Neuroblastoma pathophysiology: Difference between revisions

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Revision as of 23:51, 7 October 2015

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

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:

Bone (most common)
Liver (diffuse infiltration that is more common in stage 4S nueroblastoma)
Lungs and pleura (present as discrete nodules or diffuse consolidation)
Brain and meninges (dural metastases can be diffuse of nodular)

Genetics

Development of neuroblasotma is the result of multiple genetic mutations.^[1]^[2]
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 chromosome 1
KIF1B gene on chromosome 1
ALK gene on chromosome 2
LMO1 gene on chromosome 11
PHOX2A gene on chromosome 11

MYCN oncogene amplification is a common finding among neuroblastoma patients.

Associated Conditions

Neuroblastoma is associated with a number of syndromes that include:^[1]^[2]

Neurofibromatosis type 1 (von Recklinghausen disease)
Beckwith-Wiedemann syndrome
DiGeorge syndrome
Hirschsprung disease
Hutchinson syndrome
Pepper syndrome

Gross Pathology

On gross pathology, a well defined, bulky, and tan colored mass is a characteristic finding of neuroblastoma.^[1]^[4]
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:^[4]

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:^[4]^[5]^[6]

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:^[5]

Undifferentiated neruoblastoma
Poorly differentiated neuroblastoma
Differentiating neuroblastoma

The table below summarizes the differnces between the three histological subtypes of neurublastoma:^[5]

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^[4]
Adrenal neuroblastoma^[4]
Adrenal neuroblastoma^[4]
Adrenal neuroblastoma^[4]
Adrenal neuroblastoma^[4]
Adrenal neuroblastoma^[4]
Adrenal neuroblastoma^[4]
Adrenal neuroblastoma^[4]
Adrenal neuroblastoma^[4]

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015
↑ ^2.0 ^2.1 ^2.2 Neuroblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/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
↑ ^4.00 ^4.01 ^4.02 ^4.03 ^4.04 ^4.05 ^4.06 ^4.07 ^4.08 ^4.09 ^4.10 ^4.11 Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015
↑ ^5.0 ^5.1 ^5.2 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.

Template:WikiDoc Sources

[radio-1] 1.0 ^1.1 ^1.2 ^1.3 Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015

[wiki-2] 2.0 ^2.1 ^2.2 Neuroblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Neuroblastoma Accessed on October, 5 2015

[gov-3] 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

[patho-4] 4.00 ^4.01 ^4.02 ^4.03 ^4.04 ^4.05 ^4.06 ^4.07 ^4.08 ^4.09 ^4.10 ^4.11 Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015

[Stanford-5] 5.0 ^5.1 ^5.2 Neuroblastoma, Ganglioneuroblastoma and Ganglioneuroma. Stanford Medicine Surgical Pathology Criteria(2015) http://surgpathcriteria.stanford.edu/srbc/neuroblastoma-ganglioneuroblastoma-ganglioneuroma/ Accessed on October, 5 2015

[pmid11745303-6] 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.

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@@ Line 3: / Line 3: @@
 {{CMG}} {{AE}}{{HL}}
 ==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>
+* 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 is frequently observed along the sympathetic nervous system structures. Specific sites may include:
 :* Adrenal glands (35% of the cases)