The most common tumors in the central nervous system (CNS) are metastases from distant neoplasms, with lung cancer accounting for nearly half of such tumors. Primary brain tumors (PBTs) are a heterogeneous group of neoplasms originating from CNS tissue and meninges. These tumors range from benign to aggressive. Although primary CNS tumors have historically been named according to their cellular origin and histologic appearance, advances in molecular genetics have led to further characterization and classification based on phenotypic and genotypic parameters. The official classification of brain tumors by the World Health Organization includes key genetic information in the grading of tumors, leading to “integrated diagnoses” and allowing for improved tumor grading. As for location, PBT can occur anywhere in the intracranial or spinal space. In adults, 70% of PBTs are supratentorial, and of those, 80% to 90% are gliomas and meningiomas. The remaining 30% of PBTs in adults are infratentorial, including schwannoma, hemangioblastoma, and meningioma in adults. In children, approximately 70% of PBTs are infratentorial, most commonly medulloblastoma, cerebellar astrocytoma, brainstem glioma, and ependymoma.

EPIDEMIOLOGY

Approximately 79,000 new cases of CNS tumors are diagnosed in the United States each year. These include primary malignant and nonmalignant tumors. At present, there are more than 100 histologically distinct types of primary CNS tumors. Approximately one-third of these tumors are malignant. Overall survival after diagnosis with a PBT varies significantly by age, histology, and molecular markers. The median age at diagnosis of all PBTs is 59, with PBTs being the 10th leading cause of death in adults in the United States. PBTs are also the most common cancers of childhood and have surpassed leukemia as the leading cause of cancer-related death in children under age 14. In general, CNS tumors are more common in men (male to female ratio of 1.5:1) with the exception of meningiomas, which are more common in women (1:1.8).

CAUSES AND GENETICS

PBTs generally originate from genetic disruptions in cells, causing them to bypass normal growth regulatory mechanisms, with simultaneous evasion of the immune system. Some brain tumors have a strong hereditary component (Table 19-1). Ionizing radiation used in therapeutic dosages has been associated with an increased risk of meningiomas, astrocytomas, and sarcomas. The use of mobile phones, low-frequency electromagnetic fields, specific infections (various viruses, Toxoplasma gondii, etc.), diet (nitrates, aspartame), tobacco, alcohol, and history of head trauma have not been validated in epidemiologic studies as risk factors for CNS tumors.

•Imaging: CT or MRI demonstrates a solitary brain lesion (commonly in the deep white matter, basal ganglia, or thalamus; rarely infratentorial) with contrast enhancement and surrounding edema. About 4% to 10% of glioblastoma multiforme (GBM) do not enhance. Commonly, the tumor infiltrates white matter tracts involving the corpus callosum, producing the typical “butterfly” pattern (Fig. 19-1).

•Treatment: Current standard treatment options include maximal-safe surgical resection followed by radiation with concurrent temozolomide (TMZ; a cytotoxic alkylating agent), followed by adjuvant TMZ for 6 months. Treatment with TMZ is maximally beneficial for patients with a methylated form of O6-MGMT. Stereotactic radiosurgery and antiangiogenesis therapies such as the humanized monoclonal antibody bevacizumab (which sequesters vascular endothelial growth factor that is highly expressed in gliomas) can be used for local recurrences. More antiangiogenic agents are being evaluated. GBMs contain nests of “cancer stem cells” that are resistant to chemotherapy and radiation and can repopulate the entire tumor. These stem cells represent a new target for future therapies.

•Prognosis: Poor outcome, with median life expectancy of 15 to 17 months; fewer than 16% survive more than 3 years.

FIGURE 19-1. Contrast-enhanced computed tomographic scan of the brain showing glioblastoma multiforme (arrow). Note the irregular enhancement pattern with a central area of necrosis. The tumor has also crossed the corpus callosum. (Reproduced with permission from Patel P. Lecture Notes: Radiology. Oxford, UK: Blackwell Publishing; 2005:268.)

LOW-GRADE GLIOMAS (GRADE I AND II)

•Origin: Astrocytes (glial cells) or ependymal cells.

•Epidemiology: Up to 10% of PBTs; can occur throughout the brain; in children, more common in the cerebellar hemispheres.

•More common in the fourth decade of life.

•Pathology: Genotype–phenotype correlation defines the tumor grade. Examples of grade I tumors include pilocytic astrocytoma and subependymal giant cell astrocytoma. Examples of grade II include diffuse astrocytoma with IDH-mutant and pleomorphic xanthoastrocytoma.

•Presentation: Seizure is a typical presentation of slow-growing tumors.

•Imaging: MRI with contrast is the study of choice. Most lesions are bright on T2 and fluid-attenuated inversion recovery, usually without enhancement (Fig. 19-2).

•Treatment: Close observation with serial neuroimaging may be the first approach, depending on prognostic factors. Surgical removal can be curative for grade I astrocytomas; it can be considered for grade II tumors if a “gross total” resection is possible, but it is often not curative. Radiation or chemotherapy can be used depending on other prognostic factors.

FIGURE 19-2. T2-weighted magnetic resonance imaging scan of the brain showing a large glioma characterized by high-intensity signal in the right hemisphere. The tumor is displacing and compressing the ventricular system. (Reproduced with permission from Armstrong P, Wastie M, Rockall A. Diagnostic Imaging. 5th ed. Oxford, UK: Blackwell Publishing; 2004:401.)

OLIGODENDROGLIOMA

•Origin: Arises from oligodendrocytes. High frequency of co-deletion of chromosomal arms 1p and 19q is considered a “genetic signature” of oligodendroglioma.

•Epidemiology: 10% of all gliomas; 2% to 4% of PBTs; peak incidence at age 35 to 45. Common in the frontal lobes, but can appear in the basal ganglia and thalamus. Typically very slow growth.

•Pathology: Calcifications are common. Most distinctive microscopic feature is the “fried egg” appearance (perinuclear halos with swollen cytoplasm).

•Presentation: Seizures in up to 70%.

•Imaging: MRI shows low intensity on T1, high intensity on T2; vasogenic edema uncommon. Contrast enhancement is a negative prognostic factor, usually seen with anaplastic oligodendroglioma. CT scan better to visualize intratumoral calcifications.

•Treatment: Total resection if possible, local radiation and PCV (procarbazine, lomustine, and vincristine) chemotherapy. TMZ is used increasingly and is less marrow-toxic. Patients with 1p/19q co-deletion seem to have a better response to therapy.

•Prognosis: Better survival with surgery plus radiation; can be decades. Tends to recur locally and progress into a malignant form.

EPENDYMOMA

•Origin: Arises from ependymal lining of the ventricles.

•Epidemiology: 6% to 9% of PBTs; 30% of PBTs in children under age 3. In children, 90% are intracranial (often in the fourth ventricle) with a tendency toward subarachnoid spread. In adults, 75% arise within the spinal canal as intramedullary tumors.

•Pathology: Perivascular pseudorosettes (a halo of cells surrounding a central vascular lumen) are the histologic hallmark.

•Presentation: Intraventricular location can produce obstructive hydrocephalus with raised intracranial pressure (papilledema, cranial nerve palsies, cerebellar dysfunction, etc.). Myxopapillary ependymomas of the conus and cauda equina can produce conus medullaris or cauda equina syndromes.

•Imaging: MRI enhancement is variable.

•Treatment: Surgery to decrease tumor burden, followed by radiation and chemotherapy. Recurrence rates are high; close MRI follow-up is necessary.

•Prognosis: Overall 10-year survival 45% to 55%, depending on tumor grade.

Meningioma

•Origin: Arises from meningothelial (mesodermal) cells of the dura mater. Almost always benign. Can occur intracranially (with predilection for cerebral convexities, falx cerebri, and the sphenoid wing) or within the spinal canal.

•Epidemiology: Second most common PBT after GBM; 15% to 20% of all PBTs. More common in women between the ages of 40 and 60. Incidence increases with age. Some genetic conditions are associated with an increased susceptibility to develop meningiomas, as with NF-2 (Table 19-1), associated with abnormalities on chromosome 22.

•Pathology: Histology shows sheets of plump, uniform meningothelial cells with the tendency to form whorls. Progesterone receptors are found frequently.

•Presentation: Slow growth; symptoms produced by local impingement on brain (seizures) and nerves (weakness) or compression of nearby structures (weakness, headache, apathy).

•Imaging: MRI usually shows a rounded extra-axial mass adjacent to dura. In general, isointense on T1 and T2, with intense contrast enhancement and associated “dural tail” of enhancement (Fig. 19-3).

•Calcification is seen on CT. Angiography can show rich vascularization. Also noted on CT or plain X-rays is “hyperostosis” (osteoblastic reaction) that may represent tumor invasion of the bone.

•Treatment: Surgical removal, often preceded by endovascular embolization of the feeding vessels, but many lesions <4 cm are treated with radiosurgery, with good control rates. Stereotactic radiosurgery such as gamma knife radiosurgery is an option when resection or other radiation is difficult or dangerous. Recurrent meningiomas are difficult to treat.

•Prognosis: 5-year survival is 70% to 95%; malignant transformation is very rare.

FIGURE 19-3. Axial (A) and sagittal (B) magnetic resonance imaging scans of the brain showing a brightly enhancing meningioma (arrows). On the sagittal view, the arrow tip points to the dural tail at the margin of the tumor. (Reproduced with permission from Patel P. Lecture Notes: Radiology. Oxford, UK: Blackwell Publishing; 2005:269.)

MEDULLOBLASTOMA

•Origin: Primarily at the medullary velum of the fourth ventricle (Fig. 19-4); up to 30% from the cerebellar hemispheres. It is among the primitive neuroectodermal tumors.

•Epidemiology: Rare in adults, accounting for less than 2% of PBTs, but common in children, making up 18% of all pediatric brain tumors. More than 70% are diagnosed in children under age 10.

•Pathology: Small round cells with a high mitotic index.

•Presentation: Rapidly growing tumor that infiltrates surrounding tissue and extends toward the fourth ventricle, producing hydrocephalus (with morning headache, unsteadiness, nausea, and vomiting); may spread via the cerebrospinal fluid (CSF) intracranially, and to the spinal cord (“drop metastases”). Can also spread extracranially to bone and bone marrow.

•Imaging: MRI of the brain usually shows a heterogenous contrast enhancing midline tumor compressing the fourth ventricle. MRI of the brain and spinal cord helps to evaluate subarachnoid metastasis. CSF studies are often done to look for malignancy (if no contraindication). Bone scan and bone marrow aspiration are indicated due to the possible extracranial extension of the tumor.

FIGURE 19-4. Medulloblastoma (arrow) in a child, as shown by sagittal magnetic resonance imaging scan with contrast enhancement. Note that the fourth ventricle and middle portion of the cerebral aqueduct are obliterated, resulting in hydrocephalus, including dilatation of the third and lateral ventricles. (Reproduced with permission from Patel P. Lecture Notes: Radiology. Oxford, UK: Blackwell Publishing; 2005:271.)

•Treatment: Surgery plus radiation and chemotherapy. Corticosteroids for vasogenic edema. Children <3 years are more susceptible to adverse effect of radiation on brain development. In those cases, chemotherapy may allow the delay of radiation treatment. High recurrence rate.

•Prognosis: 20% to 30% relapse after initial treatment. Poor prognosis in children with metastatic disease or subtotal resection. Good prognostic factors include radical resection and radiation dose above 50 Gy to the entire neuroaxis. Under these conditions, recurrence-free survival is >50% at 5 years.

SCHWANNOMA

•Origin: Arises from Schwann cells.

•Epidemiology: ~7% of all intracranial tumors and the most common tumor of peripheral nerves. More common in middle-aged women. More common in the vestibular (VIII) cranial nerve (acoustic neuromas) where they can occupy the cerebellopontine angle, involving trigeminal and facial nerves. Bilateral acoustic schwannomas can be associated with NF-2 (neurofibromatosis).

•Pathology: Tumor is made up of sheets of uniform spindle cells, forming palisades called “Verocay bodies.”

•Presentation: Can be asymptomatic, or present with loss of function of the affected nerve (hearing loss, vestibular symptoms, facial paresthesias, or pain, etc.).

•Imaging: MRI with contrast tends to show circumscribed lesions which displace but do not invade adjacent structures. Larger tumors show cystic degeneration.

•Treatment: If symptomatic, stereotactic radiosurgery (i.e., gamma knife) is the first choice, particularly when the lesion does not compress the brainstem and is smaller than 3 cm. Surgery (microsurgical approach) is an alternative but can be complicated by focal nerve deficits.

•Prognosis: Good.

LESS COMMON PRIMARY BRAIN TUMORS

GANGLIOGLIOMA

These infrequent PBTs are commonly seen in children and young adults and include a mixture of neurons and glial cells. They are usually located in the cerebral hemisphere and characterized by slow growth, with long duration of symptoms (e.g., seizures). MRI shows increased T2 signal with characteristic swollen gyri. Surgical removal usually produces an excellent outcome. Radiation is reserved for those with frankly malignant features, or inoperable or recurrent tumors.

HEMANGIOBLASTOMA

These uncommon cystic lesions account for nearly 2% of intracranial tumors, with a predilection for the posterior fossa. Approximately 10% of patients with hemangioblastoma are affected with von Hippel–Lindau disease (hereditary retinal angiomas, pancreatic cysts, and kidney tumors). Hemangioblastomas can occur at any age but are most common in patients in the fourth decade.

PRIMARY CNS LYMPHOMA

Lymphoma involving the CNS can be primary or metastatic from systemic non-Hodgkin lymphoma. Primary CNS lymphoma (PCNSL) accounts for less than 2% of PBTs, affecting men more than women (2:1) and with a higher incidence in acquired immunodeficiency syndrome patients. PCNSLs are almost exclusively intermediate to high-grade non-Hodgkin lymphomas of B cell origin. The clinical presentation is usually insidious, with progressive neurologic dysfunction (change in mental status, seizures, focal deficits, etc.). Ocular lymphoma may occur in up to 20% of patients prior to CNS manifestations. A systemic work up is appropriate to rule out disseminated disease, as CSF analysis shows tumor dissemination in up to 40% of cases. MRI appearance varies significantly, with single or multiple lesions, a butterfly appearance, enhancing or non-enhancing lesions, etc.

The role of surgery in CNS lymphoma is limited to biopsy. Prognosis is poor, with survival approximately 1.5 months if untreated, 10 to 18 months after radiation therapy, and 44 months after chemotherapy plus radiation. High-dose systemic methotrexate-based chemotherapies (along with cytarabine, TMZ, rituximab) with or without radiation are the treatment of choice. PCNSL are radiosensitive, but radiation is used as palliation. A dementia incidence of up to 50%, however, can be observed in patients who survive more than 18 months on these regimens (often ascribed to the radiation therapy). PCNSL can show a dramatic response to steroids, but the tumor invariably recurs within months. Even with best treatment, recurrence is very common (median time to recurrence: 4 to 5 years).

SELLAR AND SUPRASELLAR TUMORS

Pituitary tumors originate in the pituitary gland in the sellar region (Fig. 19-5). They can be classified as microadenomas (<1 mm) and macroadenomas (>1 mm). Their histologic cell of origin is responsible for the initial symptoms, usually related to the production of pituitary hormone. When tumors become large enough, they can compress neighboring structures (optic chiasm, cavernous sinus, etc.), producing focal symptoms. In general, diagnosis is by imaging studies and laboratory evaluation of hormonal status. Surgical removal may be through a trans-sphenoidal approach.

FIGURE 19-5. Sagittal (A) and coronal (B) post-contrast magnetic resonance imaging scans of the brain demonstrating a pituitary adenoma (arrows). Note that the tumor is anterior to the brainstem and extends upward, compressing the optic chiasm. (Reproduced with permission from Armstrong P, Wastie M, Rockall A. Diagnostic Imaging. 5th ed. Oxford, UK: Blackwell Publishing; 2004:406.)

Suprasellar craniopharyngioma is a slow-growing tumor characterized by the benign nature of its cells but malignant behavior of its growth. It accounts for 1% to 3% of intracranial tumors and 13% of suprasellar tumors in adults and 50% in children. It tends to invade neighboring structures, complicating treatment. Tumors present with headache, visual disturbance, and endocrine dysfunction. The radiologic hallmark is the appearance of a suprasellar calcified cyst. Treatment can entail full surgical resection, or minimal resection with radiation or radiosurgery.

SECONDARY (METASTATIC) BRAIN TUMORS

Metastases are the most common brain tumors and originate from malignant neoplasms outside the CNS. Metastatic lesions occur in 100,000 to 200,000 cases per year in the U.S. and account for 20% of cancer deaths annually. The most frequent metastatic brain tumors originate in the lung, skin (melanoma), kidney (renal cell carcinoma), breast, and colon. Malignant cells reach the brain via the bloodstream (crossing the blood–brain barrier) or through Batson’s plexus (pelvic and gastrointestinal tumors). In general, metastatic lesions are located at the junction of white and gray matter and tend to be solitary, but multiple metastases are not unusual. MRI with contrast is the preferred diagnostic study (Fig. 19-6). Treatment depends on the number of metastases, the immediate mass effect of the lesion(s), and the general status of the patient. Single lesions can be resected, followed by whole brain radiation or radiosurgery. Radiosurgery is used more often for three or fewer lesions, especially if the systemic disease is under good control—to prevent the long-term side effects of whole brain radiation, chemotherapy, or both. The prognosis is poor because metastases usually represent a more advanced stage and extension of the primary cancer.

FIGURE 19-6. Contrast-enhanced computed tomographic scan of the brain showing several metastatic lesions characterized by rounded areas of hyperdensity. (Reproduced with permission from Armstrong P, Wastie M, Rockall A. Diagnostic Imaging. 5th ed. Oxford, UK: Blackwell Publishing; 2004:402.)

Related posts:

The Sensory System The Approach to Coma and Altered Consciousness Head Trauma Radiculopathy, Plexopathy, and Peripheral Neuropathy Demyelinating Diseases of the Central Nervous System Disorders of the Spinal Cord

Stay updated, free articles. Join our Telegram channel

Join