title: Outcomes in multifocal neuroblastoma as part of the neurocristopathy syndrome.
abstract: The neurocristopathy syndrome occurs because of a germline mutation of the paired-like homeobox 2b (PHOX2B) gene at 4p12, a neurogenesis regulator gene. The result is abnormal neural crest cell development resulting in congenital central hypoventilation syndrome, Hirschsprung disease, and neuroblastoma (NB), which is often multifocal and disseminated in its presentation. Previously, such widespread disease was regarded as highly aggressive and treated either with palliative intent or, conversely, with very intense, high-dose chemotherapy. We now present a patient who had neurocristopathy syndrome who had multifocal NB associated with an underlying germline PHOX2B mutation. He was treated conservatively with surgery and low-dose chemotherapy. After treatment he had extensive residual disease that has continued to mature despite no further treatment. A literature review identified 26 similar patients presenting with multifocal NB as part of the neurocristopathy syndrome. In all cases the NB behaved in an indolent manner with no deaths from tumor reported when patients received appropriate treatment. These provocative findings suggest for the first time that children who have neurocristopathy-associated NB should be treated conservatively, despite the aggressive appearance of their disease.
authors: Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia;
authors: Phoebe
authors: P
authors: Williams
authors: Prince of Wales Hospital, Randwick, New South Wales, Australia.
authors: Eva
authors: E
authors: Wegner
authors: Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia;School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Australia; and d.ziegler@unsw.edu.au.
authors: David S
authors: DS
authors: Ziegler
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002114:Calcinosis; D018095:Germ-Line Mutation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D009419:Nerve Tissue Proteins; D014157:Transcription Factors
keywords: PHOX2B; bilateral neuroblastoma; familial neuroblastoma; multifocal neuroblastoma; neurocristopathy syndrome