Neuro Neoplasms

A patient has a MRI performed and a *colloid cyst of the third ventricle* is identified. The most common complication of this lesion is a. Bitemporal hemianopsia b. Hydrocephalus c. Gait ataxia d. Optic atrophy e. Oscillopsia

*HYDROCEPHALUS* Colloid cysts may produce transient or persistent obstruction of the flow of CSF. Because this is an especially deep-seated lesion, it may be more practical to simply shunt the fluid from the lateral ventricles rather than attempt to excise the cyst. These cysts are usually lined with epithelial cells and may arise from a variety of sources, including low-grade neoplasms that involute early in their evolution.

A 13-year-old girl has headaches and diplopia. On examination, she has impaired upward gaze, lid retraction, and convergence-retraction nystagmus. Her pupils react on convergence but not to light

*Pineocytomas* are histologically benign lesions affecting the region of the pineal gland. They arise from the parenchymal cells of the pineal gland. This patient's symptoms and signs constitute *Parinaud syndrome*, which may include *loss of vertical gaze, loss of pupillary light reflex, lid retraction, and convergenceretraction nystagmus, in which the eyes appear to jerk back into the orbit on attempted upgaze*. This syndrome occurs in lesions due to involvement of the dorsal midbrain in the region of the superior colliculus. Other tumors appearing in the pineal region that can produce a similar clinical picture include germ cell tumors (germinomas), teratomas, and gliomas. Malignant pineal tumors, or pineoblastomas, may also occur, and are similar histologically to medulloblastomas.

Breakdown of spinal cord malignancies

10% intramedullary, 90% extramedullary Intramedullary = ependymoma, glioma Extramedullary = extradural vs intradural Extradural = mets and myeloma Intradural = neurofibromas, meningiomas

A 9-year-old girl with papilledema and precocious puberty is most likely to have a. A pineal region tumor b. An oligodendroglioma c. A Kernohan class II astrocytoma d. A brainstem glioma e. An ependymoma

A PINEAL REGION TUMOUR The pineal region is the source of an extraordinarily diverse group of tumor types, ranging from astrocytomas (derived from glial tissue) to chemodectomas (derived from sympathetic nervous tissue). Several different types of germ cell tumors arise from the tissues in this region, presumably from embryonal cell rests. In the United States, pineal tumors account for only 1% of intracranial tumors, but one-third of these pineal tumors are germ cell tumors, including germinomas and choriocarcinomas.

The incidence of primary brain tumors in children—about 1 to 5 per 100,000 per year—is mainly accounted for by a. Meningiomas and neurofibromas b. Astrocytomas and medulloblastomas c. Melanomas and choriocarcinomas d. Gliomas and adenomas e. Colloid cysts of the third ventricle

ASTROCYTOMAS AND MEDULLOBLASTOMAS Central nervous system tumors account for a large proportion of the tumors seen in childhood. In fact, they are second in frequency only to childhood leukemias and account for 15 to 20% of childhood tumors.

Metastatic lesions to the brain most often appear a. At the gray-white junction b. In the thalamus c. In the posterior fossa d. In the caudate e. In the sella turcica

AT THE GRAY WHITE JXN Metastatic lesions are spread primarily by the vascular system. The gray-white junction (where the white matter and the gray matter meet) is the interface at which blood-borne cells are most likely to lodge and grow. No part of the brain is exempt from the spread of metastases, but the cerebral hemispheres and the cerebellum are especially vulnerable.

A 37-year-old man presents with visual impairment. Examination reveals a bitemporal hemianopsia. Which of the following tumors is most likely responsible for this finding? a. Optic glioma b. Occipital astrocytoma c. Brainstem glioma d. Pituitary adenoma e. Sphenoid wing meningioma

BITEMPORAL HEMIAOPSIA With bitemporal hemianopsia, the visual fields in both eyes are impaired, but only the temporal quadrants of the field in each eye are affected. Pressure on the optic chiasm inferiorly by a tumor arising in or near the sella turcica will crush the fibers crossing in the chiasm from the medial aspects of the optic nerves. The most medial fibers in both optic nerves are contributed by the nasal aspects of the retina. The nasal or medial aspects of the retina receive light from the temporal or lateral aspects of the visual field.

__________ usually develop intraventricularly and do not extend down into the sella turcica. These tumors affect both children and adults, but they are rare. They are benign if they are surgically accessible and are extirpated early in their evolution.

Choroid plexus papillomas

Epithelial neoplasms arising in the sellar and third ventricular regions. They may cause hypopituitarism and visual field disturbances.

Craniopharyngioma

Ependyma

Ependyma is the thin epithelium-like lining of the ventricular system of the brain and the spinal cord. Ependyma is one of the four types of neuroglia in the central nervous system (CNS). It is involved in the production of cerebrospinal fluid (CSF).

A 65-year-old right-handed woman began having neurological problems about 1 week ago. She began experiencing nausea, vomiting, and numbness in the left hand and left foot. Today she had a generalized convulsion, and since then she has had a throbbing headache that is worse when she bends forward. On examination, the only deficits she has are loss of double simultaneous tactile stimulation and left lower facial droop when smiling. MRI reveals a lesion suggestive of a primary brain tumor. The most common *sources* of primary brain tumors are a. Glial cells b. Neurons c. Meningeal cells d. Lymphocytes e. Endothelial cells

GLIAL CELLS Between 2 and 5% of all tumors occurring in the general population are primary CNS tumors. *In adults, the most common primary brain tumor is the astrocytoma*. In children, brain tumors are more likely to arise in the posterior fossa. Even in childhood, glial cell tumors, such as the cerebellar astrocytoma and the optic glioma, are common.

A 56-year-old right-handed woman who had breast cancer 1 year ago began having neurological problems about 1 week ago. She began experiencing nausea, vomiting, and numbness in the right hand and foot. Today she is experiencing crescendo pain in the left retroorbital area. Her headache is throbbing and positional, particularly when she tries to bend forward. The headache was intense in the morning, and at times it woke her up last night. On examination, the only deficits are loss of double simultaneous tactile stimulation and right lower facial droop when smiling. The most appropriate next action would be to a. Administer intravenous prochlorperazine b. Give the patient a prescription for zolmitriptan c. Make a follow-up appointment for next month d. Order an electroencephalogram to rule out seizures e. Get a brain MRI

Get a brain MRI The headache is typical of that caused by intracranial hypertension. Additionally, the patient has focal neurological symptoms and signs. This creates particular concern about a brain tumor or hemorrhage, and the patient should be evaluated as soon as possible. An appointment next month is too late. Intravenous prochlorperazine is a good treatment for status migrainosus; however, this history is atypical for such a diagnosis and more serious problems should be ruled out first in the emergency room.

A 70-year-old man with a history of lung cancer develops n/v and then becomes lethargic. On exam, he is lethargic but arousable, and disoriented and inattentive. He is weak proximally and has diminished reflexes.

HYPERCALCEMIA Hypercalcemia may occur as a complication of cancer in up to 5% of patients. It may be a result of parathyroid-related peptide secreted by the tumor itself (usually a lung cancer) or of bone destruction by metastatic disease. The elevated serum calcium decreases membrane excitability, leading to the clinical syndrome of fatigability, lethargy, generalized weakness, and areflexia. In more severe cases, coma and even convulsions can occur. Symptoms usually do not occur until levels reach 14 mg/dL or higher.

A 9-year-old girl presents with precocious puberty and episodes of uncontrollable laughter. Which of the following mass lesions might explain her symptoms? a. Craniopharyngioma b. Choroid plexus papilloma c. Giant aneurysm d. Metastatic carcinoma e. Hypothalamic hamartoma

HYPOTHALAMIC HARMARTOMA Hypothalamic hamartomas are nonneoplastic malformations involving neurons and glia in the region of the hypothalamus. They may be discovered incidentally, either on imaging performed for other reasons or at autopsy, or they may cause symptoms referable to the hypothalamus. Most often, the latter involves neuroendocrine functions, causing precocious puberty or acromegaly due to overproduction of growth hormone-releasing hormone. Patients may also experience paroxysms of laughter, known as *gelastic seizures*. They may be cured surgically.

Most brain tumors in children are a. Metastatic lesions from outside the central nervous system (CNS) b. Oligodendrogliomas c. Glioblastomas multiforme d. Meningiomas e. Infratentorial

INFRATENTORIAL The *posterior fossa* is the usual location for brain tumors in children. *Medulloblastomas, ependymomas, and cerebellar (or brainstem) gliomas* account for most of the tumors that occur before puberty. Other common tumors developing intracranially in children include optic gliomas and metastatic leukemias.

Further evaluation reveals multiple brain masses. The most common source of metastatic tumors to the brain is the a. Breast b. Lung c. Kidney d. Skin e. Uterus

LUNG The breast, lung, kidney, skin, and uterus are all common sources of metastases to the brain. The incidences of metastases from the lung and breast in women are very close, but with the climbing rates of pulmonary carcinoma in women, the lung has become the more common source. Skin lesions metastasizing to the brain include malignant melanomas.

A 57-year-old woman with a history of smoking has a 3-month history of hip and shoulder weakness. She also complains of xerostomia (dry mouth). There are no sensory symptoms, and she is cognitively intact. On exam, she is orthostatic. There is proximal muscle weakness, but she has increasing muscle strength with repetitive activity of her muscles. Eye movements are normal. (SELECT 1 DISORDER)

Lambert Eaton myasthenia syndrome The Lambert-Eaton myasthenic syndrome (LEMS) shares some features with myasthenia gravis, notably *proximal muscle weakness*. It usually develops subacutely, however, and spares the bulbar musculature and eyes. There is also little response to anticholinesterase drugs. A characteristic feature is the increase in strength briefly after repeated muscle activation. Most cases are associated with an underlying oat cell carcinoma of the lung or other malignancy. In other cases, LEMS may be associated with other autoimmune illness. The underlying defect is the loss of function of the voltage-sensitive calcium channels in the presynaptic nerve terminal at the neuromuscular junction, due to cross-linking and aggregation by pathologic IgG autoantibodies. Various immune-modulating therapies, as well as 3,4-diaminopyridine, have been used with varying success. Removal of the underlying malignancy may also be curative.

The shortest life expectancy with metastatic disease to the brain will be found in the patient with metastatic a. Malignant melanoma b. Breast cancer c. Lung cancer d. Renal cancer e. Prostate cancer

MALIGNANT MELANOMA The outlook with malignant melanoma, breast cancer, lung cancer, or renal cancer metastatic to the brain is poor and limited to a matter of months, but malignant melanoma is especially grim because it is *highly likely to bleed after it metastisizes to the brain*. Malignant melanoma and *choriocarcinoma* are likely to produce lethal intracranial hemorrhages, and the former may in fact first become apparent only after it has precipitated an intracranial hemorrhage.

A 4-year-old boy presents with ataxia, lethargy, and obstructive hydrocephalus. (SELECT 1 TUMOR)

MEDULLOBLASTOMA Medulloblastomas are one of the most common CNS tumors of childhood. They typically develop in the *cerebellum*, causing ataxia. Astrocytomas may also occur in children infratentorially, primarily in the cerebellum and brainstem. In either location, hydrocephalus may develop because of obstruction at the level of the fourth ventricle. The astrocytoma that develops in the cerebellum is usually cystic. Medulloblastomas are invariably infratentorial, at least initially. They may extend supratentorially or become disseminated supratentorially through seeding of cells carried in the CSF. Ependymomas, another common tumor type in children, are derived from the lining of the ventricles and also carry the risk of hydrocephalus and seeding throughout the CNS.

A 72-year-old woman has a head CT performed because of headaches. It is significant for a left hemisphere mass with an overlying hyperostosis of the skull. She most likely has which of the following? a. Meningioma b. Pituitary adenoma c. Astrocytoma d. Schwannoma e. Hemangioblastoma 171. A 9-year-old girl with

MENINGIOMA Hyperostosis is thickening of the bone and is much less commonly induced by tumors in or about the brain than is thinning of the bone. Thinning occurs especially with pituitary adenomas, which may cause erosions in the floor of the sella turcica as an early feature. Calcifications may develop in schwannomas or astrocytomas, but both of these tumor types will usually cause bony erosions where they impinge on the skull. Calcifications may develop in many primary or metastatic brain tumors, but calcification sufficient to be readily seen on a skull x-ray suggests an astrocytoma, meningioma, oligodendroglioma, or metastatic tumor. Calcification can be visualized on CT scan in about 17% of medulloblastomas. With meningiomas, hyperostosis may develop in the bone adjacent to the tumor even if there is no infiltration of the bone by the tumor.

Anti-Hu

PARANEOPLASTIC

A 67-year-old woman has a 2-month history of progressive gait disturbance. On exam, she has dysmetria of the limbs; a wide-based, unsteady gait; and hypermetric saccades. A hard, firm breast lump is discovered. (SELECT 1 DISORDER)

PARANEOPLASTIC CEREBELLAR DEGENERATION Paraneoplastic cerebellar degeneration (PCD) is characterized by subacute and relentlessly progressive *ataxia, dysarthria, and nystagmus*. Myoclonus, opsoclonus (irregular jerking of the eyes in all directions), diplopia, vertigo, and hearing loss may also occur. Imaging may eventually reveal cerebellar atrophy, and pathology will disclose loss of Purkinje cells in the cerebellum as the primary abnormality. The most common associated tumor types are small cell carcinoma of the lung, ovarian carcinoma, and lymphoma, in that order. Approximately 50% of patients may harbor anti-Purkinje cell antibodies (called *anti-Yo antibodies*), and these are especially commonly found in women with breast cancer or other gynecologic malignancies. Interestingly, the symptoms of PCD often precede the symptoms of the underlying tumor itself, leading to speculation that the immune reaction that damages the nervous system may, in fact, be protective against the tumor.

A 65-year-old woman develops pain and paresthesias in her feet. On examination, she has loss of reflexes, stocking distribution sensory loss, and mild distal weakness. Serum protein electrophoresis reveals a monoclonal gammopathy, and bone marrow biopsy reveals plasma cell dyscrasia. (SELECT 1 DISORDER)

PARAPROTEINEMIC NEUROPATHY Polyneuropathy may occur in up to 15% of patients with multiple myeloma. This generally takes the form of a chronic distal symmetrical sensory or sensorimotor neuropathy. In some cases, the neuropathy progresses more aggressively, and the patient becomes confined to a wheelchair. Spinal fluid protein may be elevated, and the illness has the appearance of a chronic inflammatory demyelinating polyneuropathy. Up to 20% of patients referred for evaluation of polyneuropathy may have an underlying monoclonal paraproteinemia. In the a ABsence of an obvious malignancy, this is called a monoclonal gammopathy of undetermined significance, but a hematologic malignancy may later turn up in as many as one-third of such patients.

A 30-year-old man with the acquired immune deficiency syndrome (AIDS) develops headaches and left hemiparesis and is found to have a right frontal white matter homogeneously enhancing lesion. (SELECT 1 TUMOR)

PRIMARY CNS LYMPHOMA Patients with AIDS are at risk for numerous CNS infections, but have an increased frequency of only two tumor types: lymphoma and Kaposi's sarcoma. KS may metastasize to the CNS, but lymphoma is routinely primary to the CNS. This tumor may produce blindness through direct invasion of the optic nerve.

The tumor type that is common in the brain of patients with AIDS, but otherwise extremely rare, is a. Lymphocytic leukemia b. Metastatic lymphoma c. Primary lymphoma d. Kaposi's sarcoma e. Lymphosarcoma

PRIMARY LYMPHOMA Kaposi's sarcoma is unusually common in patients with AIDS, but it is rarely metastatic to the brain. Metastatic lymphomas producing meningeal lymphomatosis are not especially rare in the general population, but primary lymphomas (that is, lymphomas apparently arising in the CNS) were rare before the AIDS epidemic. The primary brain lymphoma usually presents as a solitary mass and can occur anywhere in the brain, but it does have a predilection for the periventricular structures.

A 55-year-old woman presents with mild unsteadiness, tinnitus, and hearing loss.

SCHWANNOMA Schwannomas usually develop on the vestibular division of cranial nerve VIII and are pathologically derived from Schwann cells rather than nerve tissue, and are therefore more appropriately called vestibular schwannomas than acoustic neuromas, the traditional name. Although this is not the division of the nerve that carries information from the cochlea, the cochlear division is crushed as the tumor expands. This type of tumor is especially likely with neurofibromatosis type 2, a hereditary disorder characterized by a variety of tumors in the skin and nervous system.

With an ependymoma of the posterior fossa, the patient is at risk of dying because of a. Transforaminal herniation b. Emboli from the tumor c. Vascular occlusion by the tumor d. Hemorrhagic necrosis of the tumor e. Status epilepticus

TRANSFORAMINAL HERNIATION As a tumor of the posterior fossa enlarges, the contents of the posterior fossa will be compressed and ultimately forced upward or downward. If the herniation is upward, it is called transtentorial because it is across the tentorium cerebelli. If it is downward, it is called transforaminal because it is across the foramen magnum. Ependymomas are not especially vulnerable to hemorrhagic necrosis. Tumors in the posterior fossa generally do not produce seizures.

The most common type of primary brain tumor is a. Meningioma b. Astrocytoma c. Lymphosarcoma d. Oligodendroglioma e. Medulloblastoma

The most common primary brain tumors are *malignant astrocytomas*. These are classified as grade 3 or 4. *Grade 4 astrocytoma is more commonly called glioblastoma multiforme*. It is malignant in the very conventional sense that it invades adjacent tissue. This type of glial tumor is usually seen in adults; men are more susceptible than women.

A 15-year-old boy has multiple angiomatoses of the retina and cysts of the kidney and pancreas. The brain tumor that is most likely to develop in this child is which of the following? a. Glioblastoma multiforme b. Meningioma c. Hemangioblastoma d. Ependymoma e. Pinealoma

With von Hippel-Lindau syndrome, the patient may exhibit tumors in multiple organs. In the brain, hemangioblastomas are the tumors most likely to arise, and these tumors are usually limited to the cerebellum or brainstem. Hemangioblastomas are often multiple and become symptomatic by bleeding into themselves. The initial episode of bleeding may prove lethal.