Medulloblastoma

Background

Medulloblastomas are the most common malignant brain tumor of childhood and occur exclusively in the cerebellum.

Medulloblastoma is the most common malignant brain tumor of childhood, accounting for approximately 20 percent of all primary tumors of the central nervous system among children less than 19 years of age.  Approximately 500 children are diagnosed with a medulloblastoma each year in the United States. The peak incidence is between five and nine years of age. ¹

Associated symptoms

 Patients with medulloblastoma present with a combination of signs and symptoms evolving over a period of weeks to a few months. 

• increased intracranial pressure
  • ​pressure inside the skull can leads to nocturnal or morning headaches, nausea, vomiting, and altered mental status
  • prolonged elevation of intracranial pressure which can lead to papilledema and complete or partial loss of vision.
  •  infants may present with irritability, anorexia, and developmental delay.
• cerebellar dysfunction
  • tumors in the midline may cause gait ataxia or truncal instability, whereas tumors in the lateral cerebellar hemispheres are more likely to cause limb clumsiness or incoordination.

Physical examination

Neurologic exam findings depend upon the location of the tumor within the posterior fossa. Cranial nerve deficits may occur in conjunction with these signs, either from direct involvement of specific nerves or from cranial nerve dysfunction due to increased intracranial pressure. As an example, elevated intracranial pressure can induce dysfunction of the abducens nerves, causing diplopia especially with lateral gaze.

Differential diagnosis

Differential for a brain tumor in the posterior fossa mass in a child includes:

• pilocytic astrocytoma
• lymphoma
• ependymoma
• atypical teratoid/rhabdoid tumors (ATRT)

While each of these entities is ultimately distinguished based on surgical pathology, certain imaging findings can help to point to one tumor over another

Neuroimaging

Magnetic resonance imaging (MRI) is the best imaging modality.  It reveals a contrast-enhancing midline or paramedian cerebellar tumor which often compresses the fourth ventricle leading to enlarged ventricles due to obstruction.  It is important to note that medulloblastomas may be missed on computed tomography (CT) scan. The classic CT finding is a contrast enhancing hyperdense mass - a very nonspecific finding.  Regardless, without tissue, radiologist speculate as to the type of tumor based on pattern – only tissue can diagnosis cancer. 

CT scan, showing a tumorous mass in the posterior fossa, giving rise to obstructive hydrocephalus, in a six-year-old girl https://en.wikipedia.org/wiki/Medulloblastoma

For more MRI images, click here

Staging of disease

Approximately one-third of medulloblastomas metastasize. After brain MRIs suggest a brain tumor, spine MRI and lumbar puncture for cerebrospinal fluid (CSF) cytology should be performed as to assess the extent of disease evaluation. Pathologic examination of the CSF and radiologic review of spinal MRI may suggest spread cancer cells spread throughout the central nervous system following cerebral spinal fluid (CSF) pathways including the leptomeninges.  The combination of both tests is more sensitive than either one individually ³

Given the increased intracranial pressure, many patients are not candidates for a lumbar puncture prior to surgery. In this case, it is important to wait two weeks to avoid potential contamination with surgical debris. Ideally spine MRI should be performed preoperatively or two weeks after the surgery with the spinal tap.

There are a variety of staging modalities for medulloblastoma.  One of the best know is the modified Chang system which is based on the size of the primary tumor and the extent of nervous system and extraneural spread. ⁵

 Histologic Findings

Medulloblastomas are undifferentiated embryonal neuroepithelial tumors (often called small blue cell tumor) of the cerebellum. They are highly cellular, soft, and friable tumors composed of cells with deeply basophilic nuclei of variable size and shape, little discernible cytoplasm, and often abundant mitoses (see the images below). These tumors express neuronal and neuroendocrine markers, including synaptophysin and neurofilament proteins.

Treatment

Ideally, directed therapy against the tumor is a combination of surgical resection, radiation therapy as the site of the tumor as well as along the spine, and systemic chemotherapy. 

Surgery

Surgical resection confirms diagnosis, relieves intracranial pressure and improves survival.  Safe resection is a key component of the treatment of all patients with medulloblastoma, because of the potential for neurologic complications, total resection is not always possible. 

Radiation therapy

Radiation therapy is an integral component of therapy and generally used after surgery.  It is used to treat residual tumor at the primary site as well as any spread to the craniospinal axis. Toxicity to the brain and spine limits the dosages used in therapy.  For most infants, radiation therapy is not recommended as the toxicity dose is so low. 

Chemotherapy

In average risk and young children, chemotherapy regimens (likely specific to institution_ are used following surgery and radiation.  However in cases that are not amenable to surgical resection, high dose chemotherapy combined with radiation therapy is used in high-risk disease. 

Increased intracranial pressure

The optimal initial treatment of patients with medulloblastoma combines directed therapy against the tumor as well as therapy directed at alleviating increased intracranial pressure.  Placement of a cerebrospinal fluid (CSF) shunt to relieve hydrocephalus can be done before or during surgery depending on the patient. 

Physical therapy

Multidisciplinary rehabilitative services are recommended for all patients after initial therapy. Individualized Educational Plans (IEP) often are required when patients return to school.  ²

Recurrent disease

Despite the improved treatment and prognosis, an estimated 20 to 30 percent will relapse following their initial treatment.  Relapses tend to be local in approximately one third of patients, disseminated (brain or spine) in one third, and both local and disseminated in the remaining third.  Most relapses occur in the firs three years after diagnosis and treatment and survival rates decreases substantially when recurrent disease is found.⁶

Medullobastomas are associated with a number of syndromes, including:

• Coffin-Siris
• Cowden
•  Gardner
• Li-Fruameni
• Turcot

References

1.         Bartlett, F., Kortmann, R. & Saran, F. Medulloblastoma. Clin. Oncol. R. Coll. Radiol. G. B. 25, 36–45 (2013).

2.         Martin, A. M., Raabe, E., Eberhart, C. & Cohen, K. J. Management of pediatric and adult patients with medulloblastoma. Curr. Treat. Options Oncol. 15, 581–594 (2014).

3.         Fouladi, M. et al. Comparison of CSF cytology and spinal magnetic resonance imaging in the detection of leptomeningeal disease in pediatric medulloblastoma or primitive neuroectodermal tumor. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 17, 3234–3237 (1999).

4.         Medulloblastoma | American Brain Tumor Association. at <http://www.abta.org/brain-tumor-information/types-of-tumors/medulloblast...

5.         C.H. Chang, E.M. Housepian, C. Herbert Jr. An operative staging system and a megavoltage radiotherapeutic technique for cerebellar medulloblastomas Radiology. (1969).

6.         Aref, D. & Croul, S. Medulloblastoma: recurrence and metastasis. CNS Oncol. 2, 377–385 (2013).