Introduction
Lateral radiograph of the skull in a 44-year-old man with a 3-year history of epileptic seizures. This radiograph shows a left frontal oligodendroglioma. Note the vermicular calcifications that are projecting on the frontal lobe.
Computed tomography scan of a low-grade oligodendroglioma. (Same patient as in the angiograph below.) This image shows hypoattenuation of the left frontal lobe without contrast enhancement.
Background
Oligodendroglioma is a well-differentiated, diffusely infiltrating tumor of adults that is typically located in the cerebral hemispheres and is predominantly composed of cells that morphologically resemble oligodendroglia.1,2
In 1900, Robertson first recognized oligodendroglial cells as the myelin-forming unit of the neuroglial portion of the central nervous system (CNS).
In 1924, Bailey and Hiller suggested that the oligodendrocyte may be a constituent of certain CNS tumors.3
In 1926, Bailey and Cushing first described oligodendrogliomas in a histogenetic classification of gliomas.4
In 1929, Bailey and Bucy described 13 cases of oligodendroglioma, including the tumor's clinical and pathologic characteristics.5
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Oligodendroglioma (from Neurology)
Neoplasms, Brain
Brain, Metastases
Brainstem Gliomas
EEG in Brain Tumors
Frequency
United States
In 2005, the US Central Brain Tumor Registry reported an annual incidence of oligodendroglial tumors of 0.35 cases per 100,000 individuals.6
International
According to conventional histologic classifications, oligodendrogliomas are uncommon neoplasms, accounting for 2-4% of primary brain tumors or 5-18% of cerebral gliomas. Their frequency is probably underestimated; some authors believe they account for approximately 30% of gliomas.
Oligodendroglioma may be the second most common glioma in adults after glioblastoma multiforme.6
Mortality/Morbidity
Median postoperative survival times ranging from 3 to 5 years have been reported in patients with oligodendrogliomas of all histologic grades. Median survival time is less than 2 years for patients with anaplastic oligodendrogliomas and approximately 10 years for persons with low-grade oligodendrogliomas.
According to several studies, survival is not correlated with tumor location or surgical removal. Rather, survival seems to be primarily correlated with the histologic features, clinical findings (age at onset, epilepsy vs deficit), and radiologic criteria (especially contrast enhancement).7,8,9,10 Retrospective studies have shown that the deletions of chromosome 1p and 19q may predict a good response to chemotherapy and a better prognosis.8,9
- Oligodendrogliomas generally recur locally.
- Malignant progression with recurrence is not uncommon, although this is considered less frequent with oligodendrogliomas than with diffuse astrocytomas.
- Concerning anaplastic oligodendrogliomas, patients may develop metastases via the cerebrospinal fluid (CSF) or even systemic metastases (the skeletal system, lymph nodes, lung and pleura, and liver are the most commonly reported extraneural sites).
Sex
The incidence of oligodendrogliomas is reportedly equal between men and women, although some authors report a higher male preponderance.8
Age
Most oligodendrogliomas arise in adults, with a peak incidence in the fourth or fifth decades of life.8 Approximately 6% of oligodendrogliomas arise during infancy and childhood.8
Presentation
Natural history and presentation
The tumor is supratentorial in 92% of patients. In adults, oligodendrogliomas arise within the cortex and further extend into the white matter of the cerebral hemispheres in rough proportion to the mass of each lobe (frontal, parietal, temporal, and occipital). The lesion is predominantly peripheral, rarely affecting median structures. In tumors that are adjacent to the ventricular system or the subarachnoid spaces, seeding of the CSF pathways may occur. On occasion, frontal lobe tumors may extend through the corpus callosum.
Infratentorial locations are possible but uncommon. Packer et al reported 4 oligodendrogliomas of the posterior fossa in children and suggested that these tumors may behave aggressively in this location.11 Intramedullary oligodendrogliomas have been reported in rare cases, with exceptional case reports describing holocord localization. Primary leptomeningeal oligodendrogliomas have also been reported.
Oligodendrogliomas seem much more complex than their classic description suggests. Several systems have been used for the histologic grading of oligodendroglial tumors, including the Kernohan, Smith, Ringertz, and Saint Anne/Mayo (St. Anne-Mayo) (originally designed for astrocytic tumors) systems.
The classic method is the World Health Organization (WHO) grading system.12 Histologically, oligodendroglial tumors comprise a continuous spectrum of lesions, ranging from well-differentiated neoplasms to frankly malignant tumors. The WHO grading system recognizes 2 grades for oligodendroglial tumors: WHO grade II for well-differentiated tumors and WHO grade III for anaplastic oligodendroglioma.
Gross morphologic features
Macroscopically, oligodendrogliomas are usually solid, relatively well-defined, soft gray-pink tumors. Cases with extensive mucoid degeneration may appear gelatinous. The tumor is typically located in the cortex and white matter, and infiltration of the overlying leptomeninges may be seen. Calcification is frequent. Necrosis, cyst formation, and hemorrhage are possible.
Microscopic features
Well-differentiated oligodendrogliomas are composed of cells with uniform, round to oval nuclei and a fine chromatin pattern with small nucleoli. Perinuclear halos are characteristic and are a result of autolysis because of a delay in fixation. The tumor cells exhibit a clear, swollen cytoplasm that is surrounded by a well-defined membrane, which lends a fried-egg or honeycomb appearance, and the cells are associated with capillary-sized blood vessels that are arranged in an acutely branching or chicken-wire pattern.
The tumor cells are present in sheets and lobular groups between a prominent vascular network that is composed of branching capillaries. Infiltration of the tumor into the cerebral cortex results in perineuronal satellitosis and perivascular and subpial tumor cell aggregates. Circumscribed leptomeningeal infiltration may induce a marked desmoplastic reaction.
As the tumors become more anaplastic (WHO grade III), the oligodendrogliomas typically become more cellular, with increased nuclear pleomorphism, marked cytologic atypia, high mitotic activity, developing vascular proliferation, and areas of focal tumor necrosis. Whereas low-grade oligodendrogliomas lack astrocytic features, histologically malignant oligodendroglial tumors tend to develop certain astrocytic features.
Ultrastructural features
Oligodendroglial tumor cells contain variable amounts of cytoplasm that are often rich in organelles, including numerous microtubules, free ribosomes, and mitochondria. An associated prominent Golgi apparatus may be present. Usually, large compact bundles of glial filaments, as seen in astrocytomas, are absent.
Immunohistochemistry
No specific marker that is equivalent to astrocytomal glial filament acidic protein has been found to identify tumoral oligodendrocytes.
Catherine Daumas-Duport developed another approach to identifying oligodendrogliomas.13,14 She concluded that these tumors are not monomorphous tumors as their classic description suggests and has distinguished 2 different growth patterns of gliomas. First, with solid tumor tissue, tumor cells are in contact with each other and are associated with newly formed microblood vessels.13 Second, with isolated tumor cells (ITCs), the tumor cells permeate largely intact brain parenchyma that is without neovascularity but has edema.
Daumas-Duport classified gliomas as follows: structure type I, which is solid tumor tissue only; structure type II, which is tumor tissue and ITCs; and structure type III, which are ITCs only.13 Oligodendrogliomas exhibit a structure type II or III growth pattern, but these tumors never adopt a structure type I pattern. According to Daumas-Duport, the "diffuse fibrillary astrocytomas" are composed of isolated tumoral oligodendrocytes, which induce chronic fibrillary astrogliosis in the infiltrated white matter.13
Oligodendrogliomas reveal a variable appearance according to their pattern of growth. The classic morphologic features, a honeycomb appearance, and a rich capillary network with a chicken-wire pattern are seen in the tumor tissue, whereas ITC components usually exhibit the morphologic appearance of the diffuse fibrillary astrocytomas. Therefore, oligodendrogliomas occur much more frequently than previously believed and probably account for one third of gliomas.13 The tumor tissue destroys the brain parenchyma and exhibits newly formed microblood vessels, whereas ITCs do not destroy brain parenchyma and are not accompanied by microangiogenesis.
Delayed angiogenesis is a crucial event in the tumor's progression toward more aggressive behavior. Endothelial hyperplasia and contrast enhancement are powerful negative prognostic factors (contrast enhancement is strongly related to the degree of microvascularity). Daumas-Duport suggested the following new grading system based on morphologic and imaging criteria: grade A, which is the absence of endothelial hyperplasia and contrast enhancement, and grade B, which is the presence of endothelial hyperplasia and/or contrast enhancement.14
The median survival in Daumas-Duport's series was 11 years for patients classified with grade A oligodendrogliomas and 3.5 years for those with grade B. This classification requires close cooperation between the neuroradiologist and pathologist.
The problem of mixed oligodendrogliomas remains a matter of debate. (Note the lack of interobserver reproducibility concerning pathologic diagnosis in this field). The distinction between an oligoastrocytoma and astrocytoma is more than simply academic interest, because there is a marked difference in response to chemotherapy with procarbazine, lomustine, and vincristine (PCV).
Because of the typically slow growth of oligodendrogliomas, the elapsed time between the initial symptoms and clinical diagnosis may vary from 1 week to 12 years. However, with easy access to magnetic resonance imaging (MRI), this interval has been greatly reduced.
Common symptoms
Seizures are the most common presenting symptom of oligodendrogliomas. The frequency of seizures reported in the literature ranges from 24-100%. The high incidence of seizures may be related to the tendency of these tumors to diffusely infiltrate the cerebral cortex. Although generalized convulsions occur at a higher rate, various types of seizures may occur in relation to tumoral localization. For many years, epilepsy may be the only manifestation of intracerebral tumors that behave in a relatively benign manner. In this instance, epilepsy is a clinically favorable prognostic factor.
Headache is another frequent symptom. The remainder of the symptoms vary and include intracranial hypertension and focal neurologic deficit. The neurologic deficits often occur secondarily in patients who at first present with seizures only. Some authors report the negative prognostic implication of presentation with a focal neurologic deficit.
Treatment
The optimum management of patients with low-grade glioma remains largely undefined.
The standard treatment of high-grade oligodendroglial tumors is based on surgery, radiotherapy, and chemotherapy. The benefit of the extent of surgical resection is a controversial issue. The efficacy of radiotherapy on overall survival is demonstrated, but the optimal timing is unknown. Although immediate postoperative radiation therapy is indicated for incompletely resected higher-grade oligodendrogliomas, its use for partially resected low-grade tumors is controversial.15
Oligodendroglial tumors exhibit a particular therapeutic chemosensitivity that is different from that of astrocytic tumors, particularly glioblastoma multiforme. Responses of these tumors to a variety of drugs have been observed, principally with alkylating agents, but combination PCV chemotherapy has emerged as the treatment of choice.
Approximately two thirds of anaplastic oligodendrogliomas and oligoastrocytomas respond to a combination of surgery, radiation, and PCV chemotherapy. The place of chemotherapy, either in the adjuvant setting or at recurrence, remains a matter of debate.
Objective responses to such first-line therapy are observed in 60-80% of patients with newly diagnosed aggressive pure or mixed oligodendrogliomas, with complete response and partial response in 20-60% of patients and a time to progression of 14-48 months. Despite the success of front-line therapy, most patients with malignant gliomas experience tumor recurrence. Response rates to second-line chemotherapy vary from 10-40%, with a progression-free survival of 6-9 months. Studies of temozolomide given after PCV failure have shown encouraging results, with an objective response rate of approximately 40%, including a complete response rate of approximately 20%. Furthermore, a good correlation exists between quality of response and progression-free survival.
In newly diagnosed low-grade oligodendroglial tumors, however, the benefit of surgical resection and postoperative radiotherapy on survival has not been clearly demonstrated. The standard treatment is based on surgery and radiotherapy in cases in which the resection is partial. The usefulness and timing of chemotherapy remain under investigation.
The heterogeneous responses of anaplastic oligodendrogliomas and oligoastrocytomas to chemotherapy may be the result of the unique genetic alteration in these tumors. The combined loss of chromosome arms 1p and 19q that is known to occur in 50-70% of anaplastic oligodendrogliomas could represent a significant predictor of chemotherapeutic response and survival in anaplastic oligodendrogliomas.8,9 On diffusion-weighted and perfusion-weighted MRIs, tumors with these deletions demonstrate better chemosensitivity in focal areas of lower ADC and higher relative cerebral rCBV. Oligodendrogliomas with 1p and 19q deletions appear to have a better biologic behavior and are more likely to respond to PCV chemotherapy.16
Preferred Examination
Computed tomography (CT) scanning and MRI are complementary exploratory techniques that are suitable for imaging oligodendrogliomas.17 However, tumor calcification is better defined on CT scans than on MRI.18
Differential Diagnoses
Astrocytoma, Brain
Brain, Stroke
Ganglioglioma
Ganglioneuroma and Ganglioneuroblastoma
Glioblastoma Multiforme
Other Problems to Be Considered
Central neurocytoma
Dysembryoplastic neuroepithelial tumor
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References
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Further Reading
Related eMedicine topics:
Oligodendroglioma (from Neurology)
Neoplasms, Brain
Brain, Metastases
Brainstem Gliomas
EEG in Brain Tumors
Keywords
oligodendroglioma, oligodendroglial cells, oligodendrocyte, oligodendroglial tumor cells, cerebral oligodendroglioma, oligodendroglia, intramedullary oligodendrogliomas, primary leptomeningeal oligodendrogliomas, Kernohan grading system, Smith grading system, Ringertz grading system, Saint Anne/Mayo (St. Anne-Mayo) grading system, Daumas-Duport grading system
