While there is no racial variation in incidence, there are racial differences in tumor biology, with African Americans more likely to have high-risk disease and fatal outcome.[8,9]
Population-based studies of screening for infants with neuroblastoma have demonstrated that spontaneous regression of neuroblastoma without clinical detection in the first year of life is at least as prevalent as clinically detected neuroblastoma.[10,11,12]
Neuroblastoma originates in the adrenal medulla or the paraspinal sites where sympathetic nervous system tissue is present.
Figure 1. Neuroblastoma may be found in the adrenal glands and paraspinal nerve tissue from the neck to the pelvis.
Little is known about the events that predispose to the development of neuroblastoma. Parental exposures have not been definitively linked to neuroblastoma.
Germline deletion at the 1p36 or 11q14-23 locus is associated with neuroblastoma, and the same deletions are found somatically in sporadic neuroblastomas.[13,14]
About 1% to 2% of patients with neuroblastoma have a family history of neuroblastoma. These children are on average younger (9 months at diagnosis), and about 20% have multifocal primary neuroblastomas. The primary cause of familial neuroblastoma is a germline mutation in the ALK gene. Familial neuroblastoma is rarely associated with congenital central hypoventilation syndrome (Ondine's curse), which is caused by a germline mutation of the PHOX2B gene.
Biologic and Molecular Features
On the basis of biologic factors and an improved understanding of the molecular development of the neural crest cells that give rise to neuroblastoma, neuroblastic tumors have been categorized into the following three biological types:
- Type 1: Characterized by gains and losses of whole chromosomes. It expresses the TrkA neurotrophin receptor, is hyperdiploid, and tends to spontaneously regress.[17,18]
- Type 2A: Characterized by copy number alterations in portions of chromosomes. Type 2A expresses the TrkB neurotrophin receptor and its ligand, has gained an additional copy of chromosome 17q, has loss of heterozygosity of 14q or 11q, and is genomically unstable.[17,18]
- Type 2B: Generally has the MYCN gene amplified and has a gain of chromosome 17q, loss of chromosome 1p, and expression of the TrkB neurotrophin receptor and its ligand.[17,18]