Neurosurg Focus 12 (2):Article 1, 2002, Click here to return to Table of Contents Low-grade central nervous system tumors M. BEATRIZ S. LOPES, M.D., AND EDWARD R. LAWS, JR., M.D. Departments of Pathology (Neuropathology) and Neurological Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia Low-grade tumors of the central nervous system constitute 15 to 35% of primary brain tumors. Although this cate- gory of tumors encompasses a number of different well-characterized entities, low-grade tumors constitute every tumor not obviously malignant at initial diagnosis. In this brief review, the authors discuss the pathological classification, diagnostic procedures, treatment, and possible pathogenic mechanisms of these tumors. Emphasis is given in the neu- roradiological and pathological features of the several entities. KEY WORDS • glioma • astrocytoma • treatment outcome Low-grade gliomas of the brain represent a large pro- toses. The pilocytic (juvenile) astrocytoma is a character- portion of primary brain tumors, ranging from 15 to 35% istic, more circumscribed lesion occurring primarily in in most reported series.1–5 They include a remarkable di- childhood and with a predilection for being located in the versity of lesions, all of which have been lumped together cerebellum. It usually appears as a cystic tumor with a under the heading of "low-grade glioma." This category mural nodule. The tumor tissue itself may have features of includes virtually every tumor of glial origin that is not microcystic degeneration and Rosenthal fibers which are overtly malignant at the time of initial diagnosis. degenerative structures in the astrocytic processes. Other reasonably common types of low-grade gliomas include CLASSIFICATION OF GLIOMAS the low-grade oligodendroglioma and the low-grade ependymoma, which is usually anatomically related to the Table 1 provides a classification of low-grade tumors of ventricular ependymal lining. the central nervous system. The most common low-grade There is a large variety of uncommon tumors also cate- glioma is the ordinary astrocytoma. Once divided into fib- gorized as low-grade gliomas. The optic nerve glioma is rillary and protoplasmic subtypes, this lesion currently is very frequently found in the context of NF Type 1. It can thought to be derived from ordinary astrocytes, and it usu- occur as an "anterior" lesion that affects one or both optic ally occurs as a relatively homogeneous but infiltrative le- nerves, primarily evolving in the optic nerve sheath, or a sion. Closely related is the mixed glioma (mixed oligoas- "posterior" lesion that involves the optic chiasm and occa- trocytoma) that consists of both astrocytoma cells and sionally the hypothalamus. In approximately 40% of pa- oligodendroglioma phenotypes in varying proportions. tients harboring these lesions evidence of NF Type 1 is The subcategory "low-grade" tends to exclude those le- observed.2 sions with features of a high degree of pleomorphism, Another genetically related low-grade glioma is the necrosis, or vascular proliferation, or large numbers of mi- subependymal giant cell astrocytoma associated with tu- berous sclerosis. The characteristic location as well as its Abbreviations used in this paper: CT = computerized tomo- association with giant cells help define this lesion. There graphy; EEG = electroencephalogram; GFAP = glial fibrillary acid- are some indolent tumors categorized as low-grade glio- ic protein; MR = magnetic resonance; NF = neurofibromatosis; mas that commonly present with seizures. They include SEGA = subependymal giant cell astrocytoma; WHO = World two mixed neuronal–glial tumors: the ganglioglioma, Health Organization. which may also be cystic and partially calcified, and the Neurosurg. Focus / Volume 12 / February, 2002 1 Unauthenticated | Downloaded 09/29/21 11:11 AM UTC M. B. S. Lopes and E. R. Laws, Jr. TABLE 1 TABLE 2 Classification of low-grade tumors of the central nervous system Modalities used in the diagnosis of glioma gliomas neurological exam: papilledema, localizing signs astrocytoma (astrocytoma WHO Grade II; low-grade astrocytoma, EEG: focal changes, delta activity, epileptiform discharges ordinary astrocytoma) CT scan & MR imaging oligodendroglioma (oligodendroglioma WHO Grade II; low-grade angiography (when indicated) oligodendroglioma) lumbar puncture (generally not indicated) mixed oligoastrocytoma (mixed oligoastrocytoma WHO Grade II; low-grade mixed glioma) pilocytic astrocytoma (juvenile pilocytic astrocytoma; WHO Grade I) optic nerve glioma pleomorphic xanthoastrocytoma (WHO Grade II) DIAGNOSTIC PROCEDURES FOR LOW-GRADE subependymal giant cell astrocytoma (WHO Grade I) GLIOMAS ependymoma (variants: cellular, papillary, clear cell) myxopapillary ependymoma A summary of diagnostic procedures is provided in subependymoma Table 2. In patients presenting with seizure disorders, choroid plexus papilloma EEG can be used to diagnose the disease. The characteris- neuronal & mixed glial–neuronal tumors gangliocytoma tic EEG appearance of a low-grade glioma includes slow central neurocytoma or delta waves as well as any associated epileptiform ganglioglioma activity. Currently the most commonly used diagnostic dysembryoplastic neuroepithelial tumor modality is the imaging study, usually MR imaging, desmoplastic infantile ganglioglioma which provides exquisite detail both of the anatomy of the lesion and often of its pathophysiology (Tables 3 and 4). A stereotactic biopsy sampling procedure is commonly performed in attempts to diagnose presumed low-grade dysembryoplastic neuroepithelial tumor, which is usually gliomas detected by imaging studies. These biopsy proce- located in the temporal lobe. The pleomorphic xanthoas- dures are usually effective; however, because the patho- trocytoma is a characteristic superficial tumor also associ- logical findings are occasionally equivocal, one must al- ated with seizures. These lesions ordinarily have quite a ways be concerned with a sampling error in tumors that low proliferative activity and often can be controlled by contain areas of differing degrees of malignancy. treatment with radical but subtotal resection alone. The central neurocytoma is a peculiar and uncommon TREATMENT OF LOW-GRADE GLIOMAS tumor, likely of neuronal derivation. These tumors are fre- quently associated with the third ventricle and also have In a significant proportion of detected low-grade glio- an indolent course. mas the patients may be appropriate candidates for con- Some investigators classify choroid plexus papillomas servative management. Patients harboring these lesions together with the gliomas. These tumors arise from the can be treated with anticonvulsant medication and re- choroid plexus, either in the lateral ventricles, the third peated neurodiagnostic imaging studies, withholding in- ventricle, or the fourth ventricle, and frequently present as tervention until there has been a change either clinically or obstructive masses. radiologically. Partial resection may be appropriate for some low-grade astrocytomas, particularly those that are near important areas of the brain. Partial resection can CLINICAL FEATURES OF LOW-GRADE result in long-term favorable results in patients with pilo- GLIOMAS cytic astrocytomas, dysembryoplastic neuroepithelial tu- It is clear that the location of the lesion tends to be the mors, and some gangliogliomas and pleomorphic xantho- most important factor in determining the nature of the astrocytomas. symptoms and signs. Because these lesions are usually Radical or total resection is the surgical procedure of slow growing, seizures may be the presenting clinical choice for all forms of glioma, because in many of the symptom and may precede the diagnosis by many years. Seizures are particularly likely to occur in cases in which the lesions involve the temporal and the frontal lobes. TABLE 3 Visual symptoms are relatively common in low-grade Magnetic resonance imaging features of low-grade astrocytoma gliomas, depending on the actual location of the tumor, and its involvement of the optic apparatus or optic pathways. pathological features detectable cysts In cases of slowly progressive lesions that expand to necrosis affect important areas of the brain, the patients may pre- hemorrhage sent with progressive neurological deficits such as hemi- edema paresis, sensory changes, or difficulty with speech and blood–brain barrier disruption language. lesion analysis In cases in which lesions occlude or obstruct the ce- circumscribed compared w/ infiltrative unifocal compared w/ multifocal or diffuse rebrospinal fluid pathways, the patients may present with “benign” compared w/ “malignant” progressive signs of increased intracranial pressure. 2 Neurosurg. Focus / Volume 12 / February, 2002 Unauthenticated | Downloaded 09/29/21 11:11 AM UTC Low-grade CNS tumors TABLE 4 Magnetic resonance imaging features of various types of low-grade tumors MR Imaging Tumor Type T1-Weighted Gadolinium Enhancement low-grade astrocytoma hypointense none low-grade astrocytoma, optic nerve glioma isointense, expansive little or none & brainstem glioma low-grade oligoastrocytoma (infiltrative) hyperintense, homogeneous indistinct borders slight pilocytic astrocytoma hyperintense, well demarcated, cystic yes ganglioglioma cystic, isointense or hyper- yes intense borders anaplastic astrocytoma heterogeneous heterogeneous patients with these tumors complete removal of the lesion more recent laboratory work seems to support the concept can result