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BRAIN TUMOUR

Brain tumors may originate from neural elements within the brain, or they may represent spread of distant cancers. Primary brain tumors arise from CNS tissue and account for roughly half of all cases of intracranial neoplasms. The remainder of brain neoplasms are caused by metastatic lesions. In adults, two thirds of primary brain tumors arise from structures above the tentorium (supratentorial), whereas in children, two thirds of brain tumors arise from structures below the tentorium (infratentorial). Gliomas, metastases, meningiomas, pituitary adenomas, and acoustic neuromas account for 95% of all brain tumors. Classification by tumor cell type is irrelevant to the emergency physician because emergent treatment is the same regardless of the tumor type.

Pathophysiology

Tumors of the brain produce neurologic manifestations through a number of mechanisms. Small, critically located tumors may damage specific neural pathways traversing the brain. Tumors can invade, infiltrate, or supplant normal parenchymal tissue, disrupting normal function. Because the brain dwells in the limited volume of the cranial vault, growth of intracranial tumors with accompanying edema may cause increased intracranial pressure. Tumors adjacent to the third and fourth ventricles may impede the flow of cerebrospinal fluid, leading to obstructive hydrocephalus. In addition, tumors generate new blood vessels (ie, angiogenesis), disrupting the normal blood-brain barrier and promoting edema.

BRAIN TUMOUR Brain tumors may originate from neural elements within the brain, or they may representGliomas , metastases, meningiomas , pituitary adenomas , and acoustic neuromas account for 95% of all brain tumors. Classification by tumor cell type is irrelevant to the emergency physician because emergent treatment is the same regardless of the tumor type. Pathophysiology Tumors of the brain produce neurologic manifestations through a number of mechanisms. Small, critically located tumors may damage specific neural pathways traversing the brain. Tumors can invade, infiltrate, or supplant normal parenchymal tissue, disrupting normal function. Because the brain dwells in the limited volume of the cranial vault, growth of intracranial tumors with accompanying edema may cause increased intracranial pressure. Tumors adjacent to the third and fourth ventricles may impede the flow of cerebrospinal fluid, leading to obstructive hydrocephalus. In addition, tumors generate new blood vessels (ie, angiogenesis), disrupting the normal blood-brain barrier and promoting edema. Neoplasms, brain. Colloid cyst of the third ventricle with obstructive hydrocephalus. Image courtesy of Peter Ferrera, MD. The cumulative effects of tumor invasion, edema, and hydrocephalus may elevate the intracranial pressure (ICP) and impair cerebral perfusion. Intracranial compartmental rise in ICP may provoke shifting or herniation of tissue under the falx cerebri, through the tentorium cerebelli, or through the foramen magnum. Slow-growing tumors, particularly tumors expanding in the so-called silent areas of the brain, such as the frontal lobe, may be associated with a more insidious clinical course. These tumors tend to be larger at detection. Most primary brain tumors do not metastasize, but if they do metastasize, intracranial spread generally precedes distant dissemination. " id="pdf-obj-0-20" src="pdf-obj-0-20.jpg">

Neoplasms, brain. Colloid cyst of the third ventricle with obstructive hydrocephalus. Image courtesy of Peter Ferrera, MD.

The cumulative effects of tumor invasion, edema, and hydrocephalus may elevate the intracranial pressure (ICP) and impair cerebral perfusion. Intracranial compartmental rise in ICP may provoke shifting or herniation of tissue under the falx cerebri, through the tentorium cerebelli, or through the foramen magnum.

Slow-growing tumors, particularly tumors expanding in the so-called silent areas of the brain, such as the frontal lobe, may be associated with a more insidious clinical course. These tumors tend to be larger at detection.

Most primary brain tumors do not metastasize, but if they do metastasize, intracranial spread generally precedes distant dissemination.

Metastatic brain tumors from non-CNS primary tumors may be the first sign of malignancy, or they may herald a relapse. Nonetheless, the signs and symptoms of brain metastases simulate those of primary brain tumors.

Leptomeningeal infiltration may present with dysfunction of multiple cranial nerves.

pidemiology

Frequency

United States

Estimates of the annual incidence rate of primary brain tumors range from 7-19.1 cases per 100,000 population. Metastatic tumors to the brain are more common with more than 200,000 patients per year in the United States with a new diagnosis of intracranial metastases. An increase in the prevalence of HIV infection corresponds to an increase in the occurrence of primary CNS lymphoma. Pituitary adenomas are exceptionally common, and they are frequent incidental findings on autopsy. Autopsy series of patients with systemic cancer show that intracranial metastases are present in 18-24% of patients.

International

The international incidence is not known, but it is thought to parallel that of the United States.

Mortality/Morbidity

In the United States in 1999, primary cancers of the central nervous system were the cause of

death in approximately 13,100 people. Brain tumors are the second most common cancer in children, comprising 15-25% of all

pediatric malignancies. Perhaps no other cancer is as feared as brain tumor since severe disability, including paralysis, seizures, gait disturbances, and impairment of intellectual capacity may occur.

Race

Differences are seen between ethnic groups within the same country, and a 3-fold difference in incidence has been reported between countries worldwide. Developed countries appear to have the highest rates, but this may reflect better registration systems.

Sex

Meningiomas and pituitary adenomas are slightly more common in women than in men.

Males are more likely to be diagnosed with brain tumors than females, with a male-to-female ratio of 1.5:1.

Age

Tumors in the posterior fossa predominate in preadolescent children, with the incidence of

supratentorial tumors increasing from adolescence to adulthood. Low-grade gliomas, such as astrocytomas, are more common in younger people than in older

people. High-grade gliomas, such as anaplastic astrocytoma and glioblastoma multiforme, tend to originate in the fourth or fifth decade or beyond. In children, brain tumors are the most prevalent solid tumor, second only to leukemia as a cause of pediatric cancer. The incidence rate of primary CNS neoplasms is 3.6 cases per 100,000 children each year.

n 1993 the WHO ratified a new comprehensive classification of neoplasms affecting the central nervous system. The classification of brain tumors is based on the premise that each type of tumor results from the abnormal growth of a specific cell type. To the extent that the behavior of a tumor correlates with basic cell type, tumor classification dictates the choice of therapy and predicts prognosis. The new WHO system is particularly useful in this regard with only a few notable exceptions (for example all or almost all gemistocytic astrocytomas are actually anaplastic and hence grade III or even IV rather than grade II as designated by the WHO system). The WHO classification also provides a parallel grading system for each type of tumor. In this grading sytem most named tumors are of a single defined grade. The new WHO classification provides the standard for communication between different centers in the United States and around the world. An outline of this classification is provided below.

Neuroepithelial Tumors of the CNS

  • 1. Astrocytic tumors [glial tumors--categories I-V, below--may also be subclassified as invasive or non-invasive, although this is not formally part of the WHO system, the non-invasive tumor types are indicated below. Categories in italics are also not recognized by the new WHO classification system, but are in common use.]

    • 1. Astrocytoma (WHO grade II)

      • 1. variants: protoplasmic, gemistocytic, fibrillary, mixed

    • 2. Anaplastic (malignant) astrocytoma (WHO grade III)

      • 1. hemispheric

      • 2. diencephalic

      • 3. optic

      • 4. brain stem

      • 5. cerebellar

  • 3. Glioblastoma multiforme (WHO grade IV)

    • 1. variants: giant cell glioblastoma, gliosarcoma

  • 4. Pilocytic astrocytoma [non-invasive, WHO grade I]

    • 1. hemispheric

    • 2. diencephalic

    • 3. optic

    • 4. brain stem

    • 5. cerebellar

  • 5. Subependymal giant cell astrocytoma [non-invasive, WHO grade I]

  • 6. Pleomorphic xanthoastrocytoma [non-invasive, WHO grade I]

  • 2. Oligodendroglial tumors

    • 1. Oligodendroglioma (WHO grade II)

    • 2. Anaplastic (malignant) oligodendroglioma (WHO grade III)

  • 3.

    Ependymal cell tumors

    • 1. Ependymoma (WHO grade II)

    1.

    variants: cellular, papillary, epithelial, clear cell, mixed

    • 2. Anaplastic ependymoma (WHO grade III)

    • 3. Myxopapillary ependymoma

     
    • 4. Subependymoma (WHO grade I)

    • 4. Mixed gliomas

    • 1. Mixed oligoastrocytoma (WHO grade II)

    • 2. Anaplastic (malignant) oligoastrocytoma (WHO grade III)

    • 3. Others (e.g. ependymo-astrocytomas)

    • 5. Neuroepithelial tumors of uncertain origin

    • 1. Polar spongioblastoma (WHO grade IV)

    • 2. Astroblastoma (WHO grade IV)

    • 3. Gliomatosis cerebri (WHO grade IV)

    • 6. Tumors of the choroid plexus

     
    • 1. Choroid plexus papilloma

    • 2. Choroid plexus carcinoma (anaplastic choroid plexus papilloma)

    • 7. Neuronal and mixed neuronal-glial tumors

    • 1. Gangliocytoma

     
    • 2. Dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos)

    • 3. Ganglioglioma

     
    • 4. Anaplastic (malignant) ganglioglioma

    • 5. Desmoplastic infantile ganglioglioma

    1.

    desmoplastic infantile astrocytoma

    • 6. Central neurocytoma

     
    • 7. Dysembryoplastic neuroepithelial tumor

    • 8. Olfactory neuroblastoma (esthesioneuroblastoma)

    1.

    variant: olfactory neuroepithelioma

    • 8. Pineal Parenchyma Tumors

     
    • 1. Pineocytoma

    • 2. Pineoblastoma

    • 3. Mixed pineocytoma/pineoblastoma

    • 9. Tumors with neuroblastic or glioblastic elements (embryonal tumors)

    • 1. Medulloepithelioma

     
    • 2. Primitive neuroectodermal tumors with multipotent differentiation

    1.

    medulloblastoma

     

    1.

    variants: medullomyoblastoma, melanocytic medulloblastoma,

     

    desmoplastic medulloblastoma

    2.

    cerebral primitive neuroectodermal tumor

    • 3. Neuroblastoma

     

    1.

    variant: ganglioneuroblastoma

    • 4. Retinoblastoma

     
    • 5. Ependymoblastoma

    Other CNS Neoplasms

    • 1. Tumors of the Sellar Region

      • 1. Pituitary adenoma

      • 2. Pituitary carcinoma

    3.

    Craniopharyngioma

    • 2. Hematopoietic tumors

      • 1. Primary malignant lymphomas

      • 2. Plasmacytoma

      • 3. Granulocytic sarcoma

      • 4. Others

  • 3. Germ Cell Tumors

    • 1. Germinoma

    • 2. Embryonal carcinoma

    • 3. Yolk sac tumor (endodermal sinus tumor)

    • 4. Choriocarcinoma

    • 5. Teratoma

    • 6. Mixed germ cell tumors

  • 4. Tumors of the Meninges

    • 1. Meningioma

      • 1. variants: meningothelial, fibrous (fibroblastic), transitional (mixed), psammomatous, angiomatous, microcystic, secretory, clear cell, chordoid, lymphoplasmacyte-rich, and metaplastic subtypes

    • 2. Atypical meningioma

    • 3. Anaplastic (malignant) meningioma

  • 5. Non-menigothelial tumors of the meninges

    • 1. Benign Mesenchymal

      • 1. osteocartilaginous tumors

      • 2. lipoma

      • 3. fibrous histiocytoma

      • 4. others

  • 2. Malignant Mesenchymal

    • 1. chondrosarcoma

    • 2. hemangiopericytoma

    • 3. rhabdomyosarcoma

    • 4. meningeal sarcomatosis

    • 5. others

  • 3. Primary Melanocytic Lesions

    • 1. diffuse melanosis

    • 2. melanocytoma

    • 3. maliganant melanoma

      • 1. variant meningeal melanomatosis

  • 4. Hemopoietic Neoplasms

    • 1. malignant lymphoma

    • 2. plasmactoma

    • 3. granulocytic sarcoma

  • 5. Tumors of Uncertain Histogenesis

    • 1. hemangioblastoma (capillary hemangioblastoma)

  • 6. Tumors of Cranial and Spinal Nerves

    • 1. Schwannoma (neurinoma, neurilemoma)

      • 1. cellular, plexiform, and melanotic subtypes

    • 2. Neurofibroma

      • 1. circumscribed (solitary) neurofibroma

      • 2. plexiform neurofibroma

  • 3. Malignant peripheral nerve sheath tumor (Malignant schwannoma)

    • 1. epithelioid

    • 2. divergent mesenchymal or epithelial differentiation

    • 3. melanotic

    • 7. Local Extensions from Regional Tumors

      • 1. Paraganglioma (chemodectoma)

      • 2. Chordoma

      • 3. Chodroma

      • 4. Chondrosarcoma

      • 5. Carcinoma

  • 8. Metastatic tumours

  • 9. Unclassified Tumors

  • 10. Cysts and Tumor-like Lesions

    • 1. Rathke cleft cyst

    • 2. Epidermoid

    • 3. Dermoid

    • 4. Colloid cyst of the third ventricle

    • 5. Enterogenous cyst

    • 6. Neuroglial cyst

    • 7. Granular cell tumor (choristoma, pituicytoma)

    • 8. hypothalamic neuronal hamartoma

    • 9. nasal glial herterotopia

    10. plasma cell granuloma

    A number of grading systems are in common use for tumors of astrocytic lineage (i.e. astrocytomas, anaplastic astrocytomas and glioblastomas). Grades are assigned solely based on the microsopic appearance of the tumor. The numerical grade assigned for a given tumor, however, can vary depending on which grading system is used as illustrated by the following table. Thus, it is important to specify the grading system referred to when a grade is specified. The St. Anne/Mayo grade has proven to correlate better with survival than the previously common Kernohan grading system. It can only be applied to invasive tumors of astrocytic lineage; it is otherwise similar to the WHO grading system.

    Grading of astrocytic tumors

    WHO designation

    WHO grade*

    Kernohan grade*

    St. Anne/Mayo grade

    St. Anne/Mayo criteria pilocytic astrocytoma

    I

    I

    excluded

    -

    astrocytoma

    II

    I, II

    1

    no criteria fulfilled

     

    2

    one criterion: usually nuclear atypia

    anaplastic

    III

    II, III

    3

    two criteria: usually

    (malignant)astrocytoma

     

    nuclear atypia and

    mitosis

    glioblastoma

    IV

    III, IV

    4

    three or four criteria:

    usually the and/or necrosis

    *The WHO and Kernohan systems are not criteria based. Thus, a given tumor may not fall under the same designation in all three systems.

    Mutations leading to infiltrative astrocytic tumors.

    Molecular studies have identified some of the genetic changes that underlie the pathologic differences among astrocytic tumors; progression in tumor grade is associated with an ordered accumulation of mutations (Fig. below). Approximately 33% of low grade infiltrating astrocytomas (St. Anne/Mayo grade 2) have mutations detected in the p53 gene on chromosome 17p. Anaplastic astrocytomas (grade 3)- whether found in preexistent low grade astrocytomas or detected de novo-have a similar incidence of p53 mutations but, in addition, show a loss of heterozygosity on chromosome 19q in more than 40% of cases. Progression from astrocytoma to anaplastic astrocytoma also involves mutations in other tumor suppressor genes including the retinoblastoma gene on chromosome 13q. Finally, glioblastomas have the same incidence of these genetic aberrations and in addition 70 percent have lost heterozygosity for chromosome 10 and one third have amplification of the epidermal growth factor receptor gene. Many of these correlations have been defined largely through work in the MGH Molecular Neurooncology laboratory.

    Mutations leading to infiltrative astrocytic tumors. Molecular studies have identified some of the genetic changes thatMolecular Neurooncology laboratory. Molecular genetic alterations in infiltrative astrocytic tumors . The genetic aberrations identified accumulate in a fixed percentage of tumors at each stage of malignancy. The proportion of tumors with mutations characteristic of less anaplastic tumors remains constant as anaplasticity increases. Thus, astrocytic tumors vary with respect to the subset of these mutations which are detected. Neoplastic cells are clonal. Abbreviations: LOH = loss of heterozygosity, p = short arm of chromosome, q = long arm of chromosome, Rb = retinoblastoma gene, EGFr = epidermal growth factor receptor. DAFTAR PUSTAKA " id="pdf-obj-6-14" src="pdf-obj-6-14.jpg">

    Molecular genetic alterations in infiltrative astrocytic tumors . The genetic aberrations identified accumulate in a fixed percentage of tumors at each stage of malignancy. The proportion of tumors with mutations characteristic of less anaplastic tumors remains constant as anaplasticity increases. Thus, astrocytic tumors vary with respect to the subset of these mutations which are detected. Neoplastic cells are clonal. Abbreviations: LOH = loss of heterozygosity, p = short arm of chromosome, q = long arm of chromosome, Rb = retinoblastoma gene, EGFr = epidermal growth factor receptor.

    DAFTAR PUSTAKA