Medulloblastoma

• Photothermal Prussian blue nanoparticles generate potent multi-targeted tumor-specific T cells as an adoptive cell therapy
• Evolving driver mutations in adult-onset SHH-medulloblastoma originated from radiological cerebellar abnormality
• Melanoma antigens in pediatric medulloblastoma contribute to tumor heterogeneity and species-specificity of group 3 tumors
• KBTBD4 Cancer Hotspot Mutations Drive Neomorphic Degradation of HDAC1/2 Corepressor Complexes
• The Proteasome Inhibitor CEP-18770 Induces Cell Death in Medulloblastoma
• Retrospective experience of children with relapsed brain tumors treated with oral combination of axitinib and metronomic etoposide
• Optimising craniospinal irradiation for medulloblastoma: a dosimetric comparison of two VMAT planning methods
• Structure and mechanism of the human CTDNEP1-NEP1R1 membrane protein phosphatase complex necessary to maintain ER membrane morphology

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”

see Medulloblastoma epidemiology.

see Medulloblastoma classification.

Medulloblastoma Etiology.

Medulloblastoma Pathogenesis.

Medulloblastoma clinical features.

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)}.

see Medulloblastoma diagnosis.

Medulloblastoma Differential diagnosis

Medulloblastoma treatment.

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⁾.

see Medulloblastoma outcome.

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⁾.

Medulloblastoma case series.

Medulloblastoma case reports.