Medulloblastoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2] Associate Editor(s)-in-Chief: Syed Musadiq Ali M.B.B.S.[3]

Medulloblastoma is a malignant primary brain tumor that originates in either the cerebellum or the posterior cranial fossa. The term medulloblastoma was first used to describe the tumor by Dr. Harvey Cushing, an American neurosurgeon, in 1924. Medulloblastoma may be classified into several subtypes based on the WHO histological classification system (classic vs variant medulloblastoma) and the molecular subtypes classification system (WNT subgroup vs SHH subgroup vs Group 3 medulloblastoma vs Group 4 medulloblastoma). Medulloblastoma arises from the cerebellar stem cells, which are normally involved in the anatomical development of the cerebellum and posterior cranial fossa structures. Medulloblastoma is an invasive and rapidly growing brain tumor which may metastasize to different organs of the body. Genes involved in the pathogenesis of medulloblastoma include CTNNB1 gene, PTCH1 gene, and MLL2 gene. 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. Medulloblastoma must be differentiated from other diseases that cause morning headache, recurrent vomiting, nausea, restlessness, and poor feeding among children such as ependymoblastoma, cerebral neuroblastoma, and pineal tumor. Physical examination of patients with medulloblastoma is usually remarkable for strabismus, nystagmus, motor weakness, and ataxia. Common complications of medulloblastoma include hydrocephalus, decerebrate attacks, and cranial nerve palsies. Medulloblastoma is the second most common brain tumor among the pediatric population. Prognosis is generally good, the 5-year survival rate of patients with medulloblastoma is approximately 69%. The staging of medulloblastoma is based on the modified Chang’s staging system. Medulloblastoma patients are risk stratified into either standard risk group or high risk group based on the tumor stage, patient’s age, and the extent of any previous surgical resection. Brain MRI with gadolinium based contrast is the investigation of choice for the diagnosis of medulloblastoma. On a T1 weighted brain MRI image, medulloblastoma is characterized by a hypointense mass located at the posterior cerebral fossa that may demonstrate calcification and necrosis. According to the risk stratification criterion for medulloblastoma patients, surgery must be followed by the appropriate radiotherapy or chemotherapy management.

The term medulloblastoma was first used to describe the tumor by Dr. Harvey Cushing, an American neurosurgeon, in 1924.

Medulloblastoma may be classified into several subtypes based on the WHO histological classification system (classic vs variant medulloblastoma) and the molecular subtypes classification system (WNT subgroup vs SHH subgroup vs Group 3 medulloblastoma vs Group 4 medulloblastoma).

Medulloblastoma arises from the cerebellar stem cells, which are normally involved in the anatomical development of the cerebellum and posterior cranial fossa structures. Medulloblastoma is an invasive and rapidly growing brain tumor which may 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. 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.

There are no established direct causes for medulloblastoma. The development of medulloblastoma is the result of multiple genetic mutations.

Medulloblastoma must be differentiated from other diseases that cause morning headache, recurrent vomiting, nausea, restlessness, and poor feeding among children such as ependymoblastoma, cerebral neuroblastoma, and pineal tumor.

Medulloblastoma is the second most common brain tumor among the pediatric population. The overall age adjusted incidence rate of medulloblastoma is approximately 0.71 per 100,000 individuals in the United States. The incidence of medulloblastoma decreases with age; the median age at diagnosis is between 5 to 7 years. Males are more commonly affected with medulloblastoma than females. The male to female ratio is approximately 1.44 to 1.

There are no established risk factors for medulloblastoma.

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for medulloblastoma.

If left untreated, patients with medulloblastoma may progress to develop ataxia, nystagmus, and positional dizziness. Common complications of medulloblastoma include hydrocephalus, decerebrate attacks, and cranial nerve palsies. Prognosis is generally good, the 5-year survival rate of patients with medulloblastoma is approximately 69%.

The staging of medulloblastoma is based on the modified Chang’s staging system. Medulloblastoma patients are risk stratified into either standard risk group or high risk group based on the tumor stage, patient’s age, and the extent of any previous surgical resection.

The hallmark of medulloblastoma is morning headache. Other common symptoms of medulloblastoma include recurrent vomiting, restlessness, and frequent falls.

Patients with medulloblastoma usually appear restless. Physical examination of patients with medulloblastoma is usually remarkable for strabismus, nystagmus, motor weakness, and ataxia.

There are no diagnostic lab findings associated with medulloblastoma.

On head CT scan, medulloblastoma is characterized by a hyperdense mass arising from the cerebellar vermis, effacement of the fourth ventricle, and dilated ventricles due to obstructive hydrocephalus.

Brain MRI with gadolinium based contrast is the investigation of choice for the diagnosis of medulloblastoma. On a T1 weighted brain MRI image, medulloblastoma is characterized by a hypointense mass located at the posterior cerebral fossa that may demonstrate calcification and necrosis.

Magnetic resonance spectroscopy (MR spectroscopy) study for medulloblastoma demonstrates an elevated choline level and a reduced N-acetyl aspartate level. MR spectroscopy study also demonstrates a peak in taurine level.

Bromodeoxyuridine labeling study may be helpful in the diagnosis of medullblastoma. An elevated bromodeoxyuridine labeling index is suggestive of a rapid growth rate of medulloblastoma.

Risk stratification determines the protocol of management used for medulloblastoma patients. Radiotherapy is the mainstay of treatment for medulloblastoma. Radiotherapy for medulloblastoma must be started within the 6 weeks period following surgery. Adjunctive chemotherapy is also required for the management of certain medulloblastoma patients. Recommended chemotherapeutic regimens used for the management of standard risk medulloblastoma patients include a combination of lomustine AND vincristine AND cisplatin.

Surgical intervention alone is not recommended as a single therapeutic modality for the management of medulloblastoma. According to the risk stratification criterion for medulloblastoma patients, surgery must be followed by the appropriate radiotherapy or chemotherapy management. Surgical excision of medulloblastoma may be done either via a posterior fossa craniectomy approach or a suboccipital craniectomy approach. Complications related to surgery may include aseptic meningitis, haematoma formation, and posterior fossa syndrome.

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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] Associate Editor(s)-in-Chief: Syed Musadiq Ali M.B.B.S.[3]

The term medulloblastoma was first used to describe the tumor by Dr. Harvey Cushing, an American neurosurgeon, in 1924.^[1]

The term medulloblastoma was first used to describe the tumor by Dr. Harvey Cushing, an American neurosurgeon, in 1924.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2] Associate Editor(s)-in-Chief: Syed Musadiq Ali M.B.B.S.[3]

Medulloblastoma is classified into several subtypes based on the WHO histological classification system (classic vs. variant medulloblastoma) and the molecular subtypes classification system (WNT subgroup vs. SHH subgroup vs. Group 3 medulloblastoma vs. Group 4 medulloblastoma).^{[1][2][3][4][5]}

• Medulloblastoma is classified into two main subtypes based on the WHO histological classification system which include classic medulloblastoma and variant medulloblastoma.^[2][4][5]
• Variant medulloblastoma may be further classified into desmoplastic medulloblastoma, large cell medulloblastoma, anaplastic​ medulloblastoma, and medulloblastoma with extensive nodularity.

• Medulloblastoma may be classified into at least four major subgroup based on the molecular classification system which include WNT subgroup, SHH subgroup, Group 3, and Group 4.^[1][3]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2] Associate Editor(s)-in-Chief: Syed Musadiq Ali M.B.B.S.[3]

Medulloblastoma arises from the cerebellar stem cells, which are normally involved in the anatomical development of the cerebellum and posterior cranial fossa structures. Medulloblastoma is an invasive and rapidly growing brain tumor which may 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 are 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]

• Medulloblastoma arises from the cerebellar stem cells, which are normally involved in the anatomical development of the cerebellum and posterior cranial fossa structures.^[1][3]
• 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.
• Medulloblastoma is an invasive and rapidly growing brain tumor.
• Unlike most brain tumors, medulloblastoma may spread through the cerebrospinal fluid and metastasize to different organs of the body.

• Development of medulloblastoma is the result of multiple genetic mutations.^[1][4][5][6]
• Genes involved in the pathogenesis of medulloblastoma include:

• 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 system which includes:^[7][8][9]

• 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:

• Present among 30% of medulloblastoma patients
• Cytogenetic markers include isochromosome 17q
• Molecular markers include MYC activation

• Group 4:

• Present among 35% of medulloblastoma patients
• Cytogenetic markers include isochromosome 17q
• Molecular markers are still under investigation

• Medulloblastoma is associated with a number of syndromes that include:^[1][10]

• Gorlin syndrome^[11]
• Turcot syndrome
• Coffin-Siris syndrome
• Cowden syndrome
• Gardner syndrome
• Li-Fraumeni syndrome
• Rubinstein-Taybi syndrome

• 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:

• On microscopic histopathological analysis, round tumor cells, elevated mitotic rate, increased nucleus:cytoplasm ratio, and Homer-Wright rosettes are characteristic findings of medulloblastoma.^[2][12]
• Medulloblastoma may be classified into two subtypes based on WHO histological classification system 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][10]
  
• The table below differentiates between the five main groups of medulloblastoma according to the WHO histological classification system:^[13]

• Shown below is a series of microscopic images observed in medulloblastoma:

• 
  Medulloblastoma ^[2]
• 
  Medulloblastoma^[2]
• 
  Medulloblastoma demonstrating Homer-Wright rosettes^[2]
• 
  Medulloblastoma demonstrating cerebellar infiltrative growth^[2]
• 
  Medulloblastoma demonstrating demsomplastic nodular growth^[2]
• 
  Anaplastic large cell medulloblastoma^[2]
• 
  Medulloblastoma^[2]
• 
  Desmoplastic medulloblastoma on reticulin stain demonstrating pale islands structure^[2]
• 
  Desmoplastic medulloblastoma on MIB-1 immunostaining^[2]
• 
  Medulloblastoma demonstrating areas of geographic necrosis^[2]
• 
  Medulloblastoma demonstrating epitheloid ribboning and nuclear moulding of tumor cells^[2]
• 
  Medulloblastoma demonstrating partial MAP2 immunoreactivity^[2]

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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]

There are no established direct causes for medulloblastoma. The development of medulloblastoma is the result of multiple genetic mutations.^[1]

There are no established direct causes for medulloblastoma. The development of medulloblastoma is the result of multiple genetic mutations.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D. Syed Musadiq Ali M.B.B.S.[2]

On the basis of seizure, visual disturbance, and constitutional symptoms, medulloblastomamust be differentiated from oligodendroglioma, meningioma, hemangioblastoma, pituitary adenoma, schwannoma, primary CNS lymphoma, astrocytoma, ependymoma, craniopharyngioma, pinealoma, AV malformation, brain aneurysm, bacterial brain abscess, tuberculosis, toxoplasmosis, hydatid cyst, CNS cryptococcosis, CNS aspergillosis, and brain metastasis.

On the basis of seizure, visual disturbance, and constitutional symptoms, medulloblastoma must be differentiated from oligodendroglioma, meningioma, hemangioblastoma, pituitary adenoma, schwannoma, primary CNS lymphoma, astrocytoma, ependymoma, craniopharyngioma, pinealoma, AV malformation, brain aneurysm, bacterial brain abscess, tuberculosis, toxoplasmosis, hydatid cyst, CNS cryptococcosis, CNS aspergillosis, and brain metastasis.

ABBREVIATIONS

CNS=Central nervous system, AV=Arteriovenous, CSF=Cerebrospinal fluid, NF-2=Neurofibromatosis type 2, MEN-1=Multiple endocrine neoplasia, GFAP=Glial fibrillary acidic protein, HIV=Human immunodeficiency virus, BhCG=Human chorionic gonadotropin, ESR=Erythrocyte sedimentation rate, AFB=Acid fast bacilli, MRA=Magnetic resonance angiography, CTA=CT angiography

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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] Syed Musadiq Ali M.B.B.S.[3]

Medulloblastoma is the second most common brain tumor among the pediatric population.^[1] The overall age adjusted incidence rate of medulloblastoma is approximately 0.71 per 100,000 individuals in the United States.^[2] The incidence of medulloblastoma decreases with age; the median age at diagnosis is between 5 to 7 years.^[3] Males are more commonly affected with medulloblastoma than females. The male to female ratio is approximately 1.44 to 1.^[2]

• Medulloblastoma is the second most common brain tumor among the pediatric population.^[1]
• Medulloblastoma is considered a rare tumor among adults, as it comprises fewer than 2% of all brain tumors among that age group.

• The overall age adjusted incidence rate of medulloblastoma is approximately 0.71 per 100,000 individuals in the United States.^[2]

• The incidence of medulloblastoma decreases with age; the median age at diagnosis is between 5 to 7 years.^[3]
• The molecular subgroup of medulloblastoma has an influence on the age of presentation such as:^[4]

• WNT medulloblastoma subgroup presents among older children
• SHH medulloblastoma subgroup presents among infants and adults
• Group 3 medulloblastoma presents among younger children
• Group 4 medulloblastoma presents among younger children

• The overall age adjusted incidence rate of medulloblastoma among males is approximately 0.84 per 100,000 individuals in the United States.^[2]
• The overall age adjusted incidence rate of medulloblastoma among females is approximately 0.58 per 100,000 individuals in the United States.
• Males are more commonly affected with medulloblastoma than females. The male to female ratio is approximately 1.44 to 1.

• There is no racial predilection to medulloblastoma.^[5]

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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]Associate Editor(s)-in-Chief: Syed Musadiq Ali M.B.B.S.[3]

There are no established risk factors for medulloblastoma.

There are no established risk factors for medulloblastoma.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Syed Musadiq Ali M.B.B.S.[2]Haytham Allaham, M.D. [3]

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for medulloblastoma.^[1]

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for medulloblastoma.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Syed Musadiq Ali M.B.B.S.[2]Haytham Allaham, M.D. [3]

If left untreated, patients with medulloblastoma may progress to develop ataxia, nystagmus, and positional dizziness. Common complications of medulloblastoma include hydrocephalus, decerebrate attacks, and cranial nerve palsies. Prognosis is generally good, the 5-year survival rate of patients with medulloblastoma is approximately 69%.^[1]

• Most patients with medulloblastoma are initially asymptomatic. If left untreated, most of the patients with medulloblastoma will develop ataxia, nystagmus, and positional dizziness within a few months.^[1]

• Common complications of medulloblastoma include:^[1]

• Increased intracranial pressure
• Third, fourth, and sixth cranial nerve palsy
• Decerebrate attacks

• Medulloblastoma prognosis is generally good.
• The 5-year survival rate of patients with medulloblastoma is approximately 69%.^[1]
• The 10-year survival rate of patients with medulloblastoma is approximately 52%.
• Younger age in children is associated with worse prognosis.^[2]
• The prognosis varies with the molecular subgroup of medulloblastoma, such as:^[1]

• Medulloblastoma WNT molecular subgroup is associated with the most favorable prognosis.
• Medulloblastoma Group 4 and SHH molecular subgroups are associated with an intermediate prognosis.
• Medulloblastoma Group 3 molecular subgroup is associated with a poor prognosis.

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