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==Overview==
==Overview==
According to the conventional International Neuroblastoma Staging System (INSS), there are 6 stages of neuroblastoma based on the tumor size, lymph node involvement, and presence of metastesis. However, according to a newly proposed International Neuroblastoma Risk Group Staging System (INRGSS), there are four stages of neuroblastoma based on the extent of dissemination and image findings. Neuroblastoma patients are risk stratified according to the Children Oncology Group (COG) risk stratification system into a low risk group, an intermediate risk group, and a high risk group based on the [[tumor]] INSS stage, the patient's age, tumor grade, and the amplification of ''MYCN'' gene.
According to the conventional International Neuroblastoma Staging System (INSS), there are 6 stages of neuroblastoma based on the [[tumor]] size, [[lymph node]] involvement, and presence of [[metastasis]]. However, according to a newly proposed International Neuroblastoma Risk Group Staging System (INRGSS), there are four stages of neuroblastoma based on the extent of dissemination and image findings. Neuroblastoma patients are risk stratified according to the Children Oncology Group (COG) risk stratification system into a low risk group, an intermediate risk group, and a high risk group based on the [[tumor]] INSS stage, the [[Patient|patient's]] [[age]], [[tumor]] grade, and the amplification of ''MYCN'' [[gene]].


==Neuroblastoma Staging==
==Neuroblastoma Staging==
===International Neuroblastoma Staging System (INSS)===
===International Neuroblastoma Staging System (INSS)===
*According to the conventional International Neuroblastoma Staging System (INSS), there are 6 stages of neuroblastoma based on the tumor size, lymph node involvement, and presence of metastesis.<ref name="pmid22248965">{{cite journal| author=Davidoff AM| title=Neuroblastoma. | journal=Semin Pediatr Surg | year= 2012 | volume= 21 | issue= 1 | pages= 2-14 | pmid=22248965 | doi=10.1053/j.sempedsurg.2011.10.009 | pmc=PMC3261589 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22248965  }} </ref><ref name="pmid21736987">{{cite journal| author=Colon NC, Chung DH| title=Neuroblastoma. | journal=Adv Pediatr | year= 2011 | volume= 58 | issue= 1 | pages= 297-311 | pmid=21736987 | doi=10.1016/j.yapd.2011.03.011 | pmc=PMC3668791 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21736987  }} </ref><ref>{{Cite journal
*According to the conventional International Neuroblastoma Staging System (INSS), there are 6 stages of neuroblastoma based on the [[tumor]] size, [[lymph node]] involvement, and presence of [[metastasis]].<ref name="pmid22248965">{{cite journal| author=Davidoff AM| title=Neuroblastoma. | journal=Semin Pediatr Surg | year= 2012 | volume= 21 | issue= 1 | pages= 2-14 | pmid=22248965 | doi=10.1053/j.sempedsurg.2011.10.009 | pmc=PMC3261589 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22248965  }} </ref><ref name="pmid21736987">{{cite journal| author=Colon NC, Chung DH| title=Neuroblastoma. | journal=Adv Pediatr | year= 2011 | volume= 58 | issue= 1 | pages= 297-311 | pmid=21736987 | doi=10.1016/j.yapd.2011.03.011 | pmc=PMC3668791 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21736987  }} </ref><ref>{{Cite journal
  | author = [[H. Shimada]], [[S. Umehara]], [[Y. Monobe]], [[Y. Hachitanda]], [[A. Nakagawa]], [[S. Goto]], [[R. B. Gerbing]], [[D. O. Stram]], [[J. N. Lukens]] & [[K. K. Matthay]]
  | author = [[H. Shimada]], [[S. Umehara]], [[Y. Monobe]], [[Y. Hachitanda]], [[A. Nakagawa]], [[S. Goto]], [[R. B. Gerbing]], [[D. O. Stram]], [[J. N. Lukens]] & [[K. K. Matthay]]
  | title = International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors: a report from the Children's Cancer Group
  | title = International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors: a report from the Children's Cancer Group
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{| style="cellpadding=0; cellspacing= 0; width: 950px;"
{| style="cellpadding=0; cellspacing= 0; width: 950px;"
|-
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align=center |'''Stage'''||style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=center |'''Description'''
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''Stage'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="center" |'''Description'''
|-
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=center |'''Stage 1''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=left |
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="center" |'''Stage 1''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align="left" |
* Localized tumor
* Localized tumor
* Complete gross excision
* Complete gross excision
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|-
|-


|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=center |'''Stage 2A''' ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=left |
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="center" |'''Stage 2A''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align="left" |
* Localized tumor
* Localized tumor
* Incomplete gross resection
* Incomplete gross resection
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|-
|-


|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=center |'''Stage 2B''' ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=left |
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="center" |'''Stage 2B''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align="left" |
* Localized tumor
* Localized tumor
* Complete or incomplete gross resection
* Complete or incomplete gross resection
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|-
|-


|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=center |'''Stage 3''' ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=left |
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="center" |'''Stage 3''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align="left" |
* Localized unilateral tumor with contralateral lymph nodes involvement positive under microscopic examination
* Localized unilateral tumor with contralateral lymph nodes involvement positive under microscopic examination
<center>'''or'''</center>
<center>'''or'''</center>
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|-
|-


|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=center |'''Stage 4''' ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=left |
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="center" |'''Stage 4''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align="left" |
* Metastasis of the tumor to distant lymph nodes
* Metastasis of the tumor to distant lymph nodes
* Metastasis of the tumor to liver, skin, bone and/or other organs (except as defined by Stage 4S)
* Metastasis of the tumor to liver, skin, bone and/or other organs (except as defined by Stage 4S)
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|-
|-


|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=center |'''Stage 4S''' ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=left |
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="center" |'''Stage 4S''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align="left" |
* Limited to infants <1 year of age
* Limited to infants <1 year of age
* Localized primary tumor (as defined for stage 1, 2A, or 2B)
* Localized primary tumor (as defined for stage 1, 2A, or 2B)
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{| style="cellpadding=0; cellspacing= 0; width: 800px;"
{| style="cellpadding=0; cellspacing= 0; width: 800px;"
|-
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align=center |'''Stage'''||style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=center |'''Description'''
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''Stage'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="center" |'''Description'''
|-
|-


|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=center |'''Stage L1'''||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=left |
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="center" |'''Stage L1'''|| style="font-size: 100; padding: 0 5px; background: #F5F5F5" align="left" |
* Localized disease without image-defined risk factors
* Localized disease without image-defined risk factors
|-
|-


|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=center |'''Stage L2''' ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=left |
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="center" |'''Stage L2''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align="left" |
* Localized disease with image-defined risk factors
* Localized disease with image-defined risk factors


|-
|-


|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=center |'''Stage M''' ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=left |
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="center" |'''Stage M''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align="left" |
* Metastatic disease
* Metastatic disease


|-
|-


|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=center |'''Stage MS''' ||style="font-size: 100; padding: 0 5px; background: #F5F5F5" align=left |
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="center" |'''Stage MS''' || style="font-size: 100; padding: 0 5px; background: #F5F5F5" align="left" |
* Metastatic disease '''limited''' to skin, liver and/or bone marrow  
* Metastatic disease '''limited''' to skin, liver and/or bone marrow  
* Bone marrow involvement in stage MS should be '''minimal''' (<10% of total nucleated cells identified as malignant on bone marrow biopsy)
* Bone marrow involvement in stage MS should be '''minimal''' (<10% of total nucleated cells identified as malignant on bone marrow biopsy)

Revision as of 14:15, 4 March 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2] Zahir Ali Shaikh, MD[3]

Overview

According to the conventional International Neuroblastoma Staging System (INSS), there are 6 stages of neuroblastoma based on the tumor size, lymph node involvement, and presence of metastasis. However, according to a newly proposed International Neuroblastoma Risk Group Staging System (INRGSS), there are four stages of neuroblastoma based on the extent of dissemination and image findings. Neuroblastoma patients are risk stratified according to the Children Oncology Group (COG) risk stratification system into a low risk group, an intermediate risk group, and a high risk group based on the tumor INSS stage, the patient's age, tumor grade, and the amplification of MYCN gene.

Neuroblastoma Staging

International Neuroblastoma Staging System (INSS)

  • According to the conventional International Neuroblastoma Staging System (INSS), there are 6 stages of neuroblastoma based on the tumor size, lymph node involvement, and presence of metastasis.[1][2][3][4][5]
Stage Description
Stage 1
  • Localized tumor
  • Complete gross excision
  • Ipsilateral lymph nodes involvement negative under microscopic examination
Stage 2A
  • Localized tumor
  • Incomplete gross resection
  • Ipsilateral lymph nodes involvement negative under microscopic examination
Stage 2B
  • Localized tumor
  • Complete or incomplete gross resection
  • Ipsilateral lymph nodes involvement positive under microscopic examination
  • Enlarged contralateral lymph nodes but with negative involvement under microscopic examination
Stage 3
  • Localized unilateral tumor with contralateral lymph nodes involvement positive under microscopic examination
or
  • Unresectable unilateral tumor infiltrating across the midline with positive or negative regional lymph node involvement
or
  • Unresectable midline tumor with bilateral infiltration or lymph node involvement
Stage 4
  • Metastasis of the tumor to distant lymph nodes
  • Metastasis of the tumor to liver, skin, bone and/or other organs (except as defined by Stage 4S)
Stage 4S
  • Limited to infants <1 year of age
  • Localized primary tumor (as defined for stage 1, 2A, or 2B)
  • Metastasis of the tumor limited to skin, liver and/or bone marrow
  • Bone marrow involvement in stage 4S should be minimal (<10% of total nucleated cells identified as malignant on bone marrow biopsy)

International Neuroblastoma Risk Group Staging System (INRGSS)

According to a newly proposed International Neuroblastoma Risk Group Staging System (INRGSS), there are four stages of neuroblastoma based on the extent of dissemination and image findings.[2][6][7][8]

Stage Description
Stage L1
  • Localized disease without image-defined risk factors
Stage L2
  • Localized disease with image-defined risk factors
Stage M
  • Metastatic disease
Stage MS
  • Metastatic disease limited to skin, liver and/or bone marrow
  • Bone marrow involvement in stage MS should be minimal (<10% of total nucleated cells identified as malignant on bone marrow biopsy)

Risk Stratification

Children's Oncology Group Risk Stratification

  • Children Oncology Group (COG) risk stratification system determines the protocol of management used for neuroblastoma patients.[9]
  • Neuroblastoma patients are risk stratified into a low risk group, intermediate risk groups, and a high risk group based on the INSS stage, the patient's age, histological grade, and the amplification of MYCN gene.[1][2][10]


 
 
 
 
 
 
 
 
 
 
 
 
  • INSS stage 1
  • Irrespective of age
  • Irrespective of grade
  • Irrespective of molecular pathway
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low risk neuroblastoma patients (group 1)
 
 
 
 
  • INSS stage 2A/2B (>50% resected)
  • Irrespective of age
  • Irrespective of grade
  • MYCN not amplified
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  • INNS stage 4S
  • <365 days of age
  • Favorable histology
  • DNA index >1
  • MYCN not amplified
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
  • INNS stage 2A/2B (<50% resected)
  • 0-12 years of age
  • Irrespective of grade
  • MYCN not amplified
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  • INSS stage 3
  • <365 days of age
  • Favorable histology
  • DNA index >1
  • MYCN not amplified
 
 
 
 
 
 
 
 
 
 
Intermediate risk neuroblastoma patients (group 2)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  • INNS stage 3
  • 1-12 years of age
  • Favorable histology
  • MYCN not amplified
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  • Symptomatic INNS stage 4S
  • <365 days of age
  • Favorable histology
  • DNA index >1
  • MYCN not amplified
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
  • INSS stage 3
  • <365 days of age
  • Unfavorable histology
  • DNA index=1
  • MYCN not amplified
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intermediate risk neuroblastoma patients (group 3)
 
 
 
 
  • INSS stage 4
  • <365 days of age
  • Favorable histology
  • DNA index >1
  • MYCN not amplified
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  • INNS stage 4S
  • <365 days of age
  • Unfavorable histology
  • DNA index=1
  • MYCN not amplified
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
  • INSS stage 4
  • <365 days of age
  • Unfavorable histology
  • DNA index=1
  • MYCN not amplified
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intermediate risk neuroblastoma patients (group 4)
 
 
 
 
  • INSS stage 3
  • 365-547 days of age
  • Unfavorable histology
  • MYCN not amplified
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  • INNS stage 4
  • 365-547 days of age
  • Favorable histology
  • DNA index>1
  • MYCN not amplified
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
  • INNS stage 2A/2B, Stage 3 , Stage 4 or Stage 4S
  • Irrespective of age
  • Irrespective of grade
  • MYCN amplified
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  • INSS stage 3
  • >547 days of age
  • Unfavorable histology
  • MYCN not amplified
 
 
 
 
 
 
 
 
 
 
High risk neuroblastoma patients (group 5)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  • INNS stage 4
  • 365-547 days of age
  • Unfavorable histology
  • DNA index=1
  • MYCN not amplified
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  • INNS stage 4
  • >547 days of age
  • Irrespective grade
  • Irrespective MYCN amplification state
 
 
 
 
 
 
 
 

References

  1. ↑ 1.0 1.1 Davidoff AM (2012). "Neuroblastoma". Semin Pediatr Surg. 21 (1): 2–14. doi:10.1053/j.sempedsurg.2011.10.009. PMC 3261589. PMID 22248965.
  2. ↑ 2.0 2.1 2.2 Colon NC, Chung DH (2011). "Neuroblastoma". Adv Pediatr. 58 (1): 297–311. doi:10.1016/j.yapd.2011.03.011. PMC 3668791. PMID 21736987.
  3. ↑ H. Shimada, S. Umehara, Y. Monobe, Y. Hachitanda, A. Nakagawa, S. Goto, R. B. Gerbing, D. O. Stram, J. N. Lukens & K. K. Matthay (2001). "International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors: a report from the Children's Cancer Group". Cancer. 92 (9): 2451–2461. PMID 11745303. Unknown parameter |month= ignored (help)
  4. ↑ D. de Sa (2000). "Neuroblastoma classification". Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 3 (5): 506–507. PMID 10890940. Unknown parameter |month= ignored (help)
  5. ↑ S. Goto, S. Umehara, R. B. Gerbing, D. O. Stram, G. M. Brodeur, R. C. Seeger, J. N. Lukens, K. K. Matthay & H. Shimada (2001). "Histopathology (International Neuroblastoma Pathology Classification) and MYCN status in patients with peripheral neuroblastic tumors: a report from the Children's Cancer Group". Cancer. 92 (10): 2699–2708. PMID 11745206. Unknown parameter |month= ignored (help)
  6. ↑ Susan L. Cohn, Andrew D. J. Pearson, Wendy B. London, Tom Monclair, Peter F. Ambros, Garrett M. Brodeur, Andreas Faldum, Barbara Hero, Tomoko Iehara, David Machin, Veronique Mosseri, Thorsten Simon, Alberto Garaventa, Victoria Castel & Katherine K. Matthay (2009). "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. 27 (2): 289–297. doi:10.1200/JCO.2008.16.6785. PMID 19047291. Unknown parameter |month= ignored (help)
  7. ↑ Tom Monclair, Garrett M. Brodeur, Peter F. Ambros, Herve J. Brisse, Giovanni Cecchetto, Keith Holmes, Michio Kaneko, Wendy B. London, Katherine K. Matthay, Jed G. Nuchtern, Dietrich von Schweinitz, Thorsten Simon, Susan L. Cohn & Andrew D. J. Pearson (2009). "The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report". Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 27 (2): 298–303. doi:10.1200/JCO.2008.16.6876. PMID 19047290. Unknown parameter |month= ignored (help)
  8. ↑ Sidharth Mahapatra & Kishore B.. Challagundla (2018). "Cancer, Neuroblastoma". PMID 28846355. Unknown parameter |month= ignored (help)
  9. ↑ Neuroblastoma treatment–for health professionals. National Cancer Institute (2015) http://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq#section/_1 Accessed on October, 8 2015
  10. ↑ Nadja C. Colon & Dai H. Chung (2011). "Neuroblastoma". Advances in pediatrics. 58 (1): 297–311. doi:10.1016/j.yapd.2011.03.011. PMID 21736987.


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