Prognostic markers
Pathology
Etiology
Incidence
Neuroblastoma is responsible for 7-10% of all childhood tumors and 15% of all cancer deaths. This tumor occurs in approximately 1 in 7000-18,000 live births. There is no ethnic prevalence. There is a slight male predominance with a ratio of 1.2:1 (male to female). The median age at diagnosis is 18-22 months, and 97% of neuroblastomas are diagnosed in children less than 10 years of age. The incidence is biphasic with a peak at less than 1 year of age and a second peak at 2-4 years. Prenatal or postnatal exposure to drugs, chemicals or radiation has not been unequivocally demonstrated to increase the incidence of neuroblastoma.
The etiology of neuroblastoma is not well understood. Although most cases of neuroblastoma are thought to be sporadic, there is a subset of patients that exhibit a predisposition to develop disease in an autosomal dominant pattern. About 22% of neuroblastomas are thought to be the result of a germinal mutation.
Heredity
In about 1% to 2% of all neuroblastomas, children may have inherited an increased risk of developing neuroblastoma. But the vast majority of neuroblastomas do not seem to be inherited.
The hereditary form of the disease has an earlier mean age at diagnosis (9 months versus 22 months) and has a higher incidence of bilaterality and multifocal tumors (20%).
Neuroblastoma is thought to follow a two-mutation hypothesis of tumorogenesis.
Neuroblastomas arise from the primitive pluripotential sympathetic cells that are derived from neural crest cell and normally differentiate to form tissues of the sympathetic nervous system. All fetuses have neuroblastic nodules between 17-20 weeks gestational age. Most regress before birth or shortly thereafter. Neuroblastoma in situ is frequently found in infants 3 months or younger dying from other causes. Therefore the cells that form neuroblastoma may be fetal remnants that fail to regress.
Neuroblastomas belong to a group of tumors classified as the “small round blue cell” tumors. Others in this category include Ewing’s sarcoma, non-Hodgkin’s lymphoma, primitive neuroectodermal tumors (PNETs) and undifferentiated soft tissue sarcomas such as rhabdomyosarcoma. Neuroblastomas can be differentiated from other tumors in this category by using immunohistochemistry.
Prognostic markers are features that help predict whether the child's outlook for cure is better or worse than would be predicted by the stage alone. The following markers are used to help determine a child's prognosis.
Age – younger children (under 12-18 months) are more likely to be cured than older children.
Tumor histology – tumor histology is based on how the neuroblastoma cells look under the microscope. Tumors that contain more normal-looking cells and tissues tend to have a better prognosis and are said to have a favorable histology. Tumors whose cells and tissues look more abnormal under a microscope tend to have a poorer prognosis and are said to have an unfavorable histology.
DNA ploidy – the amount of DNA in each cell, known as ploidy or the DNA index, can be measured by special lab tests, such as flow cytometry or imaging cytometry. Neuroblastoma cells with about the same amount of DNA as normal cells (a DNA index of 1) are classified as diploid. Cells with increased amounts of DNA (a DNA index higher than 1) are termed hyperdiploid.
In infants, hyperdiploid cells tend to be associated with earlier stages of disease, respond better to chemotherapy, and usually predict a more favorable prognosis (outcome) than diploid cells. Ploidy is not as useful a factor in older children.
MYCN gene amplifications –MYCN is an oncogene, a gene that helps regulate cell growth. Changes in oncogenes can make cells grow and divide too quickly, as with cancer cells.
Neuroblastomas with too many copies (amplification) of the MYCN oncogene tend to grow quickly and are less likely to mature. Children whose neuroblastomas have this feature tend to have a worse prognosis than other children with neuroblastoma.