In children, medulloblastoma has a proclivity for the midline posterior fossa; it often obstructs the 4th ventricle and affects the cerebellar vermis.
Medulloblastoma
Overview
- Malignant (rapidly growing and invasive), pediatric-onset, embryonal tumor of the cerebellum.
- Sporadic, typically, but infrequently will occur with certain hereditary syndromes (see below).
- Accounts for 20% of malignant CNS pediatric tumors.
Clinical Highlights
Aggressive, malignant neoplasms (note that they are all Grade 4*) that typically manifest in midline regions within children, especially the cerebellar vermis (often in the lateral cerebellar hemispheres in adults).
- Children < 3 yo have a poorer prognosis.
- Present with cerebellar dysfunction and symptoms of 4th ventricle obstruction (nausea/vomiting, etc...).
Histopathology
- Dense cellularity with undifferentiated small blue cells: they are small, hyperchromatic cells with scant cytoplasm (a high nuclear to cytoplasm ratio).
- The cells have oval to carrot-shaped nuclei (and minimal cytoplasm).
- The proliferation is so dense, it is termed "sheet-like".
- They have frequent mitoses, necrotic regions, and a propensity to metastasize to CSF spaces (see 4th ventricle tumors)
- Homer Wright rosettes are ball-like cluster of cells that enclose a meshwork of fibers. The cells are differentiated tumor cells and they group around a central neuropil-region (the fiber meshwork).
- If Homer Wright rosettes are discovered in a posterior fossa tumor, think: medulloblastoma but they can occur in other tumors, as well (including supratentorial PNET (primitive neuroectodermal tumor), neuroblastoma (adrenal and sympathetic tumors), and pinealoblastoma).
- Compare to Flexner-Wintersteiner rosettes, true ependymal rosettes, and pseudoperivascular rosettes
Drop Metastasis
- Medulloblastoma can produce drop metastases to the spinal cord.
Genetics
- Typically develops sporadically but can occur with the following hereditary syndromes:
- Turcot's syndrome
- APC gene mutation (germline mutation of the adenomatous polyposis coli)
- Gorlin's syndrome
- PCTH gene mutation (nevoid basal cell carcinoma syndrome).
Select Molecular Findings & Prognosis
- Chromosome 17 abnormalities are an important a negative prognostic indicator in medulloblastoma.
- Key tumor suppressor genes exist on chromosome 17 (eg, TP53, tumor protein) and if they are dysfunctional, the tumor behaves more aggressively.
- N-myc amplification carries a poorer prognosis.
Tumor Differential
- Anaplastic ependymoma
- Atypical Teratoid/Rhabdoid Tumor (AT/RT)
- Small cell glioblastoma
- Additional metastatic small cell tumors
Posterior Fossa Mutism
Post-surgical resection complication.
- Pathology is secondary to dentatorubral-thalamocortical tracks.
- These tracks are the deep component of the cortico-ponto-cerbellar pathway.
- Mutism
- Presents anywhere from 6 to 48 hours after surgery.
- Emotional lability
- Supranuclear palsies
References
- “A Closer Look at IDH Mutations | Astrocytoma Options.” Accessed May 31, 2018. http://astrocytomaoptions.com/idh1-mutation/.
- Adesina, Adekunle M., Tarik Tihan, Christine E. Fuller, and Tina Young Poussaint. Atlas of Pediatric Brain Tumors. Springer, 2016.
- Chakrabarti, Indranil, Kaushik Majumdar, and Amita Giri. “Infratentorial Medulloepithelioma with Divergent Differentiation: Possibly a Predictor of Poor Outcome.” Journal of Pediatric Neurosciences 7, no. 2 (2012): 142–45. https://doi.org/10.4103/1817-1745.102581.
- “Childhood Central Nervous System Embryonal Tumors.” PdqCancerInfoSummary. National Cancer Institute. Accessed June 14, 2018. https://www.cancer.gov/types/brain/hp/child-cns-embryonal-treatment-pdq.
- Gupta, Anshu, and Tanima Dwivedi. “A Simplified Overview of World Health Organization Classification Update of Central Nervous System Tumors 2016.” Journal of Neurosciences in Rural Practice 8, no. 4 (2017): 629–41. https://doi.org/10.4103/jnrp.jnrp_168_17.
- Holcomb, George W., Jerry D. Murphy, and Daniel J. Ostlie. Ashcraft’s Pediatric Surgery E-Book. Elsevier Health Sciences, 2014.
- Institute, Dr Maria Tsokos, National Cancer. Shown Is a Microscopic View of a Typical Neuroblastoma with Rosette Formation. Magnified X40. December 1993. http://visualsonline.cancer.gov/details.cfm?imageid=2593. https://commons.wikimedia.org/wiki/File:Neuroblastoma_rosettes.jpg.
- Jensflorian. English: Histology of Anaplastic Medulloblastoma with Increased Mitotic Activity and Cell Pleomorphim. October 11, 2010. Own work. https://commons.wikimedia.org/wiki/File:Anaplastic_medulloblastoma_x200.jpg.
- Louis, David N., Arie Perry, Guido Reifenberger, Andreas von Deimling, Dominique Figarella-Branger, Webster K. Cavenee, Hiroko Ohgaki, Otmar D. Wiestler, Paul Kleihues, and David W. Ellison. “The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A Summary.” Acta Neuropathologica 131, no. 6 (June 1, 2016): 803–20. https://doi.org/10.1007/s00401-016-1545-1.
- “Meeting Library | New Classification for Central Nervous System Tumors: Implications for Diagnosis and Therapy.” Accessed May 31, 2018. https://meetinglibrary.asco.org/record/138232/edbook#fulltext.
- Newton, Herbert B. Handbook of Brain Tumor Chemotherapy, Molecular Therapeutics, and Immunotherapy. Academic Press, 2018.
- Orkin, Stuart H., David E. Fisher, A. Thomas Look, Samuel Lux, David Ginsburg, and David G. Nathan. Oncology of Infancy and Childhood E-Book. Elsevier Health Sciences, 2009.
- Perry, Arie. “WHO’s Arrived in 2016! An Updated Weather Forecast for Integrated Brain Tumor Diagnosis.” Brain Tumor Pathology 33, no. 3 (July 1, 2016): 157–60. https://doi.org/10.1007/s10014-016-0266-4.
- Prayson, Richard A., and Mark L. Cohen. Practical Differential Diagnosis in Surgical Neuropathology. Springer Science & Business Media, 2000.
- Reni, Michele, Elena Mazza, Silvia Zanon, Gemma Gatta, and Charles J. Vecht. “Central Nervous System Gliomas.” Critical Reviews in Oncology/Hematology 113 (May 2017): 213–34. https://doi.org/10.1016/j.critrevonc.2017.03.021.
- Ryall, Scott, Uri Tabori, and Cynthia Hawkins. “A Comprehensive Review of Paediatric Low-Grade Diffuse Glioma: Pathology, Molecular Genetics and Treatment.” Brain Tumor Pathology 34, no. 2 (April 1, 2017): 51–61. https://doi.org/10.1007/s10014-017-0282-z.
- Wippold, F. J., and A. Perry. “Neuropathology for the Neuroradiologist: Rosettes and Pseudorosettes.” American Journal of Neuroradiology 27, no. 3 (March 1, 2006): 488–92.
Image Reference
- Homer Wright rosette adapted from:
- Institute, Dr Maria Tsokos, National Cancer. Shown Is a Microscopic View of a Typical Neuroblastoma with Rosette Formation. Magnified X40. December 1993. http://visualsonline.cancer.gov/details.cfm?imageid=2593. https://commons.wikimedia.org/wiki/File:Neuroblastoma_rosettes.jpg.