Medulloblastoma: Background, Pathophysiology, Epidemiology

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Sections Medulloblastoma
Overview
Presentation
- History
- Physical
- Causes
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Treatment
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References

Overview

Background

First used by Bailey and Cushing in 1925^[1], the term medulloblastoma described a series of tumors found in the cerebella of children. Originally classified as a glioma, medulloblastoma is referred to now as a primitive neuroectodermal tumor (PNET). This tumor accounts for approximately 7-8% of all intracranial tumors and 30% of pediatric brain tumors.

Pathophysiology

In the brain, medulloblastoma most often arises in the posterior fossa as shown in the image below. The tumor has the propensity of spreading throughout the CNS. Systemic metastases of this tumor, especially to bone, also have been recognized.

CT scan demonstrates a hyperdense lesion within the posterior fossa of an 8-year-old boy who presented with nausea and vomiting.

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Frequency

United States

Incidence of medulloblastoma is 1.5-2 cases per 100,000 population, with 350 new cases in the United States each year. Although the majority occur as sporadic cases, hereditary conditions have been associated with medulloblastoma, including (1) Gorlin syndrome (nevoid basal cell carcinoma syndrome), (2) blue rubber-bleb nevus syndrome, (3) Turcot syndrome (eg, glioma polyposis syndrome), and (4) Rubinstein-Taybi syndrome.

International

Incidence of medulloblastoma worldwide seems to approximate that in the United States.

Mortality/Morbidity

See the list below:

Hydrocephalus: The most common complication is hydrocephalus due to compression of the normal cerebrospinal fluid (CSF) pathways. Although this is a common complication, only 10-50% of patients with preoperative hydrocephalus will need a long-term ventricular shunt. Some children can be treated with an endoscopic third ventriculostomy.
Cerebellar dysfunction: Tumor infiltration of the cerebellum usually is in the midline, leading to difficulties with ambulation and truncal ataxia. This is more common than signs attributable to the cerebellar hemisphere (eg, extremity dysmetria).
Leptomeningeal dissemination: One of the most feared complications of medulloblastoma is dissemination within the CSF. Medical and, less commonly, surgical therapy must be directed at controlling dissemination to cranial nerves and spinal cord and related structures. This dissemination of disease portends to a high-risk stratification.

Race

No specific predilection for a particular racial or ethnic group has been noted.

Sex

Medulloblastoma is more common in males than females (1.5:1). Males also tend to have a poorer prognosis.

Age

Although predominantly a pediatric tumor, medulloblastoma can affect patients of any age from neonates to the elderly. Three quarters of all cases occur in children, with a median age of 9 years.

Clinical Presentation

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Haddy N, Mousannif A, Tukenova M, et al. Relationship between the brain radiation dose for the treatment of childhood cancer and the risk of long-term cerebrovascular mortality. Brain. 2011 May. 134:1362-72. [Medline].
Martin AM, Raabe E, Eberhart C, Cohen KJ. Management of Pediatric and Adult Patients with Medulloblastoma. Curr Treat Options Oncol. 2014 Sep 7. [Medline].
Adamski J, Ramaswamy V, Huang A, Bouffet E. Advances in managing medulloblastoma and intracranial primitive neuro-ectodermal tumors. F1000Prime Rep. 2014. 6:56. [Medline]. [Full Text].
Albright AL, Wisoff JH, Zeltzer PM, Boyett JM, Rorke LB, Stanley P. Effects of medulloblastoma resections on outcome in children: a report from the Children's Cancer Group. Neurosurgery. 1996 Feb. 38(2):265-71. [Medline].
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Blaser SI, Harwood-Nash DC. Neuroradiology of pediatric posterior fossa medulloblastoma. J Neurooncol. 1996 Jul. 29(1):23-34. [Medline].
Carrie C, Muracciole X, Gomez F, et al. Conformal radiotherapy, reduced boost volume, hyperfractionated radiotherapy, and online quality control in standard-risk medulloblastoma without chemotherapy: results of the French M-SFOP 98 protocol. Int J Radiat Oncol Biol Phys. 2005 Nov 1. 63(3):711-6. [Medline].
Chang CH, Housepian EM, Herbert C. An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology. 1969 Dec. 93(6):1351-9. [Medline].
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Dennis M, Spiegler BJ, Hetherington CR, et al. Neuropsychological sequelae of the treatment of children with medulloblastoma. J Neurooncol. 1996 Jul. 29(1):91-101. [Medline].
Dufour C1, Kieffer V, Varlet P, Raquin MA, Dhermain F, Puget S, et al. Tandem high-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high-risk medulloblastoma or supratentorial primitive neuro-ectodermic tumors. [Full Text].
Dunkel IJ, Boyett JM, Yates A, Rosenblum M, Garvin JH Jr, Bostrom BC, et al. High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. Children's Cancer Group. J Clin Oncol. 1998 Jan. 16(1):222-8. [Medline].
Friedberg MH, David O, Adelman LS. Recurrence of medulloblastoma: violation of Collins' law after two decades. Surg Neurol. 1997 Jun. 47(6):571-4. [Medline].
Giordana MT, Cavalla P, Dutto A, et al. Is medulloblastoma the same tumor in children and adults?. J Neurooncol. 1997 Nov. 35(2):169-76. [Medline].
Giordana MT, Migheli A, Pavanelli E. Isochromosome 17q is a constant finding in medulloblastoma. An interphase cytogenetic study on tissue sections. Neuropathol Appl Neurobiol. 1998 Jun. 24(3):233-8. [Medline].
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Giralt J, SÃ¡nchez de Toledo J, Moraga F, et al. Improving survival of medulloblastoma: results in two groups of patients. Oncology. 1996 Jan-Feb. 53(1):38-42. [Medline].
Hutzen B, Bid HK, Houghton PJ, Pierson CR, Powell K, Bratasz A, et al. Treatment of medulloblastoma with oncolytic measles viruses expressing the angiogenesis inhibitors endostatin and angiostatin. March,19,2014. [Full Text].
Hye Sook Min,* Ji Yeoun Lee,† Seung-Ki Kim,† and Sung-Hye Park*‡. Genetic Grouping of Medulloblastomas by Representative Markers in Pathologic Diagnosis1. [Full Text].
Jenkin D. The radiation treatment of medulloblastoma. J Neurooncol. 1996 Jul. 29(1):45-54. [Medline].
Kiltie AE, Lashford LS, Gattamaneni HR. Survival and late effects in medulloblastoma patients treated with craniospinal irradiation under three years old. Med Pediatr Oncol. 1997 May. 28(5):348-54. [Medline].
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Miralbell R, Bieri S, Huguenin P, et al. Prognostic value of cerebrospinal fluid cytology in pediatric medulloblastoma. Swiss Pediatric Oncology Group. Ann Oncol. 1999 Feb. 10(2):239-41. [Medline].
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Pollack IF, Polinko P, Albright AL, et al. Mutism and pseudobulbar symptoms after resection of posterior fossa tumors in children: incidence and pathophysiology. Neurosurgery. 1995 Nov. 37(5):885-93. [Medline].
Rajurkar M1, Huang H, Cotton JL, Brooks JK, Sicklick J, McMahon AP, et al. Distinct cellular origin and genetic requirement of Hedgehog-Gli in postnatal rhabdomyosarcoma genesis. [Full Text].
Rossi A, Caracciolo V, Russo G, Reiss K, Giordano A. Medulloblastoma: from molecular pathology to therapy. Clin Cancer Res. 2008 Feb 15. 14(4):971-6. [Medline].
Rutka JT, Hoffman HJ. Medulloblastoma: a historical perspective and overview. J Neurooncol. 1996 Jul. 29(1):1-7. [Medline].
Saran FH, Driever PH, Thilmann C, et al. Survival of very young children with medulloblastoma (primitive neuroectodermal tumor of the posterior fossa) treated with craniospinal irradiation. Int J Radiat Oncol Biol Phys. 1998 Dec 1. 42(5):959-67. [Medline].
Schmandt S, Kuhl J. Chemotherapy as prophylaxis and treatment of meningosis in children less than 3 years of age with medulloblastoma. J Neurooncol. 1998 Jun-Jul. 38(2-3):187-92. [Medline].
Sure U, Berghorn WJ, Bertalanffy H. Collins' law. Prediction of recurrence or cure in childhood medulloblastoma?. Clin Neurol Neurosurg. 1997 May. 99(2):113-6. [Medline].
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Media Gallery

CT scan demonstrates a hyperdense lesion within the posterior fossa of an 8-year-old boy who presented with nausea and vomiting.
T1-weighted sagittal MRI of an 8-year-old boy who presented with nausea and vomiting reveals an enhancing tumor within the fourth ventricle. The child underwent a suboccipital craniotomy and resection of his medulloblastoma.
T1-weighted sagittal MRI of 4-year-old boy who presented with gait ataxia and precocious puberty. MRI shows a heterogenous enhancing tumor located within the fourth ventricle with marked hydrocephalus.
T1-weighted axial MRI shows heterogeneous enhancement of the medulloblastoma in a 4-year-old boy who presented with gait ataxia and precocious puberty.
Coronal MRI confirms the presence of the tumor within the fourth ventricle of a 4-year-old boy who presented with gait ataxia and precocious puberty.
High-power magnification hematoxylin and eosin (H&E) section of a typical medulloblastoma

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Author

George I Jallo, MD Professor of Neurosurgery, Pediatrics, and Oncology, Director, Clinical Pediatric Neurosurgery, Department of Neurosurgery, Johns Hopkins University School of Medicine

George I Jallo, MD is a member of the following medical societies: American Association of Neurological Surgeons, American Medical Association, American Society of Pediatric Neurosurgeons

Disclosure: Nothing to disclose.

Coauthor(s)

David A Chesler, MD, PhD Clinical Assistant Professor of Neurological Surgery and Pediatrics, Stony Brook University Hospital; Co-Director of Pediatric Neurosurgery, New York Spine and Brain Surgery, UFPC

David A Chesler, MD, PhD is a member of the following medical societies: American Association of Neurological Surgeons, American Medical Association, Congress of Neurological Surgeons, International Society of Pediatric Neurosurgery, Medical Society of the State of New York, Suffolk Pediatric Society

Disclosure: Nothing to disclose.

Faisal A Almayman, MBBS Post Doctorate Research Fellow, Department of Neurosurgery, Johns Hopkins University School of Medicine

Faisal A Almayman, MBBS is a member of the following medical societies: American Association of Neurological Surgeons, Saudi Stroke Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Kenneth J Mack, MD, PhD Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic

Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, Society for Neuroscience

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock (managed by a financial services company) in AbbVie, Allergan, Celgene, Cellectar Biosciences, Danaher Corp, Mckesson.

Additional Contributors

Raj D Sheth, MD Chief, Division of Pediatric Neurology, Nemours Children's Clinic; Professor of Neurology, Mayo College of Medicine; Professor of Pediatrics, University of Florida College of Medicine

Raj D Sheth, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Neurological Association, Child Neurology Society

Disclosure: Nothing to disclose.

Acknowledgements

Alvin Marcovici, MD Consulting Staff, Southcoast Neurosurgery

Alvin Marcovici, MD is a member of the following medical societies: American Association of Neurological Surgeons, Congress of Neurological Surgeons, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Sections Medulloblastoma
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Medication
Follow-up
Media Gallery
References

Medulloblastoma

Background

Pathophysiology

Epidemiology

Frequency

Mortality/Morbidity

Race

Sex

Age

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Medulloblastoma

Background

Pathophysiology

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Mortality/Morbidity

Race

Sex

Age

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