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Harrison's Manual of Medicine, 19e

Chapter 189: Tumors of the Nervous System

INTRODUCTION
APPROACH TO THE PATIENT: Tumors of the Nervous System

Clinical Presentation: Brain tumors of any type can present with general and/or focal symptoms and signs.
General nonspecific symptoms include headache with or without nausea and vomiting, cognitive
di!iculties, personality change, and gait disorder. The classic headache associated with a brain tumor is
most evident in the morning and improves during the day, but this pattern is actually seen in only a
minority of pts. Papilledema may suggest elevated intracranial pressure. Focal symptoms and signs include
hemiparesis, aphasia, or visual field deficit; these are typically subacute and progressive. Seizures are a
common presentation, occurring in about 25% of pts with brain metastases or malignant glioma.

Evaluation: Primary brain tumors, unlike metastases, have no serologic features of malignancy such as an
elevated ESR or tumor-specific antigens. Cranial MRI with contrast is the preferred diagnostic test for any pt
suspected of having a brain tumor; CT should be reserved for pts unable to undergo MRI. Malignant brain
tumors typically enhance with contrast and may have central areas of necrosis; they are characteristically
surrounded by edema of the neighboring white matter. Low-grade gliomas typically do not enhance.
Additional testing such as cerebral angiogram, EEG, or lumbar puncture is rarely indicated or helpful.

TREATMENT: TUMORS OF THE NERVOUS SYSTEM

SYMPTOMATIC TREATMENT

Glucocorticoids (dexamethasone 12–16 mg/d in divided doses PO or IV) to temporarily reduce edema

Anticonvulsants (levetiracetam, topiramate, lamotrigine, valproic acid, or lacosamide) for pts who present
with seizures; there is no role for prophylactic anticonvulsant drugs

Low-dose SC heparin for immobile pts

DEFINITIVE TREATMENT

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Based on the specific tumor types and includes surgery, radiotherapy (RT), and chemotherapy

PRIMARY INTRACRANIAL TUMORS

Astrocytomas

Infiltrative tumors with a presumptive glial cell of origin. Most common primary intracranial neoplasm.
Only known risk factors are ionizing radiation and uncommon hereditary syndromes (neurofibromatosis,
tuberous sclerosis). Infiltration along white matter pathways o"en prevents total resection. Imaging studies
(Fig.
Fig. 189-1
189-1) fail to indicate full tumor extent. Grade I tumors (pilocytic astrocytomas) are the most
common tumor of childhood, typically in the cerebellum; can be cured if completely resected. Grade II
astrocytomas usually present with seizures in young adults; if feasible should be surgically resected. RT is
helpful and chemotherapeutic agents such as temozolomide are increasingly used. Grade III (anaplastic
astrocytoma) and grade IV (glioblastoma) astrocytomas are treated similarly with maximal safe surgical
resection followed by RT with concomitant temozolomide, followed by 6–12 months of adjuvant
temozolomide. Median survival in glioblastoma is 12–15 months. Glioblastomas invariably recur, and
treatment options include reoperation, carmustine wafer implantation, and chemotherapeutic regimens
including bevacizumab. The most important adverse prognostic factors in high-grade astrocytomas are
older age, histologic features of glioblastoma, poor performance status, and unresectable tumor.

FIGURE 189-1
Postgadolinium T1 MRI of a large cystic le" frontal glioblastoma.

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Oligodendrogliomas

Generally more responsive to therapy and have a better prognosis than pure astrocytic tumors. Usually
nonenhancing; o"en partially calcified. Treated with surgery and, if necessary, RT and chemotherapy.
Median survival in excess of 10 years. Chemotherapy response improved when deletions of chromosomes
1p and 19q present.

Ependymomas

Derived from ependymal cells; highly cellular. Location—spinal canal more than intracranial in adults. If
total excision possible, may be curable. Partially resected tumors will recur and require irradiation.

Primary CNS Lymphomas

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B-cell malignancy; most occur in immunosuppressed pts (organ transplantation, HIV). May present as a
single mass lesion or as multiple mass lesions or meningeal disease. Dramatic, transient responses occur
with glucocorticoids; therefore, whenever possible, steroids should be withheld until a"er biopsy has been
obtained. Pts should be tested for HIV and the extent of disease assessed by performing positron emission
tomography (PET) or CT of the body, MRI of the spine, CSF analysis, and slit-lamp examination of the eye. In
immunocompetent pts, high-dose methotrexate produces median survival up to 50 months, which may be
increased with concurrent whole-brain RT and combinations of other chemotherapeutic agents such as
cytarabine or rituximab. In immunocompromised pts, prognosis is worse and treatment is with high-dose
methotrexate, whole-brain RT, and, in HIV, antiretroviral therapy.

Medulloblastomas

Most common malignant brain tumor of childhood. Half in posterior fossa; highly cellular; derived from
neural precursor cells. Treatment with surgery, RT, and chemotherapy. Approximately 70% of pts have long-
term survival, but usually at the cost of significant neurocognitive impairment.

Meningiomas

The most common primary brain tumor. Extra-axial mass attached to dura; dense and uniform contrast
enhancement is diagnostic (Fig.
Fig. 189-2
189-2). Total surgical resection of large, symptomatic benign
meningiomas is curative. With subtotal resection, local RT reduces recurrence. Small, asymptomatic
meningiomas may be followed radiologically without surgery. Treat rare aggressive meningiomas with
excision and RT.

FIGURE 189-2
Postgadolinium T1 MRI demonstrating multiple meningiomas along the falx and le" parietal cortex.

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Schwannomas

Vestibular schwannomas present as progressive, unexplained unilateral hearing loss. MRI reveals dense,
uniformly enhancing tumor at the cerebellopontine angle. Surgical excision may preserve hearing.

TUMORS METASTATIC TO THE NERVOUS SYSTEM

Hematogenous spread most common. Skull metastases rarely invade CNS; may compress adjacent brain or
cranial nerves or obstruct intracranial venous sinuses. Primary tumors that commonly metastasize to the
nervous system are listed in Table 189-1
189-1. Brain metastases are well demarcated by MRI and enhance with
gadolinium. Ring enhancement is nonspecific; di!erential diagnosis includes brain abscess, radiation
necrosis, toxoplasmosis, granulomas, tuberculosis, sarcoidosis, demyelinating lesions, primary brain
tumors, CNS lymphoma, stroke, hemorrhage, and trauma. Screen for occult cancer: examine skin and
thyroid gland; blood carcinoembryonic antigen (CEA) and liver function tests; CT of chest, abdomen, and

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pelvis. In approximately 10% of pts, a systemic cancer may present with brain metastases; biopsy of
primary tumor or accessible brain metastasis is needed to plan treatment. Treatment with glucocorticoids,
anticonvulsants, RT, or surgery. Whole-brain RT is o"en given because multiple microscopic tumor deposits
are likely throughout the brain; stereotaxic radiosurgery is of benefit in pts with three or fewer metastases
demonstrated by MRI. If a single metastasis is found, it may be surgically excised followed by whole-brain
RT. Systemic chemotherapy may produce dramatic responses in rare cases of a highly chemosensitive
tumor type such as germ cell tumors or small-cell lung cancer harboring specific epidermal growth factor
receptor (EGFR) mutations that sensitize them to EGFR inhibitors.

TABLE 189-1
FREQUENCY OF NERVOUS SYSTEM METASTASES BY COMMON PRIMARY TUMORS

Brain % LM % ESCC %

Lung 41 17 15

Breast 19 57 22

Melanoma 10 12  4

Prostate  1  1 10

GIT  7 —  5

Renal  3  2  7

Lymphoma <1 10 10

Sarcoma  7  1  9

Other 11 — 18

Abbreviations: ESCC, epidural spinal cord compression; GIT, gastrointestinal tract; LM, leptomeningeal metastases.

Leptomeningeal Metastases

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Presents as headache, encephalopathy, cranial nerve, or polyradicular symptoms. Diagnosis by CSF

cytology, MRI (nodular meningeal tumor deposits or di!use meningeal enhancement), or meningeal
biopsy. Associated with hydrocephalus due to CSF pathway obstruction. Treatment is palliative, o"en with
RT or chemotherapy (systemic or intrathecal).

Spinal Cord Compression from Metastases

(See
See Chap. 20
20) Expansion of vertebral body metastasis posteriorly into epidural space compresses cord.
Most common primary tumors are breast, lung, prostate, kidney, lymphoma, and myeloma. Back pain
(>90%) precedes development of weakness, sensory level, or incontinence. Medical emergency; early
recognition of impending spinal cord compression essential to avoid devastating sequelae. Diagnosis is by
spine MRI.

COMPLICATIONS OF RADIATION THERAPY

Three patterns of radiation injury a"er CNS RT:

1. Acute: headache, sleepiness, worse neurologic deficits during or immediately a"er RT. Rarely seen with
current protocols. Can be both prevented and treated with glucocorticoids.

2. Early delayed: somnolence (children), Lhermitte’s sign; within weeks to months of RT. Increased T2
signal and sometimes enhancement on MRI that can mimic tumor recurrence (“pseudoprogression”).
Self-limited and improves with glucocorticoids; if very symptomatic may require resection.

3. Late delayed: dementia or other progressive neurologic deficits; typically months to years a"er RT.
White matter abnormalities on MRI (leukoencephalopathy) or ring-enhancing mass (radiation necrosis).
PET can distinguish delayed necrosis from tumor recurrence as can MR perfusion sequences.
Progressive radiation necrosis is best treated palliatively with surgical resection unless it can be
managed with glucocorticoids. Radiation injury of large arteries accelerates the development of
atherosclerosis, increasing the risk of stroke years a"er RT. Endocrine dysfunction due to hypothalamus
or pituitary gland injury can be due to delayed e!ects of RT. Development of a second neoplasm a"er
RT also is a risk year a"er exposure.

For a more detailed discussion, see DeAngelis LM, Wen PY: Primary and Metastatic Tumors of the Nervous
System, Chap. 118, p. 598, in HPIM-19.

McGraw Hill
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