Current methods of diagnosis and treatment of medulloblastoma, and the influence of new biological advances in the development of more effective and less toxic therapies are reviewed by researchers at Children’s National Medical Center, The George Washington University, Washington, DC. Medulloblastoma accounts for 16% of all pediatric brain tumors, and 40% of cerebellar tumors. The incidence peaks bimodally at 3 to 4 and 8 to 9 years of age. Associated disorders in 1-2% of patients include a nevoid basal carcinoma (Gorlin’s syndrome), and familial adenomatous polyposis (Turcot’s syndrome). CNS dissemination in 11-43% of patients, especially infants, is a predictor of poor outcome. Diagnosis is made on clinical presentation (vomiting 67%, headache 60%, ataxia 40%), CT findings of midline, homogeneous, contrast-enhancing cerebellar vermian mass in 30-55% patients, and MRI showing a heterogeneous hypointense mass on T1-weighted imaging. T2- weighted sequences are intermediate between grey and white matter. Drop metastases having a “zuckerguss” (icing sugar) appearance occur in up to 40% patients, in spinal MRIs. Magnetic resonance spectroscopy (MRS) determines the biochemical composition of the tumor (increase in choline and decreased N-acetyl aspartate and taurine). SPECT helps differentiate postradiation changes and tumor recurrence. Changes in diffusion tensor imaging after treatment are associated with poor intellectual outcome. Variants of medulloblastoma (classic, desmoplastic, anaplastic large cell, and nodular) are distinguished only by histological examination. Staging (M0-M4) and risk stratification are crucial in management, and are determined by lumbar CSF analysis and MRI. Risk is based on age, extent of disease, and dissemination.

Advances in molecular biology show that medulloblastoma arises from two germinomal zones of the cerebellum, the ventricular zone for midline tumors, and the external granular layer for lateral desmoplastic tumors. Research involving the signal transduction mechanisms that promote oncogenesis includes sonic hedgehog (Shh), wingless (Wnt) growth factor receptors, receptor tyrosine kinases, retinoids that induce apoptosis, and notch and CXCR4 signalling ligands and inhibitors of apoptosis proteins that are associated with a poor prognosis. Determining the mechanisms of signal transduction in neurooncogenesis and the genetics of medulloblastoma will aid the development of more specifically targeted therapies. [1]

COMMENT. The addition of chemotherapy in the past 2-3 decades has increased the survival rate compared to surgical resection and radiotherapy alone. Controversial methods of management include total tumor resection that might account for the increased incidence of posterior fossa mutism; whole body radiation that causes long-term intellectual deterioration; and the incorporation of biological therapeutics in combination with radiation or chemotherapy. Altered classification of tumors based on more advanced neuroimaging may explain an apparent improvement in survival rates in response to new treatments.