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Medulloblastoma

Medulloblastomas are malignant primitive neuroectodermal tumors that arise in the posterior fossa in children. Medulloblastomas are the most common malignant brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tumors in children. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with medulloblastoma present with symptoms of increased intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension and cerebellar signs, which both evolve and worsen over weeks to a few months. Magnetic resonance imaging is the imaging modality of choice and typically shows a midline or paramedian cerebellar mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast that enhances with contrast, but histopathological analysis after surgical resection is required for diagnosis. Treatment involves a combination of surgery, radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy, and chemotherapy Chemotherapy Osteosarcoma. Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas depends on a variety of factors, but with modern multimodality therapy, roughly 75% of children diagnosed with medulloblastoma survive into adulthood.

Last updated: 3 Jun, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Medulloblastoma is a highly malignant primitive neuroectodermal tumor Tumor Inflammation that develops in the posterior fossa in children. It is an embryonal tumor Tumor Inflammation, arising from neuronal progenitor cells, and generally has a poor prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas.

Classification of nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification tumors

Table: Classification of nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification tumors
Categories Specific tumors
Neuroepithelial tumors in the CNS
  • Astrocytomas, including glioblastoma multiforme Glioblastoma multiforme Glioblastoma multiforme is a high-grade astrocytoma, an aggressive brain tumor arising from astrocytes, with an unknown cause and a poorly understood link to risk factors. There are two main types: primary, a more aggressive form seen more commonly in older patients, and secondary, developing from lower-grade astrocytomas and seen more commonly in younger patients. Glioblastoma Multiforme
  • Oligodendroglioma Oligodendroglioma Oligodendrogliomas are malignant CNS tumors arising from neural glial cell precursors. Oligodendrogliomas often arise in the frontal lobes of the brain and have a generally favorable prognosis when compared to other gliomas. Oligodendrogliomas are the 3rd most common CNS tumor. The most frequent presenting symptom is a seizure. Oligodendroglioma
  • Ependymoma Ependymoma Ependymomas are glial cell tumors arising from CSF-producing ependymal cells lining the ventricular system. Ependymomas most commonly occur within the posterior fossa in contact with the 4th ventricle, or within the intramedullary spinal cord. Ependymoma and choroid Choroid The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. Eye: Anatomy-plexus tumors
  • Medulloblastomas (embryonal tumors)
Meningeal tumors
  • Meningiomas
  • Hemangioblastomas Hemangioblastomas A benign tumor of the nervous system that may occur sporadically or in association with von Hippel-Lindau disease. It accounts for approximately 2% of intracranial tumors, arising most frequently in the cerebellar hemispheres and vermis. Histologically, the tumors are composed of multiple capillary and sinusoidal channels lined with endothelial cells and clusters of lipid-laden pseudoxanthoma cells. Usually solitary, these tumors can be multiple and may also occur in the brain stem, spinal cord, retina, and supratentorial compartment. Cerebellar hemangioblastomas usually present in the third decade with intracranial hypertension, and ataxia. Von Hippel-Lindau Disease
Sellar region tumors
  • Craniopharyngioma Craniopharyngioma Craniopharyngiomas are rare squamous epithelial tumors with a solid and/or cystic structure that arise from the remnants of Rathke’s pouch along the pituitary stalk, in the suprasellar region. Craniopharyngiomas are histologically benign but tend to invade surrounding structures; thus, they should be treated as low-grade malignancies. Craniopharyngioma
  • Pituitary adenoma Pituitary adenoma Pituitary adenomas are tumors that develop within the anterior lobe of the pituitary gland. Non-functioning or non-secretory adenomas do not secrete hormones but can compress surrounding pituitary tissue, leading to hypopituitarism. Secretory adenomas secrete various hormones depending on the cell type from which they evolved, leading to hyperpituitarism. Pituitary Adenomas
  • Pinealoma/pinealoblastoma
Primary CNS lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum Primary CNS lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum
Metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis to the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification (5x more common than primary brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tumors) Most commonly arising from:
  • Lung, breast, and renal cell carcinomas
  • Melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma
Peripheral tumors
  • Schwannomas, including acoustic neuroma Acoustic neuroma Acoustic neuroma, also referred to as vestibular schwannoma, is a benign tumor arising from Schwann cells of the vestibular component of the cranial nerve VIII. Acoustic neuroma forms within the internal auditory meatus and extends into the cerebellopontine angle. Acoustic Neuroma
  • Neuroblastoma Neuroblastoma Neuroblastoma is a malignancy that arises from the neural crest cell derivatives along the sympathetic chain (neuroblasts) and is most commonly located in the adrenal medulla. The tumor often presents in childhood with a flank mass that crosses the midline. Neuroblastoma

Epidemiology

  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency
    • Approximately 2 per 100,000 population in the United States
    • Approximately 500 children are diagnosed per year in the United States.
    • Most common malignant brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tumor Tumor Inflammation in children
    • Approximately 10%–20% of all primary CNS tumors in children ≤ 18 years of age
  • Age:
    • Peak incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is between 5 and 9 years of age.
    • 70%–80% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are diagnosed before age 20.
    • The disease is extremely rare in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship over 30.
  • Sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria: male-to-female ratio is approximately 1.5 to 1.
  • Race: higher rates in whites than blacks (80% white)

Classification

The WHO has developed both genetic and histologic classifications for medulloblastomas.

  • Medulloblastomas, genetically defined:
    • Wingless-related integration site (Wnt) activated
    • Sonic hedgehog (SHH) activated:
      • SHH activated and TP53 mutant
      • SHH activated and TP53 wild type
    • Non-Wnt/non-SHH:
      • Group 3: characterized by amplification of the oncogene MYC 
      • Group 4: characterized by amplification of oncogenes Oncogenes Genes whose gain-of-function alterations lead to neoplastic cell transformation. They include, for example, genes for activators or stimulators of cell proliferation such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of ‘v-‘ before oncogene symbols indicates oncogenes captured and transmitted by retroviruses; the prefix ‘c-‘ before the gene symbol of an oncogene indicates it is the cellular homolog (proto-oncogenes) of a v-oncogene. Carcinogenesis MYCN and cyclin-dependent kinase 6 (CDK6)
  • Medulloblastomas, histologically defined:
    • Classic medulloblastoma
    • Desmoplastic/nodular medulloblastoma
    • Medulloblastoma with extensive nodularity
    • Large-cell/anaplastic medulloblastoma
  • Medulloblastoma, not otherwise specified

Etiology and pathophysiology

  • Most cases occur sporadically.
  • Most cases arise in the posterior fossa.
  • Metastasize through the CNS and to bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types
  • Genetic mutations Genetic Mutations Carcinogenesis involved in WHO classification:
    • Wnt: a family of signaling oncoproteins involved in patterning decisions during embryonic development
    • SHH: stimulates proliferation of the granule cell progenitors in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
    • Tumor Tumor Inflammation protein 53 (p53): a tumor Tumor Inflammation suppressor protein
    • MYC: an oncogene encoding a multifunctional nuclear protein involved in regulating cell growth, cell division Cell Division A type of cell nucleus division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. Cell Cycle, apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage, and metabolism
  • Approximately 5%–6% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have a cancer predisposition syndrome, including:
    • Familial adenomatous polyposis Familial Adenomatous Polyposis Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis ( FAP FAP Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis): caused by inactivating mutations in the APC APC A polyposis syndrome due to an autosomal dominant mutation of the apc genes on chromosome 5. The syndrome is characterized by the development of hundreds of adenomatous polyps in the colon and rectum of affected individuals by early adulthood. Familial Adenomatous Polyposis gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (part of a complex in the Wnt-signaling pathway)
    • Nevoid basal cell Basal Cell Erythema Multiforme carcinoma syndrome (NBCCS): caused by germline mutations in the PTCH1 PTCH1 A patched receptor for several hedgehog proteins that associates with the smoothened receptor to modulate hedgehog signaling. It is also a tumor suppressor protein; mutations in the patched-1 gene are associated with basal cell nevus syndrome; squamous cell carcinoma of the esophagus; trichoepitheliomas, and carcinoma, transitional cell of the urinary bladder. Basal Cell Carcinoma (BCC) gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (involved in SHH signaling)
    • Li-Fraumeni syndrome: caused by mutations in p53
    • Other germline mutations, including:
      • BRCA2
      • PALB2
      • GPR161

Clinical Presentation

Medulloblastomas typically arise in the cerebellum Cerebellum The cerebellum, Latin for “little brain,” is located in the posterior cranial fossa, dorsal to the pons and midbrain, and its principal role is in the coordination of movements. The cerebellum consists of 3 lobes on either side of its 2 hemispheres and is connected in the middle by the vermis. Cerebellum: Anatomy, so patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship typically present with cerebellar symptoms and—since the most common complication of medulloblastoma is hydrocephalus Hydrocephalus Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial. Subarachnoid Hemorrhage—signs of increased intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension ( ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP)).

  • Cerebellar signs and symptoms:
    • Midline cerebellar tumors: 
      • Gait ataxia Gait ataxia Impairment of the ability to coordinate the movements required for normal ambulation (walking) which may result from impairments of motor function or sensory feedback. This condition may be associated with brain diseases (including cerebellar diseases and basal ganglia diseases); spinal cord diseases; or peripheral nervous system diseases. Friedreich’s Ataxia: broad-based gait Gait Manner or style of walking. Neurological Examination and/or difficulty with heel-to- toe walking Toe Walking Becker Muscular Dystrophy
      • Truncal instability
      • Head titubation (bobbing)
      • Nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism
    • Lateral cerebellar tumors: limb clumsiness or incoordination 
      • Dysmetria Dysmetria Cerebellar Disorders on finger-to- nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose and Nasal Cavity: Anatomy touching
      • Intention tremor Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease. Myotonic Dystrophies
      • Difficulty with heel-to- shin Shin Erythema Nodosum touching
  • Signs and symptoms of ↑ ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP):
    • Nocturnal or morning headaches
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and potentially severe vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
    • Altered mental status Altered Mental Status Sepsis in Children 
    • Papilledema Papilledema Swelling of the optic disk, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause optic atrophy and visual loss. Idiopathic Intracranial Hypertension
  • Brainstem involvement may lead to cranial nerve deficits:
    • Diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis
    • Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
    • Facial weakness 
    • Head tilt
  • Dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome) or double vision Vision Ophthalmic Exam can be due to either cerebellar, brainstem, or cranial nerve involvement.
  • Leptomeningeal dissemination can result in: 
    • Spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy compression Compression Blunt Chest Trauma → paraplegia
    • Nerve root compression Compression Blunt Chest Trauma radiculopathy Radiculopathy Disease involving a spinal nerve root which may result from compression related to intervertebral disk displacement; spinal cord injuries; spinal diseases; and other conditions. Clinical manifestations include radicular pain, weakness, and sensory loss referable to structures innervated by the involved nerve root. Rheumatoid Arthritis

Diagnosis

Imaging

Magnetic resonance imaging is the imaging test of choice. Due to the fact that 20%–25% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have spinal involvement at presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor, MRI of both the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy should be performed. Findings include:

Head mri showing a cerebellar medulloblastoma

Head MRI showing a cerebellar medulloblastoma in sagittal Sagittal Computed Tomography (CT) and horizontal views:
Sagittal Sagittal Computed Tomography (CT) view shows a midline posterior fossa medulloblastoma with intermediate signal intensity. There is an obstruction to the flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure of CSF, marked hydrocephalus Hydrocephalus Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial. Subarachnoid Hemorrhage, and edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema.
Horizontal view shows a homogenous enhancing medulloblastoma arising from the right cerebellar hemisphere with displacement Displacement The process by which an emotional or behavioral response that is appropriate for one situation appears in another situation for which it is inappropriate. Defense Mechanisms of the vermis.

Image: “Pediatric medulloblastoma – update on molecular classification driving targeted therapies” by DeSouza RM, Jones BR, Lowis SP, Kurian KM KM KM is the substrate concentration at which half-maximal velocity (½ Vmax) is reached (KM is measured on the x-axis while ½ Vmax is measured on the y-axis). Enzyme Kinetics. License: CC BY 3.0

Cerebrospinal fluid Cerebrospinal Fluid A watery fluid that is continuously produced in the choroid plexus and circulates around the surface of the brain; spinal cord; and in the cerebral ventricles. Ventricular System: Anatomy analysis

Cerebrospinal fluid Cerebrospinal Fluid A watery fluid that is continuously produced in the choroid plexus and circulates around the surface of the brain; spinal cord; and in the cerebral ventricles. Ventricular System: Anatomy analysis is important in the evaluation for metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis since approximately ⅓ of medulloblastomas metastasize through the CSF. These medulloblastomas show:

  • Neoplastic cells on cytopathologic examination
  • Elevated protein and mild pleocytosis Pleocytosis Tick-borne Encephalitis Virus (nonspecific findings)
  • ↑ Risk of relapse Relapse Relapsing Fever and poorer prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas
  • Note: Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with ↑ ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP) and/or hydrocephalus Hydrocephalus Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial. Subarachnoid Hemorrhage, requiring lumbar puncture Lumbar Puncture Febrile Infant to be delayed until after surgical resection to prevent brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification herniation Herniation Omphalocele.

Histopathology

Diagnosis requires confirmation by histopathologic examination at the time of surgical resection.

  • Gross characteristics: 
    • Well-circumscribed, gray, soft, friable tumors 
    • Usually have associated necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
  • Microscopic characteristics:
    • Highly cellular tumors with abundant dark staining
    • Small cells with little cytoplasm
    • Oval or round, hyperchromatic nuclei that are elongated or crescent Crescent Rapidly Progressive Glomerulonephritis shaped.
    • Often have abundant mitosis Mitosis A type of cell nucleus division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. Cell Cycle
    • Homer Wright rosettes found in up to 40% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
  • Markers expressed in histopathological studies:
    • Synaptophysin Synaptophysin A marvel domain-containing protein found in the presynaptic vesicles of neurons and neuroendocrine cells. It is commonly used as an immunocytochemical marker for neuroendocrine differentiation. Gastrinoma
    • Neuron-specific enolase Enolase A hydro-lyase that catalyzes the dehydration of 2-phosphoglycerate to form phosphoenolpyruvate. Several different isoforms of this enzyme exist, each with its own tissue specificity. Glycolysis
    • Nestin (a marker of primitive neuroepithelial cells)
    • Nuclear β-catenin staining: present in Wnt pathway tumors
    • P53 mutations
Microphotograph of medulloblastoma

Microphotograph of medulloblastoma (H&E, ×20):
The image shows a highly cellular tumor Tumor Inflammation composed of rosettes of small round cells, with high nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles-cytoplasm ratio.

Image: “Extra axial Axial Computed Tomography (CT) adult cerebellopontine angle Cerebellopontine angle Junction between the cerebellum and the pons. Acoustic Neuroma medulloblastoma: An extremely rare site of tumor Tumor Inflammation with metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis” by Singh M, Cugati G, Symss NP, Pande A, Vasudevan MC, Ramamurthi R. License: CC BY 2.0

Management and Prognosis

Management

The standard of care Standard of care The minimum acceptable patient care, based on statutes, court decisions, policies, or professional guidelines. Malpractice for management of medulloblastoma is combined modality therapy, including surgery, chemotherapy Chemotherapy Osteosarcoma, and radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma.

  • Goals of therapy:
    • Remove the tumor Tumor Inflammation
    • Alleviate ↑ ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP)
    • Prevent recurrence
  • Surgery with maximal safe resection of the tumor Tumor Inflammation
  • Systemic chemotherapy Chemotherapy Osteosarcoma
  • Craniospinal radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy (RT):
    • Higher doses are associated with better tumor Tumor Inflammation control.
    • Craniospinal RT in children can cause: 
      • Significant neurocognitive impairment
      • Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
      • Growth abnormalities
      • Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism
      • Adrenal insufficiency Adrenal Insufficiency Conditions in which the production of adrenal corticosteroids falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the adrenal glands, the pituitary gland, or the hypothalamus. Adrenal Insufficiency and Addison’s Disease
      • Hypogonadism Hypogonadism Hypogonadism is a condition characterized by reduced or no sex hormone production by the testes or ovaries. Hypogonadism can result from primary (hypergonadotropic) or secondary (hypogonadotropic) failure. Symptoms include infertility, increased risk of osteoporosis, erectile dysfunction, decreased libido, and regression (or absence) of secondary sexual characteristics. Hypogonadism and infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility
    • RT may be avoided or given in lower doses in infants and very young children.
  • For high-risk disease (metastatic, unresectable, or recurrent disease):
    • Optimal therapy is unknown.
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should be included in a clinical study if possible.

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

  • Survival in children:
    • With modern combined modality therapy, approximately 75% of children who are diagnosed with medulloblastoma survive into adulthood.
    • 5-year survival: 
      • Children diagnosed before age 3: 40%–50%
      • If the disease is disseminated at the time of diagnosis: 15%–30% 
  • Survival in adults:
    • 5-year survival rate: 65%
    • 10-year survival rate: 52%
  • Wnt tumors are associated with an excellent prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas.
  • Factors associated with poor prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas:
    • Young age (< 3 years old)
    • Disseminated or metastatic disease at diagnosis
    • Residual tumor Tumor Inflammation post-resection
    • Large cell or anaplastic histology
    • Non-Wnt/non-SHH group 3 and 4 tumors
  • In 80% of survivors, there are treatment-related morbidities, especially those caused by the craniospinal radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy listed above.

Differential Diagnosis

The following posterior fossa tumors are differential diagnoses for medulloblastoma:

  • Pilocytic astrocytoma Pilocytic Astrocytoma Astrocytoma: 2nd most common brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tumor Tumor Inflammation in children. Magnetic resonance imaging can help distinguish this tumor Tumor Inflammation from others. For example, pilocytic astrocytomas are usually solitary cystic Cystic Fibrocystic Change lesions with a mural nodule Nodule Chalazion, or they have central necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage with a thick rim of enhancing tissue. In contrast, medulloblastomas tend to have multiple smaller cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change, if cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change are present at all. 
  • Ependymoma Ependymoma Ependymomas are glial cell tumors arising from CSF-producing ependymal cells lining the ventricular system. Ependymomas most commonly occur within the posterior fossa in contact with the 4th ventricle, or within the intramedullary spinal cord. Ependymoma: a tumor Tumor Inflammation that arises from the ependymal lining of the ventricular system Ventricular System The ventricular system is an extension of the subarachnoid space into the brain consisting of a series of interconnecting spaces and channels. Four chambers are filled with cerebrospinal fluid (CSF): the paired lateral ventricles, the unpaired 3rd ventricle, and the unpaired 4th ventricle. Ventricular System: Anatomy, typically at the base of the 4th ventricle. Tumors are usually intracranial in children and in the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy in adults. Ependymomas more commonly extend through the foramen of Magendie Foramen of Magendie Ventricular System: Anatomy (inferiorly) or Luschka (laterally), while this type of extension Extension Examination of the Upper Limbs is rare in medulloblastoma. Magnetic resonance imaging is the standard imaging technique, but histologic confirmation is required for diagnosis. Treatment involves surgical resection and adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma and/or chemotherapy Chemotherapy Osteosarcoma (based on age). 
  • Atypical teratoid/rhabdoid tumors (AT/RT): a rare, aggressive primary CNS tumor Tumor Inflammation arising from embryonal cells that can appear similar to a medulloblastoma on MRI. Atypical teratoid/rhabdoid tumors can form anywhere in the CNS but typically develop in the cerebellum Cerebellum The cerebellum, Latin for “little brain,” is located in the posterior cranial fossa, dorsal to the pons and midbrain, and its principal role is in the coordination of movements. The cerebellum consists of 3 lobes on either side of its 2 hemispheres and is connected in the middle by the vermis. Cerebellum: Anatomy, most commonly in children < 3 years old. These tumors contain neuroepithelial, rhabdoid, epithelial, and mesenchymal cells. Compared with medulloblastomas, AT/RTs are more likely to involve the lateral hemispheres or cerebellopontine angle Cerebellopontine angle Junction between the cerebellum and the pons. Acoustic Neuroma and contain hemorrhage within the tumor Tumor Inflammation.

References

  1. DeAngelis, LM, Wen, PY. (2018). Primary and metastatic tumors of the nervous system. In Jameson, J., et al. (Eds.), Harrison’s Principles of Internal Medicine, 20e. McGraw-Hill. https://accessmedicine-mhmedical-com.aucmed.idm.oclc.org/content.aspx?bookid=2129&sectionid=192016511
  2. National Organization of Rare Diseases. (2013). Medulloblastoma. Retrieved April 14, 2021, from https://rarediseases.org/rare-diseases/medulloblastoma/
  3. Pomeroy, SL. (2019). Clinical presentation, diagnosis, and risk stratification of medulloblastoma. UpToDate. Retrieved April 14, 2021, from https://www.uptodate.com/contents/clinical-presentation-diagnosis-and-risk-stratification-of-medulloblastoma
  4. Pomeroy, SL. (2020). Histopathology, genetics, and molecular groups of medulloblastoma. UpToDate. Retrieved April 14, 2021, from https://www.uptodate.com/contents/histopathology-genetics-and-molecular-groups-of-medulloblastoma 
  5. Pomeroy, SL. (2021). Treatment and prognosis of medulloblastoma. UpToDate. Retrieved April 14, 2021, from https://www.uptodate.com/contents/treatment-and-prognosis-of-medulloblastoma
  6. Gilbertson, RJ. (2004). Medulloblastoma: Signaling a change in treatment. Lancet Oncol. 5(4), 209‒218. https://pubmed.ncbi.nlm.nih.gov/15050952/
  7. Rossi, A, et al. (2008). Medulloblastoma: From molecular pathology to therapy. Clin Cancer Res. 14(4), 971‒976. https://pubmed.ncbi.nlm.nih.gov/18281528/
  8. Pfister, S, et al. (2009). Outcome prediction in pediatric medulloblastoma based on DNA copy-number aberrations of chromosomes 6q and 17q and the MYC and MYCN loci. J Clin Oncol. 27(10), 1627‒1636. https://pubmed.ncbi.nlm.nih.gov/19255330/

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