Embryonal Brain Tumors, Medulloblastoma & Supratentorial PNETs

What are medulloblastoma and supratentorial PNETs?

Embryonal, malignant tumors of the central nervous system characterized by rapid growth, yet with meaningful potential for cure through combined-modality therapy.

Primitive neuroectodermal tumors (PNETs) are malignant neoplasms arising from immature neuroectodermal cells. Depending on their location:

• when they occur below the tentorium of the cerebellum and extend into the fourth ventricle, they are classically termed medulloblastoma;
• when they arise above the tentorium (within the cerebral hemispheres, thalamus, or periventricular regions), they are referred to as supratentorial PNETs (sPNETs).

Both tumor types have a propensity to disseminate through the cerebrospinal fluid (CSF) to other regions of the brain or the spinal axis. For this reason, management is not limited to surgery alone but is complemented by radiotherapy and chemotherapy.

How common are they and at what ages do they occur?

Among the most frequent malignant brain tumors in childhood, yet rare in the general population.

Medulloblastoma accounts for approximately 15–30% of all primary pediatric brain tumors and up to 50% of tumors of the posterior fossa. The median age at diagnosis is approximately 5–7 years.

Supratentorial PNETs are less common (approximately 2.5–6% of pediatric brain tumors) and typically present at even younger ages, often in children under 5 years. Despite their rarity, they require highly organized and aggressive treatment strategies.

What are the typical symptoms?

Symptoms of raised intracranial pressure, gait disturbance, or focal neurological deficits, often with relatively rapid onset.

Because these tumors grow relatively quickly, symptoms usually develop over weeks to a few months. Common signs and symptoms include:

• Headache (often worse in the morning and may awaken the child from sleep),
• recurrent vomiting without another obvious cause,
• unsteadiness, difficulty walking, or ataxia (the child “wobbles” when attempting to stand or walk),
• behavioral changes, fatigue, decreased appetite, or reduced interest in play,
• diplopia, nystagmus, strabismus, or other disturbances of eye movements,
• in supratentorial PNETs: focal neurological deficits (weakness of an arm/leg, seizures, speech or behavioral changes),
• in cases of spinal dissemination: persistent back pain, gait difficulty, or bladder dysfunction.

The combination of prolonged headaches, vomiting, and gait disturbance in a child warrants urgent evaluation by a pediatrician and, when indicated, a pediatric neurosurgeon.

Why do they develop – what do we know at the molecular level?

These tumors are not caused by parental actions, but by complex genetic alterations in developing brain cells.

In most cases, the underlying cause is unknown. They are not related to trauma, diet, or anything a family “did” or “did not do.” Rather, they arise from sporadic genetic alterations during brain development.

Contemporary research has demonstrated that medulloblastoma is not a single disease entity but comprises at least four distinct molecular subgroups:

• WNT – generally associated with an excellent prognosis,
• SHH (sonic hedgehog) – intermediate prognosis,
• Group 3 & Group 4 – more aggressive behavior, particularly Group 3.

Certain chromosomal abnormalities (e.g., 17p deletion, amplification of the MYC oncogene) are associated with more aggressive disease. In a small subset of children, medulloblastoma occurs in the context of hereditary syndromes such as Gorlin or Turcot syndrome, in which case specialized genetic counseling and testing are indicated.

Understanding molecular subgroups now allows treatment to be increasingly tailored: in some groups, therapy intensity may be safely reduced, while in others more targeted approaches may be explored within clinical trials.

How is the diagnosis made and what is the initial evaluation?

Advanced neuroimaging of the brain and spine, surgical biopsy or resection, and assessment for possible dissemination.

The diagnostic workup typically includes:

• Contrast-enhanced brain MRI to define tumor location, size, and characteristics (often solid, heterogeneously enhancing, with possible cysts or calcifications).
• Spinal MRI prior to surgery to evaluate for dissemination along the CSF pathways (nodular lesions or leptomeningeal enhancement).
• After surgical decompression, and when safe, a lumbar puncture may be performed for CSF cytology.

Definitive diagnosis is established through histopathologic and molecular analysis of tumor tissue obtained at surgery. In specialized centers, specimens undergo immunohistochemistry and molecular profiling, which directly influence the final treatment plan.

How is the disease staged – what does “average-risk” and “high-risk” mean?

Age, extent of resection, and presence of dissemination determine risk category and treatment intensity.

Traditionally, the Chang staging system is used, incorporating tumor size (T stage) and degree of CSF dissemination (M stage). Clinically, however, children are often categorized into two principal groups:

• Average-risk: age > 3–5 years, near-total resection (residual tumor < ~1.5 cm²), and no evidence of CSF or spinal dissemination.
• High-risk: age < 3 years, larger residual tumor, and/or metastatic disease within the CSF or spinal axis.

Risk category influences:

• the dose and distribution of radiotherapy,
• the intensity and number of chemotherapy cycles,
• consideration of enrollment in clinical trials.

What are the main treatment options?

A combined approach of surgery, radiotherapy, and chemotherapy, tailored to age and disease risk.

Management is always coordinated within a multidisciplinary tumor board including pediatric neurosurgeons, pediatric oncologists, radiation oncologists, neuroradiologists, endocrinologists, and comprehensive supportive care specialists.

The overarching treatment strategy includes:

• Maximal safe surgical resection of the tumor, with concurrent management of hydrocephalus (external ventricular drainage, endoscopic third ventriculostomy, or permanent shunt when required).
• Radiotherapy to the posterior fossa or resection cavity and the entire craniospinal axis (craniospinal irradiation), in appropriately aged children.
• Chemotherapy administered in cycles, often at high doses, with or without autologous stem cell rescue, depending on protocol.

In very young children, efforts are made to delay or limit radiotherapy (given the risk of significant neurocognitive injury) through intensified chemotherapy and, where available, proton beam radiotherapy.

What is the role of surgery?

Maximal safe resection is one of the most important prognostic factors—always prioritizing the child’s neurological safety.

The objectives of surgery are:

• to remove as much tumor as possible (ideally complete resection),
• to decompress the brain and manage hydrocephalus,
• to obtain sufficient tissue for precise histologic and molecular diagnosis.

At Neuroknife, we emphasize:

• use of neuronavigation, high-definition operative microscopy, and, when available, intraoperative imaging,
• meticulous preservation of critical neural structures (cerebellar nuclei, brainstem, cranial nerves),
• achieving the optimal balance between extent of resection and neurological safety.

Even if a small residual tumor remains, adjuvant radiotherapy and chemotherapy aim to eradicate remaining malignant cells.

What do radiotherapy and chemotherapy involve?

Targeted irradiation of the entire central nervous system and the resection cavity, combined with specialized chemotherapy protocols.

Following postoperative recovery, radiotherapy is planned by a specialized pediatric radiation oncologist:

• irradiation of the entire craniospinal axis (craniospinal irradiation) due to the risk of CSF dissemination,
• an additional “boost” dose to the resection cavity or posterior fossa,
• in younger children, proton beam therapy may be used when feasible to reduce radiation exposure to healthy tissues.

Chemotherapy is administered in cycles by pediatric oncologists, using tailored protocols based on:

• the child’s age and general condition,
• risk category,
• the tumor’s molecular subgroup.

In selected protocols—particularly for high-risk disease or very young children—high-dose chemotherapy with autologous hematopoietic stem cell support may be employed.

What are the potential complications and late effects?

While treatment is aimed at cure, careful long-term follow-up is required to address neurological, endocrine, and cognitive effects.

Short-term risks primarily relate to:

• surgery (bleeding, infection, transient or permanent neurological deficits),
• radiotherapy (fatigue, nausea, hair loss),
• chemotherapy (myelosuppression, infections, nausea, appetite loss).

Long-term, because treatment is delivered to a developing brain, particular attention is given to:

• neurocognitive function (memory, concentration, academic performance),
• endocrine health (growth hormone, thyroid function, pubertal development),
• hearing, vision, balance, fine motor skills,
• secondary malignancies in very long-term survivors.

For this reason, children who complete therapy are enrolled in structured long-term survivorship follow-up with pediatric oncologists, endocrinologists, neuropsychologists, and allied specialists to address emerging needs and support reintegration into school and everyday life.

What is the prognosis and what does this mean for the child’s future?

Despite their aggressive nature, long-term cure rates are substantial in modern treatment centers—particularly when complete resection is achieved and no dissemination is present.

In children with average-risk medulloblastoma, with complete or near-complete resection and no CSF dissemination, 5-year survival rates with contemporary protocols may reach or exceed 70–80%.

In high-risk cases (young age, residual tumor, metastatic disease), outcomes are lower but have improved significantly with intensified regimens and advanced radiotherapy techniques.

Historically, supratentorial PNETs carried a poorer prognosis than medulloblastoma; however, with modern protocols and improved molecular stratification, outcomes continue to improve.

Every child is unique. Our team takes the time to explain individualized prognostic factors (tumor type, molecular subgroup, extent of resection, treatment response) and to plan the next steps together with the family—medically, psychologically, and socially.