Cancer, Neuroblastoma


Article Author:
Sidharth Mahapatra


Article Editor:
Kishore Challagundla


Editors In Chief:
Yvonne Carter
Jason Wallen


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Pritesh Sheth
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes
Kavin Sugumar


Updated:
5/12/2019 1:48:52 PM

Introduction

Neuroblastoma (NB) is the most frequently-occurring extracranial childhood tumor. It is classified as an embryonal neuroendocrine tumor, originating from neural crest progenitor cells.[1] Hence, it can occur anywhere along the sympathetic nervous system, including the superior cervical, paraspinal, and celiac ganglia; the majority arise in the adrenal glands.[2] Due to the high variability in its presentation, clinical signs and symptoms at presentation can range from benign palpable mass with distension to major illness from substantial tumor spread. Although overall increases in five-year event-free survival have been reported, subgroup-specific analysis of mortality has revealed discordance between the high cure rates for the more benign low-risk forms and little improvement in the high-risk groups.[3][4] Thus, the impetus for the development of targeted therapeutics in the intensive management of high-risk groups is strong.

Etiology

Risk factors for the acquisition of mutations in key genes leading to neuroblastoma have yet to be identified although exposures during conception and pregnancy are a topic of investigation. Neuroblastoma can develop either sporadically or be transmitted in the germline. Most familial cases of neuroblastoma occur due to the inheritance of highly penetrant mutations in either the ALK or PHOX2B genes.[2] [5] A small subset of familial NB demonstrates autosomal dominant inheritance.[6] Although up to 15% of sporadic cases of neuroblastoma arise from mutations in ALK, more common transforming mutations involve polymorphisms in BARD1 (2q35), LIN28B (6q16.3), or FLJ22536 (6p22.3). Cytogenetic aberrations can further include loss of chromosome 1p and 11q, copy number variation in 1q21, and gain of 17q.[1][7][8][9] Notably, amplification of MYCN oncogene is seen in approximately 25% of patients and is associated with the poorest prognosis; 17q gain and 1p loss correlate with MYCN amplification.[1][10]

Epidemiology

Neuroblastoma is the most common tumor of the sympathetic nervous system (97%) and the most common malignancy of infancy with a median age of diagnosis of 17 months.[11] It accounts for 15% of pediatric cancer-related deaths.[12] The annual incidence of neuroblastoma in the United States is approximately 650 cases, i.e., 10.2 per million children (65 per million infants), with little change (0.4%) over time.[2] While an overall improvement in five-year mortality has been noted between 1975 through 2005, subgroup-specific mortality paints a different picture.

History and Physical

Given the wide areas populated by neural crest cells, neuroblastoma can present in the neck, chest, abdomen, or pelvis. With the most frequent site of origin being the adrenal medulla, patients often present with a solid abdominal mass. With involvement of the superior cervical ganglia, aside from a neck mass, Horner syndrome (ptosis, miosis, anhydrosis) can be observed. If tumor involves the spinal cord, cord compression or paralysis may be seen. Furthermore, tumor behavior can range from spontaneous regression to widespread dissemination at presentation. With over half of all neuroblastoma patients having hematogenous spread at diagnosis, the disease can involve the bone and bone marrow (56% and 71%, respectively), followed by lymph nodes (31%), and lungs (3%). Non-specific clinical signs include fever, weight loss, and fatigue. Thus, signs and symptoms, which can range from an asymptomatic palpable mass to significant critical illness, are highly variable and dependent upon factors now linked with prognosis.

Evaluation

Subgroup Classification

The widespread variability in neuroblastoma tumor behavior is linked to multiple factors now linked with patient prognosis. Classic prognostic categorization by Children’s Oncology Group (COG) divides patients into four groups based on patient age, post-surgical stage, MYCN amplification, histology, and DNA ploidy [3]:

  1. Low risk: localized tumor only, greater than 90% survival
  2. Intermediate risk: localized tumor with regional extension and/or metastases to bone and bone marrow, 90% to 95% survival
  3. High risk: widely disseminated disease (excluding infants), 40% to 50% survival
  4. Tumor stage 4S: widely disseminated disease in infants, greater than 90% survival due to spontaneous regression of the tumor.

However, COG classification of neuroblastoma has differed from the European SIOPEN and other cooperative groups. In 2004, the International Neuroblastoma Risk Group (INRG), a task force of pediatric neuroblastoma experts worldwide, met with the primary aim of developing a consensus approach to neuroblastoma risk stratification pre-treatment.[13] Using patient age, tumor stage, tumor grade and differentiation, tumor histology, MYCN amplification, cytogenetic aberrations in 11q, and DNA ploidy, the group defined 16 pre-treatment groups broadly divisible into four prognostic subgroups based on five-year event-free survival (EFS):

  1. Very low risk: five-year event-free survival (EFS) greater than 85%
  2. Low risk: five-year EFS 75% to 85%
  3. Intermediate risk: five-year EFS 50% to 75%
  4. High risk: five-year EFS less than 50%

Over 50% of newly diagnosed neuroblastoma are very-low or low-risk.[13] Negative prognostic markers include age older than 18 months, metastasis at diagnosis, and presence of MYCN amplification, 1p loss, 11q loss, 17q gain, or DNA copy number alterations.[1][13]

Clinical Evaluation

Diagnostic evaluation relies not only on a careful history and physical, but also on biochemical, histologic, and radiographic analyses. Histologic confirmation is required to establish a diagnosis of neuroblastoma. Histologically, small round pale blue cells, known as Homer-Wright pseudorosettes, can be seen; these are similarly seen in Wilm's tumor and Ewing sarcoma, leading to their common group categorization as small blue cell tumors.[1] If a biopsy sample is tumor-positive, DNA ploidy and MYCN gene status are further evaluated. Since neuroblastoma cells originate from neural crest cells destined to differentiate into sympathetic peripheral neurons, cells often produce catecholamines; break-down products of these catecholamines are homovanillic acid (HVA) and vanillylmandelic acid (VMA). Thus, in over 90% of neuroblastoma, elevation in these catecholamine breakdown products in urine is diagnostic.[14] Preliminary imaging is preferentially conducted with MRI for good resolution and surgical excision planning. Further exploiting sympathetic neuronal uptake of mIBG (metaiodobenzylguanidine), due to its analogous nature to norepinephrine, the extent of neuroblastoma metastasis can be delineated with an mIBG scan with high accuracy and quality.[15] To complete tumor staging, bone marrow biopsies are required.[1] Of note, common paraneoplastic conditions associated with neuroblastoma include opsoclonus-myoclonus syndrome and intractable secretory diarrhea due to vasoactive intestinal peptide (VIP) secretion.[16][17]

Treatment / Management

Given the heterogeneity in tumor location, grade, and stage at diagnosis, treatment modalities include simple observation, surgical resection, chemotherapy, radiation therapy, stem cell transplantation, and immunotherapy. Patients with low-risk NB have localized tumor, some (infants) with a high propensity for spontaneous tumor regression.[18] Thus, children with small tumors (less than 5 cm) can simply be observed with imaging done every six to 12 weeks to monitor tumor growth, thus avoiding surgery in the young infant altogether.[1] For larger, localized tumors, in patients past infancy, surgical resection is pursued. For patients younger than 18 months of age, the observational approach is currently under international investigation by COG (NCT02176967) and SIOPEN (NCT01728155) cooperative groups. For children who present with symptoms, limited chemotherapy is given without surgical palliation or radiation therapy.[1] The intermediate-risk group presents with localized metastasis, i.e., to the lymph node or bone marrow (in infants). They are usually managed with chemotherapy alone and possible surgical resection if able.[19] The high-risk group has the worst prognosis and presents with widespread metastatic disease to the bone marrow, bone, lungs, and liver. They receive induction chemotherapy to reduce tumor burden at both the primary and metastatic locations, followed by maximal surgical resection, followed by myeloablative chemotherapy and stem-cell transplantation. After that, patients are managed on a combination of maintenance chemotherapy and immunotherapy.[20] A monoclonal antibody, dinutuximab (Unituxin), that attaches to a carbohydrate molecule (GD2) on the surface of many neuroblastoma cells, is being used as an immunotherapy drug for neuroblastoma treatment. Dinutuximab treatment is reported to improve the two-year event-free survival of high-risk neuroblastoma patients from 46% to 66%.[21]

Enhancing Healthcare Team Outcomes

Neuroblastoma is a rare abdominal tumor in young children. However, if the diagnosis is missed, the tumor is fatal. Hence, the diagnosis and treatment of neuroblastoma are best managed by a multidisciplinary team that includes a pediatrician, a pediatric surgeon, oncologist, radiation therapist, social workers, and NICU nurses. The tumor may occur anywhere along the sympathetic chain and can be mistaken for a Wilms tumor. Over the past decade the survival of these patients has slightly improved for early-stage lesions, but for late stages the survival is abysmal. Thus, the impetus for the development of targeted therapeutics in the intensive management of high-risk groups is strong.[22][23]


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Cancer, Neuroblastoma - Questions

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What is the most common mediastinal mass in childhood?



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Which of the following is true about the most malignant neurogenic tumor of childhood?



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Which of the following neurogenic tumors of the mediastinum produce vasoactive substances?



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A 2-year-old child with an abdominal mass undergoes a biopsy which reveals Homer Wright pseudo rosettes. He may have which of the following?



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A 2-year-old child with an abdominal mass undergoes a biopsy which reveals Homer Wright pseudorosettes. Which of the following might be present in this child?



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An 18-month-old infant is seen with a distended abdomen. CT scan reveals a large mass with calcification. Urine exam reveals presence of elevated metanephrines. Biopsy of the mass reveals multiple sheets of blue cells. The infant may have which of the following conditions?



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Which of the following is not true of neuroblastomas?



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Which of the following is not true of a neuroblastoma?



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Which of the following is true of a neuroblastoma?



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High levels of vanillylmandelic acid in the urine of a 2-year-old child is indicative of what condition?



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Which is the MOST common extracranial solid tumor of childhood?



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Which of the following is the most common extra cranial solid tumor in children?



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Which of the following may cause opsoclonus-myoclonus?



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Which of the following diseases commonly presents as a palpable abdominal mass?



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An 18-month-old female is brought in for deteriorating gait, random eye movements, and myoclonic movements. The patient is found to have an abdominal mass. Select the most probable diagnosis.



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A 2-year-old has Horner syndrome on the left. Chest radiograph shows a mass in the upper mediastinum. Which of the following is the most likely diagnosis?



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Which of the following molecular abnormalities is associated with neuroblastoma?



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Which of the following statements is true regarding neuroblastoma?



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A 2-year old child with abdominal pain, weight loss, and anorexia is seen in the clinic. The mother also claims that the child does not walk properly because of pain in his bones. The medical history is otherwise unremarkable. Exam reveals a large mass in the abdomen and a slightly elevated blood pressure. CT scan reveals a 4 x 9 cm mass arising from the upper pole of the kidney. A laparoscopic biopsy is performed which reveals Homer Wright pseudo-rosettes. What is his diagnosis?



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Cancer, Neuroblastoma - References

References

Zage PE, Novel Therapies for Relapsed and Refractory Neuroblastoma. Children (Basel, Switzerland). 2018 Oct 31     [PubMed]
Bansal D,Totadri S,Chinnaswamy G,Agarwala S,Vora T,Arora B,Prasad M,Kapoor G,Radhakrishnan V,Laskar S,Kaur T,Rath GK,Bakhshi S, Management of Neuroblastoma: ICMR Consensus Document. Indian journal of pediatrics. 2017 Jun     [PubMed]
Matthay KK,Maris JM,Schleiermacher G,Nakagawara A,Mackall CL,Diller L,Weiss WA, Neuroblastoma. Nature reviews. Disease primers. 2016 Nov 10;     [PubMed]
Maris JM, Recent advances in neuroblastoma. The New England journal of medicine. 2010 Jun 10;     [PubMed]
Maris JM,Hogarty MD,Bagatell R,Cohn SL, Neuroblastoma. Lancet (London, England). 2007 Jun 23;     [PubMed]
Linabery AM,Ross JA, Childhood and adolescent cancer survival in the US by race and ethnicity for the diagnostic period 1975-1999. Cancer. 2008 Nov 1;     [PubMed]
Mossé YP,Laudenslager M,Longo L,Cole KA,Wood A,Attiyeh EF,Laquaglia MJ,Sennett R,Lynch JE,Perri P,Laureys G,Speleman F,Kim C,Hou C,Hakonarson H,Torkamani A,Schork NJ,Brodeur GM,Tonini GP,Rappaport E,Devoto M,Maris JM, Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008 Oct 16;     [PubMed]
Knudson AG Jr,Strong LC, Mutation and cancer: neuroblastoma and pheochromocytoma. American journal of human genetics. 1972 Sep;     [PubMed]
Maris JM,Mosse YP,Bradfield JP,Hou C,Monni S,Scott RH,Asgharzadeh S,Attiyeh EF,Diskin SJ,Laudenslager M,Winter C,Cole KA,Glessner JT,Kim C,Frackelton EC,Casalunovo T,Eckert AW,Capasso M,Rappaport EF,McConville C,London WB,Seeger RC,Rahman N,Devoto M,Grant SF,Li H,Hakonarson H, Chromosome 6p22 locus associated with clinically aggressive neuroblastoma. The New England journal of medicine. 2008 Jun 12;     [PubMed]
Capasso M,Devoto M,Hou C,Asgharzadeh S,Glessner JT,Attiyeh EF,Mosse YP,Kim C,Diskin SJ,Cole KA,Bosse K,Diamond M,Laudenslager M,Winter C,Bradfield JP,Scott RH,Jagannathan J,Garris M,McConville C,London WB,Seeger RC,Grant SF,Li H,Rahman N,Rappaport E,Hakonarson H,Maris JM, Common variations in BARD1 influence susceptibility to high-risk neuroblastoma. Nature genetics. 2009 Jun;     [PubMed]
Diskin SJ,Capasso M,Schnepp RW,Cole KA,Attiyeh EF,Hou C,Diamond M,Carpenter EL,Winter C,Lee H,Jagannathan J,Latorre V,Iolascon A,Hakonarson H,Devoto M,Maris JM, Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma. Nature genetics. 2012 Oct;     [PubMed]
Heukamp LC,Thor T,Schramm A,De Preter K,Kumps C,De Wilde B,Odersky A,Peifer M,Lindner S,Spruessel A,Pattyn F,Mestdagh P,Menten B,Kuhfittig-Kulle S,Künkele A,König K,Meder L,Chatterjee S,Ullrich RT,Schulte S,Vandesompele J,Speleman F,Büttner R,Eggert A,Schulte JH, Targeted expression of mutated ALK induces neuroblastoma in transgenic mice. Science translational medicine. 2012 Jul 4;     [PubMed]
Althoff K,Beckers A,Bell E,Nortmeyer M,Thor T,Sprüssel A,Lindner S,De Preter K,Florin A,Heukamp LC,Klein-Hitpass L,Astrahantseff K,Kumps C,Speleman F,Eggert A,Westermann F,Schramm A,Schulte JH, A Cre-conditional MYCN-driven neuroblastoma mouse model as an improved tool for preclinical studies. Oncogene. 2015 Jun;     [PubMed]
London WB,Castleberry RP,Matthay KK,Look AT,Seeger RC,Shimada H,Thorner P,Brodeur G,Maris JM,Reynolds CP,Cohn SL, Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005 Sep 20;     [PubMed]
Cohn SL,Pearson AD,London WB,Monclair T,Ambros PF,Brodeur GM,Faldum A,Hero B,Iehara T,Machin D,Mosseri V,Simon T,Garaventa A,Castel V,Matthay KK, The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2009 Jan 10;     [PubMed]
LaBrosse EH,Com-Nougué C,Zucker JM,Comoy E,Bohuon C,Lemerle J,Schweisguth O, 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 research. 1980 Jun;     [PubMed]
Vik TA,Pfluger T,Kadota R,Castel V,Tulchinsky M,Farto JC,Heiba S,Serafini A,Tumeh S,Khutoryansky N,Jacobson AF, (123)I-mIBG scintigraphy in patients with known or suspected neuroblastoma: Results from a prospective multicenter trial. Pediatric blood     [PubMed]
Kaplan SJ,Holbrook CT,McDaniel HG,Buntain WL,Crist WM, Vasoactive intestinal peptide secreting tumors of childhood. American journal of diseases of children (1960). 1980 Jan     [PubMed]
Brunklaus A,Pohl K,Zuberi SM,de Sousa C, Investigating neuroblastoma in childhood opsoclonus-myoclonus syndrome. Archives of disease in childhood. 2012 May     [PubMed]
Matthay KK, Stage 4S neuroblastoma: what makes it special? Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1998 Jun     [PubMed]
Baker DL,Schmidt ML,Cohn SL,Maris JM,London WB,Buxton A,Stram D,Castleberry RP,Shimada H,Sandler A,Shamberger RC,Look AT,Reynolds CP,Seeger RC,Matthay KK, Outcome after reduced chemotherapy for intermediate-risk neuroblastoma. The New England journal of medicine. 2010 Sep 30     [PubMed]
Park JR,Bagatell R,London WB,Maris JM,Cohn SL,Mattay KK,Hogarty M, Children's Oncology Group's 2013 blueprint for research: neuroblastoma. Pediatric blood & cancer. 2013 Jun     [PubMed]
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, Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. The New England journal of medicine. 2010 Sep 30     [PubMed]

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