Neuroblastoma pathophysiology: Difference between revisions
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==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> | ||
* 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: | * 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 | :* ''PHOX2A'' gene locatefdon chromosome 11 | ||
* ''MYCN'' [[oncogene]] amplification is | * Gain of chromosome 17q is the most common genetic mutation among neuroblastoma patients. | ||
* ''MYCN'' [[oncogene]] (chromosome 2p24) amplification predicts a more aggressive nature of the tumor. | |||
* Deletion of the chromosome 1p36 is associated with an increased recurrence rate among patients with localis neurblastoma | |||
* Deletions of chromosome 11q is associated with poor prognosis among nueroblastoma patients. | |||
==Associated Conditions== | ==Associated Conditions== | ||
Revision as of 12:28, 8 October 2015
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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]
Overview
Neuroblastoma arises from neural crest cells, which are normally involved in the development of the sympathetic nervous system and adrenal glands. Neuroblastoma is frequently observed along the sympathetic nervous system structures. Genes involved in the pathogenesis of neuroblastoma includeNBPF10 gene, KIF1B gene, and ALK gene. Neuroblastoma is associated with a number of syndromes that includeNeurofibromatosis 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.[1][2][3]
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]
- Neuroblastoma is frequently observed along the sympathetic nervous system structures. Specific sites may include:
- Adrenal glands (35% of the cases)
- Retroperitoneal organs (30% of the cases):
- Organ of Zuckerkandl
- Coeliac axis
- Paravertebral sympathetic chain
- 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 catecholamines 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 generally occurs only in tumors with 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][2][4]
- 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 locatefdon 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 the tumor.
- Deletion of the chromosome 1p36 is associated with an increased recurrence rate among patients with localis neurblastoma
- 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][5]
- 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.
- Other findings of neuroblastoma on light microscopy may include:[5]
- Homer-Wright rosettes (rosettes with a small meshwork of fibers at the center)
- Neuropil-like stroma (paucicellular stroma with a cotton candy-like appearance)
- 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 positivity
- Monoclonal antibody NB84 positivity
- Synaptophysin positivity
- CD99 marker negativity
- 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:[5][6][7]
Neuroblastic tumors | |||||||||||||||||||||||||||||
| Schwannian stroma rich group | Schwannian stroma poor group | ||||||||||||||||||||||||||||
Undifferentiated neuroblastoma Poorly differentiated neuroblastoma Differentiating neuroblastoma |
Nodular ganglioneuroblastoma Intermixed ganglioneuroblastoma Maturing ganglioneuroma Mature ganglioneuroma | ||||||||||||||||||||||||||||
- 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:[6]
- Undifferentiated neruoblastoma
- Poorly differentiated neuroblastoma
- Differentiating neuroblastoma
- The table below summarizes the differnces between the three histological subtypes of neurublastoma:[6]
| 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[5]](/images/1/19/120px-Adrenal_Neuroblastoma_2_HP_CTR.jpg)
Adrenal neuroblastoma[5] -
![Adrenal neuroblastoma[5]](/images/2/2b/120px-Adrenal_Neuroblastoma_2_MP_CTR.jpg)
Adrenal neuroblastoma[5] -
![Adrenal neuroblastoma[5]](/images/4/43/120px-Adrenal_Neuroblastoma_3_HP_CTR.jpg)
Adrenal neuroblastoma[5] -
![Adrenal neuroblastoma[5]](/images/e/e7/120px-Adrenal_Neuroblastoma_HP_CTR.jpg)
Adrenal neuroblastoma[5] -
![Adrenal neuroblastoma[5]](/images/c/cb/120px-Adrenal_Neuroblastoma_HP2_CTR.jpg)
Adrenal neuroblastoma[5] -
![Adrenal neuroblastoma[5]](/images/e/eb/120px-Adrenal_Neuroblastoma_M2P_PA.JPG)
Adrenal neuroblastoma[5] -
![Adrenal neuroblastoma[5]](/images/4/46/120px-Adrenal_Neuroblastoma_MP_CTR.jpg)
Adrenal neuroblastoma[5] -
![Adrenal neuroblastoma[5]](/images/3/3a/120px-Adrenal_Neuroblastoma_MP_PA.JPG)
Adrenal neuroblastoma[5] -
![Adrenal neuroblastoma[5]](/images/1/1c/120px-Adrenal_Neuroblastoma_MP3_PA.JPG)
Adrenal neuroblastoma[5]
![Adrenal neuroblastoma[5]](/index.php/File:120px-Adrenal_Neuroblastoma_2_HP_CTR.jpg)
![Adrenal neuroblastoma[5]](/index.php/File:120px-Adrenal_Neuroblastoma_2_MP_CTR.jpg)
![Adrenal neuroblastoma[5]](/index.php/File:120px-Adrenal_Neuroblastoma_3_HP_CTR.jpg)
![Adrenal neuroblastoma[5]](/index.php/File:120px-Adrenal_Neuroblastoma_HP_CTR.jpg)
![Adrenal neuroblastoma[5]](/index.php/File:120px-Adrenal_Neuroblastoma_HP2_CTR.jpg)
![Adrenal neuroblastoma[5]](/index.php/File:120px-Adrenal_Neuroblastoma_M2P_PA.JPG)
![Adrenal neuroblastoma[5]](/index.php/File:120px-Adrenal_Neuroblastoma_MP_CTR.jpg)
![Adrenal neuroblastoma[5]](/index.php/File:120px-Adrenal_Neuroblastoma_MP_PA.JPG)
![Adrenal neuroblastoma[5]](/index.php/File:120px-Adrenal_Neuroblastoma_MP3_PA.JPG)
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015
- ↑ 2.0 2.1 2.2 2.3 Neuroblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Neuroblastoma Accessed on October, 5 2015
- ↑ 3.0 3.1 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
- ↑ Colon NC, Chung DH (2011). "Neuroblastoma". Adv Pediatr. 58 (1): 297–311. doi:10.1016/j.yapd.2011.03.011. PMC 3668791. PMID 21736987.
- ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015
- ↑ 6.0 6.1 6.2 Neuroblastoma, Ganglioneuroblastoma and Ganglioneuroma. Stanford Medicine Surgical Pathology Criteria(2015) http://surgpathcriteria.stanford.edu/srbc/neuroblastoma-ganglioneuroblastoma-ganglioneuroma/ Accessed on October, 5 2015
- ↑ Shimada H, Umehara S, Monobe Y, Hachitanda Y, Nakagawa A, Goto S; et al. (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): 2451–61. PMID 11745303.