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neuroblastoma

Epidemiology: - one of most common solid tumors in childhood - 90% of cases diagnosed before age 5 years - ~50% arise in adrenal medulla - others usually arise in paraspinal location in chest or abdomen Pathology: - tumor derived from primitive cells of the sympathetic nervous system - neuroblastomas have a highly variable clinical course: may regress spontaneously, may mature into ganglioneuroma or may have extensive metastatic disease with poor overall prognosis Microscopic Pathology: - sheets of small cells with hyperchromatic nuclei and scanty cytoplasm, poorly defined borders - Homer Wright pseudorosettes ~30% of cases - one end of a spectrum: neuroblastoma -> ganglioneuroblastoma -> ganglioneuroma - International Neuroblastoma Pathology Classification (modified Shimada system) Electron microscopy: - neurosecretory granules (20-50 nm) - cell processes with microtubules - 10 nm cytoplasmic filaments - glycogen deposits +/- - synapse-like cell junctions Immunohistochemistry: - chromogranin + - synaptophysin + - NB84 + - neurofilament + - neuron-specific enolase + Genetics: - near triploidy associated with favorable outcome - N-myc amplification (~22%), allelic loss at chromosome 1p associated with poor prognosis - high expression of TrkA favorable - lack of expression of HTATIP2 gene - chromosomal translocation t(1;15)(p36.2;q24) involving RERE - single nucleotide polymorphisms at 6p22 predicted to contain FLJ22536 FLJ44180 - may be associated with defects in NBL1 - impaired telomere maintenance associated with good prognosis* [3] - NRAS gene mutation & Tp53 gene mutation associated with poor prognosis* [3] - other implicated genes: - NAG, MYC, NAV3, LRRC17, DUSP26, ARID3B, CDCA7L, C1orf76, NBPF (NBPF1 NBPF3 NBPF4 NBPF5 NBPF6 NBPF7 NBPF8 NBPF9 NBPF10 NBPF11 NBPF12 NBPF14 NBPF15 NBPF20) C4orf6, LYN, NME1, XRRA1, ASXL3, CASP8, PHOX2B, TP73, ENC1 * impaired telomere maintenance, no NRAS or Tp53 gene mutation associated with 100% survival [3] Laboratory: - catecholamines found in urine (screening) - see ARUP consult [4] Staging: 1) I confined to organ of origin 2) II extends in continuity beyond organ of origin, doesn't cross midline, variable ipsilateral nodal metastases 3) III extends in continuity beyond midline; variable ipsilateral nodal metastases 4) IV metastatic to viscera, distal lymph nodes, soft tissue, skeletal 5) IV-S (special): stage I or II with distant liver, skin, bone marrow disease (no bony destruction) Complications: - platinum-based chemotherapy appears to cause clonal hematopoiesis that results in myeloid neoplasms in pediatric patients with neuroblastoma [6] Differential diagnosis: - rhabdomyosarcoma - Ewings sarcoma/PNET - lymphoma - Wilms tumor Management: 1) treatment is dependent upon staging a) surgery b) radiation therapy c) iodine 131-MIBG therapy d) chemotherapy: avoid platinum-based chemotherapy (see complications) e) high-dose chemotherapy & radiation therapy with stem cell rescue 2 Screening: - Two large studies, screening 476654 children at 3 weeks & 6 months of age & 1,475,733 children at 1 year of age did NOT reduce mortality. [1]

Related

chromosomal deletion 1p36 (neuroblastoma) Shimada classification of neuroblastomas

Specific

esthesioneuroblastoma; olfactory neuroblastoma ganglioneuroblastoma

General

embryonal neoplasm neuroendocrine neoplasm neuroepithelial neoplasm (includes glial, pineal, choroid plexus, ganglion cell neoplasms and others)

Database Correlations

OMIM correlations

References

  1. Journal Watch 22(10):80, 2002 - Wood WG et al, N Engl J Med 346:1041, 2002 - Schilling FH et al, N Engl J Med 346:1047, 2002 - Cuningham G, N Engl J Med 346:1084, 2002
  2. Brodeur. Nature Reviews Cancer 3:203-216, 2003
  3. Ackermann S, Cartolano M, Hero B et al. A mechanistic classification of clinical phenotypes in neuroblastoma. Science. 2018 Dec 7;362(6419):1165-1170. PMID: 30523111 http://science.sciencemag.org/content/362/6419/1165
  4. http://www.pathologyoutlines.com/adrenal.html
  5. ARUP Consult: Neuroblastoma The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/neuroblastoma
  6. Forster V Platinum Chemotherapy Appears to Cause Clonal Expansion Leading to Myeloid Neoplasms in Children With Neuroblastoma. Cancer Therapy Advisor. July 16, 2021 https://www.cancertherapyadvisor.com/home/cancer-topics/pediatric-cancer/neuroblastoma-platinum-chemotherapy-cause-clonal-expansion-treatment/