Oligodendroglioma and Oligoastrocytoma

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Pathogenesis and Pathophysiology. Because these tumors arise from oligodendrocytes, they usually occur in the white matter of the cerebrum, and because there are relatively more oligodendrocytes in the frontotemporal area, oligodendrogliomas have a predilection for these areas. Usually surgical specimens contain areas that are identifiable as astrocytoma. Increasing difficulty in the diagnosis of these tumors centers on the percentage of oligodendro-glioma cells needed to categorize these tumors as pure oligodendrogliomas rather than mixed oligodendroglioma-astrocytoma (oligoastrocytoma). The grading system of Smith y has been used by most neuropathologists for the histological categorization of oligodendroglioma. Only necrosis has been found to be a predictor of biological behavior; mitotic activity apparently becomes more important with advancing age.y On microscopic examination most tumors show tumor cell infiltration into the cortex, and many tumor cells show an artifactual halo around the nucleus (the so-called fried-egg appearance). A delicate vascular pattern is also a prominent feature ( .Fig 46-5 ).

Epidemiology and Risk Factors. Oligodendrogliomas occur most commonly in young adults. Peak incidence occurs in the third to fifth decade, and the tumor occurs predominantly among men. There are no known established risk factors. Recent epidemiological work has suggested that gliomas may be associated with repeated exposure to high-voltage electrical lines. These tumors have a poorer prognosis with age. Although typically considered to represent about 2 percent of intracranial primary tumors, recently the incidence has been increasing owing to changes in neuropathological diagnostic criteria. For example, at the University of Iowa, 25 patients were diagnosed with oligodendroglioma from 1961 to 1991, whereas from 1992 to 1995, 48 such diagnoses were made.

Clinical Features and Associated Disorders. Because of their infiltrative nature, oligodendrogliomas commonly cause seizures. Occasionally, patients with medically refractory seizures who undergo surgical abolition are found to have an oligodendroglioma. These tumors can infiltrate and surround the neuronal networks without causing loss of function until they achieve a rather large volume. Retrospectively, subtle neurobehavioral changes can be detected long before the tumor is discovered. As with other gliomas, patients may also present with symptoms of hydrocephalus,

Figure 46-5 Histopathologic,! picture of an oligodendroglioma; nuclei are surrounded by swollen, clear cytoplasm, demonstrating a "fried-egg" appearance, and fine vascular channels.

headache, and sudden focal neurological findings consistent with acute hemorrhage into the tumor. There is also a higher risk of dissemination through the cerebrospinal pathways resulting in spinal cord or patchy symptoms within the neuroaxis, which are sometimes confused with metastatic disease. y Rarely, oligodendrogliomas can metastasize outside the central nervous system.

Differential Diagnosis and Evaluation. Evaluation of oligodendrogliomas is the same as that discussed earlier for astrocytomas and glioblastoma multiforme. The differential diagnosis for oligodendroglioma and oligoastrocytoma is similar to that for astrocytomas. Since oligodendrogliomas are more often non-contrast-enhancing on MRI scans, they may be confused with low-grade gliomas. With CT imaging, hypodense areas may also cause confusion with stroke or gliosis. Oligodendrogliomas are commonly found to have calcium deposits, and in many cases, contrast-enhancing areas are also found in the lesions on CT imaging. However, patients should undergo MRI to better define the areas of tumor involvement. Surgical diagnosis and attempts to achieve maximum cytoreduction are mandatory. Small stereotactic or open biopsies may lead to a misdiagnosis of astrocytomas, thereby affecting subsequent radiotherapy and chemotherapy treatment of these tumors.

Management. Neurological problems such as seizures should be treated with appropriate medications as discussed earlier for astrocytomas. Patients should be monitored closely for tumor regrowth or dissemination within the neuroaxis. The treatment of these tumors has become increasingly controversial. Some believe that these tumors are biologically less aggressive and can be observed with serial imaging until tumor growth is apparent either clinically or radiographically. Others believe that all oligodendrogliomas should be treated with radiation after histological confirmation. A large study at Duke University has suggested that radiotherapy may not benefit patients with oligodendrogliomas^ Recent studies have also suggested that anaplastic oligodendrogliomas are more responsive to chemotherapy and should be treated with PCV in addition to radiation, especially for Smith grade B, C, and D lesions. y y y Others have suggested that although chemotherapy for these oligodendrogliomas before radiotherapy may be harmful, this combination of chemotherapeutic agents is beneficial for patients with oligoastrocytomas. y Finally, some reports have appeared of treatment with chemotherapy alone for patients who have a more benign appearing histological diagnosis. y An ongoing RTOG study of anaplastic oligodendrogliomas randomized between radiotherapy alone and chemotherapy with PCV followed by radiotherapy may shed further light on this discussion. Until better information is available, every effort should be made to enroll all patients in clinical studies.

Prognosis and Future Perspectives. Patients with oligodendrogliomas presenting with seizures seem to survive longer, possibly due to earlier discovery of the tumor. Reported overall median survival ranges from 5 to 10 years depending on the study, the reporting period, and the treatment regimen. Survival statistics will probably change as the diagnostic criteria continue to evolve. Survival for patients with oligoastrocytomas is similar to that for patients with anaplastic astrocytomas. Better neuropathological criteria for diagnosis of these tumors and higher enrollment of patients into clinical trials will provide better and more timely data on the optimal treatment for these tumors. As molecular definitions of these tumors are further refined, we may begin to base treatment of these tumors less on histological criteria and more on the presence of genetic abnormalities.

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