnosis is dependent on histopathologic examination of the biopsy specimen.
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:
- Brain tumors can be complex and require a combination of treatments for the 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.
- Some of them are listed below:
- Brachytherapy:
- Destroys tumors by implanting radioactive medicine directly to or near the treatment site.
- Chemotherapy:
- Reaches cancer that may have spread, even microscopically, throughout the body.
- Craniotomy:
- Intensity-modulated radiation therapy:
- Minimally invasive cranial base surgery:
- Uses smaller incisions and specially designed instruments to eliminate a tumor while saving the surrounding tissue from damage.
- Stereotactic radiosurgery & radiotherapy:
- Brachytherapy:
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.