neuroblastoma
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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)
- neurosecretory granules (20-50 nm)
- cell processes with microtubules
- 10 nm cytoplasmic filaments
- glycogen deposits +/-
- synapse-like cell junctions
Immunophenotype
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:
* 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
- I confined to organ of origin
- II extends in continuity beyond organ of origin, doesn't cross midline, variable ipsilateral nodal metastases
- III extends in continuity beyond midline; variable ipsilateral nodal metastases
- IV metastatic to viscera, distal lymph nodes, soft tissue, skeletal
- 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
Management
- treatment is dependent upon staging
- surgery
- radiation therapy
- iodine 131-MIBG therapy
- chemotherapy: avoid platinum-based chemotherapy (see complications)
- 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]
More general terms
More specific terms
Additional terms
References
- ↑ 1.0 1.1 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 - ↑ Brodeur. Nature Reviews Cancer 3:203-216, 2003
- ↑ 3.0 3.1 3.2 3.3 Ackermann S, Cartolano M, Hero B et al. A mechanistic classification of clinical phenotypes in neuroblastoma. Science. 2018 Dec 7;362(6419):1165-1170. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/30523111 <Internet> http://science.sciencemag.org/content/362/6419/1165
- ↑ 4.0 4.1 http://www.pathologyoutlines.com/adrenal.html
- ↑ ARUP Consult: Neuroblastoma The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/neuroblastoma
- ↑ 6.0 6.1 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/
Patient information
neuroblastoma patient information