What blood work and initial treatment are recommended for a patient suspected of having neuroblastoma?

Recommended Blood Work and Initial Treatment for Suspected Neuroblastoma

For patients suspected of having neuroblastoma, essential blood work includes CBC with differential, comprehensive metabolic panel, urine catecholamines (HVA and VMA), serum ferritin, and LDH, followed by appropriate imaging and tissue sampling for definitive diagnosis. 1

Initial Laboratory Workup

Essential Laboratory Tests

• Complete Blood Count (CBC) with differential - to assess for bone marrow involvement and general health status 1
• Comprehensive Metabolic Panel - to evaluate organ function, particularly liver and kidneys 1
• Urine Catecholamines:
  • Homovanillic acid (HVA)
  • Vanillylmandelic acid (VMA)
  • These are elevated in the majority of neuroblastoma patients 1, 2
  • Diagnostic utility varies by stage: present in 50% of Stage I/II, 88% of Stage III, 93% of Stage IV, and 100% of Stage IV-S cases 2

Additional Recommended Tests

• Lactate dehydrogenase (LDH) - elevated levels associated with worse prognosis 1, 3
• Serum ferritin - elevated levels associated with worse prognosis 1, 3
• Prothrombin time/INR - particularly if liver involvement or bleeding concerns exist 1

Important Considerations for Catecholamine Testing

• Certain foods (e.g., bananas) can cause false-positive results by increasing urinary HVA levels 2
• Consider dietary restrictions 24 hours before sample collection 2
• Note that urine catecholamine testing is only required for diagnosis if bone marrow is the only diagnostic tissue obtained 1

Imaging Studies

Initial Imaging

• Cross-sectional imaging (MRI with/without contrast or CT with contrast) to evaluate soft tissue disease 1
• 123I-MIBG scan - highly specific and sensitive for detecting neuroblastoma (detects 90-95% of cases) 1, 4
  • Should include SPECT or SPECT/CT if available at sites of known/suspected disease 1
• MRI of spine with/without contrast - if paraspinal disease or concerns about nerve root/spinal cord involvement 1
• 18F-FDG-PET/CT - for patients with MIBG-nonavid disease or suspected mixed-avidity disease 1

Tissue Sampling and Pathology

Recommended Sampling Approach

• Coordinated diagnostic sampling involving pathologists, oncologists, surgeons, and radiologists 1
• Bone marrow sampling:
  • First bone marrow aspirate (2-5 ml) from each iliac crest into anticoagulant (EDTA or Heparin) 1
  • Bilateral bone marrow biopsies 1

Acceptable Tissue Sampling Methods

• Surgical resection (if clinically indicated)
• Incisional biopsy (>1 cm³)
• Tissue cores (at least 10 cores, ideally 20-30 mm in length using a 16-gauge needle) 1

Molecular Testing

• Molecular genetic testing for prognostic biomarkers, including MYCN amplification and ALK status 1
• Immunohistochemical stains (chromogranin, synaptophysin, PHOX2B, tyrosine hydroxylase) for small samples or undifferentiated subtypes 1

Initial Treatment Considerations

Treatment Approach Based on Risk Classification

• Treatment depends on age, stage of disease, and biological/biochemical markers 4
• Risk stratification is essential to determine appropriate treatment intensity 1

For High-Risk Disease

• Dinutuximab (Unituxin) in combination with GM-CSF, IL-2, and 13-cis-retinoic acid for high-risk patients who achieve at least partial response to prior first-line therapy 5
• Required premedication before dinutuximab:
  • IV hydration (0.9% Sodium Chloride 10 mL/kg over 1 hour)
  • Analgesics (morphine sulfate 50 mcg/kg IV followed by infusion)
  • Antihistamines (diphenhydramine 0.5-1 mg/kg)
  • Antipyretics (acetaminophen 10-15 mg/kg) 5

Clinical Pearls and Pitfalls

• Pitfall: Relying solely on tumor markers for diagnosis or monitoring. Studies show that tumor markers alone have limited sensitivity for detecting relapse or progression (54% for urine VMA/HVA, 61% for NSE) 6
• Pitfall: Interpreting elevated serum ferritin without considering blood transfusions. Iron load from transfusions can affect serum ferritin levels independent of tumor activity 7
• Important: Adult neuroblastoma is extremely rare and may have different presentation and prognosis compared to pediatric cases 8
• Caution: Bilateral bone marrow biopsies and clot sections alone may not be sufficient to assess all characteristics relevant to the International Neuroblastoma Pathology Classification system 1

Follow-up and Monitoring

• Monitoring approach varies based on risk classification:
  • For low-risk: H&P every 3 months in year 1, then every 6 months in year 2
  • For intermediate-risk: H&P every 3 months for year 1, every 6 months for year 2
  • For high-risk: H&P every 3 months for year 1, then every 6 months for years 2-5 1
• Cross-sectional imaging and functional imaging (MIBG or FDG-PET) at intervals determined by risk group 1

By following this comprehensive diagnostic and initial treatment approach, clinicians can ensure appropriate management of patients suspected of having neuroblastoma, leading to optimal outcomes in terms of morbidity and mortality.