Medulloblastoma pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]
Overview
Medulloblastoma arises from the cerebellar stem cells, which are normally involved in the anatomical development of the cerebellum and other posterior fossa structures. Medulloblastoma is an invasive and rapidly growing brain tumor which frequently metastasize to different organs of the body. Genes involved in the pathogenesis of medulloblastoma include CTNNB1 gene, PTCH1 gene, MLL2 gene, SMARCA4 gene, DDX3X gene, CTDNEP1 gene, KDM6A gene, and TBR1 gene. Medullobastomas is associated with a number of syndromes that include Gorlin syndrome and Turcot syndrome.[1] On gross pathology, a pink, solid, and well circumscribed mass is a characteristic finding of medulloblastoma. On microscopic histopathological analysis, round tumor cells, elevated mitotic rate, increased nucleus:cytoplasmic ratio, and Homer-Wright rosettes are characteristic findings of medulloblastoma.[2]
Pathogenesis
- Medulloblastoma arises from the cerebellar stem cells, which are normally involved in the anatomical development of the cerebellum and other posterior fossa structures.[1]
- Medulloblastoma is usually located at the infratentorial region, where it forms a mass between the brain stem and the cerebellum in the vicinity of the fourth ventricle.[1]
- Medulloblastoma is an invasive and rapidly growing brain tumor.[1]
- Unlike most brain tumors, medulloblastoma may spread through the cerebrospinal fluid and metastasize to different organs of the body.[1]
Genetics
- Development of medulloblastoma is the result of multiple genetic mutations.[1]
- Genes involved in the pathogenesis of medulloblastoma include:[1]
- CTNNB1 gene on chromosome 3
- PTCH1 gene located on chromosome 9
- MLL2 gene located on chromosome 12
- SMARCA4 gene located on chromosome 19
- DDX3X gene located on X chromosome
- CTDNEP1 gene located on chromosome 17
- KDM6A gene located on X chromosome
- TBR1 gene located on chromosome 2
- Medulloblastoma may be classified into at least four major subtypes based on a molecular classification criterion which include:[3][4]
- WNT subgroup:
- Present among 10% of medulloblastoma patients
- Cytogenetic markers include classic monosomy 6
- Molecular markers include beta-catenin
- SHH subgroup:
- Present among 25% of medulloblastoma patients
- Cytogenetic markers include chromosome 9q deletion
- Molecular markers include SFRP1 or GAB1
- Group 3 medulloblastoma:
- Present among 30% of medulloblastoma patients
- Cytogenetic markers include isochromosome 17q
- Molecular markers include MYC activation
- Group 4 medulloblastoma:
- Present among 35% of medulloblastoma patients
- Cytogenetic markers include isochromosome 17q
- Molecular markers are still under investigation
Associated Conditions
Gross Pathology
- On gross pathology, a pink, solid, and well circumscribed mass is a characteristic finding of medulloblastoma.[1]
- The following image demonstrates the gross pathology observed in medulloblastoma:
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Medulloblastoma pink and well circumscribed mass[5]
Mircoscopic Pathology
- On microscopic histopathological analysis, round tumor cells, elevated mitotic rate, increased nucleus:cytoplasm ratio, and Homer-Wright rosettes are characteristic findings of medulloblastoma.[2]
- Medulloblastoma may be classified into two subtypes based on WHO histological classification criterion which include classic medulloblastoma and variant medulloblastoma
- Variant medulloblastoma may be further classified into desmoplastic medulloblastoma, large cell medulloblastoma, anaplastic medulloblastoma and medulloblastoma with extensive nodularity.[2][5]
- The table below differentiates between the five main groups of medulloblastoma according to WHO histological classification:[6]
Grade | Histologic features |
---|---|
Classic medulloblastoma |
Dense sheet like growth of cells, hyperchromatic round-to-oval nucleus, increased mitotic activity, conspicuous apoptosis, Homer-Wright rosettes, and necrosis is less common |
Desmoplastic medulloblastoma variant |
Brain tissue invasion, 4 or more mitosis/10 HPF, necrosis, increased cell count, high nucleus:cytoplasm ratio, increased nucleoli size, and presence of sheeting |
Medulloblastoma with extensive nodularity variant |
Cellular uniformity, fine fibrillary matrix, and occasional presence of mature ganglion cells |
Large cell / anaplastic medulloblastoma variant |
Both variants demonstrate high mitotic activity, pleomorphism, large round nucleus with variable eosinophilic cytoplasm, hemorrhage, and necrosis is common |
- Shown below is a series of microscopic images observed in medulloblastoma:
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Medulloblastoma[2]
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Medulloblastoma[2]
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Medulloblastoma demonstrating Homer-Wright rosettes[2]
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Medulloblastoma demonstrating cerebellar infiltrative growth[2]
-
Anaplastic large cell medulloblastoma[2]
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Medulloblastoma[2]
-
Desmoplastic medulloblastoma on MIB-1 immunostaining[2]
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Medulloblastoma demonstrating partial MAP2 immunoreactivity[2]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September, 28 2015
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28 2015
- ↑ Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T; et al. (2012). "Subgroup-specific structural variation across 1,000 medulloblastoma genomes". Nature. 488 (7409): 49–56. doi:10.1038/nature11327. PMC 3683624. PMID 22832581.
- ↑ Leary SE, Olson JM (2012) The molecular classification of medulloblastoma: driving the next generation clinical trials. Curr Opin Pediatr 24 (1):33-9. DOI:10.1097/MOP.0b013e32834ec106 PMID: 22189395
- ↑ 5.0 5.1 5.2 Medulloblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/medulloblastoma Accessed on September, 28 2015
- ↑ Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A; et al. (2007). "The 2007 WHO classification of tumours of the central nervous system". Acta Neuropathol. 114 (2): 97–109. doi:10.1007/s00401-007-0243-4. PMC 1929165. PMID 17618441.