medulloblastoma

Medulloblastoma

Embryonal small round blue cell tumor usually arises in the roof of the fourth ventricle (fastigium).

● A small-cell embryonal tumor WHO grade IV that occurs predominantly in the posterior fossa of children (peak: 1st decade). The most common pediatric brain malignancy

● Usually arises in the cerebellar vermis (near the apex of the roof of fourth ventricle) or in the posterior brainstem, often producing hydrocephalus. Rarely supratentorial

● 4 genetic “clusters” (categories): 1) WNT-activated; 2) SHH-activated (TP53-mutant & -wildtype); 3) non-WNT/non-SHH, group 3; 4) non-WNT/non-SHH, group 4

● The 4 genetic clusters are further characterized by 4 histologic types: classic; desmoplastic/nodular; extensive nodularity; large cell/anaplastic

Brainstem invasion usually limits complete surgical excision

● All patients must be evaluated for “drop metastases

Several lines of evidence implicate granule neuron precursors (GNP) in the external granule layer (EGL) of the developing cerebellum as likely cells of origin for certain classes of medulloblastomas.

1). For example, cells that compose a preneoplastic stage of medulloblastoma colocalize with GNPs in the EGL and they express molecular markers of immature granule neurons ( 2). Another possible medulloblastoma cell of origin has been identified: a neural progenitor located in the cerebellar white matter and expressing both nestin and prominin ( 3). Signal transduction pathways that stimulate proliferation and inhibit differentiation of GNPs and other neural progenitor cells during development have been implicated in medulloblastoma. Thus, understanding the mitogenic functions of these pathways will yield insights into medulloblastoma formation.

The overexpression of proteins that normally stimulate proliferation of neural progenitor cells may initiate medulloblastoma formation. Two known mitogens for neural progenitors are the c-Myc oncoprotein and Sonic hedgehog (Shh), a crucial determinant of embryonic pattern formation in the central nervous system.

Several genes have been implicated in the development of medulloblastoma in children, including Patched-1 and Smoothened. The protein products of these genes function within the sonic hedgehog molecular signaling pathways, which are important in neural development and disease.

Cerebrospinal fluid (CSF) dissemination to the cranio-spinal axis occurs in 30% to 40% of cases 1).

However, medulloblastoma primarily presenting with symptoms related to spinal metastases is extremely rare 2) 3).

To date, there are only a limited number of cases that have been reported in the literature 4) 5) 6).

Hydrocephalus.

Obstructive hydrocephalus by blocking CSF pathways around the aqueduct. Extraneural metastases is probably a relatively low risk of cerebrospinal fluid shunt 7). A tumor filter may eventually become occluded by tumor cells and need replacement; may be able to radiate tumor filter to “sterilize” it 8).

Lack of standard response criteria in clinical trials for medulloblastoma and other seeding tumors complicates assessment of therapeutic efficacy and comparisons across studies. An international working group was established to develop consensus recommendations for response assessment. The aim is that these recommendations be prospectively evaluated in clinical trials, with the goal of achieving more reliable risk stratification and uniformity across clinical trials. Current practices and literature review were performed to identify major confounding issues and justify subsequently developed recommendations; in areas lacking scientific investigations, recommendations were based on experience of committee members and consensus was reached after discussion. Recommendations apply to both adult and pediatric patients with medulloblastoma and other seeding tumors. Response should be assessed using MR imaging (brain and spine), Cerebrospinal fluid cytology, and neurologic examination. Clinical imaging standards with minimum mandatory sequence acquisition that optimizes detection of leptomeningeal metastases are defined.

Warren et al. recommend central review prior to inclusion in treatment cohorts to ensure appropriate risk stratification and cohort inclusion. Consensus recommendations and response definitions for patients with medulloblastomas and other seeding tumors have been established; as with other RANO recommendations, these need to now be prospectively validated in clinical trials 9).


1) , 2) , 5)
Park TS, Hoffman HJ, Hendrick EB, Humphreys RP, Becker LE. Medulloblastoma: clinical presentation and management. Experience at the hospital for sick children, Toronto, 1950-1980. J Neurosurg. 1983;58:543–552. doi: 10.3171/jns.1983.58.4.0543.
3)
Laurent JP. Brain tumors in children. J Pediatr Neurosci. 1985;1:15–32.
4)
Allen JC. Childhood brain tumors: current status of clinical trials in newly diagnosed and recurrent disease. Pediatr Clin North Am. 1985;32:633–651.
6)
Stanley P, Suminski N. The incidence and distribution of spinal metastases in children with posterior fossa medulloblastomas. Am J Pediatr Hematol Oncol. 1988;10:283–287. doi: 10.1097/00043426-198824000-00002.
7)
Berger MS, Baumeister B, Geyer JR, Milstein J, et al. The Risks of Metastases from Shunting in Children with Primary Central Nervous System Tumors. J Neurosurg. 1991; 74:872–877
8)
Kessler LA, Dugan P, Concannon JP. Systemic Metastases of Medulloblastoma Promoted by Shunting. Surg Neurol. 1975; 3:147–152
9)
Warren KE, Vezina G, Poussaint TY, Warmuth-Metz M, Chamberlain MC, Packer RJ, Brandes AA, Reiss M, Goldman S, Fisher MJ, Pollack IF, Prados MD, Wen PY, Chang SM, Dufour C, Zurakowski D, Kortmann RD, Kieran MW. Response Assessment in Medulloblastoma and Leptomeningeal Seeding Tumors: Recommendations from the Response Assessment in Pediatric Neuro-Oncology Committee. Neuro Oncol. 2017 Apr 25. doi: 10.1093/neuonc/nox087. [Epub ahead of print] PubMed PMID: 28449033.
  • medulloblastoma.txt
  • Last modified: 2022/11/28 22:04
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