Residency · Residency · Neurosurgery
Pediatric Brain Tumors: Medulloblastoma and Posterior Fossa Tumors
Overview
Brain tumors are the most common solid tumors in children and the leading cause of cancer-related death in the pediatric population. Posterior fossa tumors account for approximately 50 to 60 percent of pediatric brain tumors. The three most common posterior fossa tumors in children are pilocytic astrocytoma, medulloblastoma, and ependymoma. Treatment is multimodal, combining surgery, radiation therapy that is age-dependent, and chemotherapy. Molecular classification has revolutionized risk stratification and treatment planning over the past decade.
Medulloblastoma
Epidemiology
Medulloblastoma is the most common malignant brain tumor in children, with peak incidence between 5 and 9 years and a second smaller peak in young adults. There is a male predominance at 1.5:1. It is classified as WHO Grade IV and belongs to the embryonal tumor family. In children, medulloblastoma typically arises from the cerebellar vermis, while in adolescents and adults it more often arises from the cerebellar hemisphere. The tumor has a propensity for CSF dissemination, with leptomeningeal metastasis present in 30 to 40 percent of patients at the time of diagnosis.
Molecular Subgroups
The 2021 WHO classification recognizes four molecular subgroups that fundamentally determine prognosis and treatment strategy.
WNT-activated medulloblastoma accounts for 10 percent of cases and carries the best prognosis with greater than 95 percent five-year survival. It occurs in older children and adolescents with a midline location. Molecular hallmarks include nuclear beta-catenin accumulation on immunohistochemistry and monosomy 6. The metastatic risk is lower than other subgroups. Given the excellent outcomes, de-escalation of therapy is being actively investigated.
SHH-activated medulloblastoma, subdivided into TP53-wildtype and TP53-mutant, accounts for 30 percent of cases. It has a bimodal age distribution affecting infants and adults and arises from the cerebellar hemisphere, with the desmoplastic variant being common in infants. TP53-mutant tumors carry a very poor prognosis while TP53-wildtype tumors have intermediate outcomes. SHH pathway inhibitors such as vismodegib and sonidegib are under investigation. Germline associations include PTCH1 mutations in Gorlin syndrome, SUFU mutations, and TP53 mutations in Li-Fraumeni syndrome.
Group 3 medulloblastoma accounts for 25 percent of cases and carries the worst prognosis with approximately 50 percent five-year survival. It affects young children with a male predominance and has a high rate of metastasis at diagnosis, reaching 40 to 50 percent. MYC amplification is a poor prognostic marker. The histology is typically classic or large cell/anaplastic.
Group 4 medulloblastoma is the most common subgroup at 35 percent of cases with intermediate prognosis. It peaks between 5 and 10 years with a male predominance. Isochromosome 17q is common. Metastatic risk is intermediate, and these patients may be candidates for reduced-dose craniospinal irradiation.
| Molecular Subgroup | Frequency | Age | 5-Year Survival | Key Features |
|---|---|---|---|---|
| WNT-activated | 10% | Older children/adolescents | >95% | Monosomy 6, nuclear β-catenin; de-escalation trials |
| SHH-activated | 30% | Bimodal (infants + adults) | Variable (TP53 status) | Desmoplastic variant; Gorlin/Li-Fraumeni associations |
| Group 3 | 25% | Young children | ~50% | MYC amplification; high metastatic rate (40-50%) |
| Group 4 | 35% | 5-10 years | Intermediate | Isochromosome 17q; most common subgroup |
Histological Subtypes
The classic subtype shows sheets of small round blue cells with Homer Wright rosettes. The desmoplastic/nodular subtype features reticulin-free zones called pale islands and carries a better prognosis in infants. Extensive nodularity is a variant of the desmoplastic subtype with excellent prognosis in infants. The large cell/anaplastic subtype demonstrates high mitotic rate and nuclear pleomorphism with aggressive behavior.
Clinical Presentation
Children present with obstructive hydrocephalus causing headache, vomiting, papilledema, and lethargy. Cerebellar signs include truncal ataxia from vermian tumors and appendicular ataxia from hemispheric tumors. Head tilt may reflect tonsillar herniation or trochlear nerve involvement. Symptom progression is typically rapid, over weeks to months. Cranial nerve palsies, particularly sixth and seventh nerves, result from brainstem involvement or hydrocephalus. Spinal metastases produce back pain, radiculopathy, or myelopathy.
Workup
Brain MRI with and without gadolinium provides full evaluation of the tumor and ventricular system. Spine MRI with gadolinium must be obtained preoperatively for staging of drop metastases. CSF cytology is collected postoperatively, at least two weeks after surgery to avoid false positives from surgical debris. Complete staging determines the risk category.
Risk Stratification
Standard risk requires age greater than 3 years, near-total resection with less than 1.5 square centimeters of residual tumor, no metastatic disease, and non-anaplastic histology. High risk includes age less than 3 years, subtotal resection with more than 1.5 square centimeters residual, metastatic disease, large cell/anaplastic histology, or MYC amplification. Molecular subgroup is increasingly integrated into risk stratification.
Surgical Management
The goal is maximal safe resection, with gross total resection achievable in approximately 70 to 80 percent of cases. The approach is a suboccipital midline craniotomy in the prone or sitting position, though the sitting position carries risk of venous air embolism. The midline vermian or telovelar approach provides access to the fourth ventricle. The ultrasonic aspirator is used for tumor debulking with careful dissection at the floor of the fourth ventricle to avoid injury to critical brainstem structures including the facial colliculus and dorsal vagal nuclei.
Hydrocephalus management begins with a preoperative EVD if the patient is acutely symptomatic. Many patients, approximately 60 to 70 percent, do not require permanent CSF diversion after tumor resection. VP shunt or ETV is placed for persistent hydrocephalus.
Cerebellar Mutism Syndrome
Cerebellar mutism syndrome, also called posterior fossa syndrome, occurs in 10 to 30 percent of children after posterior fossa tumor resection, particularly medulloblastoma. It typically develops 1 to 5 days postoperatively and features mutism or severe dysarthria, emotional lability, hypotonia, and ataxia. It usually resolves partially over weeks to months, with full recovery in approximately 50 percent. The etiology involves damage to the dentato-thalamo-cortical pathway and cerebellar efferent tracts. No proven prevention exists, though meticulous surgical technique and preservation of the cerebellar peduncles may reduce risk. Preoperative family counseling is essential.
Adjuvant Therapy
Craniospinal irradiation is standard for children older than 3 years. Standard-risk patients receive 23.4 Gy to the craniospinal axis with a posterior fossa boost to 54 to 55.8 Gy. High-risk patients receive 36 Gy craniospinal with a posterior fossa boost. Proton beam therapy reduces dose to non-target structures and is preferred when available. Chemotherapy regimens include cisplatin, vincristine, cyclophosphamide, and lomustine. The Packer regimen combines concurrent vincristine with craniospinal irradiation followed by maintenance cisplatin, vincristine, and CCNU.
For infants under 3 years, radiation is avoided or delayed due to devastating neurocognitive effects on the developing brain. Chemotherapy-only protocols such as Head Start and COG ACNS0334 are used, with focal radiation or delayed craniospinal irradiation in some protocols.
Outcomes
Overall five-year survival is 70 to 80 percent for standard risk and 50 to 60 percent for high risk. WNT subgroup tumors achieve greater than 95 percent survival, prompting trials exploring therapy reduction. Group 3 with MYC amplification has less than 50 percent survival. Long-term sequelae include neurocognitive deficits especially after craniospinal irradiation, endocrine dysfunction, hearing loss, and secondary malignancies.
Cerebellar Pilocytic Astrocytoma
Overview
Pilocytic astrocytoma is the most common posterior fossa tumor in children overall. It is WHO Grade I, benign, and curable with complete resection. Peak age is 5 to 15 years. It arises from the cerebellar hemisphere more commonly than the vermis.
Imaging
The classic MRI appearance is a cystic tumor with an enhancing mural nodule. It can also present as a solid enhancing mass. The tumor is well-demarcated from surrounding cerebellum, and calcification may be present.
Treatment
Gross total resection is curative, yielding greater than 95 percent ten-year survival. The cyst wall is not neoplastic and does not require resection. If GTR is not possible due to brainstem involvement, observation with serial MRI is appropriate. Adjuvant therapy is not indicated for pilocytic astrocytoma unless progressive unresectable disease develops. Recurrence after GTR is less than 5 percent, and re-resection is effective. NF1-associated optic pathway gliomas are pilocytic astrocytomas but behave differently and are typically managed with observation.
Ependymoma
Overview
Ependymoma is the third most common posterior fossa tumor in children, classified as WHO Grade II or III (anaplastic). Peak age is 1 to 5 years, younger than medulloblastoma. It arises from the ependymal lining of the fourth ventricle and tends to extend through the foramina of Luschka laterally, wrapping around the brainstem in a plastic fashion.
Molecular Classification
Posterior fossa Group A affects younger children with worse prognosis, characterized by H3K27me3 loss on immunohistochemistry. Posterior fossa Group B occurs in older children and adults with better prognosis. Supratentorial ependymomas are classified by RELA fusion or YAP1 fusion subtypes.
Treatment
Surgery is the primary treatment, with gross total resection being the most important prognostic factor. Resection is often technically challenging due to tumor adherence to the brainstem and cranial nerves, with GTR achievable in approximately 50 to 70 percent of cases. Second-look surgery is recommended when residual tumor remains. Conformal radiation therapy is delivered to the tumor bed at 54 to 59.4 Gy, not craniospinal, because ependymoma has a lower risk of CSF dissemination. Proton therapy is preferred to reduce dose to the developing brain. Chemotherapy has a limited role and is used primarily in infants to delay radiation. Five-year progression-free survival is approximately 50 to 65 percent overall, improving to 70 to 80 percent with GTR plus radiation. Recurrence is typically local, and re-resection with re-irradiation can be considered.
Diffuse Intrinsic Pontine Glioma / Diffuse Midline Glioma
Overview
DIPG is a devastating brainstem tumor in children with a median survival of only 9 to 11 months. Peak age is 5 to 9 years. Under the 2021 WHO classification, it is designated as a Grade IV H3K27M-mutant diffuse midline glioma. Diagnosis is often made on MRI alone based on the classic appearance, though biopsy is increasingly performed for molecular characterization and clinical trial enrollment.
Imaging
MRI reveals a T2/FLAIR hyperintense expansile mass centered in the pons that engulfs the basilar artery. Enhancement is minimal or absent. More than 50 percent of the pons is involved.
Treatment
Surgery is limited to biopsy only; resection is not feasible because the tumor infiltrates diffusely within the brainstem. Radiation at 54 Gy in 30 fractions provides temporary improvement lasting weeks to months. Chemotherapy has no proven benefit, though multiple clinical trials are ongoing. ONC201, a dRD2 agonist and TRAIL-inducing agent, has shown promising early results in clinical trials. The prognosis is uniformly fatal with two-year survival less than 10 percent.
Other Posterior Fossa Tumors
Atypical teratoid/rhabdoid tumor is highly aggressive, occurs in infants, is characterized by INI1/SMARCB1 loss, and requires aggressive multimodal therapy. Choroid plexus papilloma and carcinoma can occur in the fourth ventricle and may cause hydrocephalus from CSF overproduction.
<image>Sagittal T1-weighted post-contrast MRI of the brain in a child with a large midline posterior fossa medulloblastoma, showing a homogeneously enhancing mass filling the fourth ventricle, compressing the brainstem anteriorly and causing obstructive hydrocephalus with dilated lateral and third ventricles</image>
<image>Axial T1-weighted post-contrast MRI demonstrating a cerebellar pilocytic astrocytoma in a child, showing the classic appearance of a large cystic mass in the right cerebellar hemisphere with a brightly enhancing mural nodule, well-demarcated from the surrounding cerebellar parenchyma</image>
<image>Axial T2-weighted MRI at the level of the pons in a child with diffuse intrinsic pontine glioma (DIPG), showing a diffusely hyperintense expansile mass centered in the pons, engulfing the basilar artery with expansion of the pons to more than twice its normal size, and effacement of the fourth ventricle posteriorly</image>
<image>Intraoperative photograph during posterior fossa craniotomy for medulloblastoma resection, showing the telovelar approach to the fourth ventricle with the inferior vermis retracted superiorly and the tumor mass visible within the fourth ventricle, with cottonoid patties protecting the surrounding cerebellar tissue</image>
Clinical Pearls
Molecular subgrouping of medulloblastoma is now essential for treatment planning; WNT-activated tumors have excellent prognosis and may be candidates for therapy de-escalation, while Group 3 with MYC amplification demands intensified treatment. Always obtain a preoperative spine MRI before posterior fossa surgery, because postoperative blood products can mimic metastatic disease on subsequent imaging and confound staging. Cerebellar mutism syndrome is common after medulloblastoma resection, and families must be counseled preoperatively about this possibility and its expected course. For pilocytic astrocytoma, the enhancing mural nodule is the tumor and the cyst wall is reactive and does not need resection; GTR of the nodule alone is curative. DIPG is diagnosed by its classic MRI appearance of an expansile pontine mass; biopsy is performed primarily for molecular characterization and clinical trial enrollment rather than for diagnostic uncertainty. Ependymomas wrap around cranial nerves and brainstem, making intraoperative neurophysiological monitoring and meticulous microsurgical technique critical; do not sacrifice brainstem integrity for extent of resection. In infants with medulloblastoma, the desmoplastic/extensive nodularity histology with SHH activation has an excellent prognosis with chemotherapy alone, potentially sparing the devastating effects of craniospinal irradiation on the developing brain.
References
- Taylor MD et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2012;123(4):465-472.
- Ramaswamy V et al. Recurrence patterns across medulloblastoma subgroups. Lancet Oncol. 2013;14(12):1200-1207.
- Packer RJ et al. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006;24(25):4202-4208.
- Merchant TE et al. Conformal radiotherapy after surgery for paediatric ependymoma. Lancet Oncol. 2009;10(3):258-266.
- Louis DN et al. The 2021 WHO Classification of Tumors of the Central Nervous System. Neuro Oncol. 2021;23(8):1231-1251.
