Introduction
Background
First used by Bailey and Cushing in 19251 , 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. The tumor has the propensity of spreading throughout the CNS. Systemic metastases of this tumor, especially to bone, also have been recognized.
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
- 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
History
- Hydrocephalus
- Patients with medulloblastoma most commonly have symptoms related to increased intracranial pressure (as a consequence of hydrocephalus). Symptoms usually precede presentation by no more than 2 months.
- Presenting symptoms are related to the age of the patient.
- The younger, nonverbal patient presents with behavioral change.
- Symptoms in younger children include listlessness, irritability, vomiting, and decreased social interactions.
- Older children and adults complain of headache, especially upon awakening in the morning.
- Vomiting without nausea is more common in the morning, since being recumbent (eg, sleeping) increases intracranial pressure.
- Often, symptoms of headache and vomiting prompt an extensive and lengthy workup of the gastrointestinal tract prior to consideration of the CNS.
- Patients may develop double vision as the sixth cranial nerve becomes stretched from the hydrocephalus. Visual disturbances more commonly are a result of papilledema.
- Cerebellar symptoms
- Most commonly found in children, the tumor involves the cerebellar vermis and causes gait ataxia more readily than unilateral symptoms.
- Adults more commonly harbor the desmoplastic variant of medulloblastoma, which arises in the cerebellar hemisphere. These patients often have symptoms of ipsilateral dysmetria.
- Head tilt and neck stiffness, caused by meningeal irritation, are complications of tonsillar herniation below the foramen magnum.
- Alternatively, head tilt can result from trochlear nerve palsy caused by direct tumor compression.
- Leptomeningeal dissemination
- Presenting symptoms rarely are related to dissemination of tumor in the CSF.
- Patients can complain of severe weakness from tumor compression of the spinal cord or nerve roots (eg, radiculopathy).
Physical
- Physiognomy
- Increasing head circumference often is the only presenting symptom in infants.
- These infants have full anterior fontanelles with widely split cranial sutures.
- Funduscopic examination
- Visual difficulty usually is due to papilledema; however, it also may originate from cranial nerve palsy.
- Some studies have found papilledema (the most common physical finding) to be present in as many as 90% of patients.
- Extraocular examination
- As a consequence of hydrocephalus, the sixth cranial nerve can be compressed at the petroclival ligament, resulting in diplopia and lateral gaze paresis.
- Fourth cranial nerve palsy can be detected on careful extraocular examination and should be considered in any patient with a head tilt.
- Patients with fourth cranial nerve dysfunction have greatest difficulty when eyes are rotated medially and depressed (eg, going down stairs). The fourth cranial nerve usually is compressed by direct tumor extension into the cerebral aqueduct.
- Examination of the extraocular muscles may detect nystagmus, which, although nonspecific, can be related to a lesion of the cerebellar vermis.
- Cerebellar signs
- Medulloblastoma most commonly is located midline. Therefore, unilateral dysmetria is less common than either truncal ataxia or a wide-based gait. Latter symptoms are easily observable on tandem gait.
- As stated previously, desmoplastic medulloblastoma is more common in adults and usually arises in the cerebellar hemisphere.
- Signs of ipsilateral cerebellar dysfunction in the arm or the leg are more common in this subtype.
- Torticollis: Head tilt can be a manifestation of either foramen magnum involvement or fourth cranial nerve palsy.
Causes
Debate exists over the cellular origin of medulloblastoma.
- One hypothesis is that the tumor is derived from cells of the external granular layer of the cerebellum.
- Medulloblastoma cells are cytologically similar to cells of the external granular layer.
- This is an area of germ cell origin that persists for the first year of life before involuting.
- Another proposed source of medulloblastoma is the posterior medullary velum, from which undifferentiated cells migrate to the external granular layer. These cells persist only for a short time after birth.
More on Medulloblastoma |
 Overview: Medulloblastoma |
| Differential Diagnoses & Workup: Medulloblastoma |
| Treatment & Medication: Medulloblastoma |
| Follow-up: Medulloblastoma |
| Multimedia: Medulloblastoma |
| References |
| Next Page » |
References
Bailey P, Cushing H. A common type of midcerebellar glioma of childhood. Arch Neurol Psychiatr. 1925;14:192-224.
Rorke LB. The cerebellar medulloblastoma and its relationship to primitive neuroectodermal tumors. J Neuropathol Exp Neurol. Jan 1983;42(1):1-15. [Medline].
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. Feb 1996;38(2):265-71. [Medline].
Allen JC, Epstein F. Medulloblastoma and other primary malignant neuroectodermal tumors of the CNS. The effect of patients' age and extent of disease on prognosis. J Neurosurg. Oct 1982;57(4):446-51. [Medline].
Ater JL, van Eys J, Woo SY, et al. MOPP chemotherapy without irradiation as primary postsurgical therapy for brain tumors in infants and young children. J Neurooncol. May 1997;32(3):243-52. [Medline].
Bailey CC, Gnekow A, Wellek S, et al. Prospective randomised trial of chemotherapy given before radiotherapy in childhood medulloblastoma. International Society of Paediatric Oncology (SIOP) and the (German) Society of Paediatric Oncology (GPO): SIOP II. Med Pediatr Oncol. Sep 1995;25(3):166-78. [Medline].
Balter-Seri J, Mor C, Shuper A, et al. Cure of recurrent medulloblastoma: the contribution of surgical resection at relapse. Cancer. Mar 15 1997;79(6):1241-7. [Medline].
Blaser SI, Harwood-Nash DC. Neuroradiology of pediatric posterior fossa medulloblastoma. J Neurooncol. Jul 1996;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. Nov 1 2005;63(3):711-6. [Medline].
Chang CH, Housepian EM, Herbert C. An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology. Dec 1969;93(6):1351-9. [Medline].
Cohen BH, Packer RJ. Chemotherapy for medulloblastomas and primitive neuroectodermal tumors. J Neurooncol. Jul 1996;29(1):55-68. [Medline].
Dennis M, Spiegler BJ, Hetherington CR, et al. Neuropsychological sequelae of the treatment of children with medulloblastoma. J Neurooncol. Jul 1996;29(1):91-101. [Medline].
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. Jan 1998;16(1):222-8. [Medline].
Friedberg MH, David O, Adelman LS. Recurrence of medulloblastoma: violation of Collins' law after two decades. Surg Neurol. Jun 1997;47(6):571-4. [Medline].
Giordana MT, Cavalla P, Dutto A, et al. Is medulloblastoma the same tumor in children and adults?. J Neurooncol. Nov 1997;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. Jun 1998;24(3):233-8. [Medline].
Giordana MT, Schiffer P, Schiffer D. Prognostic factors in medulloblastoma. Childs Nerv Syst. Jun 1998;14(6):256-62. [Medline].
Giralt J, Sánchez de Toledo J, Moraga F, et al. Improving survival of medulloblastoma: results in two groups of patients. Oncology. Jan-Feb 1996;53(1):38-42. [Medline].
Jenkin D. The radiation treatment of medulloblastoma. J Neurooncol. Jul 1996;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. May 1997;28(5):348-54. [Medline].
Miralbell R, Bieri S, Huguenin P, et al. Prognostic value of cerebrospinal fluid cytology in pediatric medulloblastoma. Swiss Pediatric Oncology Group. Ann Oncol. Feb 1999;10(2):239-41. [Medline].
Pollack IF, Polinko P, Albright AL, et al. Mutism and pseudobulbar symptoms after resection of posterior fossa tumors in children: incidence and pathophysiology. Neurosurgery. Nov 1995;37(5):885-93. [Medline].
Rossi A, Caracciolo V, Russo G, Reiss K, Giordano A. Medulloblastoma: from molecular pathology to therapy. Clin Cancer Res. Feb 15 2008;14(4):971-6. [Medline].
Rutka JT, Hoffman HJ. Medulloblastoma: a historical perspective and overview. J Neurooncol. Jul 1996;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. Dec 1 1998;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. Jun-Jul 1998;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. May 1997;99(2):113-6. [Medline].
Sutton LN, Phillips PC, Molloy PT. Surgical management of medulloblastoma. J Neurooncol. Jul 1996;29(1):9-21. [Medline].
Tomita T. Medulloblastomas. In: Youmans JR, ed. Neurolgical Surgery. Vol 4. 5th ed. Philadelphia: WB Saunders; 1996:2570-92.
Weil MD, Lamborn K, Edwards MS, Wara WM. Influence of a child's sex on medulloblastoma outcome. JAMA. May 13 1998;279(18):1474-6. [Medline].
Weitman DM, Cogen PH. Contemporary management of medulloblastoma. Contemporary Neurosurgery. 1998;20(2):1-8.
Whelan HT, Krouwer HG, Schmidt MH, et al. Current therapy and new perspectives in the treatment of medulloblastoma. Pediatr Neurol. Feb 1998;18(2):103-15. [Medline].
Yang SY, Wang KC, Cho BK, et al. Radiation-induced cerebellar glioblastoma at the site of a treated medulloblastoma: case report. J Neurosurg. May 2005;102(4 Suppl):417-22. [Medline].
Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB, Milstein JM, et al. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study. J Clin Oncol. Mar 1999;17(3):832-45. [Medline].
Further Reading
Keywords
medulloblastoma, tumor, primitive neuroectodermal tumor, PNET, Gorlin syndrome, nevoid basal cell carcinoma syndrome, blue rubber-bleb nevus syndrome, Turcot syndrome, glioma polyposis syndrome, Rubinstein-Taybi syndrome
