Meningiomas and Gliomas
Primary brain tumors are tumors that arise from brain tissue itself as compared with metastatic tumors, whereby tumor cells travel to the brain from a distant site. This chapter deals specifically with primary brain tumors of adults, using the subcategories of benign tumors—meningiomas, realizing that a small subset can be malignant—and malignant gliomas (oligodendrogliomas and astrocytomas).
In 1922, Cushing coined the term meningioma to describe tumors originating from the meninges.1 The World Health Organization (WHO) has now subdivided meningiomas into three separate categories defined as benign (I), atypical (II), and anaplastic or malignant (III) (Table 1).2
|I||Meningiomas, with low risk of recurrence and/or low risk of aggressive growth|
|II||Atypical meningiomas, with increased mitotic activity or three or more of the following features: increased cellularity, small cells with high nucleus-to-cytoplasm ratio, prominent nucleoli, uninterrupted patternless or sheetlike growth, and foci of spontaneous or geographic necrosis|
|III||Anaplastic (malignant) meningiomas: exhibit frank histologic features of malignancy far in excess of the abnormalities present in atypical meningiomas|
Oligodendrogliomas are composed of diffusely infiltrating cells resembling oligodendrocytes with aggressive growth potential. WHO has stratified oligodendrogliomas as well-differentiated tumors (II) and anaplastic oligodendrogliomas (III).2
Astrocytic neoplasms are characterized by varying degrees of brain infiltration and aggressive growth potential. WHO has stratified astrocytomas as diffuse astrocytoma (II), anaplastic astrocytoma (III), and glioblastoma multiforme (IV).2 For our purposes here, grade I tumors actually represent a separate tumor genotype and phenotype and are not discussed.
The Cancer Brain Tumor Registry of the United States (CBTRUS) was formed in 1992 through the American Brain Tumor Association as a resource for epidemiologic data on primary brain tumors (www.cbtrus.org). There are currently eleven state registries involved in data collection. Primary brain tumors represent only 2% of all cancers, with 35,000 new cases diagnosed each year in the United States. Meningiomas occur at a rate of 7.8 per 100,000 per year, but only 25% are believed to be symptomatic, with the others being found incidentally.3 The male-to-female ratio is 1 : 1.8, and the incidence increases with age, peaking at age 85 years.
According to CBTRUS, the incidence of oligodendrogliomas, including anaplastic oligodendrogliomas, is approximately 0.3 per 100,000 persons. Depending on the study, these tumors account for 4% to 15% of intracranial gliomas.
The most commonly diagnosed primary brain tumor of adults is glioblastoma multiforme (grade IV). The incidence is two to three cases per 100,000 population per year. An estimated 13,000 deaths in 2000 were attributed to primary malignant brain tumors (PMBTs). Approximately 19,500 cases were expected to be diagnosed in 2000. Diffuse astrocytomas (WHO II) represent 10% to 15% of astrocytic brain tumors and have an incidence of 1.4 cases per 1 million population per year.
Only about 5% of primary brain tumors have known hereditary factors. Specifically, the Li-Fraumeni syndrome, p53 defects, neurofibromatosis 1 (NF1) and 2 (NF2), tuberous sclerosis, von Hippel-Lindau disease, Turcot’s syndrome, and familial polyposis increase the risk of brain tumors. The polymerase chain reaction (PCR) assay and direct sequencing analysis can be used to diagnose von Hippel-Lindau disease.
For meningiomas, the strongest genetic link has been associated with NF2, with an almost 50% incidence. Sporadic meningiomas have been linked to chromosome 22 in the region of the NF2 gene.4 Meningiomas are known to express estrogen and progesterone receptors, with the former being more common. A high incidence of somatostatin receptors has also been found. The significance of these findings is uncertain but has led to diagnostic tests (e.g., octreotide single-photon emission computed tomography [SPECT], using the somatostatin receptors) and treatment strategies (antiprogesterone; mifepristone [RU-486]). Radiation is the only definite cause. Studies have shown that children receiving as little as 10 Gy for tinea capitis have increased risk for meningiomas, with tumor development taking at least 20 years from exposure.5,6 Head injury is often cited as a causative factor, but a prospective study of 3000 patients with head injuries found no increased incidence.7
Viral infections, specifically the JC virus, has been implicated in oligodendrogliomas, but the data are inconclusive. The incidence of PMBTs (specifically astrocytomas) is increased in children with acute lymphocytic leukemia who have had prior brain radiotherapy. There have been reports8 of low-grade astrocytoma development in patients with inherited multiple enchondromatosis type I. Even though many of the molecular alterations involved in the progression of low-grade astrocytomas to higher grade tumors (glioblastoma multiforme) are known, the underlying causative factors are not well understood (Fig. 1).
For meningiomas, the clinical symptoms are usually dependent on the anatomic site involved, but many are found incidentally. Most meningiomas are slow growing and cause signs and symptoms by compression of nearby structures. The three most common symptoms are headaches, mental status changes, and paresis, and the most common signs are paresis, normal examinations, and memory impairment.9 For PMBTs, the most common signs and symptoms are seizures and headache. The lower-grade glial tumors have a more indolent course that may persist over years, whereas the most aggressive tumors (e.g., anaplastic oligodendrogliomas, anaplastic astrocytomas, glioblastoma multiforme) may have a rapid onset of neurologic decline. Patients may, however, present with signs and symptoms of increased intracranial pressure, including nausea, vomiting, headache, and confusion.
As with most disease processes, the medical history is the most important initial step in the process of brain tumor diagnosis. Because many meningiomas are found incidentally, imaging studies are important. A physical examination usually follows the medical history. Computed tomography (CT) is probably used most often as the initial imaging study, but magnetic resonance imaging (MRI) is considered to be the gold standard when done with and without gadolinium contrast. On MRI, meningiomas are typically isodense, dura-based masses that often show homogeneous enhancement (Fig. 2).
Meningiomas typically appear as extra-axial lesions, and the presence of a dural tail aids in the diagnosis. CT can help evaluate bone involvement and the presence of calcifications, which can be seen in 30% of benign meningiomas but are rare in malignant meningiomas. Although benign tumors can have associated edema, it is much more common in malignant meningiomas. Other noninvasive imaging tests include octreotide SPECT scans, which measure somatostatin levels in meningiomas. Magnetic resonance venograms can help in determining venous sinus patency. Although noninvasive tests are helpful, the definitive diagnostic test is still histologic tissue evaluation after a surgical biopsy or larger resection. Most institutions now use the WHO histologic grading criteria. Grading of tumors is based on cell origin and biologic behavior (see Table 1). Figure 2 demonstrates a very large meningioma that crosses both sides of the tentorium on the left. This tumor was surgically resected in a staged procedure. A typical histologic appearance of a meningioma is shown in Figure 3.
As with meningiomas, MRI with and without contrast is the test of choice for PMBTs. Oligodendrogliomas are more likely to demonstrate calcifications on CT than astrocytomas. With MRI scans, PMBTs are typically hypointense on T1-weighted images and hyperintense on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. The higher-grade lesions (WHO III and IV) are more likely to demonstrate enhancement (anaplastic oligodendrogliomas, anaplastic astrocytomas, glioblastoma multiforme), although ring enhancement is less common in anaplastic oligodendrogliomas and usually is associated with a worse prognosis.10 Glioblastoma multiforme often has ring enhancement around a central area of necrosis (Fig. 4). Tumor-associated cysts are more common with the astrocytomas. The higher-grade lesions also tend to exhibit more peritumoral edema. Newer technologies such as magnetic resonance spectroscopy can help in the differential diagnosis of intracranial lesions. Gliomas tend to demonstrate decreased N-acetyl aspartate, increased choline, and decreased creatine levels. A lactate peak is common in higher grade tumors.11 The diagnosis is ultimately made histologically after surgical biopsy or resection. Figure 5 shows a hematoxylin-eosin slide from an oligodendroglioma, and Figure 6 represents a glioblastoma multiforme at low power. As we increase our understanding of the molecular genetics of tumors, this technology will play an increasing role in tumor diagnosis (see later, “Advances”).