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Pediatric and Developmental Pathology :... 2022In 2016, medulloblastoma classification was restructured to allow for incorporation of updated data about medulloblastoma biology, genomics, and clinical behavior. For... (Review)
Review
In 2016, medulloblastoma classification was restructured to allow for incorporation of updated data about medulloblastoma biology, genomics, and clinical behavior. For the first time, medulloblastomas were classified according to molecular characteristics ("genetically defined" categories) as well as histologic characteristics ("histologically defined" categories). Current genetically-defined categories include WNT-activated, SHH-activated wildtype, SHH-activated -mutant, and non-WNT/non-SHH. In this article, we review the most recent update to the classification of medulloblastomas, provide a practical approach to immunohistochemical and molecular testing for these tumors, and demonstrate how to use key molecular genetic findings to develop an integrated diagnosis.
Topics: Cerebellar Neoplasms; Humans; Medulloblastoma; World Health Organization
PubMed: 35168417
DOI: 10.1177/10935266211018931 -
Neuro-Chirurgie Feb 2021Medulloblastomas, embryonal neuroepithelial tumors developed in the cerebellum or brain stem, are mainly observed in childhood. The treatment of WHO-Grade IV tumors... (Review)
Review
Medulloblastomas, embryonal neuroepithelial tumors developed in the cerebellum or brain stem, are mainly observed in childhood. The treatment of WHO-Grade IV tumors depends on stratifications that are usually based on postoperative data, histopathological subtype, tumor extension and presence of MYC or NMYC amplifications. Recently, molecular biology studies, based on new technologies (i.e. sequencing, transcriptomic, methylomic) have introduced genetic subtypes integrated into the latest WHO-2016 neuropathological classification. According to this classification, the three genetic groups WNT, SHH, with or without mutated TP53 gene, and non-WNT/non-SHH, comprising subgroups 3 and 4, are recalled in this review. The contribution of immunohistochemistry to define these groups is specified. The four histopathological groups are detailed in comparison to the WHO-2007 classification and the molecular data: classic medulloblastoma, desmoplastic/nodular medulloblastoma, medulloblastoma with extensive nodularity, and large cell/anaplastic medulloblastoma. The groups defined on genetic and histopathological grounds are not strictly concordant. Depending on the age of the patients, their correlations are different, as well as their role in the management and prognosis of these tumors. Other embryonal tumors, for which new classifications are in progress and gliomas may be confused with a medulloblastoma and the elements of the differential diagnosis of these entities are discussed. This evolution in classification fully justifies ongoing structuring procedures such as histopathological review (RENOCLIP) and the organization of molecular biology platforms.
Topics: Adolescent; Adult; Cerebellar Neoplasms; Cerebellum; Child; Child, Preschool; Female; Humans; Male; Medulloblastoma; Neoplasms, Germ Cell and Embryonal; Prognosis; Young Adult
PubMed: 29703584
DOI: 10.1016/j.neuchi.2017.12.006 -
Child's Nervous System : ChNS :... Mar 2022Medulloblastoma (MB) is the most common malignant pediatric brain tumor, accounting for 40% of childhood tumors in posterior fossa. Metastatic disease, occurring in... (Review)
Review
BACKGROUND
Medulloblastoma (MB) is the most common malignant pediatric brain tumor, accounting for 40% of childhood tumors in posterior fossa. Metastatic disease, occurring in 20-30% of all medulloblastoma cases at diagnosis, is largely exclusive to the leptomeninges. On the contrary, primary leptomeningeal medulloblastoma or so-called chameleon medulloblastoma, defined by the absence of a detectable intraparenchymal lesion with a widespread diffusion along leptomeninges, is a rare entity of difficult diagnosis with only a few cases reported in literature.
METHODS AND RESULTS
A comprehensive literature search of three databases (PubMed, Ovid Medline, and Ovid Embase) have been conducted to identify pertinent papers focusing on the diagnostic process, management, and treatment of primary leptomeningeal medulloblastoma and its peculiar features. To our knowledge, only eight cases are described in literature, including five pediatric patients and three adults, two of which with the initial involvement of the spinal cord. In addition, we report another two pediatric cases, showing widespread primary diffusion along leptomeninges of brain and spinal cord. Finally, we analyze in-depth the peculiar morphological MRI features of this tumor.
CONCLUSION
The classification and treatment of medulloblastomas are likely to change in the coming years due to new insights into the molecular biology of medulloblastoma. Primary leptomeningeal medulloblastoma could represent another potential challenge for biologists to start exploring the underlying mechanisms of this different clinical and pathological entity, with different implications for diagnosis and its management.
Topics: Adult; Brain Neoplasms; Cerebellar Neoplasms; Child; Humans; Magnetic Resonance Imaging; Medulloblastoma
PubMed: 35059784
DOI: 10.1007/s00381-021-05435-x -
Nature Reviews. Disease Primers Feb 2019
Topics: Humans; Medulloblastoma; Quality of Life
PubMed: 30765710
DOI: 10.1038/s41572-019-0067-2 -
Neuro-Chirurgie Feb 2021Medulloblastoma is the most common malignant brain tumors in children. Current management combines surgery, radiotherapy, and chemotherapy. Current treatment of... (Review)
Review
Medulloblastoma is the most common malignant brain tumors in children. Current management combines surgery, radiotherapy, and chemotherapy. Current treatment of medulloblastoma is based on a clinical risk-stratification system that takes into account age, extent of resection and metastatic status. High-risk medulloblastoma patients are defined by the presence of metastatic disease and/or an incomplete resection with a residual amount of tumour>1.5 cm. This review describes the evolution in the management of high-risk medulloblastoma patients during recent 4 decades and recent changes in the definition of high-risk patients as a result of major advances in the understanding of the molecular heterogeneity of medulloblastomas.
Topics: Cerebellar Neoplasms; Child; Child, Preschool; Clinical Trials as Topic; Disease Management; Disease Progression; Female; Humans; Male; Medulloblastoma; Risk Factors
PubMed: 31229532
DOI: 10.1016/j.neuchi.2019.05.007 -
Clinical Oncology (Royal College of... Jan 2013Medulloblastomas are primary malignant embryonal tumours of the central nervous system. They are the most common childhood central nervous system tumour, but are rare in... (Review)
Review
Medulloblastomas are primary malignant embryonal tumours of the central nervous system. They are the most common childhood central nervous system tumour, but are rare in the adult population. They arise infratentorially in the cerebellum or fourth ventricle and hence the most common presenting symptoms are those associated with raised intracranial pressure. Several histological subtypes have been described, although the classical and desmoplastic subtypes account for the majority. Recent advances in molecular biology and cytogenetics have led to an improved understanding of the genetic abnormalities and alterations in cell signalling pathways associated with medulloblastomas, including how these relate to patient outcome. The Modified Chang Staging System is still in use, but a number of other factors, including age, completeness of resection, histological subtype and genetic markers now contribute to treatment decisions and prognostication. Patients are currently classified as being either standard or high risk in order to stratify treatment. There has been an improvement in survival of all groups over the past 20 years. A multimodality approach is the cornerstone of treatment and recent trials have concentrated on ascertaining the most efficacious treatment combinations and timings for each patient group. Advances in surgical techniques have allowed a greater attainment of the two primary surgical goals: restoring normal cerebrospinal fluid (CSF) flow and maximal tumour resection. Radiotherapy to the craniospinal axis with a boost to the posterior fossa has been standard practice, but improvement in radiotherapy techniques and quality control has enabled optimisation of the trade-off between tumour control and normal tissue late toxicities. Combination chemotherapy is usually given adjuvantly, although it may be used to delay or avoid the use of radiotherapy in infants. In the future, the treatment of medulloblastoma will probably become increasingly individualised, based on patient-specific genetic features. Attention will be focussed not only on improving survival, but also on maintaining quality of life.
Topics: Brain Neoplasms; Cerebellar Neoplasms; Child; Combined Modality Therapy; Humans; Medulloblastoma; Prognosis; Treatment Outcome
PubMed: 23245832
DOI: 10.1016/j.clon.2012.09.008 -
JAAPA : Official Journal of the... Oct 2017Brain tumors are the most common solid tumor malignancies in childhood, and among them, medulloblastoma occurs with the greatest frequency. Because medulloblastomas... (Review)
Review
Brain tumors are the most common solid tumor malignancies in childhood, and among them, medulloblastoma occurs with the greatest frequency. Because medulloblastomas occur in the posterior fossa, the presenting symptoms often are vague complaints and diagnosis may be delayed. Between 70% and 80% of patients who are diagnosed before metastatic dissemination survive, compared with 30% to 40% of those in higher risk groups. This article reviews the diagnosis, treatment, and prognosis for medulloblastoma.
Topics: Cerebellar Neoplasms; Humans; Medulloblastoma; Neoplasm Staging; Prognosis
PubMed: 28953021
DOI: 10.1097/01.JAA.0000524717.71084.50 -
No Shinkei Geka. Neurological Surgery Jan 2022Current treatment protocols for medulloblastomas(MBs)stratify patients into high and average risk groups according to their age, metastatic status, and residual tumor...
Current treatment protocols for medulloblastomas(MBs)stratify patients into high and average risk groups according to their age, metastatic status, and residual tumor volume after resection. Recent genetic and molecular biological reserach revealed that MBs are classified into at least four core subgroups - WNT, SHH, Group 3, and Group 4 - based on differences in their cytogenetics, mutational spectra, and gene expression signatures, as well as in their clinical phenotypes and prognosis. Latest studies suggest more distinct subtypes of MBs by DNA methylation profiles. In addition to conventional clinical risk stratification, new molecular risk stratification using molecular subgroups/subtypes, cytogenetic features and copy number aberrations help understand the outcome of current standard and/or experimental therapies. To achieve further improvement in prognosis and reduce treatment-related adverse events, the efficiency and safety of low-dose craniospinal irradiation and novel molecular targeted drugs, including SMO inhibitors, cyclin-dependent kinases 4/6, or checkpoint kinase 1/2 inhibitors, have been examined with respect to the molecular properties of each tumor. The molecular information of each MB is indispensable for precision medicine of MBs, strongly promoting the development of advanced therapeutic strategies of MBs.
Topics: Cerebellar Neoplasms; Disease Progression; Humans; Medulloblastoma; Prognosis; Risk Factors
PubMed: 35169088
DOI: 10.11477/mf.1436204533 -
Acta Bio-medica : Atenei Parmensis Jun 2020The lack of success of standard therapies for medulloblastoma has highlighted the need to plan a new therapeutic approach. The purpose of this article is to provide an... (Review)
Review
BACKGROUND
The lack of success of standard therapies for medulloblastoma has highlighted the need to plan a new therapeutic approach. The purpose of this article is to provide an overview of the novel treatment strategies based on the molecular characterization and risk categories of the medulloblastoma, also focusing on up-to-date relevant clinical trials and the challenges in translating tailored approaches into clinical practice.
METHODS
An online search of the literature was carried out on the PubMed/MEDLINE and ClinicalTrials.gov websites about molecular classification of medulloblastomas, ongoing clinical trials and new treatment strategies. Only articles in the English language and published in the last five years were selected. The research was refined based on the best match and relevance.
RESULTS
A total 58 articles and 51 clinical trials were analyzed. Trials were of phase I, II, and I/II in 55%, 33% and 12% of the cases, respectively. Target and adoptive immunotherapies were the treatment strategies for newly diagnosed and recurrent medulloblastoma in 71% and 29% of the cases, respectively.
CONCLUSION
Efforts are focused on the fine-tuning of target therapies and immunotherapies, including agents directed to specific pathways, engineered T-cells and oncoviruses. The blood-brain barrier, chemoresistance, the tumor microenvironment and cancer stem cells are the main translational challenges to be overcome in order to optimize medulloblastoma treatment, reduce the long-term morbidity and increase the overall survival.
Topics: Brain Neoplasms; Cerebellar Neoplasms; Humans; Immunotherapy; Medulloblastoma; Tumor Microenvironment
PubMed: 32608377
DOI: 10.23750/abm.v91i7-S.9958 -
No Shinkei Geka. Neurological Surgery Sep 2023In the 5 edition of the WHO classification, medulloblastomas, which are representative pediatric brain tumors, are categorized into four groups: WNT, SHH-TP53 wild,...
In the 5 edition of the WHO classification, medulloblastomas, which are representative pediatric brain tumors, are categorized into four groups: WNT, SHH-TP53 wild, SHH-TP53 mutant, and non-WNT/non-SHH, based on their molecular background. While the histopathological findings still hold importance in predicting prognosis, the histopathological classification is no longer utilized in this edition. SHH medulloblastomas are further subdivided into two groups based on the presence or absence of TP53 mutation, as their clinical characteristics and prognosis differ. Group 3 and Group 4 medulloblastomas, recognized as distinct molecular groups in clinical practice, are combined into a single group called "non-WNT/non-SHH", because they lack specific molecular pathway activation. Furthermore, based on methylation profiling, dividing SHH medulloblastoma into four subgroups and non-WNT/non-SHH medulloblastoma into eight subgroups was proposed. Understanding the unique clinical characteristics and prognosis associated with each group is crucial. However, it is important to acknowledge that our current understanding of prognosis is based on treatment approaches guided by clinical risk factors such as postoperative residual tumor volume and the presence of metastatic disease. This molecular-based classification holds promise in guiding the development of optimal treatment strategies for patients with medulloblastoma.
Topics: Child; Humans; Medulloblastoma; Brain Neoplasms; Mutation; Neoplasm, Residual; Cerebellar Neoplasms
PubMed: 37743337
DOI: 10.11477/mf.1436204827