Medulloblastoma

Introduction

Medulloblatoma is the most common posterior fossa (i.e. infratentorial) tumor in children (although some sources will state that it is the second most common behind cerebellar astrocytoma), making up approximately 18% of all primary pediatric brain tumors.

  • Note: In children, brain tumors are the most common solid tumor and the second most common malignancy (after leukemia). Approximately 60% of brain tumors are infratentorial, 25% are supratentorial, and 15% arise in the midline.

It is a fast-growing, high-grade, malignant tumor that often metastasizes through the CSF tract (“drop METs”), although it rarely has been reported to metastasize to extracranial sites

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Image from: http://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/brain_tumor/center/pediatric/tumors/

 

Presentation

  • 90% of medulloblastomas develop in the cerebellar vermis, which can lead to posterior vermis syndrome (truncal dystaxia, unbalanced gait, horizontal nystagmus)
  • Patients can present with signs of increased ICP: headaches that are typically worse in the morning and can awaken the patient from sleep, nausea and vomiting, visual disturbances, lethargy, decreased appetite, poor school performance due to drowsiness, papilledema
  • On imaging, there is a midline mass in the roof of the 4th ventricle that is typically associated with ventriculomegaly and hydrocephalus.
  • This mass, on imaging, is typically heterogenous, hypointense to grey matter, and enhancing after contrast administration on T1 images, iso- to hyperintense on T2/FLAIR, and have elevated choline and decreased NAA on MR Spectroscopy (MRS). Drop METs and leptomeningeal spread are often seen.

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Images from: http://radiopaedia.org/articles/medulloblastoma

 

Differential Diagnosis

  • Medulloblastoma
  • Pilocytic Astocytoma
  • Ependymoma
  • Atypical Teratoid/Rhabdoid Tumor (ATRT)

Histology

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Image from: http://www.pubcan.org/printicdotopo.php?id=41

  • Infratentorial primitive neuroectodermal tumor that is, by definition, malignant and invasive and thus classified as Grave IV by the WHO.
  • There are different histological subtypes of medulloblastoma classified by the World Health Organization: Classic, Desmoplastic, Nodular with Neuronal Differentiation, and Anaplastic/Large Cell
  • Highly cellular neoplasms composed of cells with small, hyperchromatic nuclei and little cytoplasm, classically called a “small blue cell tumor”
  • Homer Wright rosettes may be found, where the cells surround necrotic, more eosinophilic material
  • The primitive neuroectodermal origin can be confirmed with immunohistochemistry staining for synaptophysin, neuron-specific enolase, MAP-2, and class-III beta tubulin

Genetics

  • Most common cytogentic change found in medulloblastoma is a loss of chromosome 17p, and this is frequently accompanied by a duplication of the long arm resulting in an isochromosome 17q.
  • KCTD11 is a tumor suppressor gene on 17p that inhibits the sonic hedgehog (SHH) signaling pathway, which is important for cellular proliferation and differentiation during cerebellar development.
  • 4 subgroups are defined clinically by the predominant genetic abnormality and this classification system has more prognostic and predictive capability than the classical histological subtypes: wnt pathway activation (A), SHH pathway activation (B), N-MYC amplification (C), and FOXG1 or OTX2 (C or D).

Treatment

  • Medulloblastoma is a highly radiosensitive tumor. Treatment generally includes surgical resection, craniospinal radiation therapy, and chemotherapy.
  • Link to surgical resection video on YouTube: https://www.youtube.com/watch?v=P_vE4fymAdw

Prognosis Following Treatment

  • Depends on the size, subtype, and dissemination of the tumor at the time of diagnosis.
  • Currently average risk is defined as: age between 3 – 22 years at presentation, no or minimal (< 1.5 cm diameter) residual tumor by postoperatively imaging, and no evidence of metastatic spread within the neuraxis.
  • Although the mortality rate for children with brain tumors has decreased significantly over the last 40 years, deaths from childhood brain tumors are the highest among all childhood cancer deaths. There is also significant neurological morbidity associated with brain tumors.
  • With current therapies, 60-70% of children with average-risk medulloblastoma can be expected to be alive and free of disease five years after diagnosis. This number is even higher for patients who have tumors with favorable molecular phenotypes. Even in children with high-risk disease, effective therapy is possible and results in long-term disease control in as many as 65% of patients. Outcome for infants is poorer, but for those infants with localized disease at the time of diagnosis, survival rates in the 30-50% range are reported.

 

Complications of Childhood Brain Tumors

Long-term sequelae of childhood brain tumors are often from the effects of chemotherapy and/or radiation therapy.

Common complications include:

  • Neurocognitive defects
  • Attention Deficit Disorder
  • Learning disabilities
  • Stroke
  • Endocrine abnormalities

 

References

1. Crawford, J. Childhood Brain Tumors. Pediatrics in Review 2013; 34:2.

2. Medulloblastoma. American Brain Tumor Association. http://www.abta.org/secure/medulloblastoma-brochure.pdf

3. Northcott PA, Korshunov A, Witt H, et al. Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 2011; 29:1408.

4. Clinical Presentation, Diagnosis, and Risk Stratification of Medulloblastoma. UpToDate. http://www.uptodate.com/contents/clinical-presentation-diagnosis-and-risk-stratification-of-medulloblastoma?source=machineLearning&search=medulloblastoma&selectedTitle=2~53&sectionRank=1&anchor=H5791953#H5791953

5. MacDonald, TJ. And Packer, RJ. Pediatric Medulloblastoma. http://reference.medscape.com/article/987886-overview