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Medulloblastoma

Updated : April 17, 2024





Background

Although leukemias are the common prevalent kind of cancer in children, brain neoplasms are the most frequent solid malignancies. The most prevalent malignant brain tumor in youngsters is medulloblastoma, which accounts for roughly twenty percent of the total of all juvenile cancers.  It’s classified as a cerebellar embryonal neuroepithelial carcinoma.

This is really an elevated tumor that can spread through the CSF. The mortality rate is around fifteen percent in the first several years after diagnosis; even so, with modern therapeutic modalities, treatment rates can rise significantly to sixty percent. The cornerstone of therapy is surgical excision accompanied by chemotherapy and radiotherapy, with five-year overall survival ranging from fifty percent to ninety percent.

This broad range is due to a number of factors, including the patient’s age at diagnosis, the existence of metastasis at diagnostic test, and a medulloblastoma histologic type. Treatment-related neurologic, endocrinologic, and cognitive consequences constitute a debilitating problem and a motivation for the investigation of further therapeutic methods, regardless of long-term survival.

Epidemiology

From 1973 to 2007, the yearly incidence of medulloblastoma was estimated to be 6 in every million youngsters, or about 450 new pediatric cases annually, according to data from the End-Results (SEER) database, Surveillance, and Epidemiology.

The most common age group was four to nine years old, with forty-four percent, followed by adolescents (ten to sixteen years old) with twenty-three percent, and toddlers and babies with only twelve percent (zero to three years old). The prevalence of pediatric cancer was estimated to be 10 times higher than that of adults. Males were 1.5 times more likely than females to develop medulloblastoma.

Anatomy

Pathophysiology

Tumor growth begins in the fourth ventricle and can spread to completely engulf it. It is thought to originate from granule cell precursors in the developing cerebellum’s exterior germinal layer (EGL). The malignancy then travels to the vermis of the cerebellum and the skull, populating the craniospinal axes. Medulloblastoma is a highly cancerous growth that can invade the brain and spread to other parts of the body via the subarachnoid circulation (i.e., within the skull and following the spinal column, also named as “drop mets”)

Extraneural lesions in children with medulloblastomas are uncommon (approximately 7 percent). Lymph nodes (thirty-three%), Bone (seventy-eight%), lungs (fifteen%), and liver (fifteen %) are the most common locations of extraneural metastases in children (11%). The average time for a tumor to grow following a maximal surgical excision is about 20 months. In these patients, the prognosis is poor, with most patients lasting less than 6 months.

Isochromosome 17q, for example, is the most prevalent cytogenetic mutation in medulloblastoma, arising from the deletion of the short arm (p) and the subsequent acquisition of genetic makeup out from the long arm (q). Also, removal in the short arm has been documented often, resulting in the loss of 17p heterozygosity). Surprisingly, in medulloblastoma, the downregulation of TP53, which is found on the 17p chromosome, is rarely altered. As a result, researchers are still looking for probable tumor downregulation genes on the 17p chromosome in the background of medulloblastoma.

Etiology

The cause of medulloblastoma is unknown. Some studies have discovered a link between maternal nutrition and blood/immune diseases during pregnancy.

Others have linked it to viral infections in childhood, such as early john Cunningham (JC) viral infections or human cytomegalovirus (CMV) infections.

Medulloblastomas can run in families and have been linked to the following conditions:

  • Gorlin syndrome
  • Fanconi anemia
  • Turcot syndrome
  • Li-Fraumeni syndrome

Genetics

Prognostic Factors

Age, stage, the level of remaining disease after surgery, and therapy response are all factors that influence the outcome. Children with the WNT subtype have a longer life expectancy than those with MYCN or MYC amplification. Many patients are left with lasting neurological and cognitive abnormalities even after successful treatment.

Learning difficulties exist in children, along with growth issues. In addition, gonadotrophin and thyroid hormone insufficiency is widespread. Craniospinal radiation is the primary cause of these problems. If there is no significant residual disease and no indication of dissemination, the five-year survival rate for patients with the average-risk illness is 85 percent.

The five-year survival rate in the high-risk category is less than 40% Survival rates for children under the age of three years range from 30% to 70%. Children with the metastatic illness have a terrible prognosis, whereas those with activated SHH or WNT lesions have a better prognosis.

Transcriptional and methylation profiling data, combined with cytogenic abnormalities and copy number variations, and other patient outcomes, has helped subclassify medulloblastoma into 12 subtypes: two WNT, four SHH, three groups 3, and three groups 4. The WNT subgroup has consistently had the highest 5-year survival rate, ranging from 97 to 100 percent.

The SHH subgroup continues to be intermediate, with 5-year overall survival rates ranging from 70% to 80%. Non-SHH/WNT subgroups are regarded to be the worst prognosis, while group four patients have a better prognosis. Group 4 MB has a 5-year overall survival rate of 65% to 85%, but group 3 MB has dismal rates of 40 percent to 65 percent, with myc amplification indicating the weakest prognosis.

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK431069/

Medulloblastoma

Updated : April 17, 2024




Although leukemias are the common prevalent kind of cancer in children, brain neoplasms are the most frequent solid malignancies. The most prevalent malignant brain tumor in youngsters is medulloblastoma, which accounts for roughly twenty percent of the total of all juvenile cancers.  It’s classified as a cerebellar embryonal neuroepithelial carcinoma.

This is really an elevated tumor that can spread through the CSF. The mortality rate is around fifteen percent in the first several years after diagnosis; even so, with modern therapeutic modalities, treatment rates can rise significantly to sixty percent. The cornerstone of therapy is surgical excision accompanied by chemotherapy and radiotherapy, with five-year overall survival ranging from fifty percent to ninety percent.

This broad range is due to a number of factors, including the patient’s age at diagnosis, the existence of metastasis at diagnostic test, and a medulloblastoma histologic type. Treatment-related neurologic, endocrinologic, and cognitive consequences constitute a debilitating problem and a motivation for the investigation of further therapeutic methods, regardless of long-term survival.

From 1973 to 2007, the yearly incidence of medulloblastoma was estimated to be 6 in every million youngsters, or about 450 new pediatric cases annually, according to data from the End-Results (SEER) database, Surveillance, and Epidemiology.

The most common age group was four to nine years old, with forty-four percent, followed by adolescents (ten to sixteen years old) with twenty-three percent, and toddlers and babies with only twelve percent (zero to three years old). The prevalence of pediatric cancer was estimated to be 10 times higher than that of adults. Males were 1.5 times more likely than females to develop medulloblastoma.

Tumor growth begins in the fourth ventricle and can spread to completely engulf it. It is thought to originate from granule cell precursors in the developing cerebellum’s exterior germinal layer (EGL). The malignancy then travels to the vermis of the cerebellum and the skull, populating the craniospinal axes. Medulloblastoma is a highly cancerous growth that can invade the brain and spread to other parts of the body via the subarachnoid circulation (i.e., within the skull and following the spinal column, also named as “drop mets”)

Extraneural lesions in children with medulloblastomas are uncommon (approximately 7 percent). Lymph nodes (thirty-three%), Bone (seventy-eight%), lungs (fifteen%), and liver (fifteen %) are the most common locations of extraneural metastases in children (11%). The average time for a tumor to grow following a maximal surgical excision is about 20 months. In these patients, the prognosis is poor, with most patients lasting less than 6 months.

Isochromosome 17q, for example, is the most prevalent cytogenetic mutation in medulloblastoma, arising from the deletion of the short arm (p) and the subsequent acquisition of genetic makeup out from the long arm (q). Also, removal in the short arm has been documented often, resulting in the loss of 17p heterozygosity). Surprisingly, in medulloblastoma, the downregulation of TP53, which is found on the 17p chromosome, is rarely altered. As a result, researchers are still looking for probable tumor downregulation genes on the 17p chromosome in the background of medulloblastoma.

The cause of medulloblastoma is unknown. Some studies have discovered a link between maternal nutrition and blood/immune diseases during pregnancy.

Others have linked it to viral infections in childhood, such as early john Cunningham (JC) viral infections or human cytomegalovirus (CMV) infections.

Medulloblastomas can run in families and have been linked to the following conditions:

  • Gorlin syndrome
  • Fanconi anemia
  • Turcot syndrome
  • Li-Fraumeni syndrome

Age, stage, the level of remaining disease after surgery, and therapy response are all factors that influence the outcome. Children with the WNT subtype have a longer life expectancy than those with MYCN or MYC amplification. Many patients are left with lasting neurological and cognitive abnormalities even after successful treatment.

Learning difficulties exist in children, along with growth issues. In addition, gonadotrophin and thyroid hormone insufficiency is widespread. Craniospinal radiation is the primary cause of these problems. If there is no significant residual disease and no indication of dissemination, the five-year survival rate for patients with the average-risk illness is 85 percent.

The five-year survival rate in the high-risk category is less than 40% Survival rates for children under the age of three years range from 30% to 70%. Children with the metastatic illness have a terrible prognosis, whereas those with activated SHH or WNT lesions have a better prognosis.

Transcriptional and methylation profiling data, combined with cytogenic abnormalities and copy number variations, and other patient outcomes, has helped subclassify medulloblastoma into 12 subtypes: two WNT, four SHH, three groups 3, and three groups 4. The WNT subgroup has consistently had the highest 5-year survival rate, ranging from 97 to 100 percent.

The SHH subgroup continues to be intermediate, with 5-year overall survival rates ranging from 70% to 80%. Non-SHH/WNT subgroups are regarded to be the worst prognosis, while group four patients have a better prognosis. Group 4 MB has a 5-year overall survival rate of 65% to 85%, but group 3 MB has dismal rates of 40 percent to 65 percent, with myc amplification indicating the weakest prognosis.

https://www.ncbi.nlm.nih.gov/books/NBK431069/