Diagnostic Workup for Neuroblastoma in a 5-Week-Old Infant
The recommended diagnostic workup for a 5-week-old infant with suspected neuroblastoma should include cross-sectional imaging, 123I-MIBG scanning, laboratory tests, and in most cases tissue sampling for histologic and molecular evaluation. 1
Initial Imaging Studies
Cross-sectional imaging: MRI with/without contrast or CT with contrast of the primary tumor site 1
- MRI is preferred for detailed evaluation of soft tissue involvement
- MRI of spine with/without contrast if paraspinal disease is suspected or if there are concerns about nerve root/spinal cord involvement
- MRI of brain with/without contrast or CT skull/orbits with contrast if neurologic symptoms are present
Functional imaging: 123I-MIBG scan to assess for metastatic disease 1
- High specificity and sensitivity (demonstrated in up to 90% of neuroblastoma tumors)
- SPECT or SPECT/CT should be performed if available for better anatomic localization
- 18F-FDG-PET should be obtained if tumor is MIBG non-avid or has suspected mixed avidity
Laboratory Evaluation
- Complete blood count with differential
- Comprehensive metabolic panel
- Urinary catecholamine metabolites (HVA and VMA)
- Lactate dehydrogenase (LDH)
- Ferritin
- Neuron-specific enolase (NSE)
Tissue Sampling
Surgical approach: 1
- For localized disease without image-defined risk factors (IDRFs), consider surgical resection
- For disease with IDRFs, minimally invasive biopsy is preferred
- Multiple core biopsies to ensure adequate tissue for histologic and molecular evaluation
- Fine-needle aspiration is NOT recommended
Important exception for young infants: 1
- Patients <6 months of age with L1 adrenal tumors ≤3.1 cm if solid or ≤5 cm if at least 25% cystic do not require initial biopsy or resection
- A "wait and see" strategy with monitoring may be appropriate for these small, localized tumors 2
Bone marrow assessment: 1
- Bilateral bone marrow aspirates and trephine biopsies to evaluate for metastatic disease
- Can be diagnostic if marrow is the only source of tumor material
Molecular Testing
- Next-generation sequencing (NGS) is recommended to evaluate: 1
- MYCN amplification status (critical prognostic factor)
- Segmental chromosomal aberrations (SCAs)
- ALK gene amplification or mutations (for potential targeted therapy)
- DNA ploidy status (particularly important in infants)
Special Considerations for Infants
- Infants <2 months with hepatomegaly should not undergo biopsy until after initiation of therapy and clinical stabilization 1
- Very young infants with small, localized adrenal tumors may be candidates for observation rather than immediate intervention 2, 3
- Neonatal neuroblastoma generally has a more favorable prognosis than in older children 3
Staging and Risk Classification
After completing the diagnostic workup, the International Neuroblastoma Risk Group (INRG) Staging System should be used to determine stage and risk classification, which will guide treatment decisions 1.
Pitfalls to Avoid
- Delaying emergent therapy if needed (imaging can be obtained as soon as possible afterward) 1
- Inadequate tissue sampling leading to insufficient material for molecular testing
- Failure to recognize atypical presentations (e.g., scrotal masses can be metastatic neuroblastoma) 4
- Over-treatment of small, localized tumors in young infants that may spontaneously regress 2, 3
Following this comprehensive diagnostic approach will enable accurate staging, risk classification, and appropriate treatment selection to optimize outcomes for the infant.