Medulloblastoma 3994623 224067196 2008-07-07T04:11:44Z 62.104.74.27 {{Infobox_Disease | Name = {{PAGENAME}} | Image = CompT.jpg| Caption = CT scan, showing a tumorous mass in the [[posterior fossa]], giving rise to obstructive [[hydrocephalus]], in a six year old girl.| DiseasesDB = 31105 | ICD10 = | ICD9 = | ICDO = 9470/3 | OMIM = 155255 | MedlinePlus = | eMedicineSubj = neuro | eMedicineTopic = 624 | eMedicine_mult = {{eMedicine2|ped|1396}} {{eMedicine2|radio|434}} | MeshID = D008527 | }} '''Medulloblastoma''' is a highly [[malignant]] primary [[brain tumor]] that originates in the [[cerebellum]] or [[posterior cranial fossa|posterior fossa]]. Originally considered to be a [[glioma]], medulloblastoma is now known to be of the family of cranial [[primitive neuroectodermal tumor]]s (PNET).<ref name="emed-medullo">George Jallo, MD, [http://emedicine.com/neuro/topic624.htm Medulloblastoma], eMedicine 2007.</ref> Tumors that originate in the cerebellum are referred to as [[infratentorial neoplasms|infratentorial]] because they occur below the [[tentorium cerebelli|tentorium]], a thick membrane that separates the [[cerebral hemispheres]] of the brain from the cerebellum. Another term for medulloblastoma is infratentorial PNET. Medulloblastoma is the most common PNET originating in the brain.<ref>Chris Hinz, Deneen Hesser, [http://hope.abta.org/mdl Focusing On Brain Tumors: Medulloblastoma], American Brain Tumor Association 2006, ISBN 0-944093-67-1.</ref> All PNET tumors of the brain are invasive and rapidly growing tumors that, unlike most brain tumors, spread through the [[cerebrospinal fluid]] (CSF) and frequently metastasize to different locations in the brain and spine. ==Incidence== [[Brain tumor]]s are the second most common malignancy among children less than 20 years of age. Medulloblastoma is the most common malignant brain tumor, comprising 14.5% of newly diagnosed cases.<ref name="seer">James G. Gurney, Malcolm A. Smith, Greta R. Bunin, [http://seer.cancer.gov/publications/childhood/cns.pdf CNS and Miscellaneous Intracranial and Intraspinal Neoplasms], SEER Pediatric Monograph, National Cancer Institute</ref> In adults, medulloblastoma is rare, comprising less than 2% of CNS malignancies.<ref>[http://cbtrus.org/2005-2006/tables/2006.table12.pdf Selected Primary Brain and Central Nervous System Tumor Age-Specific Incidence Rates], Central Brain Tumor Registry of the United States, 1998-2002.</ref> The incidence of childhood medulloblastoma is higher in males (62%) than females (38%). <ref>[http://cbtrus.org/2005-2006/tables/2006.table13.pdf Selected Childhood Primary Brain and Central Nervous System Tumor Incidence Rates by Major Histology Groupings, Histology and Gender] Central Brain Tumor Registry of the United States, 1998-2002.</ref> Medulloblastoma and other PNET tumors are more prevalent in younger children than older children. 40% of medulloblastoma patients are diagnosed before the age of 5, 31% are between the ages of 5 and 9, 18.3% are between the ages of 10 and 14, and 12.7% are between the ages of 15 and 19. <ref>[http://cbtrus.org/2005-2006/tables/2006.table15.pdf Selected Childhood Primary Brain and Central Nervous System Tumor Age-Specific Incidence Rates], Central Brain Tumor Registry of the United States, 1998-2002.</ref> ==Pathogenesis== Medulloblastomas usually form in the fourth ventricle, between the brainstem and the cerebellum. Tumors with similar appearance and characteristics originate in other parts of the brain, but they are not identical to medulloblastoma. <ref>Roger Packer M.D, [http://virtualtrials.com/medullo.cfm Medulloblastoma] Clinical Trials and Noteworthy Treatments for Brain Tumors 2002.</ref> Although it is thought that medulloblastomas originate from immature or embryonal cells at their earliest stage of development, the exact cell of origin, or "medulloblast" has yet to be identified.{{Fact|date=March 2008}} It is currently thought that medulloblastoma arises from cerebellar "stem cells" that have been prevented from dividing and differentiating into their normal cell types. This accounts from the varying histologic variants seen on biopsy. '''Rosette''' formation is highly characteristic of medulloblastoma and is seen in up to half of the cases. Molecular genetics reveal a loss of genetic information on the distal part of chromosome 17, distal to the ''[[p53]]'' gene, possibly accounting for the neoplastic transformation of the undifferentiated cerebellar cells. Medulloblastomas are also seen in [[Gorlin syndrome]] as well as [[Turcot syndrome]]. Another research has strongly implicated the [[JC virus]], the virus that causes [[progressive multifocal leukoencephalopathy|multifocal leukoencephalopathy]]. ==Clinical manifestation== Symptoms are mainly due to secondary increased [[intracranial pressure]] due to blockage of the [[fourth ventricle]] and are usually present for 1 to 5 months before diagnosis is made. The child typically becomes ''listless'', with repeated episodes of ''vomiting'', and a ''morning headache'', which may lead to a misdiagnosis of gastrointestinal disease or migraine. Soon, the child will develop a ''stumbling gait'', ''frequent falls'', ''[[diplopia]]'', ''[[papilledema]]'', and ''sixth cranial nerve palsy''. ''Positional dizziness'' and ''[[nystagmus]]'' are also frequent and facial sensory loss or motor weakness may be present. [[Decerebrate]] attacks appear late in the disease. Extraneural metastases to the rest of the body is rare, but usually only after [[craniotomy]]. ==Diagnosis== The tumor is distinctive on T1 and T2-weighted [[MRI]] with heterogeneous enhancement and typical location adjacent to and extension into the fourth ventricle. Histologically, the tumor is solid, pink-gray in color, and is well circumscribed. The tumor is very cellular, many mitoses, little cytoplasm, and has the tendency to form clusters and rosettes. Correct diagnosis of medulloblastoma may require ruling out [[ATRT|atypical teratoid rhabdoid tumor]] (ATRT)<ref>{{cite journal | author = Burger PC | coauthors = Yu I, Tihan T, et al | year = 1998 | title = Atypical teratoid rhabdoid tumors of the central nervous system: a highly malignant tumor of infancy and childhood frequently mistaken for medulloblastoma: a Pediatric Oncology Group Study. | journal = Am J Surg Pathol 1998 | issue = 22: | pages = 1083–92 | language = English | doi = 10.1097/00000478-199809000-00007 }}</ref> and [[primitive neuroectodermal tumor]] (PNET). == Treatment and prognosis== Treatment begins with maximal resection of the tumor. The addition of ''radiation'' to the entire neuraxis and [[chemotherapy]] may increase the disease-free survival. This combination may permit a 5 year survival in more than 80% of cases. The presence of desmoplastic features such as connective tissue formation offers a better prognosis. Prognosis is worse if child is less than 3 years old, inadequate degree of resection, or if presence of any CSF, spinal, supratentorial or systemic spread. Increase intracranial pressure may be controlled with [[corticosteroids]] or a ventriculoperitoneal [[shunt (medical)|shunt]] {{main|intracranial pressure}} ==Model== Using gene transfer of SV40 large T-antigen in neuronal precursor cells of rats, a brain tumor model was established. The PNETs were histologically indistinguashabe from the human counterparts and have been used to identify new genes involved in human brain tumor carcinogenesis. <ref>Eibl RH, Kleihues P, Jat PS, Wiestler OD (1994) A model for primitive neuroectodermal tumors in transgenic neural transplants harboring the SV40 large T antigen. Am J Pathol. 1994 Mar;144(3):556-64.</ref>. The model was used to confirm p53 as one of the genes involved in human medulloblastomas, but since only about 10 % of the human tumors showed mutations in that gene, the model can be used to identify the other binding partners of SV40 Large T- antigen, other than p53. <ref>Ohgaki H, Eibl RH, Wiestler OD, Yasargil MG, Newcomb EW, Kleihues P: p53 mutations in nonastrocytic human brain tumors. Cancer Res (1991) 51:6202-5</ref> ==References== {{Reflist|2}} ==See also== *[[List of notable brain tumor resources]] *[[List of notable childhood cancer resources]] ==External links== * [http://www.braintumourtrust.co.uk Samantha Dickson Brain Tumour Trust: brain tumour research and support charity] * [http://www.ninds.nih.gov/disorders/brainandspinaltumors/detail_brainandspinaltumors.htm Brain and Spinal Tumors: Hope Through Research (National Institute of Neurological Disorders and Stroke)] * [http://www.medulloblastoma.org Medulloblastoma support resources] * {{Chorus|00905}} *[http://www.kidcancer.org/ HELP KIDS NOW WITH MEDULLOBLASTOMA] {{Nervous tissue tumors}} [[Category:Neurology]] [[Category:Neurosurgery]] [[Category:Types of cancer]] [[de:Medulloblastom]] [[nl:Medulloblastoom]] [[ja:髄芽腫]] [[pl:Rdzeniak]]