neurologic disorders
Gliomas
Introduction
Gliomas are primary tumors that originate in brain parenchyma. Symptoms are diverse and vary by location, manifesting as focal neurologic deficits, encephalopathy, or seizures. Diagnosis is based primarily on MRI, including both standard T1- and T2-weighted imaging, preferably with gadolinium enhancement, followed by biopsy with molecular profiling. Treatment involves surgical excision, radiation therapy, and, for some tumors, chemotherapy. Excision rarely cures. Gliomas include Astrocytomas Oligodendrogliomas Glioblastoma multiforme Ependymomas Many gliomas infiltrate brain tissue diffusely and irregularly. are the most common gliomas (see also Astrocytomas ). They are classified histologically and, in some cases, based on the presence of specific genetic markers, according to the World Health Organization (WHO) classification ( In ascending order of malignancy, astrocytomas are classified as Grade I: Pilocytic astrocytomas and subependymal giant cell astrocytomas (most common in Tuberous Sclerosis Complex (TSC) ) Grade II: Low-grade astrocytomas, including pleomorphic xanthoastrocytoma Grade III: Anaplastic astrocytomas Grade IV: Glioblastomas and diffuse midline gliomas Pilocytic, other low-grade, or anaplastic astrocytomas tend to develop in younger patients. Anaplastic astrocytomas, in particular, can later evolve into glioblastomas (called secondary glioblastomas). Glioblastomas can also develop de novo (called primary glioblastomas), usually in middle-aged or older people. Glioblastomas contain chromosomally heterogeneous cells. Both primary and secondary glioblastomas have distinct genetic characteristics, which can change as the tumors evolve. Secondary glioblastomas typically have mutations in theIDH1orIDH2genes. Rarely, astrocytomas contain astrocytoma and oligodendroglioma cells. These tumors used to be designated oligoastrocytomas; however, that term is no longer used to refer to a single tumor type but rather to a mixed neoplasm. Oligodendrogliomas(WHO grade II) are among the slowest-growing gliomas. They are most common in the forebrain, particularly the frontal lobes. Oligodendrogliomas are typically characterized by deletion of the p arm of chromosome 1 and the q arm of chromosome 19 (1p/19q codeletion). These deletions are diagnostic for oligodendroglial tumors, predict longer survival, and predict a better response to radiation therapy and chemotherapy. Like astrocytomas, oligodendrogliomas can evolve into more aggressive forms, such as anaplastic oligodendrogliomas (WHO grade III), which are managed accordingly. gene and mutations in pTP53 ( General references ). Diffuse midline gliomasare high-grade (WHO grade III to IV) astrocytic tumors that primarily affect children. These tumors include diffuse intrinsic pontine gliomas, which are aggressive and typically lethal tumors that infiltrate the brain stem with rostral extension into the hypothalamus and thalamus and that infiltrate the medulla and spinal cord inferiorly. Diffuse midline gliomas typically express theH3K27Mmutation. Children with Types type 1 are at an increased risk of developing diffuse midline gliomas. occur primarily in children and young adults; they are uncommon after adolescence (see also Ependymomas ). They are classified as Grade I: Subependymoma Grade II: Ependymoma Grade III: Anaplastic ependymoma Grade IV: Ependymoblastoma (which are rare and occur primarily in infants) All ependymomas typically arise from the ventricular wall and hence may arise in the brain, brain stem, or spinal cord. As such, they are classified based on location: as supratentorial, posterior fossa, or spinal cord. Each of these categories includes 3 molecularly and histologically defined subsets, resulting in 9 types of phenotypically and molecularly distinct ependymomas, whose treatment and prognosis differ significantly from one another. Ependymomas of the 4th ventricle in particular can manifest with obstructive hydrocephalus and may therefore manifest earlier than other ependymomas ( General references ). This T2-FLAIR (fluid-attenuating inversion recovery) MRI scan shows a white signal, which may indicate a mass or edema. The left frontal signal is highly demarcated, suggesting a mass. Use of contrast does not enhance it. It is a low-grade (grade II) oligodendroglioma. Image courtesy of William R. Shapiro, MD. This T2-FLAIR MRI scan shows a white signal in the posterior temporal lobe. The signal is not enhanced by contrast. It is an anaplastic (grade III) astrocytoma. Image courtesy of William R. Shapiro, MD. The T2-FLAIR MRI scan (top) shows a large, bilateral white (hyperdensity) signal around a glioblastoma, which is the highest grade and most malignant astrocytoma. This particular glioblastoma is called a butterfly glioma because the white signal around the tumor forms the wings of the butterfly; it is caused by cerebral edema. On the T1-weighted scan (bottom), contrast outlines the edge of the tumor (ring enhancement). The edema appears as a darkened area (hypointensity) on T1. Images courtesy of William R. Shapiro, MD. 