Pediatric Neuroblastoma Clinical Presentation

  • Author: Norman J Lacayo, MD; Chief Editor: Max J Coppes, MD, PhD, MBA   more...
 
Updated: Oct 20, 2010
 

History

The following may be noted in patients with neuroblastoma:

  • Signs and symptoms of neuroblastoma vary with site of presentation. Generally, symptoms include abdominal pain, emesis, weight loss, anorexia, fatigue, and bone pain. Hypertension is an uncommon sign of the disease and is generally caused by renal artery compression, not catecholamine excess. Chronic diarrhea is a rare presenting symptom secondary to tumor secretion of vasoactive intestinal peptide secretion.
  • Because more than 50% of patients present with advanced stage disease, usually to the bone and bone marrow, the most common presentation includes bone pain and a limp. However, patients may also present with unexplained fever, weight loss, irritability, and periorbital ecchymosis secondary to metastatic disease to the orbits. The presence of bone metastases can lead to pathologic fractures.
  • Approximately two thirds of patients with neuroblastoma have abdominal primaries. In these circumstances, patients can present with an asymptomatic abdominal mass that usually is discovered by the parents or a caregiver. Symptoms produced by the presence of the mass depend on its proximity to vital structures and usually progress over time.
  • Tumors that arise from the paraspinal sympathetic ganglia can grow through the spinal foramina into the spinal canal and impinge on the spinal cord. This may result in the presence of neurologic symptoms, including weakness, limping, paralysis, and even bladder and bowel dysfunction.
  • Thoracic neuroblastomas (posterior mediastinum) may be asymptomatic and are usually diagnosed by imaging studies obtained for other reasons. Presenting signs or symptoms may be insignificant and involve mild airway obstruction or chronic cough, leading to chest radiography.
  • Thoracic tumors extending to the neck can produce Horner syndrome. Primary cervical neuroblastoma is rare but should be considered in the differential diagnosis of masses of the neck, especially in infants younger than 1 year with feeding or respiratory difficulties.
  • In a small proportion of infants younger than 6 months, neuroblastoma presents with a small primary tumor and metastatic disease confined to the liver, skin, and bone marrow (stage 4S). If this type of tumor develops in neonates, skin lesions may be confused with congenital rubella, and, if the patient has severe skin involvement, the term "blueberry muffin baby" may be used.
  • Approximately 2% of patients present with opsoclonus and myoclonus a paraneoplastic syndrome characterized by the presence of myoclonic jerking and random eye movements. These patients often have localized disease and a good long-term prognosis. Unfortunately, the neurologic abnormalities can persist or progress and can be devastating.
  • Finally, intractable diarrhea is a rare paraneoplastic symptom and is associated with more differentiated tumors and a good prognosis.
Next

Physical

The following may be noted in patients with neuroblastoma:

  • Children are usually referred to a pediatric oncologist by primary care providers who have identified a persistent unexplained symptom or sign, either upon physical examination or based on screening test findings.
  • In patients with suspected neuroblastoma, performing a thorough examination with careful attention to vital signs (eg, blood pressure), neck, chest, abdomen, skin, and nervous system is essential.
  • Metastatic lesions of the skin are common in infants younger than 6 months and may represent stage 4S disease.
  • Examination of the abdomen may reveal an abdominal mass, leading to the appropriate workup.
  • Neurologic examination may reveal Horner syndrome. In the case of dumbbell tumors, compression of the spinal cord may produce lower extremity weakness or paraplegia. Patients with neurologic involvement by tumor should be treated emergently, secondary to the risk of permanent neurologic sequelae.
Previous
Next

Causes

The cause of neuroblastoma is unknown, and no specific environmental exposure or risk factors have been identified.

Because of young age of onset with this disease, investigators have focused on events before conception and during gestation.

According to SEER data, factors investigated for which evidence is limited or inconsistent include medications, hormones, birth characteristics, congenital anomalies, previous spontaneous abortion or fetal death, alcohol or tobacco use, and paternal occupational exposures.

The vast majority of neuroblastoma arises sporadically without family history of the disease. However, 1-2% of newly diagnosed cases do have a family history of neuroblastoma. Patients with familial neuroblastoma often present at earlier age or with several distinct primary tumors.

Neuroblastoma has been known to occur in the setting of other disorders that are linked to abnormal development of neural crest tissues, such as Hirschsprung disease or central congenital hypoventilation syndrome.

Recent work using genome-wide analysis of neuroblastoma from these rare familial cases has identified a genetic defects involved in these cases.

Cases of neuroblastoma that accompany other congenital abnormalities of the neural crest have been associated with a germline mutation in PHOX2B. This gene is a homeobox gene that acts as a regulator of autonomic nervous system development.

In familial neuroblastoma cases that are not associated with other congenital disorders of neural crest development, ALK mutations have been identified in the germline.[8] These mutations largely occur in the kinase domain causing activation of ALK signaling. Efforts are ongoing to investigate the incidence of ALK mutations across all subsets of neuroblastoma, but initial evidence indicates that somatic mutations of the ALK gene are also present in some cases of sporadic neuroblastoma.

De Brouwer et al illustrate the occurrence of the ALK mutation specifically in neuroblastomas. Although they studied a small proportion of cases, mutations were found in similar frequencies in favorable and unfavorable outcome cases. The F1174L mutant was found more frequently in the poor outcome subgroup.[9] This example illustrates the heterogeneity of cancer and the likely possibility that targeted therapies to the ALK gene may be of benefit in a subset of ALK cancers, which may possibly include a small subset of MYC -amplified neuroblastomas. The challenge for drug development in neuroblastoma is to identify upfront high-risk cases that may benefit from ALK -directed therapy.

Previous
Proceed to Differential Diagnoses
 
 
Contributor Information and Disclosures
Author

Norman J Lacayo, MD  Assistant Professor, Department of Pediatrics, Division of Hematology-Oncology, Stanford University and Lucile Salter Packard Children's Hospital

Norman J Lacayo, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Hematology, and Children's Oncology Group

Disclosure: Nothing to disclose.

Coauthor(s)

Kara L Davis, DO  Fellow, Department of Pediatric Hematology/Oncology, Stanford University School of Medicine

Kara L Davis, DO is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Stephan A Grupp, MD, PhD  Director, Stem Cell Biology Program, Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania

Stephan A Grupp, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

Steven K Bergstrom, MD  Assistant to the Chairman, Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland

Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and International Society for Experimental Hematology

Disclosure: Nothing to disclose.

Helen SL Chan, MBBS, FRCP(C), FAAP  Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada

Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA  Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

References

  1. Look AT, Hayes FA, Shuster JJ, et al. Clinical relevance of tumor cell ploidy and N-myc gene amplification in childhood neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol. Apr 1991;9(4):581-91. [Medline].

  2. [Guideline] Shimada H, Chatten J, Newton WA Jr, et al. Histopathologic prognostic factors in neuroblastic tumors: definition of subtypes of ganglioneuroblastoma and an age-linked classification of neuroblastomas. J Natl Cancer Inst. Aug 1984;73(2):405-16. [Medline].

  3. [Guideline] Cohn SL, Pearson AD, London WB, et al. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol. Jan 10 2009;27(2):289-97. [Medline].

  4. National Cancer Institute. SEER Pediatric Monograph. National Cancer Institute. Available at http://www-seer.ims.nci.nih.gov/Publications/PedMono/sympathetic.pdf. Accessed February 25, 2002.

  5. Stiller CA, Parkin DM. International Variations in the incidence of neuroblastoma. International Journal of Cancer. 1992;52:538-543.

  6. Haupt R, Garaventa A, Gambini C, et al. Improved Survival of Children with Neuroblastoma Between 1979 and 2005: A Report of the Italian Neuroblastoma Registry. J Clin Oncol. Mar 29 2010;[Medline].

  7. George RE, Li S, Medeiros-Nancarrow C, et al. High-risk neuroblastoma treated with tandem autologous peripheral-blood stem cell-supported transplantation: long-term survival update. J Clin Oncol. Jun 20 2006;24(18):2891-6. [Medline].

  8. Mosse YP, Laudenslager M, Longo L, Cole KA, Wood A, Attiyeh EF. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. Oct 16 2008;455(7215):930-5. [Medline].

  9. De Brouwer S, De Preter K, Kumps C, Zabrocki P, Porcu M, Westerhout EM. Meta-analysis of neuroblastomas reveals a skewed ALK mutation spectrum in tumors with MYCN amplification. Clin Cancer Res. Sep 1 2010;16(17):4353-62. [Medline].

  10. [Guideline] Monclair T, Brodeur GM, Ambros PF, et al. The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report. J Clin Oncol. Jan 10 2009;27(2):298-303. [Medline].

  11. London WB, Castleberry RP, Matthay KK, et al. Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group. J Clin Oncol. Sep 20 2005;23(27):6459-65. [Medline].

  12. London WB, Castleberry RP, Matthay KK, Look AT, Seeger RC, Shimada H. Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group. J Clin Oncol. Sep 20 2005;23(27):6459-65. [Medline].

  13. Maris JM, Hogarty MD, Bagatell R, Cohn SL. Neuroblastoma. Lancet. Jun 23 2007;369(9579):2106-20. [Medline].

  14. Baker DL, Schmidt ML, Cohn SL, et al. Outcome after reduced chemotherapy for intermediate-risk neuroblastoma. N Engl J Med. Sep 30 2010;363(14):1313-23. [Medline].

  15. Yu AL, Gilman AL, Ozkaynak MF, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. Sep 30 2010;363(14):1324-34. [Medline].

  16. [Best Evidence] Ladenstein R, Valteau-Couanet D, Brock P, et al. Randomized Trial of prophylactic granulocyte colony-stimulating factor during rapid COJEC induction in pediatric patients with high-risk neuroblastoma: the European HR-NBL1/SIOPEN study. J Clin Oncol. Jul 20 2010;28(21):3516-24. [Medline].

  17. Acharya S, Jayabose S, Kogan SJ, et al. Prenatally diagnosed neuroblastoma. Cancer. Jul 15 1997;80(2):304-10. [Medline].

  18. Altman AJ. Management of malignant solid tumors. In: Hematology of Infancy and Childhood. 1993.

  19. Attiyeh EF, London WB, Mosse YP, et al. Chromosome 1p and 11q deletions and outcome in neuroblastoma. N Engl J Med. Nov 24 2005;353(21):2243-53. [Medline].

  20. Bagatell R, Rumcheva P, London WB, et al. Outcomes of children with intermediate-risk neuroblastoma after treatment stratified by MYCN status and tumor cell ploidy. J Clin Oncol. Dec 1 2005;23(34):8819-27. [Medline].

  21. Berthold F, Baillot A, Hero B, et al. Which cases are found and missed by neuroblastoma screening at 1 year? Results from the 1992 to 1995 study in three Federal States of Germany. J Clin Oncol. Apr 1999;17(4):1200. [Medline].

  22. Bowman LC, Castleberry RP, Cantor A, et al. Genetic staging of unresectable or metastatic neuroblastoma in infants: a Pediatric Oncology Group study. J Natl Cancer Inst. Mar 5 1997;89(5):373-80. [Medline].

  23. Brodeur GM. Molecular pathology of human neuroblastomas. Semin Diagn Pathol. May 1994;11(2):118-25. [Medline].

  24. Brodeur GM, Castleberry RP. Neuroblastoma. In: Pizzo PA, Poplack DG, eds. Principles and Practices of Pediatric Oncology. 2006:933.

  25. Brodeur GM, Nakagawara A, Yamashiro DJ, et al. Expression of TrkA, TrkB and TrkC in human neuroblastomas. J Neurooncol. Jan 1997;31(1-2):49-55. [Medline].

  26. Brodeur GM, Pritchard J, Berthold F, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. Aug 1993;11(8):1466-77. [Medline].

  27. Brodeur GM, Seeger RC, Schwab M, et al. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science. Jun 8 1984;224(4653):1121-4. [Medline].

  28. Cachat F, Guignard JP. [The kidney in children under chemotherapy]. Rev Med Suisse Romande. Dec 1996;116(12):985-93. [Medline].

  29. Cachat F, Nenadov-Beck M, Guignard JP. Occurrence of an acute Fanconi syndrome following cisplatin chemotherapy. Med Pediatr Oncol. Jul 1998;31(1):40-1. [Medline].

  30. Carlsen NL. Neuroblastoma: epidemiology and pattern of regression. Problems in interpreting results of mass screening. Am J Pediatr Hematol Oncol. May 1992;14(2):103-10. [Medline].

  31. Castleberry RP. Predicting outcome in neuroblastoma. N Engl J Med. Jun 24 1999;340(25):1992-3. [Medline].

  32. Castleberry RP, Kun LE, Shuster JJ, et al. Radiotherapy improves the outlook for patients older than 1 year with Pediatric Oncology Group stage C neuroblastoma. J Clin Oncol. May 1991;9(5):789-95. [Medline].

  33. Chan HS, Grogan TM, DeBoer G, et al. Diagnosis and reversal of multidrug resistance in paediatric cancers. Eur J Cancer. Jun 1996;32A(6):1051-61. [Medline].

  34. Chatten J, Shimada H, Sather HN, et al. Prognostic value of histopathology in advanced neuroblastoma: a report from the Childrens Cancer Study Group. Hum Pathol. Oct 1988;19(10):1187-98. [Medline].

  35. Combaret V, Gross N, Lasset C, et al. Clinical relevance of CD44 cell surface expression and MYCN gene amplification in neuroblastoma. Eur J Cancer. Oct 1997;33(12):2101-5. [Medline].

  36. De Moerloose B, Dhooge C, Laureys G, et al. Discrepant flow cytometric expression and function of P-glycoprotein in neuroblastic tumors. Cytometry. Oct 1 1999;37(2):125-32. [Medline].

  37. Dockhorn-Dworniczak B, Schafer KL, Dantcheva R, et al. [Detection of EWS-/FLI-1 gene fusion transcripts by RT-PCR as a tool in the diagnosis of tumors of the Ewing sarcoma group]. Verh Dtsch Ges Pathol. 1994;78:214-9. [Medline].

  38. Donovan J, Temel J, Zuckerman A, et al. CD34 selection as a stem cell purging strategy for neuroblastoma: preclinical and clinical studies. Med Pediatr Oncol. Dec 2000;35(6):677-82. [Medline].

  39. Downing JR, Khandekar A, Shurtleff SA, et al. Multiplex RT-PCR assay for the differential diagnosis of alveolar rhabdomyosarcoma and Ewing's sarcoma. Am J Pathol. Mar 1995;146(3):626-34. [Medline].

  40. Evans AR, Brand W, de Lorimier A, et al. Results in children with local and regional neuroblastoma managed with and without vincristine, cyclophosphamide, and imidazolecarboxamide. A report from the Children's Cancer Study Group. Am J Clin Oncol. Feb 1984;7(1):3-7. [Medline].

  41. Finklestein JZ. Neuroblastoma: the challenge and frustration. Hematol Oncol Clin North Am. Dec 1987;1(4):675-94. [Medline].

  42. Fish JD, Grupp SA. Stem cell transplantation for neuroblastoma. Bone Marrow Transplant. Jan 2008;41(2):159-65. [Medline].

  43. George RE, London WB, Cohn SL, et al. Hyperdiploidy plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol. Sep 20 2005;23(27):6466-73. [Medline].

  44. George RE, London WB, Cohn SL, et al. Hyperdiploidy plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol. Sep 20 2005;23(27):6466-73. [Medline].

  45. Gilbert F. Solid tumors of children: chromosome abnormalities and the development of cancer. J Cell Physiol Suppl. 1984;3:165-70. [Medline].

  46. Grenier MA, Lipshultz SE. Epidemiology of anthracycline cardiotoxicity in children and adults. Semin Oncol. Aug 1998;25(4 Suppl 10):72-85. [Medline].

  47. Grupp SA, Stern JW, Bunin N, et al. Tandem high-dose therapy in rapid sequence for children with high-risk neuroblastoma. J Clin Oncol. Jul 2000;18(13):2567-75. [Medline].

  48. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. Jan 7 2000;100(1):57-70. [Medline].

  49. Hann HW, Evans AE, Siegel SE, et al. Prognostic importance of serum ferritin in patients with Stages III and IV neuroblastoma: the Childrens Cancer Study Group experience. Cancer Res. Jun 1985;45(6):2843-8. [Medline].

  50. Helson L. Neuroblastoma spinal cord compression (review). Anticancer Res. Sep-Oct 1983;3(5):317-22. [Medline].

  51. Holgersen LO, Santulli TV, Schullinger JN, Berdon WE. Neuroblastoma with intraspinal (dumbbell) extension. J Pediatr Surg. Aug 1983;18(4):406-11. [Medline].

  52. Hsiao RJ, Seeger RC, Yu AL, O'Connor DT. Chromogranin A in children with neuroblastoma. Serum concentration parallels disease stage and predicts survival. J Clin Invest. May 1990;85(5):1555-9. [Medline].

  53. Joshi VV, Cantor AB, Altshuler G, et al. Age-linked prognostic categorization based on a new histologic grading system of neuroblastomas. A clinicopathologic study of 211 cases from the Pediatric Oncology Group. Cancer. Apr 15 1992;69(8):2197-211. [Medline].

  54. Joshi VV, Cantor AB, Brodeur GM, et al. Correlation between morphologic and other prognostic markers of neuroblastoma. A study of histologic grade, DNA index, N-myc gene copy number, and lactic dehydrogenase in patients in the Pediatric Oncology Group. Cancer. May 15 1993;71(10):3173-81. [Medline].

  55. Joshi VV, Rao PV, Cantor AB, et al. Modified histologic grading of neuroblastomas by replacement of mitotic rate with mitosis karyorrhexis index. A clinicopathologic study of 223 cases from the Pediatric Oncology Group. Cancer. Apr 15 1996;77(8):1582-8. [Medline].

  56. LaBrosse EH, Com-Nougue C, Zucker JM, et al. Urinary excretion of 3-methoxy-4-hydroxymandelic acid and 3-methoxy-4- hydroxyphenylacetic acid by 288 patients with neuroblastoma and related neural crest tumors. Cancer Res. Jun 1980;40(6):1995-2001. [Medline].

  57. Laug WE, Siegel SE, Shaw KN, et al. Initial urinary catecholamine metabolite concentrations and prognosis in neuroblastoma. Pediatrics. Jul 1978;62(1):77-83. [Medline].

  58. Loebstein R, Atanackovic G, Bishai R, et al. Risk factors for long-term outcome of ifosfamide-induced nephrotoxicity in children. J Clin Pharmacol. May 1999;39(5):454-61. [Medline].

  59. Lucky AW, McGuire J, Komp DM. Infantile neuroblastoma presenting with cutaneous blanching nodules. J Am Acad Dermatol. Mar 1982;6(3):389-91. [Medline].

  60. Maitra A, Yashima K, Rathi A, et al. The RNA component of telomerase as a marker of biologic potential and clinical outcome in childhood neuroblastic tumors. Cancer. Feb 1 1999;85(3):741-9. [Medline].

  61. Maris JM. Unholy matrimony: Aurora A and N-Myc as malignant partners in neuroblastoma. Cancer Cell. Jan 6 2009;15(1):5-6. [Medline].

  62. Maris JM, White PS, Beltinger CP, et al. Significance of chromosome 1p loss of heterozygosity in neuroblastoma. Cancer Res. Oct 15 1995;55(20):4664-9. [Medline].

  63. Massaron S, Seregni E, Luksch R, et al. Neuron-specific enolase evaluation in patients with neuroblastoma. Tumour Biol. 1998;19(4):261-8. [Medline].

  64. Matthay KK, Villablanca JG, Seeger RC, et al. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children's Cancer Group. N Engl J Med. Oct 14 1999;341(16):1165-73. [Medline].

  65. McLeod HL, Relling MV, Crom WR, et al. Disposition of antineoplastic agents in the very young child. Br J Cancer Suppl. Aug 1992;18:S23-9. [Medline].

  66. Nitschke R, Smith EI, Altshuler G, et al. Postoperative treatment of nonmetastatic visible residual neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol. Jul 1991;9(7):1181-8. [Medline].

  67. Nitschke R, Smith EI, Shochat S, et al. Localized neuroblastoma treated by surgery: a Pediatric Oncology Group Study. J Clin Oncol. Aug 1988;6(8):1271-9. [Medline].

  68. Norris MD, Bordow SB, Marshall GM, et al. Expression of the gene for multidrug-resistance-associated protein and outcome in patients with neuroblastoma. N Engl J Med. Jan 25 1996;334(4):231-8. [Medline].

  69. Parker L, Powell J. Screening for neuroblastoma in infants younger than 1 year of age. Review of the first 30 years. Medical Pediatric Oncology. 1998;31:455-69.

  70. Perez CA, Matthay KK, Atkinson JB, Seeger RC, Shimada H, Haase GM. Biologic variables in the outcome of stages I and II neuroblastoma treated with surgery as primary therapy: a children's cancer group study. J Clin Oncol. Jan 2000;18(1):18-26. [Medline].

  71. Peuchmaur M, d'Amore ES, Joshi VV, Hata J, Roald B, Dehner LP. Revision of the International Neuroblastoma Pathology Classification: confirmation of favorable and unfavorable prognostic subsets in ganglioneuroblastoma, nodular. Cancer. Nov 15 2003;98(10):2274-81. [Medline].

  72. Plantaz D, Mohapatra G, Matthay KK, et al. Gain of chromosome 17 is the most frequent abnormality detected in neuroblastoma by comparative genomic hybridization. Am J Pathol. Jan 1997;150(1):81-9. [Medline].

  73. Plantaz D, Rubie H, Michon J, et al. The treatment of neuroblastoma with intraspinal extension with chemotherapy followed by surgical removal of residual disease. A prospective study of 42 patients--results of the NBL 90 Study of the French Society of Pediatric Oncology. Cancer. Jul 15 1996;78(2):311-9. [Medline].

  74. Powell JE, Esteve J, Mann JR, et al. Neuroblastoma in Europe: differences in the pattern of disease in the UK. SENSE. Study group for the Evaluation of Neuroblastoma Screening in Europe. Lancet. Aug 29 1998;352(9129):682-7. [Medline].

  75. Raney B, Ensign LG, Foreman J, et al. Renal toxicity of ifosfamide in pilot regimens of the intergroup rhabdomyosarcoma study for patients with gross residual tumor. Am J Pediatr Hematol Oncol. Nov 1994;16(4):286-95. [Medline].

  76. Raschella G, Cesi V, Amendola R, et al. Expression of B-myb in neuroblastoma tumors is a poor prognostic factor independent from MYCN amplification. Cancer Res. Jul 15 1999;59(14):3365-8. [Medline].

  77. Rascher W, Kremens B, Wagner S, et al. Serial measurements of neuropeptide Y in plasma for monitoring neuroblastoma in children. J Pediatr. Jun 1993;122(6):914-6. [Medline].

  78. Romansky SG. Neural crest aggregates in the human fetal adrenal gland. Laboratory Investigations. 1979;40:9.

  79. Scanga DR, Martin WH, Delbeke D. Value of FDG PET imaging in the management of patients with thyroid, neuroendocrine, and neural crest tumors. Clin Nucl Med. Feb 2004;29(2):86-90. [Medline].

  80. Schmidt ML, Lal A, Seeger RC, et al. Favorable prognosis for patients 12 to 18 months of age with stage 4 nonamplified MYCN neuroblastoma: a Children's Cancer Group Study. J Clin Oncol. Sep 20 2005;23(27):6474-80. [Medline].

  81. Seeger RC, Siegel SE, Sidell N. Neuroblastoma: clinical perspectives, monoclonal antibodies, and retinoic acid. Ann Intern Med. Dec 1982;ID - CA 22794/CA/NCI(6):873-84. [Medline].

  82. Shimada H, Ambros IM, Dehner LP, et al. Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee. Cancer. Jul 15 1999;86(2):349-63. [Medline].

  83. Shulkin BL, Shapiro B. Current concepts on the diagnostic use of MIBG in children. J Nucl Med. Apr 1998;39(4):679-88. [Medline].

  84. Shuster JJ, McWilliams NB, Castleberry R, et al. Serum lactate dehydrogenase in childhood neuroblastoma. A Pediatric Oncology Group recursive partitioning study. Am J Clin Oncol. Aug 1992;15(4):295-303. [Medline].

  85. Srivatsan ES, Murali V, Seeger RC. Loss of heterozygosity for alleles on chromosomes 11q and 14q in neuroblastoma. Prog Clin Biol Res. 1991;366:91-8. [Medline].

  86. Tanaka T, Slamon DJ, Shimoda H, et al. Expression of Ha-ras oncogene products in human neuroblastomas and the significant correlation with a patient's prognosis. Cancer Res. Feb 15 1988;48(4):1030-4. [Medline].

  87. Tang XX, Evans AE, Zhao H, et al. High-level expression of EPHB6, EFNB2, and EFNB3 is associated with low tumor stage and high TrkA expression in human neuroblastomas. Clin Cancer Res. Jun 1999;5(6):1491-6. [Medline].

  88. Turkel SB, Itabashi HH. The natural history of neuroblastic cells in the fetal adrenal gland. Am J Pathol. Aug 1974;76(2):225-44. [Medline].

  89. Villablanca JG, Khan AA, Avramis VI, Reynolds CP. Hypercalcemia: a dose-limiting toxicity associated with 13-cis-retinoic acid. Am J Pediatr Hematol Oncol. Nov 1993;- Reynolds CP(4):410-5. [Medline].

  90. Wang Q, Diskin S, Rappaport E, et al. Integrative genomics identifies distinct molecular classes of neuroblastoma and shows that multiple genes are targeted by regional alterations in DNA copy number. Cancer Res. Jun 15 2006;66(12):6050-62. [Medline].

  91. White PS, Maris JM, Sulman EP, et al. Molecular analysis of the region of distal 1p commonly deleted in neuroblastoma. Eur J Cancer. Oct 1997;33(12):1957-61. [Medline].

  92. Woods WG, Tuchman M, Robison LL, et al. A population-based study of the usefulness of screening for neuroblastoma. Lancet. Dec 21-28 1996;348(9043):1682-7. [Medline].

  93. Yamashiro DJ, Liu XG, Lee CP, et al. Expression and function of Trk-C in favourable human neuroblastomas. Eur J Cancer. Oct 1997;33(12):2054-7. [Medline].

  94. Yamashiro DJ, Nakagawara A, Ikegaki N, Liu XG, Brodeur GM. Expression of TrkC in favorable human neuroblastomas. Oncogene. Jan 4 1996;12(1):37-41. [Medline].

  95. Yanagisawa T, Newman A, Coley H, et al. BIRICODAR (VX-710; Incel): an effective chemosensitizer in neuroblastoma. Br J Cancer. Jun 1999;80(8):1190-6. [Medline].

 
Previous
Next
 
Histologic subtypes of neuroblastoma. Top right panel, neuroblastoma: A monotonous population of hyperchromatic cells with scant cytoplasm. Bottom left panel, ganglioneuroblastoma: Increased schwannian stroma. Bottom right panel, ganglioneuroma: Mature ganglion cell with schwannian stroma.
CT scan of abdomen in a patient with a retroperitoneal mass arising from the upper pole of the left kidney and elevated urine catecholamines.
MRI of a left adrenal mass. The mass was revealed by fetal ultrasonography at 30 weeks' gestation. During infancy, the mass was found on the inferior pole of the left adrenal and was completely resected. Before surgery, the metastatic workup was negative. Surgical pathology service confirmed a diagnosis of neuroblastoma. After 3 years of follow-up care, no recurrence was observed.
A one-week-old neonate had abdominal ultrasonography for evaluation of projectile vomiting. A right adrenal mass (100% cystic) was an incidental finding. Evaluation of the mass by CT was consistent with an adrenal bleed (3.6 x 3.1 x 2.4 cc). The infant was followed at 2 weeks (2-dimensional size diminished to 1.5 x. 2.4 cm2 on ultrasonography) and then at 6 weeks to document that the adrenal bleed continued to involute. Urine catecholamines were normal.
Table. A Consensus Pretreatment Classification schema by the International Neuroblastoma Risk Group (INRG). This schema is based in the INRG stage, age, histologic category, tumor grade of differentiation, MYCN sastus, 11q-aberrations and DNA ploidy. A combination of these characteristics results in four risk groups noted in the last column: very low, low, intermediate and high risk, with the following 5 year EFS: >85%, >75%-85%, >50%-75%, and < 50%. These risk groups are distributed among the different stages and labeled alphabetically from A to R (without letters L and M to avoid confusion with the INRG stage notation). Notations in the table are as follow: L1, localized tumor confined to one body compartment; L2, locoregional tumor with presence of one or more risk factors defined radiologically; M, distant metastatic disease (except stage MS); MS, metastatic disease confined to skin, liver and/or bone marrow in children < 18 months of age. GN, ganglioneuroma; GNB, ganglioneuroblastoma; Amp, amplified; n/amp, not amplified. (Adapted from The International Neuroblastoma Risk Group (INRG) Classifications System: An INRG Task Force Report by Cohn, et al. Journal of Clinical Oncology 27(2):289-297, 2009).
Table 1. Current COG Neuroblastoma Risk Stratification
Risk GroupStageAgeMYCN Amplification StatusPloidyShimada
Low1AnyAnyAnyAny
Low2a/2bAnyNon-ampAnyAny
High2a/2bAnyAmpAnyAny
Intermediate3< 547dNon-ampAnyAny
Intermediate3≥547dNon-ampAnyFavorable
High3AnyAmpAnyAny
High3≥547dNon-ampAnyUnfavorable
High4< 365dAmpAnyAny
Intermediate4< 365dNon-ampAnyAny
High4365-547dAmpAnyAny
High4365-547dAnyDiploidAny
High4365-547AnyAnyUnfavorable
Intermediate4365-547dNon-ampHyperFavorable
High4≥547dAnyAnyAny
Low4s< 365dNon-ampHyperFavorable
Intermediate4s< 365dNon-ampDiploidAny
Intermediate4s< 365dNon-ampAnyUnfavorable
High4s< 365dAmpAnyAny
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.