The nervous system can be affected in several ways in patients with neoplastic disease:

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  Directly due to primary nervous system tumors or metastases to nervous system structures

  
  
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  Indirectly due to:

  
  
  
  
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    Tumors of non–neurologic origin impinging upon nervous system structures

    
    
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    Toxicities of chemotherapy and radiation therapy

    
    
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    Paraneoplastic syndromes affecting the nervous system

Therefore, in patients with a known history of systemic malignancy, the differential diagnosis of new neurologic symptoms includes direct effects of the cancer itself (metastases to or compression of neurologic structures), complications of treatment (radiation or chemotherapy), and paraneoplastic syndromes. Direct (metastases) or indirect (paraneoplastic) effects of systemic malignancy on the nervous system may also be the presenting feature of a systemic cancer.

Primary or metastastic intracranial tumors may present with headaches, seizures, and/or focal neurologic deficits. Progressive focal neurologic deficits can occur if the tumor affects an eloquent area (e.g., affecting motor, speech, visual, or cerebellar pathways). Diffuse infiltrative lesions or diffuse metastases can present with global cognitive dysfunction and/or personality changes without obvious focal deficits. Some patients with intracranial tumors may present first with a seizure with no preceding history of neurologic dysfunction or headache. Brain metastases may also be discovered in the presymptomatic stage as part of a staging evaluation for a known systemic malignancy.

Particular tumors to consider in particular clinical scenarios include:

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  Hearing loss, tinnitus, imbalance: cerebellopontine angle tumor (most commonly vestibular schwannoma or meningioma)

  
  
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  Bitemporal hemianopia: pituitary tumors, craniopharyngioma

  
  
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  Unilateral visual disturbance: optic glioma, optic nerve sheath meningioma, or olfactory groove meningioma (olfactory groove meningioma may also cause unilateral loss of smell)

  
  
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  Multiple cranial neuropathies: skull base lesion, brainstem lesion, or leptomeningeal metastases

In general, steroids are often used for the treatment of peritumoral vasogenic edema in patients whose brain tumors are symptomatic (e.g., headache and/or focal deficits) as a result of the location and size of the mass and its surrounding edema. It should be noted that steroids are part of the treatment for primary nervous system lymphoma and can alter biopsy results if administered prior to biopsy. Therefore, when there is concern for primary central nervous system lymphoma, steroids should ideally be avoided until after biopsy. Antiepileptics should be initiated if seizures occur due to intracranial tumors, although there is no benefit (and there may be harm) to administering prophylactic antiepileptics to patients with brain tumors who have not had seizures.

Brain Metastases

Metastases to the brain from systemic cancer are far more common than primary brain tumors. Brain metastases from lung cancer, breast cancer, melanoma, and colon cancers are most common. Metastases are most commonly found at the gray–white junction, appearing as one or more ring-enhancing lesions on contrast-enhanced neuroimaging (Fig. 24–1). Melanoma, renal cell carcinoma, thyroid carcinoma, and choriocarcinoma have the highest propensity for intratumoral hemorrhage. However, given that lung cancer is the most common cause of cerebral metastases, it is the most common cause of hemorrhagic brain metastases.

Gastrointestinal cancer metastases have a predilection for the posterior fossa. Prostate cancer only very rarely metastasizes to the brain, but can metastasize to the skull and/or dura mater, causing neurologic symptoms by impinging upon the brain and/or cranial nerevs.

The evaluation of a single brain lesion suspicious for neoplasm requires a search for systemic malignancy including imaging of the chest, abdomen, and pelvis with CT and/or PET. However, even if a systemic malignancy is found, an isolated CNS lesion could still be an independent primary brain tumor rather than a metastasis, so brain tissue may still ultimately be required for diagnosis.

Treatment of brain metastases involves surgical resection (for large, symptomatic metastases), stereotactic radiosurgery, and/or whole brain radiation.

Leptomeningeal Metastases (Carcinomatous Meningitis)

Leptomeningeal metastases (carcinomatous meningitis) can cause headache, nausea/vomiting, cranial nerve involvement, and/or confusion. Spinal leptomeningeal involvement can cause back and radicular pain due to involvement of nerve roots. Common causes of leptomeningeal metastases include breast cancer, lung cancer, hematologic malignancies, and melanoma. Leptomeningeal metastases often have no accompanying brain metastases. They may rarely be the presenting feature of a systemic malignancy. Contrast-enhanced brain imaging reveals enhancement of the leptomeninges, which can be noted in the cerebellar folia, surrounding the brainstem, and invaginating the cerebral sulci (Fig. 24–2). Hydrocephalus may also be present. A normal MRI does not exclude the possibility of leptomeningeal metastases, and definitive diagnosis is made by detecting malignant cells in the cerebrospinal fluid (CSF) by cytology/flow cytometry. Treatment of leptomeningeal metastases is directed at the primary underlying cancer, but prognosis is generally poor.

Primary Intracranial Tumors

Primary intracranial tumors can arise from any of the structures and constituent cell types of the central nervous system, including:

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  Glial cells: astrocytoma, oligodendroglioma, glioblastoma (see Table 24–1)

  
  
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  Neurons: neurocytomas, gangliogliomas, gangliocytomas

  
  
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  Neural progenitor cells: medulloblastoma, neuroblastoma

  
  
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  The meninges: meningioma

  
  
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  Choroid plexus: choroid plexus papilloma and choroid plexus carcinoma

  
  
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  Ependyma: ependymoma

  
  
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  Pineal gland: pinoplastoma, pineocytoma

  
  
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  Pituitary: pituitary adenoma

  
  
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  Hematologic system: primary CNS lymphoma, intravascular lymphoma

Meningiomas and glial tumors are the most common primary intracranial tumors, although both are less common than metastases.

Meningiomas

Meningiomas are dural based lesions that enhance uniformly on contrast-enhanced neuroimaging and often have a dural tail of enhancement at the margins of the tumor (Fig. 24–3). Compression of local nervous system structures can cause focal deficits and/or seizures. Treatment of meningiomas is surgical. Postoperative radiation therapy is used for grade 3 (anaplastic) meningiomas and incompletely resected grade 2 (atypical) meningiomas. Radiation therapy without surgery may be considered for patients whose meningiomas are inoperable, or in patients who are not good surgical candidates. Meningiomas may be discovered incidentally when brain imaging is performed for another reason. Incidentally discovered meningiomas can generally be followed with serial imaging if they are small and asymptomatic.

Gliomas

Gliomas range from low grade (grades 1–2) to high grade (grades 3–4). Grade 4 (glioblastoma) is associated with the worst prognosis (usually just over 1 year survival even with treatment), although patients with lower grade tumors can survive for over a decade with treatment.

On neuroimaging, low-grade gliomas are typically T2/FLAIR hyperintense lesions with little or no contrast enhancement (Fig. 24–4). Glioblastoma appears as a contrast-enhancing mass with a necrotic appearing center, and often progresses along white matter tracts such as across the corpus callosum (“butterfly glioma”) (Fig. 24–5).

Treatment regimens for gliomas involve maximal surgical resection (when feasible), fractionated focal radiation therapy, and chemotherapy (with temozolomide).

Gliomatosis cerebri is an infiltrating, usually high-grade, glial cell tumor that appears as diffuse and confluent on neuroimaging studies but generally does not enhance (Fig. 24–6). Given its inoperability, prognosis is poor.

Primary CNS Lymphoma

Primary CNS lymphoma is most commonly a diffuse large B-cell lymphoma. It can occur in normal healthy patients as well as in immunocompromised patients, in whom it occurs in association with Epstein-Barr virus (EBV) (e.g., in patients with HIV/AIDS). Neuroimaging demonstrates one or more contrast-enhancing lesions in the supratentorial or infratentorial white matter that may show central diffusion restriction due to high cellularity (Fig. 24–7). This appearance is not specific, and therefore biopsy is often necessary for definitive diagnosis. Lumbar puncture may reveal the diagnosis if CSF is evaluated with cytology and flow cytometry, although this can take up to three large-volume lumbar punctures to make the diagnosis. If lymphoma is under consideration, steroids should be avoided prior to biopsy as they may alter biopsy results. Treatment is with chemotherapy, and radiation is used in some cases; surgery is not indicated. Intravascular B-cell lymphoma limited to the lumen of blood vessels is discussed in Chapter 19 (see “Intravascular Lymphoma”).

Spinal tumors generally present with back pain and a subacute myelopathy (see Ch. 5). If the vertebral bodies are the site of involvement, a vertebral fracture may lead to acute myelopathy. The back pain from spinal tumors is often worse when the patient is lying down (compared to benign etiologies of back pain that tend to improve in the supine position). Spinal tumors are generally classified by their compartment: intramedullary, extramedullary intradural, or extramedullary extradural. Just as in the brain, metastases are more common in all of these compartments than primary spinal tumors.