Neuroblastoma pathophysiology: Difference between revisions
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==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.<ref>{{Cite journal | * 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 | ||
| author = [[Atsuko Nakazawa]], [[Chizuko Haga]], [[Miki Ohira]], [[Hajime Okita]], [[Takehiko Kamijo]] & [[Akira Nakagawara]] | | author = [[Atsuko Nakazawa]], [[Chizuko Haga]], [[Miki Ohira]], [[Hajime Okita]], [[Takehiko Kamijo]] & [[Akira Nakagawara]] | ||
| title = Correlation between the International Neuroblastoma Pathology Classification and genomic signature in neuroblastoma | | title = Correlation between the International Neuroblastoma Pathology Classification and genomic signature in neuroblastoma | ||
| Line 152: | Line 152: | ||
}}</ref> | }}</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> | * 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 fibers at the center) | :* 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) | :* [[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]] | ||
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:* [[Monoclonal antibody]] NB84 +ve | :* [[Monoclonal antibody]] NB84 +ve | ||
:* [[Synaptophysin]] +ve | :* [[Synaptophysin]] +ve | ||
:* CD99 marker -ve | :* [[CD99]] marker -ve | ||
* 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> | * 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> | ||
{| | {| | ||
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|- | |- | ||
| 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]] | ||
|} | |} | ||
Latest revision as of 21:32, 2 March 2019
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Neuroblastoma Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Neuroblastoma pathophysiology On the Web |
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American Roentgen Ray Society Images of Neuroblastoma pathophysiology |
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Risk calculators and risk factors for Neuroblastoma pathophysiology |
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 arises from neural crest cells, which are normally involved in the development of the sympathetic nervous system and adrenal glands.[1][2][3][4][5]
- Neuroblastoma is frequently located along the sympathetic nervous system structures. Specific sites may include:
- Adrenal glands (35% of the cases)
- Retroperitoneal organs (30% of the cases) such as:
- Posterior mediastinum (20% of the cases)
- Nerve tissues in the neck (1-5% of the cases)
- Nerve tissues in the pelvis (2-3% of the cases)
- Neuroblastoma tumor cells secrete catecholamine by-products such as:
- Vanillylmandelic acid (VMA)
- Homovanillic acid (HVA)
- 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.
- Spontaneous regression occurs only in neuroblastomas characterized by the following features:
- Near triploid number of chromosomes
- No MYCN amplification
- No loss of chromosome 1p
- Metastatic disease is common and has a variety of patterns:
Genetics
- Development of neuroblasotma is the result of multiple genetic mutations.[1][6][7][8][9][10][11]
- The vast majority of neuroblastoma cases are sporadic.
- 1-2% of neuroblastoma cases may demonstrate a familial predilection.
- Genes involved in the pathogenesis of neuroblastoma include:
- NBPF10 gene located on chromosome 1
- KIF1B gene located on chromosome 1
- ALK gene located on chromosome 2
- LMO1 gene located on chromosome 11
- PHOX2A gene located on chromosome 11
- Gain of chromosome 17q is the most common genetic mutation among neuroblastoma patients.
- MYCN oncogene (chromosome 2p24) amplification predicts a more aggressive nature of neuroblastomas.
- Deletion of chromosome 1p36 is associated with an increased recurrence rate following resection of localized neuroblastomas.
- Deletions of chromosome 11q is associated with poor prognosis among nueroblastoma patients.
Associated Conditions
Gross Pathology
- On gross pathology, a well defined, bulky, and tan colored mass is a characteristic finding of neuroblastoma.[1][12]
- Other associated findings of neuroblastoma on gross pathology may include:
- Fibrous pseudocapsule
- Necrosis
- Hemorrhage
- Calcification
Microscopic Pathology
- On microscopic histopathological analysis the presence of round blue cells separated by thin fibrous septa are characteristic findings of neuroblastoma.[13]
- Other findings of neuroblastoma on light microscopy may include:[12]
- On electron microscopy neuroblastoma is characterized by:
- Dendritic processes with longitudinally oriented microtubules
- Membrane bound electron-dense granules that contain catecholamines
- Presence of desmosomes
- Absence of glycogen
- On immunohistochemistry neuroblastoma is characterized by:
- Protein gene product (PGP) 9.5 +ve
- Monoclonal antibody NB84 +ve
- Synaptophysin +ve
- CD99 marker -ve
- 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:
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![Adrenal neuroblastoma[12]](/images/1/19/120px-Adrenal_Neuroblastoma_2_HP_CTR.jpg)
Adrenal neuroblastoma[12]
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![Adrenal neuroblastoma[12]](/images/2/2b/120px-Adrenal_Neuroblastoma_2_MP_CTR.jpg)
Adrenal neuroblastoma[12]
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![Adrenal neuroblastoma[12]](/images/4/43/120px-Adrenal_Neuroblastoma_3_HP_CTR.jpg)
-
![Adrenal neuroblastoma[12]](/images/e/e7/120px-Adrenal_Neuroblastoma_HP_CTR.jpg)
Adrenal neuroblastoma[12]
-
![Adrenal neuroblastoma[12]](/images/c/cb/120px-Adrenal_Neuroblastoma_HP2_CTR.jpg)
Adrenal neuroblastoma[12]
-
![Adrenal neuroblastoma[12]](/images/e/eb/120px-Adrenal_Neuroblastoma_M2P_PA.JPG)
Adrenal neuroblastoma[12]
-
![Adrenal neuroblastoma[12]](/images/4/46/120px-Adrenal_Neuroblastoma_MP_CTR.jpg)
Adrenal neuroblastoma[12]
-
![Adrenal neuroblastoma[12]](/images/3/3a/120px-Adrenal_Neuroblastoma_MP_PA.JPG)
Adrenal neuroblastoma[12]
-
![Adrenal neuroblastoma[12]](/images/1/1c/120px-Adrenal_Neuroblastoma_MP3_PA.JPG)
Adrenal neuroblastoma[12]
![Adrenal neuroblastoma[12]](/index.php/File:120px-Adrenal_Neuroblastoma_2_HP_CTR.jpg)
![Adrenal neuroblastoma[12]](/index.php/File:120px-Adrenal_Neuroblastoma_2_MP_CTR.jpg)
![Adrenal neuroblastoma[12]](/index.php/File:120px-Adrenal_Neuroblastoma_3_HP_CTR.jpg)
![Adrenal neuroblastoma[12]](/index.php/File:120px-Adrenal_Neuroblastoma_HP_CTR.jpg)
![Adrenal neuroblastoma[12]](/index.php/File:120px-Adrenal_Neuroblastoma_HP2_CTR.jpg)
![Adrenal neuroblastoma[12]](/index.php/File:120px-Adrenal_Neuroblastoma_M2P_PA.JPG)
![Adrenal neuroblastoma[12]](/index.php/File:120px-Adrenal_Neuroblastoma_MP_CTR.jpg)
![Adrenal neuroblastoma[12]](/index.php/File:120px-Adrenal_Neuroblastoma_MP_PA.JPG)
![Adrenal neuroblastoma[12]](/index.php/File:120px-Adrenal_Neuroblastoma_MP3_PA.JPG)
References
- ↑ 1.0 1.1 1.2 1.3 Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015
- ↑ 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
- ↑ 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) - ↑ 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) - ↑ 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) - ↑ 6.0 6.1 Neuroblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Neuroblastoma Accessed on October, 5 2015
- ↑ Colon NC, Chung DH (2011). "Neuroblastoma". Adv Pediatr. 58 (1): 297–311. doi:10.1016/j.yapd.2011.03.011. PMC 3668791. PMID 21736987.
- ↑ 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) - ↑ 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) - ↑ 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) - ↑ 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) - ↑ 12.00 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
- ↑ 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) - ↑ Neuroblastoma, Ganglioneuroblastoma and Ganglioneuroma. Stanford Medicine Surgical Pathology Criteria(2015) http://surgpathcriteria.stanford.edu/srbc/neuroblastoma-ganglioneuroblastoma-ganglioneuroma/ Accessed on October, 5 2015