Medulloblastoma+(child)

Constitutes about 25% of all childhood brain tumors1 Occurs in children 2-12 y.o1 Peak at age 5 Rarely occurs in adults1 || High incidence of spread to CSF Medulloblastoma is an undifferentiated tumor believed to arise from:2 Primitive multipotential medulloblast, embryologically located in the external granular layer of the cerebellum. It is classically identified as a primitive neuroectodermal tumor presenting in the posterior fossa. 2 || Headaches that start in the morning and get progressively better throughout the day. Headaches as a result of coughing or physical activity Vomitting shorly after waking in the morning. Papilledema--swollen optic nerve Seizures Clumsiness/unsteadiness || Lab Studies: Miscellaneous tests: Procedures: Another hypothesis proposes that medulloblastomas have more than one cell of origin. This is based on studies showing differential immunoreactivity to a neuronal calcium-binding protein that is not expressed in the external granular layer and to a beta-tubulin isotype that is expressed in the neuronal cells of the ventricular matrix and external granular layer. Numerous molecular alterations that appear to modulate the biological behavior of medulloblastoma or its response to therapy have been reported. As the tumor grows, obstruction of cerebrospinal fluid (CSF) passage through the fourth ventricle generally occurs, resulting in hydrocephaly. The tumor may spread contiguously, to the cerebellar peduncle and/or the floor of the fourth ventricle; anteriorly, to the brainstem; inferiorly, to the cervical spine; or superiorly, above the tentorium. It also may spread via the CSF intracranially or to the leptomeninges and spinal cord. Of all the pediatric CNS neoplasms, medulloblastoma has the greatest propensity for extraneural spread, especially to bone and bone marrow; however, the rate of such events is less than 4%.4 || GX – Grade cannot be assessed G1 – Well differentiated G2 – Moderately differentiated G3 – Poorly differentiated G4 - Undifferentiated || M0 – No metastasis M1 – Tumor cells found in cerebrospinal fluid <span style="color: #800080; font-family: Arial,Helvetica,sans-serif;">M2 – Gross nodular seeding in the cerebellar, cerebral subarachnoid space, or in the third or lateral ventricles <span style="color: #800080; font-family: Arial,Helvetica,sans-serif;">M3 – Gross nodular seeding in the spinal subarachnoid space <span style="color: #800080; font-family: Arial,Helvetica,sans-serif;">M4 – Metastases outside the central nervous system || > ||
 * **Epidemiolgy:** || <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Prototype posterior fossa malignancy1
 * **Etiology:** || <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Arises in midline of the cerebellum and can invade the 4th ventricle and brainstem1
 * **Signs & Symptoms:** || <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Presenting symptoms occur over a few weeks to months1Symptoms occur due to blocking of the fourth ventricle, causing hydrocephalus:1
 * **Diagnostic Procedures:** || Imaging Studies:3
 * CT scans of the head with and without contrast
 * MRI scans of the head and spinal canal with and without gadolinium should be performed on anyone suspected of having a medulloblastoma
 * Bone Scans may be useful in symptomatic patients because medulloblastoma can metastasize outside the CNS, especially to bone
 * CBC count, electrolytes, liver, and renal function tests. It is also recommended to get a baseline thyroid function study and viral titers.
 * As a result of the potential toxicity from radiation and chemotherapy, a baseline hearing test is recommended. Other protocols might require other tests such as echocardiography, pulmonary function tests, etc. to help monitor treatment-related toxicity.
 * Bone Marrow aspirate and biopsy
 * Lumbar puncture
 * Fuduscopic examination through a CT or MRI has to be performed before the lumbar puncture to rule out the presence of hydrocephaly. ||
 * **Histology:** || Medulloblastoma is a cerebellar tumor arising predominantly from the cerebellar vermis. The histogenesis of medulloblastoma remains controversial. One view suggests that the cell of origin derives from the external granular layer of the cerebellum. This is supported by the finding that the proliferation of precursor neurons in this layer is controlled by sonic hedgehog (shh), whose receptor PTCH is mutated in a subset of sporadic medulloblastomas.
 * **Lymph node drainage:** || There are no lymphatic channels in the brain.3 ||
 * **Metastatic spread:** || Tumors affecting the central nervous system rarely develop extraneural metastases due to their biological characteristics and the lack of a well-developed lymphatic drainage system in the brain. In children, however, medulloblastomas can spread through cerebrospinal fluid pathways and has a major impact on survival. 5 ||
 * **Grading:** || ** Histologic Grade ** 5
 * **Staging:** || <span style="color: #800080; font-family: Arial,Helvetica,sans-serif;">The Chang staging system is no longer used as is and has been modified. Patients are allocated to one of two risk categories: standard and high risk. M0 is considered “standard risk”, and M1-M3 is considered “high risk”.
 * <span style="color: #800080; font-family: Arial,Helvetica,sans-serif;">Modified Chang Staging System for Metastases in Patients with Medulloblastoma ** 6
 * **Radiation side effects:** || Treatment of large portions of the brain and spinal cord can be accompanied with severe late side effects. In children these effects can be worse the younger they are. These can include permanent hair loss, decreased intelligence, growth hormone deficiencies, hearing loss, and shortening of vertebral bodies resulting in irregular spine lengths.7 ||
 * **Prognosis:** || * Results for medulloblastoma, ependymoma, and pineoblastoma show less favorable prognosis for children younger than 3 to 5 years of age 2 ||
 * **Treatments:** || * For children who progress during chemotherapy or have persistent disease at completion, aggressive Craniospinal irradiation (CSI) 30 to 35 Gy has resulted in greater than 50% disease control at 5 years for medulloblastoma. Toxicities, although recognized, have been acceptable.2
 * [[image:uwlmedicaldosimetry2012/Copy_of_CranioSpinal.JPG]] ||
 * **TD 5/5:** ||  || Ear- Middle || 5000 cGy ||
 * Ear- Vestibular || 6000 cGy ||
 * Spinal cord || 4500 cGy ||
 * Brain || 4500 cGy ||
 * Optic chiasm || 4500 cGy ||
 * Optic nerve || 5000 cGy ||
 * Growing cartilage and bone || 1000 cGy ||
 * Eye-Retina || 5500 cGy ||
 * Eye-Cornea || 5000 cGy ||
 * Eye-Lens || 500 cGy ||  ||
 * **References:** || # <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Young J. Principles and Practice of Radiation Therapy. 3rd ed. St. Louis, MI: Mosby. 2010: 898.
 * 1) <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Chao KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 3rd edition. Philadelphia, PA: Lippincott Williams & Wilkins. 719.
 * 2) <span style="color: #ff0000; font-family: Arial,Helvetica,sans-serif;">Chao KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 2nd edition. Philadelphia, PA: Lippincott Williams & Wilkins. 623-628,
 * 3) Medscape. Medulloblastoma: Differential Diagnoses & Workup. Available at: [] Accessed June 26, 2012.
 * 4) <span style="color: purple; font-family: 'Arial','sans-serif'; font-size: 13px;">American Joint Committee on Cancer. //AJCC Cancer Staging Handbook//. 7th ed. New York, NY: Springer; 2010.
 * 5) <span style="color: purple; font-family: 'Arial','sans-serif'; font-size: 13px;">Perez CA, Brady LA, Halpern EC, Schmidt-Ullrich RK. Principles and Practice of Radiation Oncology. 4th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2004
 * 6) Washington CM. Principles and Practice of Radiation Therapy. 3rd ed. St. Louis, Missouri; Mosby Inc

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