Neuroblastoma pathophysiology: Difference between revisions

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__NOTOC__
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{{Neuroblastoma}}
{{Neuroblastoma}}
{{CMG}} {{AE}}{{HL}}
{{CMG}} {{AE}}{{HL}}{{ZAS}}
==Overview==
==Overview==
Neuroblastoma arises from [[neural crest]] cells, which are normally involved in the development of the [[sympathetic nervous system]] and [[adrenal gland]]s. Neuroblastoma is frequently observed along the sympathetic nervous system structures. Genes involved in the pathogenesis of neuroblastoma include''NBPF10'' gene, ''KIF1B'' [[gene]], and ''ALK'' gene. Neuroblastoma is associated with a number of syndromes that include[[Neurofibromatosis type 1]], [[Beckwith-Wiedemann syndrome]], and [[DiGeorge syndrome]]. On gross pathology, a well defined, bulky, and tan colored mass is a characteristic finding of neuroblastoma. On microscopic histopathological analysis the presence of round blue cells separated by thin [[fibrous]] septa are characteristic findings of neuroblastoma.<ref name="radio">Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015</ref><ref name="wiki">Neuroblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Neuroblastoma Accessed on October, 5 2015</ref><ref name="gov"> Neuroblastoma Treatment for health professionals. National Cancer Institute (2015) http://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq#link/_534_toc Accessed on October, 7 2015</ref>
Neuroblastoma arises from the [[Neural crest cell|neural crest cells]], which are normally involved in development of [[sympathetic nervous system]] and [[Adrenal gland|adrenal glands]]. It is frequently located along the [[sympathetic nervous system]] structures including; [[Adrenal gland|adrenal glands]], [[Retroperitoneal|retroperitoneal organs]], [[Organ of Zuckerkandl|organ of zuckerkandl]], [[Paravertebral ganglia|paravertebral]] [[sympathetic chain]] and [[posterior mediastinum]] among others. Neuroblastoma tumor cells secrete [[catecholamine]] by products including [[Vanillyl mandelic acid|vanillylmandelic acid (VMA)]] and [[Homovanillic acid|homovanillic acid (HVA)]] and [[Vasoactive intestinal peptide|vasoactive intestinal polypeptide (VIP)]] [[hormone]] as well. It can [[Metastasis|metastasize]] to [[bone]], [[liver]], [[Lung|lungs]] and [[brain]]. The various [[Gene|genes]] involved in [[pathogenesis]] of neuroblastoma include; [[NBPF10]], [[KIF1B]], ALK, [[LMO1]] and [[PHOX2A]] [[Gene|genes]]. The most common [[genetic]] [[mutation]] is [[Gain-of-function mutation|gain]] of [[Chromosome 17|chromosome 17q]] and MYCN [[oncogene]] [[amplification]] predicts more aggressive neuroblastoma. Neuroblastoma can also be associated with a number of [[Syndrome|syndromes]] including; [[neurofibromatosis type 1]], [[Beckwith-Wiedemann syndrome|beckwith-wiedemann syndrome]] and [[Hirschsprung's disease|hirschsprung disease]]. On [[gross pathology]], the characteristic finding of neuroblastoma is a well defined, bulky and tan colored [[mass]], that can be associated with fibrous pseudocapsule, [[necrosis]] or [[hemorrhage]]. On microscopic picture, the presence of round blue [[Cell (biology)|cells]] separated by thin fibrous septa are a characteristic finding.


==Pathogenesis==
==Pathogenesis==
* Neuroblastoma arises from [[neural crest]] cells, which are normally involved in the development of the [[sympathetic nervous system]] and [[adrenal gland]]s.<ref name="radio">Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015</ref><ref name="wiki">Neuroblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Neuroblastoma Accessed on October, 5 2015</ref><ref name="gov"> Neuroblastoma Treatment for health professionals. National Cancer Institute (2015) http://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq#link/_534_toc Accessed on October, 7 2015</ref>
* Neuroblastoma arises from [[Neural crest cell|neural crest cells]], which are normally involved in the [[development]] of the [[sympathetic nervous system]] and [[adrenal gland]]s.<ref name="radio">Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015</ref><ref name="gov">Neuroblastoma Treatment for health professionals. National Cancer Institute (2015) http://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq#link/_534_toc Accessed on October, 7 2015</ref><ref>{{Cite journal
* Neuroblastoma is frequently observed along the sympathetic nervous system structures. Specific sites may include:
| author = [[Nai-Kong V. Cheung]] & [[Michael A. Dyer]]
:* Adrenal glands (35% of the cases)
| title = Neuroblastoma: developmental biology, cancer genomics and immunotherapy
:* [[Retroperitoneal]] organs (30% of the cases):
| journal = [[Nature reviews. Cancer]]
| volume = 13
| issue = 6
| pages = 397–411
| year = 2013
| month = June
| doi = 10.1038/nrc3526
| pmid = 23702928
}}</ref><ref>{{Cite journal
| author = [[Julie A. Tomolonis]], [[Saurabh Agarwal]] & [[Jason M. Shohet]]
| title = Neuroblastoma pathogenesis: deregulation of embryonic neural crest development
| journal = [[Cell and tissue research]]
| volume = 372
| issue = 2
| pages = 245–262
| year = 2018
| month = May
| doi = 10.1007/s00441-017-2747-0
| pmid = 29222693
}}</ref><ref>{{Cite journal
| author = [[M. Schwab]], [[K. Alitalo]], [[K. H. Klempnauer]], [[H. E. Varmus]], [[J. M. Bishop]], [[F. Gilbert]], [[G. Brodeur]], [[M. Goldstein]] & [[J. Trent]]
| title = Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour
| journal = [[Nature]]
| volume = 305
| issue = 5931
| pages = 245–248
| year = 1983
| month = September
| pmid = 6888561
}}</ref>
* Neuroblastoma is frequently located along the [[sympathetic nervous system]] structures. Specific sites may include:
:* [[Adrenal gland|Adrenal glands]] (35% of the cases)
:* [[Retroperitoneal]] organs (30% of the cases) such as:
::* [[Organ of Zuckerkandl]]
::* [[Organ of Zuckerkandl]]
::* Coeliac axis
::* [[Celiac axis|Coeliac axis]]
::* Paravertebral [[sympathetic chain]]
::* [[Paravertebral ganglia|Paravertebral]] [[sympathetic chain]]
:* Posterior [[mediastinum]] (20% of the cases)  
:* [[Posterior mediastinum]] (20% of the cases)  
:* [[Nerve]] tissues in the neck (1-5% of the cases)  
:* [[Nerve]] tissues in the [[neck]] (1-5% of the cases)  
:* Nerve tissues in the [[pelvis]] (2-3% of the cases)
:* Nerve tissues in the [[pelvis]] (2-3% of the cases)
* Neuroblastoma tumor cells secrete [[catecholamine]]s such as:
* Neuroblastoma tumor cells secrete [[catecholamine]] by-products such as:
:* [[Vanillylmandelic acid]] (VMA)
:* [[Vanillylmandelic acid]] (VMA)
:* [[Homovanillic acid]] (HVA)
:* [[Homovanillic acid]] (HVA)
* Neuroblastoma tumor cells may secrete [[vasoactive intestinal peptide]] (VIP) hormone.
* Neuroblastoma tumor cells may secrete [[vasoactive intestinal peptide]] (VIP) [[hormone]].
* Neuroblastoma may demonstrate spontaneous regression from an undifferentiated state to a completely [[benign]] cellular state.
* Neuroblastoma may demonstrate spontaneous [[regression]] from an undifferentiated state to a completely [[benign]] cellular state.
* Spontaneous regression generally occurs only in tumors with the following features:
* Spontaneous [[regression]] occurs only in neuroblastomas characterized by the following features:
:* Near [[triploid]] number of [[chromosome]]s
:* Near [[triploid]] number of [[chromosome]]s
:* No ''MYCN'' amplification
:* No ''MYCN'' amplification
:* No loss of [[chromosome]] 1p
:* No loss of [[Chromosome 1|chromosome 1p]]
* [[Metastatic]] disease is common and has a variety of patterns:
* [[Metastatic]] [[disease]] is common and has a variety of patterns:
:* [[Bone]] (most common)
:* [[Bone]] (most common)
:* [[Liver]] (diffuse infiltration that is more common in stage 4S nueroblastoma)
:* [[Liver]] (diffuse infiltration that is more common in stage 4S neuroblastoma)
:* [[Lung]]s and pleura (present as discrete nodules or diffuse consolidation)
:* [[Lung]]s and [[pleura]] (present as discrete nodules or diffuse consolidations)
:* [[Brain]] and [[meninges]] (dural metastases can be diffuse of nodular)
:* [[Brain]] and [[meninges]] (dural metastases can be diffuse or nodular)


==Genetics==
==Genetics==
* Development of neuroblasotma is the result of multiple [[genetic mutation]]s.<ref name="radio">Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015</ref><ref name="wiki">Neuroblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Neuroblastoma Accessed on October, 5 2015</ref>
* Development of neuroblasotma is the result of multiple [[genetic mutation]]s.<ref name="radio">Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015</ref><ref name="wiki">Neuroblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Neuroblastoma Accessed on October, 5 2015</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 = [[Delphine Trochet]], [[Franck Bourdeaut]], [[Isabelle Janoueix-Lerosey]], [[Anne Deville]], [[Loic de Pontual]], [[Gudrun Schleiermacher]], [[Carole Coze]], [[Nicole Philip]], [[Thierry Frebourg]], [[Arnold Munnich]], [[Stanislas Lyonnet]], [[Olivier Delattre]] & [[Jeanne Amiel]]
| title = Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma
| journal = [[American journal of human genetics]]
| volume = 74
| issue = 4
| pages = 761–764
| year = 2004
| month = April
| doi = 10.1086/383253
| pmid = 15024693
}}</ref><ref>{{Cite journal
| author = [[Kai Wang]], [[Sharon J. Diskin]], [[Haitao Zhang]], [[Edward F. Attiyeh]], [[Cynthia Winter]], [[Cuiping Hou]], [[Robert W. Schnepp]], [[Maura Diamond]], [[Kristopher Bosse]], [[Patrick A. Mayes]], [[Joseph Glessner]], [[Cecilia Kim]], [[Edward Frackelton]], [[Maria Garris]], [[Qun Wang]], [[Wendy Glaberson]], [[Rosetta Chiavacci]], [[Le Nguyen]], [[Jayanti Jagannathan]], [[Norihisa Saeki]], [[Hiroki Sasaki]], [[Struan F. A. Grant]], [[Achille Iolascon]], [[Yael P. Mosse]], [[Kristina A. Cole]], [[Hongzhe Li]], [[Marcella Devoto]], [[Patrick W. McGrady]], [[Wendy B. London]], [[Mario Capasso]], [[Nazneen Rahman]], [[Hakon Hakonarson]] & [[John M. Maris]]
| title = Integrative genomics identifies LMO1 as a neuroblastoma oncogene
| journal = [[Nature]]
| volume = 469
| issue = 7329
| pages = 216–220
| year = 2011
| month = January
| doi = 10.1038/nature09609
| pmid = 21124317
}}</ref><ref>{{Cite journal
| author = [[Teeara Berry]], [[William Luther]], [[Namrata Bhatnagar]], [[Yann Jamin]], [[Evon Poon]], [[Takaomi Sanda]], [[Desheng Pei]], [[Bandana Sharma]], [[Winston R. Vetharoy]], [[Albert Hallsworth]], [[Zai Ahmad]], [[Karen Barker]], [[Lisa Moreau]], [[Hannah Webber]], [[Wenchao Wang]], [[Qingsong Liu]], [[Antonio Perez-Atayde]], [[Scott Rodig]], [[Nai-Kong Cheung]], [[Florence Raynaud]], [[Bengt Hallberg]], [[Simon P. Robinson]], [[Nathanael S. Gray]], [[Andrew D. J. Pearson]], [[Suzanne A. Eccles]], [[Louis Chesler]] & [[Rani E. George]]
| title = The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma
| journal = [[Cancer cell]]
| volume = 22
| issue = 1
| pages = 117–130
| year = 2012
| month = July
| doi = 10.1016/j.ccr.2012.06.001
| pmid = 22789543
}}</ref><ref>{{Cite journal
| author = [[G. M. Brodeur]], [[G. Sekhon]] & [[M. N. Goldstein]]
| title = Chromosomal aberrations in human neuroblastomas
| journal = [[Cancer]]
| volume = 40
| issue = 5
| pages = 2256–2263
| year = 1977
| month = November
| pmid = 922665
}}</ref>
* The vast majority of neuroblastoma cases are sporadic.
* The vast majority of neuroblastoma cases are sporadic.
* 1-2% of neuroblastoma cases may demonstrate a familial predilection.
* 1-2% of neuroblastoma cases may demonstrate a [[familial]] predilection.
* Genes involved in the pathogenesis of neuroblastoma include:
* [[Gene|Genes]] involved in the [[pathogenesis]] of neuroblastoma include:
:* ''NBPF10'' gene [[chromosome 1]]
:* ''[[NBPF10]]'' [[gene]] located on [[chromosome 1]]
:* ''KIF1B'' [[gene]] on chromosome 1
:* ''[[KIF1B]]'' [[gene]] located on [[chromosome 1]]
:* ''ALK'' gene on [[chromosome 2]]
:* ''ALK'' [[gene]] located on [[chromosome 2]]
:* ''LMO1'' gene on [[chromosome 11]]
:* ''[[LMO1]]'' [[gene]] located on [[chromosome 11]]
:* ''PHOX2A'' gene on chromosome 11
:* ''[[PHOX2A]]'' [[gene]] located on [[chromosome 11]]
* ''MYCN'' [[oncogene]] amplification is a common finding among neuroblastoma patients.
* [[Gain-of-function mutation|Gain]] of [[Chromosome 17|chromosome 17q]] is the most common [[genetic mutation]] among neuroblastoma [[Patient|patients]].
* ''MYCN'' [[oncogene]] ([[Chromosome 2|chromosome 2p24]]) [[amplification]] predicts a more aggressive nature of neuroblastomas.
* [[Deletion (genetics)|Deletion]] of [[Chromosome 1|chromosome 1p36]] is associated with an increased recurrence rate following [[resection]] of localized neuroblastomas.
* [[Deletion (genetics)|Deletions]] of [[Chromosome 11|chromosome 11q]] is associated with poor [[prognosis]] among nueroblastoma [[Patient|patients]].


==Associated Conditions==
==Associated Conditions==
* Neuroblastoma is associated with a number of syndromes that include:<ref name="radio">Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015</ref><ref name="wiki">Neuroblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Neuroblastoma Accessed on October, 5 2015</ref>
* Neuroblastoma is associated with a number of [[Syndrome|syndromes]] that include:<ref name="radio">Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015</ref><ref name="wiki">Neuroblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Neuroblastoma Accessed on October, 5 2015</ref>
:* [[Neurofibromatosis type 1]] ([[von Recklinghausen disease]])
:* [[Neurofibromatosis type 1]] ([[von Recklinghausen disease]])
:* [[Beckwith-Wiedemann syndrome]]
:* [[Beckwith-Wiedemann syndrome]]
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==Gross Pathology==
==Gross Pathology==
* On gross pathology, a  well defined, bulky, and tan colored mass is a characteristic finding of neuroblastoma.<ref name="radio">Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015</ref><ref name="patho"> Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015</ref>
* On [[gross pathology]], a  well defined, bulky, and tan colored [[mass]] is a characteristic finding of neuroblastoma.<ref name="radio">Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015</ref><ref name="patho">Neuroblastoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015</ref>
* Other associated findings of neuroblastoma on gross pathology may include:
* Other associated findings of neuroblastoma on [[gross pathology]] may include:
:* Fibrous pseudocapsule
:* [[Fibrous]] pseudocapsule
:* [[Necrosis]]
:* [[Necrosis]]
:* [[Hemorrhage]]
:* [[Hemorrhage]]
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==Microscopic Pathology==
==Microscopic Pathology==
* On microscopic histopathological analysis the presence of round blue cells separated by thin [[fibrous]] septa are characteristic findings of neuroblastoma.
* On [[microscopic]] [[histopathological]] analysis the presence of round blue [[Cell (biology)|cells]] separated by thin [[fibrous]] septa are characteristic findings of neuroblastoma.<ref>{{Cite journal
* Other findings of neuroblastoma on [[light microscopy]] may include:<ref name="patho"> Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015</ref>
| author = [[Atsuko Nakazawa]], [[Chizuko Haga]], [[Miki Ohira]], [[Hajime Okita]], [[Takehiko Kamijo]] & [[Akira Nakagawara]]
:* Homer-Wright rosettes (rosettes with a small  meshwork of fibers at the center)
| title = Correlation between the International Neuroblastoma Pathology Classification and genomic signature in neuroblastoma
:* Neuropil-like [[stroma]] (paucicellular stroma with a cotton candy-like appearance)
| journal = [[Cancer science]]
| volume = 106
| issue = 6
| pages = 766–771
| year = 2015
| month = June
| doi = 10.1111/cas.12665
| pmid = 25827934
}}</ref>
* Other findings of neuroblastoma on [[light microscopy]] may include:<ref name="patho">Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015</ref>
:* Homer-Wright rosettes (rosettes with a small  meshwork of [[Fiber|fibers]] at the center)
:* [[Neuropil]]-like [[stroma]] (paucicellular [[stroma]] with a cotton candy-like appearance)
* On [[electron microscopy]] neuroblastoma is characterized by:
* On [[electron microscopy]] neuroblastoma is characterized by:
:* Dendritic processes with longitudinally oriented [[microtubule]]s
:* [[Dendritic cell|Dendritic]] processes with longitudinally oriented [[microtubule]]s
:* Membrane bound electron-dense [[granule]]s that contain [[catecholamine]]s
:* [[Membrane]] bound electron-dense [[granule]]s that contain [[catecholamine]]s
:* Presence of [[desmosomes]]
:* Presence of [[desmosomes]]
:* Absence of [[glycogen]]
:* Absence of [[glycogen]]
* On [[immunohistochemistry]] neuroblastoma is characterized by:
* On [[immunohistochemistry]] neuroblastoma is characterized by:
:* Protein gene product (PGP) 9.5 positivity
:* Protein gene product (PGP) 9.5 +ve
:* [[Monoclonal antibody]] NB84 positivity
:* [[Monoclonal antibody]] NB84 +ve
:* [[Synaptophysin]] positivity
:* [[Synaptophysin]] +ve
:* CD99 marker negativity
:* [[CD99]] marker -ve
* Neuroblastic tumors may be grouped according to International Neuroblastoma Pathology Classification (Shimada classification) into two groups: a schwannian stroma rich group and a schwannian [[stroma]] poor group as illustrated below:<ref name="patho"> Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015</ref><ref name="Stanford">Neuroblastoma, Ganglioneuroblastoma and Ganglioneuroma. Stanford Medicine Surgical Pathology Criteria(2015) http://surgpathcriteria.stanford.edu/srbc/neuroblastoma-ganglioneuroblastoma-ganglioneuroma/ Accessed on October, 5 2015</ref><ref name="pmid11745303">{{cite journal| author=Shimada H, Umehara S, Monobe Y, Hachitanda Y, Nakagawa A, Goto S et al.| title=International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors: a report from the Children's Cancer Group. | journal=Cancer | year= 2001 | volume= 92 | issue= 9 | pages= 2451-61 | pmid=11745303 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11745303  }} </ref>
* Based on the degree of the cellular maturity and composition, neuroblastoma may be classified into three subtypes according to the International Neuroblastoma Pathology Classification which include:<ref name="Stanford">Neuroblastoma, Ganglioneuroblastoma and Ganglioneuroma. Stanford Medicine Surgical Pathology Criteria(2015) http://surgpathcriteria.stanford.edu/srbc/neuroblastoma-ganglioneuroblastoma-ganglioneuroma/ Accessed on October, 5 2015</ref>
<br>
{{Family tree/start}}
{{familytree  | | | | Y01 | | | | | | | | | | Y01=<div style="width: 20em; padding:0.5em;">''' Neuroblastic tumors'''</div>}}
{{familytree  | | |,|-|^|-|.| | | | | | | | }}
{{familytree  | | X01 | |  X02 | | | | | | |X01='''Schwannian stroma rich group'''| X02='''Schwannian stroma poor group'''}}
{{familytree|boxstyle= border-top: 0px;| | A01 | |  A03 | | | | | | |A01=<div style="width: 20em; padding:1em;">
'''Undifferentiated neuroblastoma'''<br>'''Poorly differentiated neuroblastoma'''<br>'''Differentiating neuroblastoma'''</div>|A03=<div style="width: 20em; padding:1em;">|A03=<div style="width: 20em; padding:1em;">
'''Nodular ganglioneuroblastoma'''<br>'''Intermixed ganglioneuroblastoma'''<br>'''Maturing ganglioneuroma'''<br>'''Mature [[ganglioneuroma]]''' </div>}}
{{Family tree/end}}
<br>
* Based on the degree of the cellular maturity and composition, neuroblastoma may be further classified into three subtypes according to the International Neuroblastoma Pathology Classification which include:<ref name="Stanford">Neuroblastoma, Ganglioneuroblastoma and Ganglioneuroma. Stanford Medicine Surgical Pathology Criteria(2015) http://surgpathcriteria.stanford.edu/srbc/neuroblastoma-ganglioneuroblastoma-ganglioneuroma/ Accessed on October, 5 2015</ref>
:* Undifferentiated neruoblastoma
:* Poorly differentiated neuroblastoma
:* Differentiating neuroblastoma
* The table below summarizes the differnces between the three histological subtypes of neurublastoma:<ref name="Stanford">Neuroblastoma, Ganglioneuroblastoma and Ganglioneuroma. Stanford Medicine Surgical Pathology Criteria(2015) http://surgpathcriteria.stanford.edu/srbc/neuroblastoma-ganglioneuroblastoma-ganglioneuroma/ Accessed on October, 5 2015</ref>
 
{|  
{|  
! style="background: #4479BA; width: 200px; color: #FFFFFF;"|'''Subtypes'''
! style="background: #4479BA; width: 200px; color: #FFFFFF;" |'''Subtypes'''


! style="background: #4479BA; width: 600px; color: #FFFFFF;"|'''Description'''
! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''


|-
|-


| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | '''Undifferentiated neuroblastoma'''|| style="padding: 5px 5px; background: #F5F5F5;" | Completely formed by [[neuroblast]]s with no maturity of ganglion cells
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | '''Undifferentiated Neuroblastoma'''|| style="padding: 5px 5px; background: #F5F5F5;" | Completely formed by [[neuroblast]]s with '''no''' maturity of [[Ganglion cell|ganglion cells]]


|-
|-


| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | '''Poorly differentiated neuroblastoma'''|| style="padding: 5px 5px; background: #F5F5F5;" |Mostly formed by neuroblasts with less the 5% maturing [[ganglion cell]]s
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | '''Poorly Differentiated Neuroblastoma'''|| style="padding: 5px 5px; background: #F5F5F5;" |Mostly formed by [[Neuroblast|neuroblasts]] with '''less''' the 5% maturing [[ganglion cell]]s


|-
|-


| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | '''Differentiating neuroblastoma'''|| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | '''Differentiating Neuroblastoma'''|| style="padding: 5px 5px; background: #F5F5F5;" |
Predominantly formed by neuroblasts but with more than 5% mature ganglion cells  
Predominantly formed by [[Neuroblast|neuroblasts]] but with '''more''' than 5% mature [[Ganglion cell|ganglion cells]]
|}
|}


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120px-Adrenal Neuroblastoma 2 MP CTR.jpg|Adrenal neuroblastoma<ref name="patho"> Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015</ref>
120px-Adrenal Neuroblastoma 2 MP CTR.jpg|Adrenal neuroblastoma<ref name="patho"> Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015</ref>
Image:
Image:
120px-Adrenal Neuroblastoma 3 HP CTR.jpg|Adrenal neuroblastoma<ref name="patho"> Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015</ref>
120px-Adrenal Neuroblastoma 3 HP CTR.jpg|[[Adrenal]] neuroblastoma<ref name="patho"> Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015</ref>
Image:
Image:
120px-Adrenal Neuroblastoma HP CTR.jpg|Adrenal neuroblastoma<ref name="patho"> Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015</ref>
120px-Adrenal Neuroblastoma HP CTR.jpg|Adrenal neuroblastoma<ref name="patho"> Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015</ref>
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Latest revision as of 21:32, 2 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

Neuroblastoma arises from the neural crest cells, which are normally involved in development of sympathetic nervous system and adrenal glands. It is frequently located along the sympathetic nervous system structures including; adrenal glands, retroperitoneal organs, organ of zuckerkandl, paravertebral sympathetic chain and posterior mediastinum among others. Neuroblastoma tumor cells secrete catecholamine by products including vanillylmandelic acid (VMA) and homovanillic acid (HVA) and vasoactive intestinal polypeptide (VIP) hormone as well. It can metastasize to bone, liver, lungs and brain. The various genes involved in pathogenesis of neuroblastoma include; NBPF10, KIF1B, ALK, LMO1 and PHOX2A genes. The most common genetic mutation is gain of chromosome 17q and MYCN oncogene amplification predicts more aggressive neuroblastoma. Neuroblastoma can also be associated with a number of syndromes including; neurofibromatosis type 1, beckwith-wiedemann syndrome and hirschsprung disease. On gross pathology, the characteristic finding of neuroblastoma is a well defined, bulky and tan colored mass, that can be associated with fibrous pseudocapsule, necrosis or hemorrhage. On microscopic picture, the presence of round blue cells separated by thin fibrous septa are a characteristic finding.

Pathogenesis

  • Neuroblastoma tumor cells secrete catecholamine by-products such as:
  • Bone (most common)
  • Liver (diffuse infiltration that is more common in stage 4S neuroblastoma)
  • Lungs and pleura (present as discrete nodules or diffuse consolidations)
  • Brain and meninges (dural metastases can be diffuse or nodular)

Genetics

Associated Conditions

Gross Pathology

Microscopic Pathology

  • Homer-Wright rosettes (rosettes with a small meshwork of fibers at the center)
  • Neuropil-like stroma (paucicellular stroma with a cotton candy-like appearance)
  • Based on the degree of the cellular maturity and composition, neuroblastoma may be classified into three subtypes according to the International Neuroblastoma Pathology Classification which include:[14]
Subtypes Description
Undifferentiated Neuroblastoma Completely formed by neuroblasts with no maturity of ganglion cells
Poorly Differentiated Neuroblastoma Mostly formed by neuroblasts with less the 5% maturing ganglion cells
Differentiating Neuroblastoma

Predominantly formed by neuroblasts but with more than 5% mature ganglion cells

Gallery

  • Illustrated below is a series of microscopic images demonstrating neuroblastoma:
  • Adrenal neuroblastoma[12]
    Adrenal neuroblastoma[12]
  • Adrenal neuroblastoma[12]
    Adrenal neuroblastoma[12]
  • Adrenal neuroblastoma[12]
    Adrenal neuroblastoma[12]
  • Adrenal neuroblastoma[12]
    Adrenal neuroblastoma[12]
  • Adrenal neuroblastoma[12]
    Adrenal neuroblastoma[12]
  • Adrenal neuroblastoma[12]
    Adrenal neuroblastoma[12]
  • Adrenal neuroblastoma[12]
    Adrenal neuroblastoma[12]
  • Adrenal neuroblastoma[12]
    Adrenal neuroblastoma[12]
  • Adrenal neuroblastoma[12]
    Adrenal neuroblastoma[12]

References

  1. ↑ 1.0 1.1 1.2 1.3 Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015
  2. ↑ Neuroblastoma Treatment for health professionals. National Cancer Institute (2015) http://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq#link/_534_toc Accessed on October, 7 2015
  3. ↑ Nai-Kong V. Cheung & Michael A. Dyer (2013). "Neuroblastoma: developmental biology, cancer genomics and immunotherapy". Nature reviews. Cancer. 13 (6): 397–411. doi:10.1038/nrc3526. PMID 23702928. Unknown parameter |month= ignored (help)
  4. ↑ Julie A. Tomolonis, Saurabh Agarwal & Jason M. Shohet (2018). "Neuroblastoma pathogenesis: deregulation of embryonic neural crest development". Cell and tissue research. 372 (2): 245–262. doi:10.1007/s00441-017-2747-0. PMID 29222693. Unknown parameter |month= ignored (help)
  5. ↑ M. Schwab, K. Alitalo, K. H. Klempnauer, H. E. Varmus, J. M. Bishop, F. Gilbert, G. Brodeur, M. Goldstein & J. Trent (1983). "Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour". Nature. 305 (5931): 245–248. PMID 6888561. Unknown parameter |month= ignored (help)
  6. ↑ 6.0 6.1 Neuroblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Neuroblastoma Accessed on October, 5 2015
  7. ↑ Colon NC, Chung DH (2011). "Neuroblastoma". Adv Pediatr. 58 (1): 297–311. doi:10.1016/j.yapd.2011.03.011. PMC 3668791. PMID 21736987.
  8. ↑ Delphine Trochet, Franck Bourdeaut, Isabelle Janoueix-Lerosey, Anne Deville, Loic de Pontual, Gudrun Schleiermacher, Carole Coze, Nicole Philip, Thierry Frebourg, Arnold Munnich, Stanislas Lyonnet, Olivier Delattre & Jeanne Amiel (2004). "Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma". American journal of human genetics. 74 (4): 761–764. doi:10.1086/383253. PMID 15024693. Unknown parameter |month= ignored (help)
  9. ↑ Kai Wang, Sharon J. Diskin, Haitao Zhang, Edward F. Attiyeh, Cynthia Winter, Cuiping Hou, Robert W. Schnepp, Maura Diamond, Kristopher Bosse, Patrick A. Mayes, Joseph Glessner, Cecilia Kim, Edward Frackelton, Maria Garris, Qun Wang, Wendy Glaberson, Rosetta Chiavacci, Le Nguyen, Jayanti Jagannathan, Norihisa Saeki, Hiroki Sasaki, Struan F. A. Grant, Achille Iolascon, Yael P. Mosse, Kristina A. Cole, Hongzhe Li, Marcella Devoto, Patrick W. McGrady, Wendy B. London, Mario Capasso, Nazneen Rahman, Hakon Hakonarson & John M. Maris (2011). "Integrative genomics identifies LMO1 as a neuroblastoma oncogene". Nature. 469 (7329): 216–220. doi:10.1038/nature09609. PMID 21124317. Unknown parameter |month= ignored (help)
  10. ↑ Teeara Berry, William Luther, Namrata Bhatnagar, Yann Jamin, Evon Poon, Takaomi Sanda, Desheng Pei, Bandana Sharma, Winston R. Vetharoy, Albert Hallsworth, Zai Ahmad, Karen Barker, Lisa Moreau, Hannah Webber, Wenchao Wang, Qingsong Liu, Antonio Perez-Atayde, Scott Rodig, Nai-Kong Cheung, Florence Raynaud, Bengt Hallberg, Simon P. Robinson, Nathanael S. Gray, Andrew D. J. Pearson, Suzanne A. Eccles, Louis Chesler & Rani E. George (2012). "The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma". Cancer cell. 22 (1): 117–130. doi:10.1016/j.ccr.2012.06.001. PMID 22789543. Unknown parameter |month= ignored (help)
  11. ↑ G. M. Brodeur, G. Sekhon & M. N. Goldstein (1977). "Chromosomal aberrations in human neuroblastomas". Cancer. 40 (5): 2256–2263. PMID 922665. Unknown parameter |month= ignored (help)
  12. ↑ 12.00 12.01 12.02 12.03 12.04 12.05 12.06 12.07 12.08 12.09 12.10 Neuroblastoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015
  13. ↑ Atsuko Nakazawa, Chizuko Haga, Miki Ohira, Hajime Okita, Takehiko Kamijo & Akira Nakagawara (2015). "Correlation between the International Neuroblastoma Pathology Classification and genomic signature in neuroblastoma". Cancer science. 106 (6): 766–771. doi:10.1111/cas.12665. PMID 25827934. Unknown parameter |month= ignored (help)
  14. ↑ Neuroblastoma, Ganglioneuroblastoma and Ganglioneuroma. Stanford Medicine Surgical Pathology Criteria(2015) http://surgpathcriteria.stanford.edu/srbc/neuroblastoma-ganglioneuroblastoma-ganglioneuroma/ Accessed on October, 5 2015


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