Medulloblastoma – Symptoms, 10 Interesting Facts, Diagnosis, Treatment and Prognosis

10 Interesting Facts of Medulloblastoma

  1. Medulloblastoma is an aggressive brain tumor that arises from the fourth ventricle at the cerebellum and presents with signs of hydrocephalus and/or cerebellar dysfunction 
  2. Symptoms of medulloblastoma include progressively worsening headache, lethargy, vomiting, loss of balance and coordination, and visual impairment; clinical findings include ataxia, truncal instability, nystagmus, cranial nerve palsies, and papilledema
  3. Suspect diagnosis based on initial history and physical examination findings; MRI confirms cerebellar mass
  4. Medulloblastoma is a highly heterogeneous tumor, and definitive diagnosis requires pathologic confirmation after resection of tumor; patients are classified into risk stratification groups according to histologic variants, molecular subtypes, and overall risk (size, location, presence of metastasis, and age at time of presentation)
  5. Initial treatment includes general measures to reduce intracranial pressure and specific treatment to eliminate tumor burden
  6. Preferred approach to tumor-directed therapy includes a combined approach with maximum safe surgical resection, postoperative radiotherapy, and chemotherapy
  7. Radiotherapy is the most important modality for cure, because medulloblastoma is a highly radiation-sensitive tumor with a propensity to spread along the cerebrospinal fluid pathway; metastasis outside the cerebrospinal fluid is rare 
  8. Overall survival for patients with average-risk disease is over 80%; overall tumor recurrence rate is 30% after initial treatment
  9. Long-term complications of disease and treatment that adversely affect overall quality of life are common and include neurocognitive deficits, endocrine deficits, hearing loss, infertility, stroke, and increased risk for secondary malignancy
  10. Monitor for 5 to 10 years after treatment for recurrent disease with serial MRI scans; monitor for 5 to 10 years after treatment for common endocrine deficiencies associated with treatment (eg, growth hormone deficiency, gonadal alterations, hypothyroidism, central adrenal insufficiency)

What is Medulloblastoma?

  • Medulloblastoma is an aggressive embryonal brain tumor that arises from the fourth ventricle at the cerebellum and presents with signs of hydrocephalus and/or cerebellar dysfunction 
  • Most common malignant brain tumor presenting in pediatric population; each year, diagnosed in 1 of 200,000 children younger than 15 years 
    • Accounts for approximately 10% to 20% of all childhood central nervous system malignancies and approximately 1% of adult central nervous system tumors 

Classification and Staging System of Medulloblastoma

  • Chang TM staging system 
    • T1: tumor is less than 3 cm in diameter and limited to midline position in vermis, roof of fourth ventricle, and occasionally cerebellar hemispheres
    • T2: tumor is 3 cm or more in diameter, invades 1 adjacent structure, and may partially fill fourth ventricle
    • T3: divided into T3a and T3b
      • T3a: tumor further invades 2 adjacent structures or completely fills fourth ventricle with extension to aqueduct of Sylvius, foramen of Magendie, or foramen of Luschka and is marked by associated internal hydrocephalus
      • T3b: tumor is more than 3 cm in diameter and arises from floor of fourth ventricle or from brainstem
    • T4: tumor is more than 3 cm in diameter and extends through aqueduct of Sylvius to involve third ventricle or midbrain, or tumor extends to upper cervical cord
    • M0: no metastasis is detected (determined by cerebrospinal fluid cytology 14 days postoperatively)
    • M1: microscopic metastasis is detected as tumor cells in cerebrospinal fluid (determined by cerebrospinal fluid cytology 14 days postoperatively)
    • M2: gross nodular seeding is found in cerebellar or cerebral subarachnoid space or in third or lateral ventricle
    • M3: gross nodular metastasis is found in spinal subarachnoid space
    • M4: metastasis is found outside cerebrospinal axis
  • Risk classification is used for tumor staging and is used for prognosis and individualized treatment planning 
    • Average-risk disease 
      • Age 3 years or older and
      • No evidence of metastatic spread (M0) or residual tumor 1.5 cm² or less after surgery and
      • Classic or desmoplastic histology
    • High-risk disease 
      • Age younger than 3 years or
      • Large cell or anaplastic histology or
      • Age 3 years or older with evidence of metastatic disease; includes any cerebrospinal fluid spread (M1-M3)
      • Incomplete resection after surgery (more than 1.5 cm²)
  • Molecular subtype classification is used for prognosis and potentially individualized treatment planning 
    • Subtype I
      • Aberrant WNT family (Wingless-type MMTV integration site family) gene expression signaling pathway 
      • Accounts for around 10% of cases 
      • Observed in older children, adolescents, and adults (rare in infants) 
      • Usually classified histologically as classic medulloblastoma 
      • Good prognosis 
    • Subtype II
      • Aberrant SHH (sonic hedgehog) gene expression signaling pathway 
      • Accounts for around 30% of cases 
      • Bimodal age distribution (children younger than 3 years and adults) 
      • Classified histologically as desmoplastic/nodular 
      • Intermediate prognosis, unless additional sequence variants (mutations) are present, which worsen prognosis 
      • Tumors of this subtype have the highest tendency to recur locally at resection site
      • 2 subtypes have been identified in young children
        • One has sequence variants of SMO (smoothened, frizzled class receptor) and is associated with favorable prognosis, whereas the other has sequence variants of SUFU (SUFU negative regulator of hedgehog signaling) and is associated with lower progression-free survival rate 
    • Subtype III
      • Variety of sequence variants, most notably in MYC (MYC proto-oncogene, bHLH transcription factor) 
      • Accounts for around 25% of cases 
      • Observed in infants and may occur in children (rare in adults) 
      • Classified histologically as large cell, anaplastic, or classic 
      • Frequently metastasized at diagnosis 
      • Poor prognosis, especially if MYC is overexpressed 
      • Tumor recurrence is usually by leptomeningeal dissemination
    • Subtype IV
      • Amplification of the following and absence of MYC amplification: 
        • OTX2 (orthodenticle homeobox 2)
        • FOXG1B (FOXG1; forkhead box G1)
        • CDK6 (cyclin-dependent kinase 6)
      • Most common subtype, accounting for around 35% of cases 
      • Mainly occurs in children (rare in infants) 
      • Classified histologically as classic, large cell, or anaplastic 
      • Variable prognosis (mostly intermediate prognosis); dissemination is common 
      • Tumor recurrence is usually by leptomeningeal dissemination
  • WHO histologic subtype classification is also used for prognostic stratification 
    • Classic medulloblastoma 
      • Variable prognosis
      • Most common subtype (80%) 
    • Medulloblastoma with extensive nodularity 
      • Occurs primarily in infants
      • Good prognosis
      • Represents 3% of all medulloblastoma 
    • Desmoplastic/nodular medulloblastoma (also called cerebellar neuroblastoma) 
      • Occurs primarily in infants and children younger than 3 years; less frequently in adolescents and adults 
      • Good to excellent prognosis 
      • 40% of desmoplastic medulloblastomas contain deletions of arm 9q 
      • Represents 7% to 15% of all medulloblastoma 
    • Large cell and anaplastic histologic variants show a significant degree of cytologic overlap and are often grouped as large cell/anaplastic medulloblastoma, with a combined frequency reported between 10% and 22% of all medulloblastoma 
      • Anaplastic medulloblastoma 
        • Primarily poor prognosis
      • Large cell medulloblastoma 
        • Primarily poor prognosis
      • Amplifications of MYC gene (MYC proto-oncogene, bHLH transcription factor) and MYCN gene (MYCN proto-oncogene, bHLH transcription factor) occur predominantly in large cell/anaplastic tumors 
  • Classification by genetic markers
    • Markers of good prognosis 
      • Sequence variants of CTNNB1 (β-catenin)
      • Overexpression of NTRK3 (TRKC; neurotrophic receptor tyrosine kinase 3)
      • Underexpression of MYC (MYC proto-oncogene, bHLH transcription factor)
      • Other WNT signaling pathway sequence variants besides those of CTNNB1
    • Markers of poor prognosis 
      • Overexpression of BIRC5 (survivin; baculoviral IAP repeat containing 5)
      • Overexpression of HES1 (hes family bHLH transcription factor 1)
      • Overexpression of ERBB2 and ERBB4 (erb-b2 receptor tyrosine kinases)
      • Amplification of MYC and MYCN (C-myc and N-myc; proto-oncogenes, bHLH transcription factors)
      • Sequence variants of TP53 (tumor protein p53) (eg, chromosome 17 imbalance) 
      • Underexpression of NTRK3 (TRKC; neurotrophic receptor tyrosine kinase 3)

Clinical Presentation


  • Symptoms evolve over a period of weeks to months; they are generally present for less than 3 months before initial diagnosis 
    • Most common presenting symptoms are emesis (68%), headache (66%), nausea (40%), and ataxia (40%) 
    • Symptom duration is inversely correlated with disease stage 
      • Median duration of symptoms in patients with high disease stage (M1-M4) at time of diagnosis is 4 weeks; median duration of symptoms in patients with low disease stage (M0) at time of diagnosis is 8 weeks 
    • Symptom duration is directly correlated with age
      • Median symptom duration for children aged 0 to 3 years is 4 weeks; median symptom duration for children aged 3 years or older is 8 weeks 
  • General symptoms (early symptoms)
    • Lethargy
    • Irritability
    • Loss of appetite
    • Declining academic performance
    • Generalized weakness
  • Headaches
    • Abrupt onset
    • Positional and typically worse in the morning
    • May wake child from sleep
  • Nausea and vomiting
    • Commonly after awakening
  • Gait disturbance
    • Truncal unsteadiness
  • Loss of balance and coordination
    • Clumsiness
    • Dropping things
  • Dizziness
  • Visual changes
    • Diplopia
    • Esotropia
    • Nystagmus
  • Difficulty hearing
    • Tinnitus
  • Stiff neck
  • Torticollis
  • Symptoms in infants are more subtle and include:
    • Irritability
      • Worse after a period of lying flat
    • Lethargy
    • Intermittent vomiting
    • Weight loss or failure to thrive
    • Feeding difficulty
    • Loss of developmental milestones
  • Symptoms of metastatic medulloblastoma depend on tumor location:
    • Extraneural metastasis (M4) is rare at time of diagnosis
      • Back pain
      • Bone pain
      • Incontinence
    • Central nervous system metastasis can present with seizures
      • Approximately 8% of patients present with seizures 
        • Dependent on tumor location and histology 

Physical examination

  • Vital signs are typically normal unless increased intracranial pressure is present
    • Hypertension, bradycardia, and/or abnormal respiratory patterns are concerning for increased intracranial pressure
  • General findings
    • Hypotonia
    • Spasticity
    • Meningismus
  • Patients present with a combination of clinical findings related to increased intracranial pressure and cerebellar dysfunction
    • Increased intracranial pressure (80% of patients present with signs of hydrocephalus)
      • Papilledema is the most common and concrete finding on examination
        • Visual impairment
      • Altered mental status
        • Irritability
        • Drowsiness
        • Lethargy
      • Cranial nerve abnormalities
        • Abducens nerve (lateral rectus palsy)
        • Trochlear nerve (superior oblique palsy)
          • Head tilt
          • Diplopia
      • Manifestations in infants
        • Macrocephaly
        • Bulging fontanel
        • Widened sutures
        • Setting sun sign (each iris resembles a sun setting beneath the lower lid)
        • Head tilt
    • Cerebellar dysfunction
      • Dysmetria
        • Abnormal finger to nose testing result
        • Intention tremor
      • Ataxia with wide-based gait
        • Inability to heel-toe walk
      • Truncal instability
      • Nystagmus
    • External ocular findings
      • Diplopia
        • Worse with lateral gaze
      • Esotropia


  • Exact cause is unknown, but each tumor on average has 11 genetic sequence variants that are responsible for dysregulation in cellular signaling involved in brain development 
  • Molecular subgrouping of medulloblastomas forms the basis of the subgroup classification system and has prognostic significance
  • Genomic data have identified multiple candidate genes that contribute to pathogenesis of different subgroups of medulloblastoma, including:
    • TP53 (tumor protein p53), encoding a tumor suppressor 
    • SUFU, an inhibitor of the sonic hedgehog pathway 
    • CTNNB1, encoding β-catenin, which is an activator of the WNT pathway 
    • MYC (MYC proto-oncogene, bHLH transcription factor), a proto-oncogene 
    • PTCH2 (patched 2), encoding a transmembrane tumor suppressor signaling protein in the hedgehog signaling pathway

Risk factors and/or associations

  • Most commonly arises during early childhood with bimodal distribution 
    • Bimodal peak incidence between the ages of 3 and 4 years and between the ages of 8 and 9 years; median age of presentation is between 5 and 7 years 
    • 10% to 15% of medulloblastomas are diagnosed in infancy 
    • Rarely medulloblastoma is diagnosed in adults aged 20 to 34 years 
  • Overall, more common in males than in females (ratios range from 1.4:1 to 2:1, depending on subtype) 
  • Primarily a sporadic disease
  • Somatic alterations in sporadic cases
    • About 30% to 45% show loss of genetic material from chromosome arm 17p, which contains tumor suppressors TP53 and KCTD11 (REN) 
  • Hereditary forms
    • Familial form of medulloblastoma (OMIM #155255) 
      • Autosomal dominant inheritance caused by germline inactivating variants in SUFU gene (SUFU negative regulator of hedgehog signaling) or BRCA2 gene (BRCA2 DNA repair associated)
    • Gorlin syndrome (basal cell nevus syndrome) (OMIM #224690) 
      • Autosomal dominant disorder of multiple tumor types, including basal cell carcinomas of skin, ovarian fibromas, and medulloblastomas 
      • Cause by germline variants in DNA mismatch repair genes (eg, PTCH1 gene involved in sonic hedgehog signaling pathway) 
      • 3% to 5% of children with Gorlin syndrome develop medulloblastoma
      • 1% to 2% of medulloblastoma overall is associated with Gorlin syndrome 
      • Most medulloblastoma in patients with Gorlin syndrome is desmoplastic with extensive nodularity; for patients with medulloblastoma who present with desmoplastic tumors with extensive nodularity, evaluate for Gorlin syndrome 
    • Turcot syndrome, subtype 2 (OMIM #276300) 
      • Autosomal recessive disorder in which medulloblastoma occurs in the setting of familial adenomatous polyposis 
      • Caused by germline variant in tumor suppressor gene APC (APC regulator of WNT signaling pathway; adenomatosis polyposis coli)
      • Medulloblastoma occurs in about 40% of patients with Turcot syndrome 
    • Li-Fraumeni syndrome (OMIM #151623) 
      • Autosomal dominant disorder caused by variants in tumor suppressor gene TP53
      • Characterized by predisposition to numerous malignancies and brain tumors, of which medulloblastoma is one 
    • Familial adenomatous polyposis (OMIM #175100) 
      • Autosomal dominant disorder caused by variants in tumor suppressor gene APC (APC regulator of WNT signaling pathway; adenomatosis polyposis coli)
      • Characterized by development of numerous colonic and rectal polyps and predisposition to numerous malignancies
      • Risk of medulloblastoma is 92 times greater than in the general population 
    • Von Hippel–Lindau syndrome (OMIM #193300) 
      • Autosomal dominant disorder caused by heterozygous variant in VHL gene (von Hippel–Lindau tumor suppressor)
      • Characterized by development of various malignant and benign neoplasms, including medulloblastoma, retinal angiomas, renal cell carcinoma, and pheochromocytoma
    • Rubinstein-Taybi syndrome 
      • Autosomal dominant multiple congenital anomaly syndrome caused by heterozygous variant in CREBBP gene, which encodes the transcriptional coactivator CREB-binding protein
      • Syndrome is characterized by distinctive facial and dysmorphic physical features, intellectual disability, variable associated congenital defects, and increased risk of certain tumors, including medulloblastoma
  • In the United States, White patients have higher risk than Black patients (1.69 per million versus 1.03 per million) 

How is Medulloblastoma Diagnosed?

  • Suspect diagnosis based on initial history and physical examination with funduscopy 
  • Perform MRI of brain and spinal cord to confirm cerebellar mass 
    • Screening CT scan to emergently investigate symptoms concerning for increased intracranial pressure, posterior fossa lesion, or other central nervous system abnormality may indicate presence of a posterior fossa mass 
    • MRI is imaging modality of choice for diagnosis, preoperative work-up, and postoperative staging 
    • Considerable heterogeneity between individual medulloblastoma tumor appearances exists on both CT and MRI 
  • Perform maximum safe resection to remove tumor for pathologic examination that will confirm the diagnosis 
  • Tumor staging to classify patients into average-risk or high-risk groups is based on presence of malignant cells in cerebrospinal fluid and postoperative residual disease on MRI
    • Postoperative MRI is done at 24 to 72 hours to examine for more than 1.5 cm² of residual disease 
    • Perform lumbar puncture 10 to 21 days after resection to further assess for cerebrospinal fluid and spinal metastasis 
  • Additional tumor-specific diagnostics (eg, histologic classification, molecular subtype classification, genetic markers) aid in staging and further stratifying risk status
  • MRI
    • MRI scan of brain and spine with and without gadolinium contrast enhancement 
      • Gold standard for detection of medulloblastoma 
        • MRI is superior to CT to investigate details of fourth ventricle and subarachnoid space 
      • Typical findings include:
        • Posterior fossa cerebellar mass, usually originating from midline vermis, with variable extension into fourth ventricle and brainstem in children; adult medulloblastoma is more likely to be located laterally in a cerebellar hemisphere 
          • Usually mass does not project into basal cisterns
        • Characteristics of mass on MRI
          • Hypointense to gray matter and heterogeneous enhancement in 90% on T1-weighted image 
          • Heterogeneous appearance owing to calcification, necrosis, and cyst formation on T2-weighted image 
          • Isointense to hyperintense to gray matter on T2-weighted image 
        • Metastasis
          • Drop metastasis presents as contrast-enhancing “sugar coating” of spinal cord or as strongly enhanced foci in spinal canal
          • Most common locations for intracranial metastases are vermis, basal cisterns, subependymal region of lateral ventricles, floor of third ventricle, and subfrontal regions
      • For patients who have signs or symptoms of hydrocephalus and require sedation for MRI, provide management of increased intracranial pressure before sedation, with general supportive measures to decrease intracranial pressure, steroids, and/or preoperative extraventricular drain to prevent acute sedation-related hypoventilation
  • CT scan
    • Secondary imaging method; used before lumbar puncture to assess for increased intracranial pressure and assess for local complications 
      • Superior to MRI for detection of hydrocephalus
    • Appearance of hyperattenuated, well-defined posterior fossa midline (occasionally hemispheric) vermian cerebellar mass with the following: 
      • Surrounding vasogenic edema 
      • Obstructive hydrocephalus 
        • Effacement of fourth ventricle and basal cisterns is present in most cases
      • Characteristics of mass on CT
        • Prominent homogeneous enhancement with contrast material is common 
        • About 90% of lesions are hyperdense (hyperattenuated) on noncontrast CT imaging 
        • 40% to 50% of cases are associated with cyst formation and necrosis 
        • Calcification is uncommon (10%-20% of cases) 


Lumbar puncture
General explanation
  • Lumbar puncture before surgical excision of tumor is discouraged, owing to increased intracranial pressure associated with tumor burden in posterior fossa
  • Insertion of a hollow-bore needle between the vertebral bodies into the subarachnoid space to obtain a specimen of cerebrospinal fluid
    • Patient is either in the lateral recumbent position or sitting upright
    • Needle appropriate for size of patient is inserted in L4-L5 interspace
    • Cerebrospinal fluid is sent for analysis, including protein level, cell counts, and microscopy
  • Perform procedure 10 to 21 days after tumor resection 
  • Assess for cerebrospinal fluid contamination of malignant cells and assess for possible metastasis to spine
  • Measure intracranial pressure
  • Uncontrolled coagulopathy
  • Skin infection at site of needle insertion
  • Patient at risk of brain herniation 
    • Best predictors of precipitating herniation (even with normal CT result) include:
      • Deteriorating level of consciousness (particularly to a Glasgow Coma Scale score of 11 or less in adults; for pediatric patients, adaptations of the Glasgow Coma Scale are available, such as the James version)
      • Brainstem signs (eg, pupillary changes, abnormal posturing, irregular respirations)
      • Very recent seizure
  • Increased intracranial pressure
  • Papilledema 
  • Acute spinal trauma 
  • Post–dural puncture headache
  • Back pain
  • Radicular injury
  • Infection
    • Epidural abscess
    • Meningitis
    • Diskitis
    • Vertebral osteomyelitis
  • Epidural hematoma
  • Cerebral herniation
  • Epidermoid tumor formation
Interpretation of results
  • Presence of tumor cells in fluid indicates metastasis of primary brain tumor and places patient in high-risk category
    • Cerebrospinal fluid dissemination occurs in up to 40% of pediatric patients with medulloblastoma 
    • Cerebrospinal fluid dissemination occurs in up to 10% of adult patients with medulloblastoma 
  • Negative cerebrospinal fluid cytology result does not exclude advanced disease

Differential Diagnosis

Most common

Treatment Goals

  • Relieve increased intracranial pressure
  • Eliminate primary tumor burden with maximum safe surgical resection
  • Prevent relapse or progression of tumor
  • Minimize adverse events of chemotherapy and radiotherapy
    • Minimize radiotherapy in young children and in patients with cancer predisposition syndromes
  • Monitor for and manage posttreatment complications

Admission criteria

All children are admitted at time of diagnosis for expedient treatment planning and management

Criteria for ICU admission
  • Craniotomy patients: admit to ICU postoperatively
  • Patients with clinical or radiographic evidence of increased intracranial pressure: admit to ICU

Recommendations for specialist referral

  • Refer to pediatric neurosurgeon for increased intracranial pressure management recommendations and surgical reduction of tumor burden
  • Refer to pediatric oncologist for diagnostic and treatment planning
  • Refer to radiation oncologist for treatment planning
  • Refer to endocrinologist for assessment and monitoring for common endocrine abnormalities after treatment of disease
  • Refer to speech, occupational, and physical therapists as needed

Treatment Options

Treatment overview 

  • Initial treatment includes general measures to reduce intracranial pressure and specific treatment to eliminate tumor burden
  • Preferred approach to tumor-directed therapy first includes maximum safe surgical resection, followed by combined postoperative radiotherapy and chemotherapy
    • Treatment approach is highly specialized and involves a multidisciplinary team with experience treating medulloblastoma
    • Treatment is based on clinicoradiologic risk stratification and molecular subtype 
    • Patients are enrolled in nationally coordinated clinical trials when available

Manage increased intracranial pressure

  • Treat vasogenic tumor edema and associated intracranial pressure with corticosteroids in conjunction with urgent neurosurgical intervention 
  • Surgical resection of tumor alleviates obstructive hydrocephalus and raised intracranial pressure; it may obviate further drainage procedures 
    • Emergent external ventricular shunt or third ventriculostomy can be used before tumor resection to decrease intracranial pressure if immediate surgery is not possible 
  • Apply general treatment for increased intracranial pressure
    • Maintain cerebral perfusion pressure and support airway
    • Avoid drugs that will increase intracranial pressure
    • Elevate head of bed and maintain patient’s head in midline position
    • Blunt noxious stimuli with appropriate analgesia
    • Administer mannitol or hypertonic saline
  • Ventriculoperitoneal shunt may be inserted to drain excess cerebrospinal fluid and relieve intracranial pressure; usually placed at time of surgical resection of tumor 
    • Increasingly, third ventriculostomy is used in an effort to avoid permanent ventriculoperitoneal shunt placement 
  • Institute standard anticonvulsant therapy for patients experiencing seizures 
    • Prophylactic anticonvulsants are not routinely indicated in patients without seizures 

Treat spinal cord compression

  • Can occur anywhere from neck (secondary to direct tumor spread or tumor compression of upper cervical cord) to lower spine (secondary to drop metastasis); treatment includes dexamethasone (to decrease edema and inflammation) and surgical decompression

Tumor-directed therapy

  • Treatment of most patients consists of surgical resection followed by radiotherapy and chemotherapy
    • Gross total resection or maximal safe resection of tumor should be performed initially 
      • Postoperative MRI is performed within 48 hours of surgery, and repeated operation is recommended if residual tumor of more than 1.5 cm² is documented
    • Craniospinal radiotherapy, with or without concomitant chemotherapy, is indicated in all patients older than 3 years 
      • Radiotherapy is avoided in children until age 3 years or older because of unacceptable adverse effects; high-dose chemotherapeutic regimens alone are typically used in an effort to avoid or delay use of radiotherapy until children are aged 3 years or older 
    • Postradiotherapy maintenance chemotherapy is recommended for patients of all ages regardless of risk category 
      • Historically, few adults received first line chemotherapy, but a large meta-analysis indicates that adults have improved long-term survival with the addition of first line adjuvant chemotherapy 
      • Packer regimen is used in both adults and children; it consists of 8 doses of vincristine during radiotherapy followed by 8 cycles of cisplatin-vincristine-lomustine 
        • Cisplatin-vincristine-cyclophosphamide is an alternative 
        • High-dose methotrexate may be administered IV or intrathecally with or without concomitant vincristine, cisplatin, cyclophosphamide, or etoposide for children younger than 3 years 
      • High-dose chemotherapy followed by autologous stem cell transplant is an emerging treatment option for children (including young children and infants) with high-risk disease; there are no data to support its use in adults 
    • Molecular profiling of tumors may allow treatment to be individualized according to the specific subtypes and genetic sequence variants involved 
      • For example, patients with recurrence of subtype II medulloblastoma may benefit from vismodegib, a sonic hedgehog pathway inhibitor 
      • There are not yet any therapeutic agents to target subgroups III and IV, which are the most common forms 


  • For surgical removal of tumor
    • Maximum safe surgical resection is performed when possible because residual tumor bulk is one of the most important predictors of 5-year progression-free survival 
    • Surgical resection of tumor bulk restores cerebrospinal fluid flow and relieves hydrocephalus in most cases
  • For radiotherapy
    • Medulloblastoma is a highly radiation-sensitive malignancy; radiotherapy is the most important adjuvant treatment providing cure 
    • Radiotherapy to the neuraxis is administered because the posterior fossa and spinal axis are the primary sites of recurrence 
  • For chemotherapy
    • Postoperative chemotherapy is part of standard adjuvant therapy for all pediatric patients and adult patients; optimal drugs, doses, timing, and schedule are not yet established 
      • Until recent years, chemotherapy has traditionally been used in those adult patients with high-risk disease or recurrence, as no strong evidence existed to support a specific chemotherapy regimen in adults with medulloblastoma 
        • Recent large meta-analysis indicates that first line chemotherapy improves short-term and long-term survival in the adult population independent of tumor stage 
    • Several studies suggest that adjuvant chemotherapy may improve overall survival and decrease disease recurrence 
      • Chemotherapy administered during and after radiotherapy is more effective than chemotherapy used before radiotherapy alone (5-year overall survival of 69.1% versus 60.7%, respectively) 
    • High-dose chemotherapeutic regimens are used over craniospinal radiotherapy in children younger than 3 years and in infants because of the detrimental effects that radiation can have on the developing nervous system 


  • Average-risk medulloblastoma
    • Standard treatment in children with average risk (ie, resection followed by radiotherapy then chemotherapy) results in greater than 80% 5-year event-free survival 
  • High-risk medulloblastoma
    • Overall 50% to 60% 5-year event-free survival is reported despite higher doses of radiotherapy and chemotherapy 
  • Young children
    • Overall very poor prognosis, with a reported 5-year event-free survival of 30% to 40% 
    • Young children have variable survival rates depending on degree of resection and presence of metastasis
      • Infants without metastatic disease and with gross total resection have slightly better outcomes, with 5-year event-free survival of up to 69% 
    • Young children and infants have variable response to chemotherapy according to histology of medulloblastoma variants in nonmetastatic disease; improved survival rates are reported with certain histologic variants 
      • 5-year event-free survival and overall survival of 90% and 100% for desmoplastic/nodular medulloblastoma variants 
      • 5-year event-free survival and overall survival of 30% and 68% for classic medulloblastoma 
  • Adults
    • In adults receiving craniospinal radiotherapy, 5-year overall survival rates range from 58% to 76% 
    • Adults who receive first line chemotherapy survive longer (median overall survival of 108 months) than those who receive radiotherapy alone (median overall survival of 57 months) 
  • Recurrent and progressive medulloblastoma
    • Very poor outcome; postrecurrence event-free survival is as follows:
      • At 2 years: 25% 
      • At 5 years: 8.7% 

Drug therapy

  • Chemotherapy 
    • Cisplatin (platinum agent)
    • Cyclophosphamide (alkylating agent)
    • Vincristine (plant alkaloid)
    • Etoposide (topoisomerase II inhibitor)
    • Lomustine (alkylating agent)
    • Methotrexate (antimetabolite)
    • Temozolomide (alkylating agent) 

Nondrug and supportive care

Surgical resection

  • Standard treatment for all patients with medulloblastoma 


  • Cornerstone of curative management is high-quality radiotherapy after resection 
  • Initial postoperative radiotherapy includes radiation to posterior fossa and entire craniospinal axis for average-risk and high-risk patients aged 3 years or older 
    • Start radiotherapy within 28 to 42 days after surgery; continue radiotherapy no longer than 50 days 
    • Deliver targeted radiation to postoperative tumor bed with an additional lower radiation dose applied to the entire craniospinal axis 
  • Postoperative radiotherapy is also recommended for adults older than 18 years 
  • Avoid radiotherapy in children younger than 3 years, owing to severe toxicity to developing brain tissue 
  • Minimize radiation exposure in any patient with a known or suspected cancer predisposition syndrome (eg, Gorlin syndrome, Li-Fraumeni syndrome)
  • Goal is to treat any disease spread along craniospinal axis and eradicate any primary residual tumor in posterior fossa

Proton therapy (instead of conventional radiotherapy) 

  • Reported in case studies and largely investigational
  • Proton therapy can achieve superior dose distribution and target conformation compared with conventional radiotherapy, thereby reducing the irradiation of nontarget tissue and reducing treatment-related adverse effects (eg, diminishing neuropsychological morbidity)

Stem cell transplant 

  • Myeloablative chemotherapy followed by autologous stem cell transplant is used in certain high-risk populations, such as infants with poor prognosis

Rehabilitation services 

  • Begin physical, occupational, and/or speech therapy as part of inpatient rehabilitation
  • Begin psychological therapy as part of outpatient rehabilitation services
Surgical resection

General explanation

  • Goal is maximum safe surgical resection 
    • Relieves intracranial pressure
    • Improves survival
    • Provides tissue for histopathology and molecular subtype classification
  • Manual and operational techniques are used to completely resect mass
  • Obtain follow-up MRI scan 48 hours after procedure to evaluate for residual mass


  • Maximum safe surgical resection is standard treatment for all patients with medulloblastoma 


  • Complete surgical resection may not be possible if tumor has invaded brainstem


  • Posterior fossa syndrome occurs in up to 20% of all posterior fossa tumors 
    • Arises 1 to 4 days after resection and is characterized by: 
      • Mutism
      • Hypotonia 
      • Swallowing difficulties
      • Severe cerebellar dysfunction (eg, ataxia, dysmetria) 
      • Emotional lability
      • Supranuclear cranial nerve palsies
      • Quadriparesis
    • In general, most deficits resolve during a period of several weeks to months after surgery; rarely some residual deficits may persist, and this postoperative complication is frequently associated with long-term neurocognitive impairment 
    • Risk factors for development of posterior fossa syndrome include: 
      • Left-handedness
      • Medulloblastoma histology
      • Localized damage within the right cerebellothalamocortical pathway
    • Avoid delay in subsequent treatments based on this common complication 
  • Surgically induced deficiencies 
    • Manifest days after surgical resection
      • Various neuroendocrine deficiencies
      • Facial nerve, abducens nerve, and lower cranial nerve palsies can result from brainstem manipulation
      • Cerebellar dysmetria can result from dissection of cerebellar peduncle
      • Syndrome of inappropriate antidiuretic hormone
  • Mechanical complications 
    • Cerebrospinal fluid leak
    • Pseudomeningocele
  • Infectious complications
    • Meningitis 
  • Other complications 
    • Central nervous system hematoma
    • Cervical instability
Ventriculoperitoneal shunt or other permanent cerebrospinal fluid shunt

General explanation

  • Surgical procedure in which one catheter is inserted behind ear and into brain and another subcutaneous catheter is placed behind ear and leading down along chest to abdominal cavity to allow drainage of excess cerebrospinal fluid from ventricles into abdominal cavity; a regulatory pump is attached to both catheters to monitor pressure and remove fluid as needed 
  • Alternatively, a communication for cerebrospinal fluid drainage can be established between the lateral ventricle and an alternative cavity suitable for collecting fluid (eg, right atrium, pleural space)
  • Timing of shunt placement is a subject of debate and is individualized according to tumor location and size 
    • Proponents of shunt placement before resection argue a reduction in technical difficulty of surgery and improvement in operative mortality 
    • Opponents argue that early shunt placement causes tumors to move close to brainstem (making surgery more hazardous) and increases infection rates 


  • Used in patients presenting with both a posterior fossa tumor and preoperative hydrocephalus 
  • Approximately 50% of patients require insertion of ventriculoperitoneal shunt during or shortly after surgery, owing to unresolving obstructive hydrocephalus 
  • Permanent ventriculoperitoneal shunt placement is required in 20% to 30% of patients with medulloblastoma, owing to scarring of cerebrospinal fluid pathways 


  • Infection at entry site
  • Coagulopathy


  • Mechanical shunt failure
  • Shunt infection/ventriculitis
  • Shunt overdrainage, resulting in headache and nausea
  • Gastrointestinal bleeding or peritonitis (after peritoneal shunt placement)


  • Genetic conditions
    • Minimize radiation exposure in any patient with a known or suspected cancer predisposition syndrome (eg, Gorlin syndrome, Li-Fraumeni syndrome) 

Special populations

  • Children younger than 3 years
    • Avoid radiotherapy, owing to extreme deleterious effects on cognitive development 
    • Children younger than 3 years often receive multiagent chemotherapy 
  • Adults
    • Historically, chemotherapy was often not used in adults (older than 18 years) for medulloblastoma because of lack of supporting evidence, but a newer meta-analysis shows improved survival independent of tumor stage with up-front chemotherapy 
    • Used in adults with recurrent or high-risk disease
  • Patients with cancer predisposition syndromes (eg, Gorlin syndrome, Li-Fraumeni syndrome)
    • Many patients with Gorlin syndrome who develop medulloblastoma present at a young age (younger than 3 years); patients with Gorlin syndrome often present with medulloblastoma with extensive nodularity 
    • Avoid radiotherapy in patients with Gorlin syndrome (and in patients who are at risk of subsequent Gorlin syndrome diagnosis), because they are at much higher risk of developing secondary tumors and nevoid basal cell carcinomas in irradiated fields
  • Medulloblastoma with extensive nodularity
    • This variant is highly sensitive to chemotherapy, and less extensive tumor resection in high-risk areas (eg, brainstem) is acceptable


  • Long-term follow-up (5-10 years) is advisable 
  • Assess for recurrence of disease
    • Individualized follow-up is determined after initial treatment and restaging based on histopathology, molecular tumor cell analysis, and postoperative MRI findings
    • In general, follow-up MRI scans of brain and spine are performed every 3 months, and spinal MRI is performed every 3 months for the first 2 to 3 years after surgery; scans are done less frequently (every 6-12 months) for 5 to 10 years and on a case by case basis after this time frame if results are negative 
  • Endocrinology evaluations
    • Screening for growth hormone deficiency 
      • Anthropometric measurements every 6 months until growth is complete and/or sexual maturity, then yearly
      • Laboratory tests are individualized according to specific endocrine recommendations. They may include insulinlike growth factor 1 level; insulinlike growth factor–binding protein 3 level; bone age determination; insulin tolerance test; and growth hormone–provocative tests, such as sleep, exercise, arginine, clonidine, and levodopa tests
    • Gonadal alterations (eg, delayed puberty, precocious puberty, hypogonadism) 
      • Screening is by history and physical examination
      • Suspected abnormalities are investigated with endocrine-directed testing. Examples include yearly estradiol levels assessment and pelvic ultrasonography in females; yearly testicular volume, testosterone levels, and β-hCG levels in males; and monitoring in both males and females of annual height and weight assessment, luteinizing hormone and follicle-stimulating hormone levels (basal and after gonadorelin stimulation), bone age, growth hormone levels, and Tanner stage
    • Screening for hypothyroidism 
      • Annual: focused history and physical examination; bone densitometry
      • Every 6 months: free thyroxine and TSH levels
    • Hyperprolactinemia 
      • Screen periodic prolactin levels (along with thyroxine and TSH levels); optimal timing of screening evaluations is not established
        • If prolactin levels are higher than 50 nanograms/mL, then obtain a pituitary MRI
    • Central adrenal insufficiency 
      • Morning serum cortisol level: obtain yearly until 15 years off therapy
        • If cortisol levels are less than 10 mcg/dL, further endocrinologic evaluation and treatment are required
  • Osteoporosis screening 
    • Bone density evaluation by DXA or quantitative CT screening: start 2 years after treatment; optimal timing for screening tests is individualized
      • Refer to a specialist if osteoporosis is suspected (eg, t score of 2.5 or more standard deviations below normal) or if history of multiple fractures exists
  • Obesity and dyslipidemia 
    • Follow annual BMI
      • Screen fasting blood glucose level and serum insulin and lipid profile every 2 years in obese or overweight patients; every 5 years in normal-weight patients
    • Monitor clinically for other comorbid conditions (eg, hypertension, glucose intolerance, diabetes mellitus, hyperinsulinism, insulin resistance)
  • Nutritional evaluation every 6 months 
  • Neuropsychiatric and targeted functional neurocognitive deficit assessment testing every 1 to 2 years 
  • Hearing screening and visual acuity testing are suggested during treatment and with regular follow-up examinations (optimal timing of these screening examinations is not rigorously established) 


  • Medulloblastoma can cause increased intracranial pressure, which can lead to brain herniation resulting in permanent neurologic damage
  • Treatment-related long-term adverse effects 
    • Neurocognitive impairment
      • Long-term cognitive, neuropsychological, and academic impairments are frequent among medulloblastoma survivors 
        • Specific neuropsychological deficits can affect cognitive development and new academic skill acquisition
          • Functional neurocognitive domains that are most frequently affected include any combination of the following: 
            • Attention
            • Executive functioning
            • Processing speed
            • Working memory
            • Learning
        • Many survivors have difficulties in problem solving, academic achievement, independent living, and quality of life in general 
      • Degree of impairment depends on age at time of radiotherapy and location of surgical resection
        • IQ declines are noted after radiotherapy; greater deficits occur with younger age and higher doses at time of treatment
          • Up to 30 points loss of IQ with radiation to central nervous system in children younger than 8 years 
        • Location and size of tumor affect the amount of functional neurocognitive impairment
          • Tumors localized to cerebellar vermis are associated with fewer global deficits
          • Tumors that spread to cerebrum, especially key functional areas thereof that control speech and memory, are associated with increased global impairment and focal neurologic deficits
    • Psychological and behavioral problems 
      • Social withdrawal
      • Depression
      • Anxiety
    • Endocrine abnormalities 
      • Neuroendocrine abnormalities after craniospinal radiotherapy for medulloblastoma are common and manifest months to years after therapy 
        • Growth hormone deficiency is very common 
          • 40% to 80% of survivors have growth hormone deficiency 
          • Commonly develops 3 months to 5 years after radiotherapy 
        • Gonadal alterations are common and depend on age at treatment (younger patients are less susceptible), concomitant radiochemotherapy, and radiotherapy doses 
          • Central hypogonadism 
          • Precocious puberty
          • Delayed puberty
        • Hypothyroidism
          • Affects up to 6% of survivors 
          • Most cases are detected within 4 years after treatment 
        • Hyperprolactinemia 
          • May develop secondary to destruction of hypothalamus-pituitary axis or to primary hypothyroidism
          • Common and usually appears 2 or more years after treatment 
          • Found in all age groups and both sexes, but most common in women
        • Central adrenal insufficiency
          • Corticotropin deficiency is not common but is potentially life-threatening 
          • May be detected years after therapy 
    • Osteopenia/osteoporosis 
      • Caused by both steroid therapy and craniospinal irradiation
      • Important preventive measures: optimization of vitamin D and calcium supplementation; endocrine replacements
    • Frequent fractures 
      • Secondary to a combination of factors, including:
        • Incoordination and frequent falls after posterior fossa tumor surgical resection
        • Reduction in bone density
    • Obesity and dyslipidemia 
      • Cranial irradiation along with certain chemotherapeutic agents (eg, heavy metal, cisplatin) can place patients at increased risk for obesity and dyslipidemia
        • Concurrent growth hormone deficiency and hypothyroidism may exacerbate excessive weight gain
      • Individualized counseling for dietary modification, exercise, and weight management are important preventive measures
    • Scoliosis/kyphosis
      • Craniospinal irradiation, steroid therapy, growth hormone and gonadotropin deficits, and/or altered food intake can all contribute to altered vertebral body growth
    • Hearing loss 
      • Cochlear irradiation during boost to posterior fossa and cisplatin use both are associated with hearing loss
    • Visual deficits
      • Impaired visual acuity mainly from intracranial hypertension
      • Nystagmus and diplopia are usually secondary to mass effects and tumor removal
    • Stroke
      • Secondary to radiation-induced vasculopathy
    • Secondary malignancies 
      • Both irradiation and chemotherapy contribute to development of second tumors 
      • Increased risk for second central nervous system tumors (eg, meningioma, cavernomas, glioblastoma) 
        • Estimated cumulative 10-year incidence rate for secondary central nervous system tumor is 4.2% 
        • Can develop up to 30 years after treatment 
      • Increased risk for acute lymphoblastic leukemia and for cancers of thyroid gland, cervix uteri, and salivary gland 
  • Recurrent disease
    • Up to 30% relapse rate is reported overall after initial medulloblastoma treatment 
      • Site of tumor recurrence involves posterior fossa in 79%, spine in 59%, supratentorial region in 47%, and site outside central nervous system in 21% 
      • More than half of relapses have a metastatic component 
    • Most relapses occur in the first 3 to 5 years after initial treatment; 75% occur within 2 years 
    • Relapse risk is closely related to quality of radiotherapy 
  • Adult survivors of childhood central nervous system malignancies have high rates of academic failure, unemployment, and reduced overall quality of life 
    • 82% of survivors reported having at least 1 chronic medical condition
    • Prevalence rates for endocrine, neurologic, and sensory complications are 49%, 37%, and 35%, respectively


  • General prognosis depends on several factors, including extent of disease at diagnosis, site of origin, age at diagnosis, residual tumor burden after resection, tumor histopathology, and biochemical/molecular tumor cell characteristics 
    • Average-risk disease
      • 5-year survival rates are over 80% 
    • High-risk disease
      • 5-year survival rates are up to 60% 
    • Extent of disease at diagnosis
      • Dissemination at time of diagnosis (10%-40% of patients) is associated with poor prognosis
        • Infants have the highest rate of disseminated central nervous system disease at diagnosis
      • Patients older than 3 years without metastatic disease (M0) have up to 70% 5-year progression-free survival; patients with M1 disease, 57%; and patients with M2 to M4 disease, less than 40% 
    • Age at diagnosis
      • Age younger than 3 years is associated with poor prognosis 
      • Overall, children younger than 3 years have estimated 5-year progression-free survival of 32%, and children aged 3 years or older have estimated 5-year progression-free survival of 58% 
      • 5-year overall survival rates for adults range from 51% to 84%; 5-year progression-free survival rates for adults range from 40% to 61% and are highly dependent on risk stratification 
    • Postresection residual tumor burden
      • Residual disease (more than 1.5 cm²) is associated with poor prognosis 
      • Overall estimated 5-year progression-free survival for patients with residual tumor is 54% (compared with 78% in patients without residual tumor burden) 
    • Tumor histopathology 
      • Anaplastic and large cell variants are associated with poor prognosis in children younger than 3 years
      • Desmoplastic/nodular variant is associated with better prognosis in children younger than 3 years
    • Biochemical/molecular tumor cell characteristics 
      • Tumors with WNT pathway activation usually have good prognosis
      • SHH pathway–activated tumors generally show an intermediate prognosis
        • Exception is tumor with SHH pathway activation secondary to TP53 sequence variant, which carries poor prognosis
      • MYC or MYCN alterations have less favorable prognosis

Screening and Prevention

At-risk populations

  • Patients with genetic predisposition to medulloblastoma

Screening tests

  • No current screening recommendations exist; for patients with genetic predisposition to medulloblastoma, refer to oncologist for individualized screening approach


Gajjar AJ et al: Medulloblastoma–translating discoveries from the bench to the bedside. Nat Rev Clin Oncol. 11(12):714-22, 2014 Reference


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