Accounts for 20%-25% of childhood CNS tumors.

Low-grade gliomas are the most common brain tumors of childhood, however medulloblastomas are the most common malignant brain tumors of childhood.

An aggressive embryonal tumor arising in the cerebellum or, less frequently,  in the dorsal brainstem.

Medulloblastomas usually arise in the cerebellum and patients present with increasing intracranial pressure or cerebellum dysfunction.

Medulloblastomas account for more than 60% of childhood embryonal  tumors. 

70% of  medulloblastomas occur and children under the age of 10 years, and affect boys more than girls. 

1/3 of cases of medulloblastomas arise children under the age of three years.

Incidence six per million in children ages 1-9 years.

Highly malignant process that arises from the cerebellum.

An embryonal CNS neoplasm.

Most common primary malignant intracranial tumor in childhood.

80% of cases diagnosed in children under the age of 15 years.

25-35% of children are under the age of three years at the time of presentation.

Median age at diagnosis is 5-8 years.

The age range runs into young adulthood.

Accounts for less than 1% of all adult brain tumors.

Accounts for approximately 140 new cases each year in the US at 15 years or greater age.
Four clinically relevant molecular sub groups exist – WNT (wingless related integrationsite),  SHH (sonic hedgehog signaling molecule) , group 3, and group 4 have been differentiated into additional subtypes.
There are fewer than 30 new cases per year among patients 40 years or older.

Incidence in adults approximately 0.5 per million per year and decreases in age.

Etiology unknown.

Factors associated with poor outcome include: large size, disseminated disease at presentation, young age of less than three years, and residual tumor of more than one and a half  centimeters squared on postoperative imaging.

Four subgroups recognized: WNT, SHH, Group 3 and Group 4.

Each subgroup is characterized by distinct clinicopathological and molecular features.

Cure rates, or five-year survival, across all four subgroups is 65 to 70%.

Patients with MB WNT have a favor prognosis of greater than 90% survival.

Primary management consists of surgical resection followed by radiation and chemotherapy.

Multimodality therapy with surgical resection, craniospinal radiation and combination chemotherapy can cure most children.

Traditionally postoperative radiotherapy (PORT) to the entire craniospinal axis, posterior fossa, and postoperative tumor bed has been standard of care.

PORT is associated with many deleterious effects on long-term survival, including neurocognitive decline, endocrinopathies, growth defects, and secondary malignant neoplasm.

Long-term sequelae are related to doses and are age dependent.

Treatment associated with postoperative neurocognitive abnormalities, postoperative mutism, endocrionopathies, sterility, and the risk of development of a meningioma or high-grade Glioma.

Recurrent disease associated with a median survival of less than six months and the two-year survival rate among such patients is approximately 9% (Zeltzer PM).

Approximately 30% of patients experience relapse, and most eventually die of their disease.

Increased risk for relapse include metastatic disease, diffuse anaplasia, and incomplete surgical resection.

Thought to arise from stem cells or early progenitor cells in the cerebellum.

Immature precursor cells in the cerebellum expand, migrate and differentiate from an external granule cell layer to form the internal granule cell layer (Wechsler-Reya RJ).

Precursor cell maturation is regulated by activation of the hedgehog pathway.

Aberrant ligand-independent activation of the hedegehog pathway promotes the development of medulloblastoma.

Develops in approximately 5% of patients with nevoid basal cell carcinoma syndrome, an autonomic dominant disorder of the germ line PTCH mutations (Gorlin’s syndrome) (Cowan R).

Mutations in genes MLL2 and MLL3 likely involved in the development of medulloblastoma.

Two main types are classical and thermoplastic, the latter having reticulin and collagen.

Prognosis not clearly related to degree of differentiation.

Approximately 2/3 of patients can be treated effectively.

Age important factor in childhood disease.

Higher incidence of the desmoplastic disease compared to classic histology and lateral cerebeller location in adults, although these findings not related to prognosis.

Often produces hydrocephalus due to its posterior fossa location.

Evaluation of entire neuraxis required because of the potential metastases to spine and brain.

Associated with increased intracranial pressure with papilledema and cerebeller changes of ataxia and nystagmus.

Positive prognostic features include a higher postoperative functional ability, absence of hydrocephalus, and presence of a ventriculoperitoneal shunt.

MDM2 overexpression associated with worse survival in adults.

Disease can rarely involve bone, soft tissues and lymph nodes.

MRI imaging technique of choice.

Lesions typically iso-hypointense on CT scanning and frequently demonstrates contrast enhancement.

Tumors mostly homogenous, but can have occasional cystic or necrotic findings on radioimaging.

Treatment consists of maximal surgical resection followed by craniospinal radiation, with or without chemotherapy.

Goal of surgery is to remove all visible tumor.

Associated hydrocephalus treated with tumor resection, external drainage procedure or shunting procedures.

Craniospinal radiation is standard treatment.

Lesions are radiosensitive.

Doses include 54 Gy to the primary site, 35-45 Gy to the brain and 30-40Gy to the spine.

In childhood disease CCNU, cisplatinum and vincristine are added as adjuvant therapy with improved survival (Prados), although this finding is not true in all series.

The role of chemotherapy in the initial management of the disease is not resolved.

A combination of temozolomide and Irinotecan are commonly used and recently augmented with bevacizumab.

The addition of carboplatinum during radiotherapy improved survival from 54% to 73% only for Children with high risk group 3 medulloblastoma.

Progression free survival 50-60% for high risk patients and 70-80% for standard risk patients.

Children with high risk medulloblastoma have relatively poor survival rates, with you studies showing durable treatment responses despite aggressive therapy.

5-year overall survival for adults 58-84%, and 5-year progression free survival rates 40-61%.

In childhood disease poor risk patients refer to those with: greater than 25% of residual tumor following resection, brainstem invasion, positive CSF cytology, or presence of distant metastases.

High risk patients treated with radiation alone have a 5 year progression free survival rates of 25-40%.

Neoadjuvant chemotherapy delays definitive radiation but does not adversely affect long term outlook.

Tends to disseminate via the neuraxis, so that lesions may exist in the spine, supratentorial cerebrum and may involve the cerebrospinal fluid.

Recurrence rates for adults 50-60% with a median time to tumor progression of nearly 30 months.

Median survival after recurrence in adults approximately 1.3 years.

Most common site of recurrent disease is in the posterior fossa, but may be in the spine cerebrospinal fluid supratentorial cerebrum, bones an soft tissues.

Late recurrences more typical of adult disease than childhood lesions.

Approximately 75% of recurrences in children occur within 2 years, while in adults 595 of recurrences occur by 2 years.

Late recurrences can occur as long as 14 years after treatment, indicating the necessity of long term follow-up.

Topotecan has a response rate of 28% when used neoadjuvantly in newly diagnosed medulloblastoma.

A metronomic antiangiogenic regimen in recurrent medulloblastoma, using daily oral thalidomide, fenofibrate, celecoxib, and alternating with low-dose, oral etoposide and cyclophosphamide supplemented by IV bevacizumab, and Intraventricular treatments alternating etoposide and cytarabine resulted in a high complete response rate and well tolerated (Peyrl, A).

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