Neuroblastoma
Neuroblastoma is the most common extracranial solid tumour of childhood and is notable for an exceptionally wide range of behaviour — from tumours that regress without treatment to aggressive high-risk disease.
Disease categories
Major disease categories
- Low-risk neuroblastoma
- Intermediate-risk neuroblastoma
- High-risk neuroblastoma
- Ganglioneuroblastoma
- Ganglioneuroma
Molecular
Molecular considerations
MYCN amplification is the single most important prognostic marker and determines risk group assignment. ALK alterations occur in a minority and are of therapeutic interest. Segmental chromosomal aberrations and tumour ploidy inform risk.
Markers commonly discussed in neuroblastoma
- MYCN amplification
- ALK
- Ploidy
- Segmental chromosomal aberrations
- Urinary catecholamines
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
MYCN status is established at diagnosis and is integral to risk stratification. ALK testing is discussed particularly in high-risk and relapsed disease.
Germline
Germline considerations
Familial neuroblastoma associated with germline ALK or PHOX2B alterations is considered where there is family history or multifocal disease.
Molecular monitoring
ctDNA and liquid biopsy considerations
An active research area in paediatric oncology, including for monitoring high-risk disease.
Single-cell & computation
Single-cell and algorithmic approaches
Paediatric tumours are frequently driven by a single fusion or copy-number event on a quiet mutational background, which makes single-cell analysis unusually informative about developmental state rather than mutational burden. Single-cell RNA sequencing is used to place a tumour along a developmental trajectory. Algorithm work includes fusion detection, methylation classification, and analysis designed for the small cohort sizes that paediatric rarity imposes.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has MYCN status been established?
- Has formal risk group assignment been made?
- Has ALK testing been performed in high-risk disease?
Resistance
Resistance and recurrence questions
- Has the molecular profile been reassessed at relapse, since ALK alterations can emerge?
Trials
Clinical trial considerations
Risk group and MYCN status are determinative; paediatric trials run through specialist networks.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.