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CHAPTER SEVEN
TUMORS OF THE CENTRAL NERVOUS SYSTEM
Page 1 | Page 2 | Page 3 | Page 4
Histogenesis-classification | Molecular-Genetic Aspects | Etiology-Pathogenesis | Genetic Tumor Syndromes | Diagnosis | Astrocytoma | Glioblastoma Multiforme | Pilocytic Astrocytoma | Oligodendroglioma | Ependymoma | Medulloblastoma | Meningioma | Schwannoma | Neurofibroma | Craniopharyngioma | Hemangioblastoma | Cerebral Lymphoma | The Effects of Brain Tumors
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MENINGIOMA
Meningiomas arise from arachnoidal cells. They constitute about 20% of BT and affect mostly adults, women almost twice as frequently as men. They may be located anywhere in the brain or spinal cord. About half of them arise over the cerebral convexities and one fifth at the sphenoid ridge.
Meningiomas are circumscribed; they may be attached to the dura, though they do not arise from the dura per se. Usually, they displace brain tissue without invading it. Some meningiomas grow flat on the surface of the brain.
meningioma meningioma meningioma
Meningioma Transitional meningioma Fibroblastic meningiomaMicroscopically, they have a variety of appearances on the basis of which they have been classified into several histological types most of which have no prognostic significance. Meningothelial meningiomas are composed of diffuse masses of arachnoidal-like cells. In transitional meningiomas, tumor cells are arranged in whorls with hyalinized and calcified centers that are called psammoma (sand) bodies because they resemble tiny grains of sand. Fibroblastic meningiomas are composed of fascicles of fiber-like cells with abundant interstitial collagen. Meningothelial, transitional, and fibroblastic are the most common histological subtypes of meningiomas but there are many more. Many meningiomas are histologically mixed.
Most meningiomas are benign and grow slowly. Because they are extra-axial, complete resection is possible in many of them and may be curative. Incomplete excision is followed by recurrence. Postoperative survival averages 12 to 15 years. Meningiomas tend to infiltrate overlying bone, even muscle. This peculiar phenomenondoes not indicate malignancy. Malignant meningiomas are relatively infrequent. They display overt histological anaplasia and increased mitoses and invade the brain. About 10% of meningiomas display histological features that are intermediate between benign and malignant meningiomas, such as increased cellularity, mitotic activity, a diffuse patternless cellular growth, and necrosis. These atypical meningiomas grow more rapidly and are more prone to recurr after surgical resection. Some histological types, such as papillary, chordoid, rhabdoid,and clear cell meningioma, also have a more aggressive behaviour and are associated with a higher rate of recurrence.
The majority of meningiomas show loss of the entire chromosome 22 or 22q. The latter contains the NF2 tumor suppressor gene, merlin. Meningiomas, especially of the fibroblastic type, are one of the BT seen in BANF. In BANF patients, meningiomas arise at a young age and may be multiple. Meningiomas also express female sex hormone receptors, explaining their rapid growth during pregnancy.
SCHWANNOMA
Schwannoma Schwannoma NF2
8th nerve Schwannoma Schwannoma: palisading pattern Bilateral 8th nerve Schwannomas in NF2Schwannomas arise most often in cranial and spinal nerve roots and peripheral nerves but can occur anywhere, including in the brain and in the ventricles. Ninety percent of schwannomas arise in the 8th nerve root (acoustic Schwannoma, cerebellopontine angle tumor). Other cranial nerves are less frequently involved. The preferential involvement of the 8th nerve may have to do with chronic exposure to loud noise (acoustic trauma). Most Schwannomas are solitary. Bilateral acoustic or multiple Schwannomas are the hallmark of NF2. Other cranial nerves are less commonly involved. Schwannomas are extra-axial, circumscribed and encapsulated and range from small and solid to large, irregular, cystic, and hemorrhagic masses. They do not invade, but rather displace the brainstem and spinal cord as they grow. Microscopically, they consist of fascicles of spindle cells that are arranged in palisades. Less frequently they form a loose reticular pattern. They are benign, slow-growing tumors, and cause symptoms by compression.
NEUROFIBROMA
plexiform neurofibroma
Plexiform neurofibromaNeurofibromas are peripheral nerve tumors composed of a mixture of Schwann cells and fibroblasts. They cause a fusiform enlargement of the nerve in which they arise. Microscopically, their cells are loosely arranged in a wavy pattern. Multiple neurofibromas that involve long segments of peripheral nerves (plexiform-from a Greek word that means braid- neurofibromas) are characteristic of NF1.
CRANIOPHARYNGIOMA
craniopharyngioma
Craniopharyngioma
Craniopharyngiomas are most frequent in children and adolescents. They are suprasellar and are thought to arise from epithelial remnants of Rathke's pouch that are trapped in the pituitary stalk. Alternatively, they may represent a form of teratoma. They grow slowly and damage the hypothalamus, compress the optic chiasm, and block the third ventricle, causing endocrine abnormalities, visual disturbances, and hydrocephalus.
Grossly, they show a mix of solid and cystic areas. Microscopically, they are composed of sheets of squamous epithelial cells and keratin, set in a loose connective tissue stroma. Islands of keratin often calcify. Cysts, calcification, and the suprasellar location are the criteria for the radiological diagnosis of craniopharyngiomas. Other common suprasellar tumors are pilocytic astrocytoma and germ cell tumors.
HEMANGIOBLASTOMA
Hemangioblastomas are sporadic or familial. The latter are associated with the von Hippel Lindau disease. They occur in young to middle-aged adults. Typically, they are found in the cerebellum as a mural nodule within a cyst. In von Hippel Lindau disease, there are multiple hemangioblastomas involving the retina, spinal cord, and brain. Hemangioblastoma is a benign tumor which consists of numerous delicate capillaries set in a background of clear foamy cells.
CEREBRAL LYMPHOMA
lymphoma, cerebral cerebral lymphoma
Cerebral lymphoma Cerebral lymphomaPrimary cerebral lymphomas are thought to arise from indigenous brain histiocytes (microglia) or from rare lymphocytes that are normally present in the meninges and around vessels. Most often, they affect immunosuppressed individuals such as patients with AIDS, but may also involve people with intact immune systems. Its high incidence in patients with AIDS and its increased frequency, even in non immunosupressed people, has made primary cerebral lymphoma a relatively common BT. The brain, especially subarachnoid space, is also a frequent site of metastasis of systemic lymphoma and leukemia. Cerebral lymphomas are single or multiple, poorly defined tumors with necrosis, similar to glioblastoma. Microscopically, most of them are large, B-cell lymphomas. The tumor cells form dense perivascular sheaths or diffuse masses. Meningeal spread is very common, and some cerebral lymphomas arise in the subarachnoid space. Cerebral lymphomas, like their extracerebral high-grade counterparts, are highly malignant.
METASTATIC TUMORS
meningeal carcinomatosis
Meningeal carcinomatosisMetastatic tumors account probably for the majority of BT that are seen in general community hospitals. Brain metastases are found at autopsy in 14% to 37% of malignant tumors. In men, the most common primary is carcinoma of the lung, which shows brain metastases in 35% of the cases; in women, it carcinoma of the breast, which metestasizes in 21% of the cases. The tumor with the highest rate of metastasis is melanoma. Metastatic tumors are frequently multiple. Meningeal carcinomatosis (diffuse spread of tumor in the subarachnoid space) is seen in 4% to 8% of metastatic BT and is more common with carcinoma of the lung, carcinoma of the breast, and acute lymphoblastic leukemia. It causes headache, drowsiness, cranial nerve deficits, spinal root pain, and paresthesias. The CSF in meningeal carcinomatosis shows high protein, low glucose, and a few lymphocytes. The often insidious onset of symptoms and the CSF findings suggest mycobacterial meningitis, especially if the primary tumor is too small to be detected. Cytological examination of CSF reveals tumor cells.
Extraneural metastases of primary BT, even highly malignant ones, such as glioblastoma and medulloblastoma, are very rare and occur usually after surgery, when tumor cells accidentally get into vessels. Spontaneous metastasis is extremely uncommon.
THE EFFECTS OF BRAIN TUMORS
The local effects of BT are loss of function (focal deficits) and seizures. An insidious onset of seizures in an otherwise healthy person strongly suggests a BT. The general effects of tumors have to do mainly with increased intracranial pressure. Increased intracranial pressure is caused by a) the mass of tumor added to the brain, b) hydrocephalus due to obstruction of CSF circulation and c) cerebral edema, i.e., accumulation of fluid in the interstitial space around the tumor. Fluid leaks from tumor vessels that do not have dense junctions as normal brain capillaries do. With some exceptions, high vascularity is a feature of rapidly growing tumors. Consequently, cerebral edema is seen in malignant BT (GBM, medulloblastoma, cerebral lymphoma, metastatic tumors). Hydrocephalus is a common feature of posterior fossa tumors, the majority of which are seen in children. Cerebral edema and hydrocephalus are life-threatening complications and may cause displacements (herniations) and compression of brain structures with lethal effects (See Chapter 4: Craniocerebral trauma and increased intracranial pressure).