Medulloblastoma is a highly
malignantMalignancy is the tendency of a medical condition, especially tumors to become progressively worse and to potentially result in death. It is characterized by the properties of anaplasia, invasiveness, and metastasis...
primary
brain tumorA brain tumor is an abnormal growth of cells within the brain or inside the skull, which can be cancerous or non-cancerous .It is defined as any intracranial tumor created by abnormal and uncontrolled cell division, normally either in the brain itself , in the cranial nerves...
that originates in the
cerebellumThe cerebellum is a region of the brain that plays an important role in the integration of sensory perception, coordination and motor control...
or
posterior fossaThe posterior cranial fossa is part of the intracranial cavity, located between the foramen magnum and tentorium cerebelli. It contains the brainstem and cerebellum.This is the most inferior of the fossae. It houses the cerebellum, medulla and pons....
.
Originally considered to be a
gliomaA glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...
, medulloblastoma is now known to be of the family of cranial
primitive neuroectodermal tumorPrimitive neuroectodermal tumor is a neural crest tumor. It is a rare tumor, usually occurring in children under 10 years old. It has a survival rate of less than 40%....
s (PNET).
Tumors that originate in the cerebellum are referred to as infratentorial because they occur below the
tentoriumThe tentorium cerebelli or cerebellar tentorium is an extension of the dura mater that separates the cerebellum from the inferior portion of the occipital lobes.-Anatomy:...
, a thick membrane that separates the cerebral hemispheres of the brain from the cerebellum.
Medulloblastoma is a highly
malignantMalignancy is the tendency of a medical condition, especially tumors to become progressively worse and to potentially result in death. It is characterized by the properties of anaplasia, invasiveness, and metastasis...
primary
brain tumorA brain tumor is an abnormal growth of cells within the brain or inside the skull, which can be cancerous or non-cancerous .It is defined as any intracranial tumor created by abnormal and uncontrolled cell division, normally either in the brain itself , in the cranial nerves...
that originates in the
cerebellumThe cerebellum is a region of the brain that plays an important role in the integration of sensory perception, coordination and motor control...
or
posterior fossaThe posterior cranial fossa is part of the intracranial cavity, located between the foramen magnum and tentorium cerebelli. It contains the brainstem and cerebellum.This is the most inferior of the fossae. It houses the cerebellum, medulla and pons....
.
Originally considered to be a
gliomaA glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...
, medulloblastoma is now known to be of the family of cranial
primitive neuroectodermal tumorPrimitive neuroectodermal tumor is a neural crest tumor. It is a rare tumor, usually occurring in children under 10 years old. It has a survival rate of less than 40%....
s (PNET).
Tumors that originate in the cerebellum are referred to as infratentorial because they occur below the
tentoriumThe tentorium cerebelli or cerebellar tentorium is an extension of the dura mater that separates the cerebellum from the inferior portion of the occipital lobes.-Anatomy:...
, a thick membrane that separates the cerebral hemispheres of the brain from the cerebellum. Another term for medulloblastoma is infratentorial PNET. Medulloblastoma is the most common PNET originating in the brain.
All PNET tumors of the brain are invasive and rapidly growing tumors that, unlike most brain tumors, spread through the
cerebrospinal fluidCerebrospinal fluid , Liquor cerebrospinalis, is a clear bodily fluid that occupies the subarachnoid space and the ventricular system around and inside the brain. In essence, the brain "floats" in it....
(CSF) and frequently metastasize to different locations in the brain and spine.
Incidence
Brain tumorA brain tumor is an abnormal growth of cells within the brain or inside the skull, which can be cancerous or non-cancerous .It is defined as any intracranial tumor created by abnormal and uncontrolled cell division, normally either in the brain itself , in the cranial nerves...
s are the second most common malignancy among children less than 20 years of age. Medulloblastoma is the most common malignant brain tumor, comprising 14.5% of newly diagnosed cases. In adults, medulloblastoma is rare, comprising less than 2% of CNS malignancies.
The incidence of childhood medulloblastoma is higher in males (62%) than females (38%). Medulloblastoma and other PNET tumors are more prevalent in younger children than older children. 40% of medulloblastoma patients are diagnosed before the age of 5, 31% are between the ages of 5 and 9, 18.3% are between the ages of 10 and 14, and 12.7% are between the ages of 15 and 19.
Pathogenesis
Medulloblastomas usually form in the fourth ventricle, between the brainstem and the cerebellum. Tumors with similar appearance and characteristics originate in other parts of the brain, but they are not identical to medulloblastoma.
Although it is thought that medulloblastomas originate from immature or embryonal cells at their earliest stage of development, the exact cell of origin, or "medulloblast" has yet to be identified.
It is currently thought that medulloblastoma arises from cerebellar "stem cells" that have been prevented from dividing and differentiating into their normal cell types. This accounts from the varying histologic variants seen on biopsy. Both perivascular pseudorosette and Homer-Wright rosette formation are highly characteristic of medulloblastoma and is seen in up to half of the cases.
Molecular genetics reveal a loss of genetic information on the distal part of chromosome 17, distal to the
p53p53 , is a transcription factor which in humans is encoded by the TP53 gene. p53 is important in multicellular organisms, where it regulates the cell cycle and thus functions as a tumor suppressor that is involved in preventing cancer...
gene, possibly accounting for the neoplastic transformation of the undifferentiated cerebellar cells. Medulloblastomas are also seen in
Gorlin syndromeGorlin syndrome can refer to:* Nevoid basal cell carcinoma syndrome* Focal dermal hypoplasia...
as well as
Turcot syndromeTurcot syndrome is the association between familial adenomatous polyposis and brain tumors like medulloblastoma, malignant glioma.It was first reported by Canadian surgeon Jacques Turcot et al. in 1959 and hence carries the first author's name....
. Other research has strongly implicated the
JC virusThe JC virus is a type of human polyomavirus and is genetically similar to BK virus and SV40. It was discovered in 1971 and named after the two initials of a patient with progressive multifocal leukoencephalopathy...
, the virus that causes
multifocal leukoencephalopathyProgressive multifocal leukoencephalopathy , also known as progressive multifocal leukoencephalitis, is a rare and usually fatal viral disease that is characterized by progressive damage or inflammation of the white matter of the brain at multiple locations...
.
Clinical manifestation
Symptoms are mainly due to secondary increased
intracranial pressureIntracranial pressure is the pressure in the cranium and thus in the brain tissue and cerebrospinal fluid ; this pressure is exerted on the brain's intracranial blood circulation vessels. ICP is maintained in a tight normal range dynamically, through the production and absorption of CSF and...
due to blockage of the
fourth ventricleThe fourth ventricle is one of the four connected fluid-filled cavities within the human brain. These cavities, known collectively as the ventricular system, consist of the left and right lateral ventricles, the third ventricle, and the fourth ventricle...
and are usually present for 1 to 5 months before diagnosis is made. The child typically becomes
listless, with repeated episodes of
vomiting, and a
morning headache, which may lead to a misdiagnosis of gastrointestinal disease or migraine. Soon, the child will develop a
stumbling gait,
frequent falls,
diplopiaDiplopia, commonly known as double vision, is the simultaneous perception of two images of a single object. These images may be displaced horizontally, vertically, or diagonally Diplopia, commonly known as double vision, is the simultaneous perception of two images of a single object. These images...
,
papilledemaPapilledema is optic disc swelling that is caused by increased intracranial pressure. The swelling is usually bilateral but can be unilateral which is extremely rare and can occur over a period of hours to weeks...
, and
sixth cranial nerve palsy.
Positional dizziness and
nystagmus are also frequent and facial sensory loss or motor weakness may be present.
DecerebrateDecerebration is the elimination of cerebral brain function in an animal by removing the cerebrum, cutting across the brain stem, or severing certain arteries in the brain stem....
attacks appear late in the disease.
Extraneural metastases to the rest of the body is rare, but usually only after
craniotomyA craniotomy is a surgical operation in which part of the skull, called a bone flap, is removed in order to access the brain. Craniotomies are often a critical operation performed on patients suffering from brain lesions or traumatic brain injury , and can also allow doctors to surgically implant...
.
Diagnosis
The tumor is distinctive on T1 and T2-weighted MRI with heterogeneous enhancement and typical location adjacent to and extension into the fourth ventricle.
Histologically, the tumor is solid, pink-gray in color, and is well circumscribed. The tumor is very cellular, many mitoses, little cytoplasm, and has the tendency to form clusters and rosettes.
Correct diagnosis of medulloblastoma may require ruling out atypical teratoid rhabdoid tumor (ATRT) and
primitive neuroectodermal tumorPrimitive neuroectodermal tumor is a neural crest tumor. It is a rare tumor, usually occurring in children under 10 years old. It has a survival rate of less than 40%....
(PNET).
Treatment and prognosis
Treatment begins with maximal resection of the tumor. The addition of
radiation to the entire neuraxis and
chemotherapyChemotherapy, in its most general sense, is the treatment of disease by chemicals especially by killing micro-organisms or cancerous cells. In popular usage, it refers to antineoplastic drugs used to treat cancer or the combination of these drugs into a cytotoxic standardized treatment regimen...
may increase the disease-free survival. This combination may permit a 5 year survival in more than 80% of cases. The presence of desmoplastic features such as connective tissue formation offers a better prognosis. Prognosis is worse if the child is less than 3 years old, there is an inadequate degree of resection, or if there is any CSF, spinal, supratentorial or systemic spread.
Increased intracranial pressure may be controlled with corticosteroids or a ventriculoperitoneal
shuntIn medicine, a shunt is a hole or passage which moves, or allows movement of fluid from one part of the body to another. The term may describe either congenital or acquired shunts; and acquired shunts may be either biological or mechanical.* Cardiac shunts may be described as right-to-left,...
.
Outcome Prediction Based on Cytogenetic Subgroups
Array-based karyotypingVirtual Karyotype Virtual Karyotype Virtual Karyotype (also Array comparative genomic hybridization, CMA, Chromosomal Microarray Analysis, Microarray-based comparative genomic hybridization, array CGH, a-CGH, aCGH, or molecular karyotyping...
of 260 medulloblastomas by Pfister S, et al. resulted in the following clinical subgroups based on cytogenetic profiles:
- Poor prognosis: gain of 6q or amplification of MYC or MYCN
- Intermediate: gain of 17q or an i(17q) without gain of 6q or amplfication of MYC or MYCN
- Excellent prognosis: 6q and 17q balanced or 6q deletion
See also:
Virtual KaryotypeVirtual Karyotype Virtual Karyotype Virtual Karyotype (also Array comparative genomic hybridization, CMA, Chromosomal Microarray Analysis, Microarray-based comparative genomic hybridization, array CGH, a-CGH, aCGH, or molecular karyotyping...
Model
Using gene transfer of SV40 large T-antigen in neuronal precursor cells of rats, a brain tumor model was established. The PNETs were histologically indistinguishable from the human counterparts and have been used to identify new genes involved in human brain tumor carcinogenesis. . The model was used to confirm p53 as one of the genes involved in human medulloblastomas, but since only about 10 % of the human tumors showed mutations in that gene, the model can be used to identify the other binding partners of SV40 Large T- antigen, other than p53.
External links