• Neuroblastomas are a heterogeneous group of tumors with a highly variable outcome ranging from spontaneous regression to death of the patient.
• Good prognosis tumors tend to have an hyperdiploid DNA content, with gains of whole chromosomes, without structural chromosomal abnormalities, and expression of the TrkA neurotrophin receptor.
• Unfavorable tumors, on the other hand, have a diploid DNA content with structural chromosomal alterations, including deletions of 1p, 11q, gain of 17q, and MYCN amplification They tend to express the TrkB neurotrophin receptor and BDNF
• Children below 1 year of age tend to have a better prognosis, even with disseminated disease, especially when disseminated disease is confined to the liver, skin, or bone marrow (stage 4S); however, with MYCN amplification, the 3-year event-free survival rate in infants with metastatic disease drops from 93% to around 10%.
• Therefore, along with age, stage, and “Shimada” histologic appearance, MYCN amplification and DNA ploidy are used to classify tumors into low-, intermediate- or high- risk groups.
• The international consensus for neuroblastoma diagnostics in 2009, included MYCN status, 11q23 losses and ploidy as obligatory markers to be used for therapy stratification, and started prospective evaluation of losses on 1p, 3p, 4p, and 11q, and gains on 1q, 2p, and 17q.
• Activating mutations ALK mutations are seen in approximately 5% to 7% of neuroblastomas, with two hot spots. Copy number gains of the ALK locus may be associated with a poor prognosis.