Primary Brain Tumors in Adults SREENIVASA r. CHANDANA, MD, PhD; SUJANA MOVVA, MD; MADAN aRORA, MD; and TREVOR SINGH, MD, Michigan State University College of Human Medicine, Lansing, Michigan Primary malignant brain tumors account for 2 percent of all cancers in U.S. adults. The most common malignant brain tumor is glioblastoma multiforme, and patients with this type of tumor have a poor prognosis. Previous expo- sure to high-dose ionizing radiation is the only proven environmental risk factor for a brain tumor. Primary brain tumors are classified based on their cellular origin and histologic appearance. Typical symptoms include persistent headache, seizures, nausea, vomiting, neurocognitive symptoms, and personality changes. A tumor can be identified using brain imaging, and the diagnosis is confirmed with histopathology. Any patient with chronic, persistent head- ache in association with protracted nausea, vomiting, seizures, change in headache pattern, neurologic symptoms, or positional worsening should be evaluated for a brain tumor. Magnetic resonance imaging is the preferred initial imaging study. A comprehensive neurosurgical evaluation is necessary to obtain tissue for diagnosis and for possible resection of the tumor. Primary brain tumors rarely metastasize outside the central nervous system, and there is no standard staging method. Surgical resection of the tumor is the mainstay of therapy. Postoperative radiation and chemotherapy have improved survival in patients with high-grade brain tumors. Recent developments in targeted chemotherapy provide novel treatment options for patients with tumor recurrence. Primary care physicians play an important role in the perioperative and supportive treatment of patients with primary brain tumors, including pal- liative care and symptom control. (Am Fam Physician. 2008;77(10):1423-1430. Copyright © 2008 American Academy of Family Physicians.) rimary malignant brain tumors are of dermatologic manifestations and are at rare, accounting for approximately increased risk of optic gliomas and astrocy- 2 percent of all cancers in U.S. tomas. Although several environmental fac- adults. The American Cancer Soci- tors have been associated with brain tumors, P ety estimates that there are more than 18,000 exposure to high-dose ionizing radiation is new diagnoses of brain and nervous system the only proven risk factor.4 Studies of other cancers causing more than 12,000 deaths environmental factors such as occupational each year in the United States.1 Data from the exposures, electromagnetic fields, pesti- Surveillance, Epidemiology, and End Results cides, cellular telephones, head trauma, and program showed an age-adjusted incidence N-nitroso compounds have had inconclusive of 6.4 per 100,000 person-years in 2003 com- results.5 Table 1 presents possible risk factors pared with 5.85 per 100,000 person-years for primary brain tumors.4,5 in 1975.2 The incidence of brain tumors is higher in men than in women (7.6 versus 5.3 Classification per 100,000 person-years),3 and the lifetime The World Health Organization classifies risk of developing a brain tumor is 0.65 per- primary brain tumors based on cellular ori- cent in men and 0.5 percent in women.2 The gin and histologic appearance (Table 2).6 incidence of brain tumors peaks between Neuroglial tumors account for more than 65 and 79 years of age. The incidence of glio- 80 percent of primary brain tumors and blastoma in white persons is approximately derive from astrocytes, oligodendrocytes, or double that in black persons.3 ependymal cells. Gliomas are divided into four grades; grades I and II tumors are low Risk Factors grade, whereas grades IIi and Iv tumors Several central nervous system (CNS) are high grade.7 Glioblastoma multiforme is tumors are associated with rare genetic the most common type of glioma. Menin- conditions, most commonly the autosomal giomas derive from meningothelial cells and dominant disorder neurofibromatosis 1. comprise about 20 percent of primary brain Patients with this disorder have a number tumors. Primary CNS lymphoma, which Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright © 2008 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. SORT: KEY RECOMMENDATIONS FOR PRACTICE Evidence Clinical recommendation rating References Patients with symptoms suggesting a brain tumor should be evaluated C 15 with gadolinium-enhanced magnetic resonance imaging. Surgery is the treatment of choice for primary brain tumors, especially C 21-24, 38 for resectable high-grade gliomas. Radiation with temozolomide (Temodar) therapy improves survival in B 28, 29, 31 patients with malignant gliomas. A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evi- dence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 1360 or http://www.aafp.org/afpsort.xml. has been increasing in the United States, a dull tension-type headache.10 Two large typically occurs in patients with immuno- studies of patients with high-grade gliomas deficiency syndromes, particularly acquired also showed that headache was the most immunodeficiency syndrome.8 common initial presenting symptom.11,12 In about 50 percent of patients, the headache is Diagnosis persistent and can last more than six months. CLINICAL PRESENTATION Headache is often associated with other Presenting signs and symptoms in patients symptoms, including seizures (50 percent of with primary brain tumors (Table 39) can be patients), visual disturbances (40 percent), generalized or focal. In the initial stages of and nausea and vomiting (38 percent).10 Any disease (low-grade tumors), most symptoms patient with chronic, persistent headache in are focal. Generalized symptoms occur with association with protracted nausea, vomit- increased tumor size. Common generalized ing, seizures, change in headache pattern, symptoms include headache, nausea, vomit- neurologic symptoms, or positional worsen- ing, seizures, and altered mental functions ing should be evaluated for a brain tumor. (e.g., personality changes).9 Seizure disorder is most common in In one large study of patients with primary patients with low-grade gliomas. The type brain tumors, 77 percent of patients reported of seizure and associated neurologic symp- toms vary with tumor location (Table 413). Seizures can present with aura and postictal Table 1. Risk Factors for Primary Brain Tumors symptoms. In two large studies, 18 percent of patients with glioblastoma multiforme 11,12 Environmental Genetic initially presented with seizures. Proven Li-Fraumeni syndrome One third of patients with high-grade High-dose ionizing radiation (P53 mutation) tumors initially present with nausea and Unproven Multiple endocrine vomiting, often in association with other neoplasia type 1 10 Alcohol use symptoms, such as headache and seizures. Neurofibromatosis 1 and 2 Cellular telephones Cognitive dysfunction also may be the ini- Nevoid basal cell carcinoma Chemical agents (e.g., hair dyes, solvents, tial symptom in patients with brain tumors. syndrome pesticides, traffic-related air pollution) Symptoms of cognitive dysfunction include Tuberous sclerosis Extremely low-frequency electromagnetic fields changes in memory, attention, orientation, Turcot’s syndrome Head trauma or injury language abilities, executive function, per- Von Hippel-Lindau disease Infections (e.g., viruses, Toxoplasma gondii, sonality, and daily activities (e.g., sleep, appe- in utero influenza, varicella) tite). These symptoms could be caused by the Nitrosamine, nitrosamide, nitrite, nitrate, tumor itself, tumor-related epilepsy, or treat- or aspartame consumption ment such as surgery, chemotherapy, cortico- Occupational exposures (e.g., rubber, vinyl chloride, petroleum) steroids, radiotherapy, and antiepileptics. Tobacco use Symptoms of cognitive dysfunction are more common in patients with low-grade Information from references 4 and 5. gliomas because of prolonged survival and cumulative treatment-related effects during 1424 American Family Physician www.aafp.org/afp Volume 77, Number 10 ◆ May 15, 2008 Table 2. WHO Classification of Primary Brain Tumors Neuroepithelial tumors Pineal tumors (grades I and IV) Astrocytic tumors Embryonal tumors (grade IV) Pilocytic astrocytoma (grade I) Tumors of cranial and paraspinal nerves Subependymal giant cell astrocytoma (grade I) Schwannoma (grade I) Diffuse astrocytoma (grade II) Neurofibroma (grade I) Pleomorphic xanthoastrocytoma (grade II) Perineurioma (grades I to III) Anaplastic astrocytoma (grade III) Malignant peripheral nerve sheath tumor Glioblastoma (grade IV) (grades II to IV) Oligodendroglial tumors Tumors of the meninges Oligodendroglioma (grade II) Meningioma (grade I) Anaplastic oligodendroglioma (grade III) Atypical meningioma (grade II) Oligoastrocytic tumors Anaplastic meningioma (grade III) Oligoastrocytoma (grade II) Lymphomas and hematopoietic neoplasms Anaplastic oligoastrocytoma (grade III) Malignant lymphoma (low and high grade) Ependymal tumors (grades I to III) Plasmacytoma Choroid plexus tumors (grades I to III) Granulocytic sarcoma Other neuroepithelial tumors Other Angiogenic glioma (grade I) Germ cell tumors Chordoid glioma of the third ventricle (grade II) Tumors