Diffusely infiltrating gliomas are a heterogenous group of central nervous system tumors arising from glial cells, such as astrocytes and oligodendrocytes. The diagnosis, classification, and treatment of gliomas have evolved significantly with increased understanding of the genetics of tumorigenesis. Seizures, focal neurologic deficits, and headache are common presenting signs and symptoms in patients with glial tumors. Initial diagnosis is typically based on contrast-enhanced brain magnetic resonance imaging (MRI).
High-grade gliomas include anaplastic gliomas (anaplastic astrocytomas and anaplastic oligodendrogliomas) and glioblastomas. These are typically hypointense on MRI T1-weighted sequences and hyperintense on T2-weighted sequences with heterogenous enhancement, surrounding vasogenic edema, and associated mass effect. A thick rim of enhancement with central clearing can be seen due to areas of central necrosis, cystic cavities, or blood products, particularly with glioblastomas. Antiepileptic therapy is indicated for clinical or subclinical seizures, but should not be given in patients with a newly diagnosed brain tumor who are seizure-free.
Low-grade gliomas include diffuse astrocytomas and oligodendrogliomas. They appear hyperintense on MRI T2-weighted sequences, typically without vasogenic edema or enhancement. Oligodendrogliomas may be partially calcified.
Surgical resection, rather than biopsy alone, allows for optimal tumor characterization and grading to guide further management. Advanced imaging, such as functional MRI and diffusion tensor imaging, can help identify eloquent cortex for surgical planning. Maximal surgical resection is favored in patients with a high-grade glioma or focal neurologic signs or symptoms. Although expectant management with serial imaging was previously used for patients with a low-grade glioma without symptoms or with medically controlled seizures, given inevitable tumor progression and evidence of improved median survival with more active, aggressive management, surgical resection is now also favored in patients with low-grade glioma. If an asymptomatic low-grade glioma is not amenable to resection, chemotherapy and/or radiation therapy may potentially be deferred until the time of clinical or radiographic progression.
Histopathologic and molecular data are used for glioma classification. The key molecular characteristics are deletions of the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q) as well as isocitrate dehydrogenase ( IDH ) 1 or 2 missense mutations. Oligodendroglial tumors, which include oligodendrogliomas and anaplastic oligodendrogliomas, are defined by the presence of 1p and 19q codeletion and IDH mutation. They comprise 5%–20% of all gliomas and are typically particularly sensitive to chemotherapy.
Histopathology is used to differentiate oligodendrogliomas and anaplastic oligodendrogliomas. Anaplastic features, such as increased mitotic activity, necrosis, and endothelial proliferation, are required for a diagnosis of anaplastic oligodendroglioma.
Following anaplastic oligodendroglioma resection, focal radiation and adjuvant chemotherapy are recommended. Procarbazine, lomustine, and vincristine (PCV) chemotherapy are typically used; studies assessing the efficacy of temozolomide, which is often better tolerated, are ongoing.
Given the high risk of tumor progression with residual disease, focal radiation and adjuvant chemotherapy (with PCV or temozolomide) are recommended in patients with subtotally resected oligodendrogliomas. Surveillance imaging following treatment should be obtained every 3–6 months for 5 years, then at least once a year thereafter.
Astrocytomas, which are defined by the absence of 1p and 19q codeletion, are further divided into mutant and wild type IDH categories. IDH wild-type tumors are associated with a poorer prognosis.
Astrocytomas are further divided based on histopathologic features into low-grade and high-grade tumors, the latter including anaplastic astrocytoma and glioblastoma. Glioblastoma, a grade IV astrocytoma, is defined by the presence of necrosis. Glioblastomas that are IDH mutant are likely secondary to a transformed low-grade astrocytoma and have a better prognosis than de novo glioblastomas that are IDH wild-type. Anaplastic astrocytoma (grade III astrocytoma) will demonstrate endothelial proliferation and/or increased mitotic activity but will not demonstrate necrosis.
Focal radiation and temozolomide are recommended in most patients with low-grade astrocytomas. In patients under the age of 40 years with gross total resection, close clinical and radiographic follow-up without initial radiation or chemotherapy may be appropriate.
Temozolomide in combination with focal radiation therapy is indicated for anaplastic astrocytoma and glioblastoma, regardless of the extent of resection. Additionally, tumor-treating fields, low-intensity intermediate-frequency alternating electrical fields applied to the scalp with antimitotic properties prolong progression-free and overall survival when used with maintenance chemotherapy in patients with glioblastoma.
Radiographic surveillance following treatment completion is recommended at 4 weeks, then every 2–4 months for at least 2–3 years for high-grade astrocytomas and glioblastomas. At tumor recurrence, treatment options include repeat maximal safe surgical resection and repeat radiation and alternative chemotherapy, such as bevacizumab. Clinical trials should also be considered.