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Neuroblastoma(NB)

MedGen UID:
18012
Concept ID:
C0027819
Neoplastic Process
Synonym: NB
SNOMED CT: NB - Neuroblastoma (87364003); Neuroblastoma (87364003); Neuroblastoma (432328008)
Modes of inheritance:
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Related genes: KIF1B, PHOX2B, ALK
 
HPO: HP:0003006
Monarch Initiative: MONDO:0005072
Orphanet: ORPHA635

Disease characteristics

Excerpted from the GeneReview: ALK-Related Neuroblastic Tumor Susceptibility
ALK-related neuroblastic tumor susceptibility is characterized by increased risk for neuroblastic tumors including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Neuroblastoma is a more malignant tumor and ganglioneuroma a more benign tumor. Depending on the histologic findings, ganglioneuroblastoma can behave in a more aggressive fashion, like neuroblastoma, or in a benign fashion, like ganglioneuroma. Preliminary data from the ten reported families with ALK-related neuroblastic tumor susceptibility suggest an overall penetrance of approximately 57% with the risk for neuroblastic tumor development highest in infancy and decreasing by late childhood. [from GeneReviews]
Authors:
Emily G Greengard  |  Julie R Park   view full author information

Additional description

From OMIM
Neuroblastoma is the most common childhood cancer diagnosed before the age of 1 year, and accounts for 10 to 15% of all cancer deaths in children. Some patients inherit a genetic predisposition to neuroblastoma due to germline mutations, whereas others develop sporadic disease that may result from either germline or somatic mutations. Neuroblastoma tumors are derived from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system (Roberts et al., 1998; Eng, 2008). Histopathologically, neuroblastoma can range in type from the most aggressive form, neuroblastoma, composed entirely of immature neural precursor cells, to ganglioneuroma, composed entirely of mature neural tissue. The most important prognostic factor for patients with neuroblastoma is the extent of the tumor at the time of diagnosis (Roberts et al., 1998). Neuroblastoma can also be part of cancer-prone syndromes, such as paragangliomas (see, e.g., PGL4; 115310). Genetic Heterogeneity of Susceptibility to Neuroblastoma Susceptibility to neuroblastoma is genetically heterogeneous and is conferred by mutation in the PHOX2B gene (603851) on chromosome 4p12 (NBLST2; 613013) and by mutation in the ALK gene (105590) on chromosome 2p23 (NBLST3; 613014). Loci implicated in the development of neuroblastoma include 6p (NBLST4; 613015), 2q35 (NBLST5; 613016), and 1q21 (NBLST6; 613017).  http://www.omim.org/entry/256700

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Conditions with this feature

Dubowitz syndrome
MedGen UID:
59797
Concept ID:
C0175691
Disease or Syndrome
Dubowitz syndrome (DS) is a rare multiple congenital syndrome characterized primarly by growth retardation, microcephaly, distinctive facial dysmorphism, cutaneous eczema, a mild to severe intellectual deficit and genital abnormalities.
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1
MedGen UID:
321945
Concept ID:
C1832388
Disease or Syndrome
RUNX1 familial platelet disorder with associated myeloid malignancies (RUNX1-FPDMM) is characterized by prolonged bleeding and/or easy bruising and an increased risk of developing a hematologic malignancy. RUNX1-FPDMM is characterized by thrombocytopenia with normal platelet size; bleeding is often greater than expected due to qualitative platelet dysfunction. Myeloid malignancies are the most common, including acute myelogenous leukemia (and myelodysplastic syndrome. T- and B-cell acute lymphoblastic leukemias and lymphomas have also been reported, as well as skin manifestations (e.g., eczema, psoriasis).
Fanconi anemia complementation group N
MedGen UID:
372133
Concept ID:
C1835817
Disease or Syndrome
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and/or lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. The incidence of acute myeloid leukemia is 13% by age 50 years. Solid tumors – particularly of the head and neck, skin, and genitourinary tract – are more common in individuals with FA.
Paragangliomas 4
MedGen UID:
349380
Concept ID:
C1861848
Neoplastic Process
Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes are characterized by paragangliomas (tumors that arise from neuroendocrine tissues distributed along the paravertebral axis from the base of the skull to the pelvis) and pheochromocytomas (paragangliomas that are confined to the adrenal medulla). Sympathetic paragangliomas cause catecholamine excess; parasympathetic paragangliomas are most often nonsecretory. Extra-adrenal parasympathetic paragangliomas are located predominantly in the skull base and neck (referred to as head and neck PGL [HNPGL]) and sometimes in the upper mediastinum; approximately 95% of such tumors are nonsecretory. In contrast, sympathetic extra-adrenal paragangliomas are generally confined to the lower mediastinum, abdomen, and pelvis, and are typically secretory. Pheochromocytomas, which arise from the adrenal medulla, typically lead to catecholamine excess. Symptoms of PGL/PCC result from either mass effects or catecholamine hypersecretion (e.g., sustained or paroxysmal elevations in blood pressure, headache, episodic profuse sweating, forceful palpitations, pallor, and apprehension or anxiety). The risk for developing metastatic disease is greater for extra-adrenal sympathetic paragangliomas than for pheochromocytomas.
Platelet disorder, undefined
MedGen UID:
401405
Concept ID:
C1868258
Disease or Syndrome
Neuroblastoma, susceptibility to, 1
MedGen UID:
412713
Concept ID:
C2749485
Finding
Neuroblastoma, susceptibility to, 2
MedGen UID:
416607
Concept ID:
C2751682
Finding
In addition, neuroblastoma tumors can release hormones that may cause other signs and symptoms such as high blood pressure, rapid heartbeat, flushing of the skin, and sweating. In rare instances, individuals with neuroblastoma may develop opsoclonus myoclonus syndrome, which causes rapid eye movements and jerky muscle motions. This condition occurs when the immune system malfunctions and attacks nerve tissue.\n\nIndividuals with neuroblastoma may develop general signs and symptoms such as irritability, fever, tiredness (fatigue), pain, loss of appetite, weight loss, or diarrhea. More specific signs and symptoms depend on the location of the tumor and where it has spread. A tumor in the abdomen can cause abdominal swelling. A tumor in the chest may lead to difficulty breathing. A tumor in the neck can cause nerve damage known as Horner syndrome, which leads to drooping eyelids, small pupils, decreased sweating, and red skin. Tumor metastasis to the bone can cause bone pain, bruises, pale skin, or dark circles around the eyes. Tumors in the backbone can press on the spinal cord and cause weakness, numbness, or paralysis in the arms or legs. A rash of bluish or purplish bumps that look like blueberries indicates that the neuroblastoma has spread to the skin.\n\nNeuroblastoma occurs most often in children before age 5 and rarely occurs in adults.\n\nNeuroblastoma is a type of cancer that most often affects children. Neuroblastoma occurs when immature nerve cells called neuroblasts become abnormal and multiply uncontrollably to form a tumor. Most commonly, the tumor originates in the nerve tissue of the adrenal gland located above each kidney. Other common sites for tumors to form include the nerve tissue in the abdomen, chest, neck, or pelvis. Neuroblastoma can spread (metastasize) to other parts of the body such as the bones, liver, or skin.
Neurofibromatosis-Noonan syndrome
MedGen UID:
419089
Concept ID:
C2931482
Disease or Syndrome
A variant of neurofibromatosis type 1 characterized by the combination of features of neurofibromatosis type 1, such as café-au-lait spots, iris Lisch nodules, axillary and inguinal freckling, optic nerve glioma and multiple neurofibromas; and Noonan syndrome, with features such as short stature, typical facial features, congenital heart defects and unusual pectus deformity.
Mismatch repair cancer syndrome 1
MedGen UID:
1748029
Concept ID:
C5399763
Disease or Syndrome
Lynch syndrome is characterized by an increased risk for colorectal cancer (CRC) and cancers of the endometrium, ovary, stomach, small bowel, urinary tract, biliary tract, brain (usually glioblastoma), skin (sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas), pancreas, and prostate. Cancer risks and age of onset vary depending on the associated gene. Several other cancer types have been reported to occur in individuals with Lynch syndrome (e.g., breast, sarcomas, adrenocortical carcinoma). However, the data are not sufficient to demonstrate that the risk of developing these cancers is increased in individuals with Lynch syndrome.
Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease
MedGen UID:
1794285
Concept ID:
C5562075
Disease or Syndrome
Congenital central hypoventilation syndrome (CCHS) represents the extreme manifestation of autonomic nervous system dysregulation (ANSD) with the hallmark of disordered respiratory control. The age of initial recognition of CCHS ranges from neonatal onset (i.e., in the first 30 days of life) to (less commonly) later onset (from 1 month to adulthood). Neonatal-onset CCHS is characterized by apparent hypoventilation with monotonous respiratory rates and shallow breathing either during sleep only or while awake as well as asleep; ANSD including decreased heart rate beat-to-beat variability and sinus pauses; altered temperature regulation; and altered pupillary response to light. Some children have altered development of neural crest-derived structures (i.e., Hirschsprung disease, altered esophageal motility/dysphagia, and severe constipation even in the absence of Hirschsprung disease) and/or tumors of neural crest origin (neuroblastoma, ganglioneuroma, and ganglioneuroblastoma). Neurocognitive delay is variable, and possibly influenced by cyanotic breath holding, prolonged sinus pauses, need for 24-hour/day artificial ventilation, and seizures. Later-onset CCHS is characterized by alveolar hypoventilation during sleep and attenuated manifestations of ANSD.

Professional guidelines

PubMed

Rossor T, Yeh EA, Khakoo Y, Angelini P, Hemingway C, Irani SR, Schleiermacher G, Santosh P, Lotze T, Dale RC, Deiva K, Hero B, Klein A, de Alarcon P, Gorman MP, Mitchell WG, Lim M; OMS Study Group
Neurol Neuroimmunol Neuroinflamm 2022 May;9(3) Epub 2022 Mar 8 doi: 10.1212/NXI.0000000000001153. PMID: 35260471Free PMC Article
Croteau N, Nuchtern J, LaQuaglia MP
Surg Oncol Clin N Am 2021 Apr;30(2):291-304. Epub 2021 Feb 10 doi: 10.1016/j.soc.2020.11.010. PMID: 33706901
Whittle SB, Smith V, Doherty E, Zhao S, McCarty S, Zage PE
Expert Rev Anticancer Ther 2017 Apr;17(4):369-386. Epub 2017 Mar 15 doi: 10.1080/14737140.2017.1285230. PMID: 28142287

Recent clinical studies

Etiology

Choi JH, Ro JY
Semin Diagn Pathol 2022 Mar;39(2):120-130. Epub 2021 Jun 15 doi: 10.1053/j.semdp.2021.06.007. PMID: 34167847
Chung C, Boterberg T, Lucas J, Panoff J, Valteau-Couanet D, Hero B, Bagatell R, Hill-Kayser CE
Pediatr Blood Cancer 2021 May;68 Suppl 2(Suppl 2):e28473. doi: 10.1002/pbc.28473. PMID: 33818884Free PMC Article
Croteau N, Nuchtern J, LaQuaglia MP
Surg Oncol Clin N Am 2021 Apr;30(2):291-304. Epub 2021 Feb 10 doi: 10.1016/j.soc.2020.11.010. PMID: 33706901
Whittle SB, Smith V, Doherty E, Zhao S, McCarty S, Zage PE
Expert Rev Anticancer Ther 2017 Apr;17(4):369-386. Epub 2017 Mar 15 doi: 10.1080/14737140.2017.1285230. PMID: 28142287
Maris JM, Hogarty MD, Bagatell R, Cohn SL
Lancet 2007 Jun 23;369(9579):2106-20. doi: 10.1016/S0140-6736(07)60983-0. PMID: 17586306

Diagnosis

DuBois SG, Macy ME, Henderson TO
Am Soc Clin Oncol Educ Book 2022 Apr;42:1-13. doi: 10.1200/EDBK_349783. PMID: 35522915
Choi JH, Ro JY
Semin Diagn Pathol 2022 Mar;39(2):120-130. Epub 2021 Jun 15 doi: 10.1053/j.semdp.2021.06.007. PMID: 34167847
Swift CC, Eklund MJ, Kraveka JM, Alazraki AL
Radiographics 2018 Mar-Apr;38(2):566-580. doi: 10.1148/rg.2018170132. PMID: 29528815
Aygun N
Curr Pediatr Rev 2018;14(2):73-90. doi: 10.2174/1573396314666180129101627. PMID: 29380702
Whittle SB, Smith V, Doherty E, Zhao S, McCarty S, Zage PE
Expert Rev Anticancer Ther 2017 Apr;17(4):369-386. Epub 2017 Mar 15 doi: 10.1080/14737140.2017.1285230. PMID: 28142287

Therapy

Del Bufalo F, De Angelis B, Caruana I, Del Baldo G, De Ioris MA, Serra A, Mastronuzzi A, Cefalo MG, Pagliara D, Amicucci M, Li Pira G, Leone G, Bertaina V, Sinibaldi M, Di Cecca S, Guercio M, Abbaszadeh Z, Iaffaldano L, Gunetti M, Iacovelli S, Bugianesi R, Macchia S, Algeri M, Merli P, Galaverna F, Abbas R, Garganese MC, Villani MF, Colafati GS, Bonetti F, Rabusin M, Perruccio K, Folsi V, Quintarelli C, Locatelli F; Precision Medicine Team–IRCCS Ospedale Pediatrico Bambino Gesù
N Engl J Med 2023 Apr 6;388(14):1284-1295. doi: 10.1056/NEJMoa2210859. PMID: 37018492
Park JR, Kreissman SG, London WB, Naranjo A, Cohn SL, Hogarty MD, Tenney SC, Haas-Kogan D, Shaw PJ, Kraveka JM, Roberts SS, Geiger JD, Doski JJ, Voss SD, Maris JM, Grupp SA, Diller L
JAMA 2019 Aug 27;322(8):746-755. doi: 10.1001/jama.2019.11642. PMID: 31454045Free PMC Article
Pinto NR, Applebaum MA, Volchenboum SL, Matthay KK, London WB, Ambros PF, Nakagawara A, Berthold F, Schleiermacher G, Park JR, Valteau-Couanet D, Pearson AD, Cohn SL
J Clin Oncol 2015 Sep 20;33(27):3008-17. Epub 2015 Aug 24 doi: 10.1200/JCO.2014.59.4648. PMID: 26304901Free PMC Article
Davidoff AM
Semin Pediatr Surg 2012 Feb;21(1):2-14. doi: 10.1053/j.sempedsurg.2011.10.009. PMID: 22248965Free PMC Article
Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK, Shimada H, Grupp SA, Seeger R, Reynolds CP, Buxton A, Reisfeld RA, Gillies SD, Cohn SL, Maris JM, Sondel PM; Children's Oncology Group
N Engl J Med 2010 Sep 30;363(14):1324-34. doi: 10.1056/NEJMoa0911123. PMID: 20879881Free PMC Article

Prognosis

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Schengrund CL
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Newman EA, Abdessalam S, Aldrink JH, Austin M, Heaton TE, Bruny J, Ehrlich P, Dasgupta R, Baertschiger RM, Lautz TB, Rhee DS, Langham MR Jr, Malek MM, Meyers RL, Nathan JD, Weil BR, Polites S, Madonna MB; APSA Cancer committee
J Pediatr Surg 2019 Mar;54(3):383-389. Epub 2018 Sep 19 doi: 10.1016/j.jpedsurg.2018.09.004. PMID: 30305231
Whittle SB, Smith V, Doherty E, Zhao S, McCarty S, Zage PE
Expert Rev Anticancer Ther 2017 Apr;17(4):369-386. Epub 2017 Mar 15 doi: 10.1080/14737140.2017.1285230. PMID: 28142287
Monclair T, Brodeur GM, Ambros PF, Brisse HJ, Cecchetto G, Holmes K, Kaneko M, London WB, Matthay KK, Nuchtern JG, von Schweinitz D, Simon T, Cohn SL, Pearson AD; INRG Task Force
J Clin Oncol 2009 Jan 10;27(2):298-303. Epub 2008 Dec 1 doi: 10.1200/JCO.2008.16.6876. PMID: 19047290Free PMC Article

Clinical prediction guides

Verhoeven BM, Mei S, Olsen TK, Gustafsson K, Valind A, Lindström A, Gisselsson D, Fard SS, Hagerling C, Kharchenko PV, Kogner P, Johnsen JI, Baryawno N
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Amelio I, Bertolo R, Bove P, Candi E, Chiocchi M, Cipriani C, Di Daniele N, Ganini C, Juhl H, Mauriello A, Marani C, Marshall J, Montanaro M, Palmieri G, Piacentini M, Sica G, Tesauro M, Rovella V, Tisone G, Shi Y, Wang Y, Melino G
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MacFarland S, Bagatell R
Curr Opin Pediatr 2019 Feb;31(1):14-20. doi: 10.1097/MOP.0000000000000711. PMID: 30480556
Auslander N, Zhang G, Lee JS, Frederick DT, Miao B, Moll T, Tian T, Wei Z, Madan S, Sullivan RJ, Boland G, Flaherty K, Herlyn M, Ruppin E
Nat Med 2018 Oct;24(10):1545-1549. Epub 2018 Aug 20 doi: 10.1038/s41591-018-0157-9. PMID: 30127394Free PMC Article
Pinto NR, Applebaum MA, Volchenboum SL, Matthay KK, London WB, Ambros PF, Nakagawara A, Berthold F, Schleiermacher G, Park JR, Valteau-Couanet D, Pearson AD, Cohn SL
J Clin Oncol 2015 Sep 20;33(27):3008-17. Epub 2015 Aug 24 doi: 10.1200/JCO.2014.59.4648. PMID: 26304901Free PMC Article

Recent systematic reviews

Hymel E, Degarege A, Fritch J, Farazi E, Napit K, Coulter D, Schmidt C, Watanabe-Galloway S
Environ Sci Pollut Res Int 2023 Nov;30(53):113193-113204. Epub 2023 Oct 19 doi: 10.1007/s11356-023-30315-z. PMID: 37858025
Lopez-Suarez L, Awabdh SA, Coumoul X, Chauvet C
Neurotoxicology 2022 Sep;92:131-155. Epub 2022 Jul 29 doi: 10.1016/j.neuro.2022.07.008. PMID: 35914637
Banik K, Khatoon E, Harsha C, Rana V, Parama D, Thakur KK, Bishayee A, Kunnumakkara AB
Phytother Res 2022 May;36(5):1854-1883. Epub 2022 Jan 31 doi: 10.1002/ptr.7386. PMID: 35102626
Müller-Schulte E, Kurlemann G, Harder A
Arch Dis Child Fetal Neonatal Ed 2018 Sep;103(5):F467-F473. Epub 2017 Nov 21 doi: 10.1136/archdischild-2017-313615. PMID: 29162685
Xicoy H, Wieringa B, Martens GJ
Mol Neurodegener 2017 Jan 24;12(1):10. doi: 10.1186/s13024-017-0149-0. PMID: 28118852Free PMC Article

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