Sandbox:patho2

# Pathogenesis
- 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. 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 may demonstrate spontaneous regression from an undifferentiated state to a completely benign cellular state.

# Genetics
- Development of neuroblasotma is the result of multiple genetic mutations.
- 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:
- Neurofibromatosis type 1 (von Recklinghausen disease)
- Beckwith-Wiedemann syndrome
- DiGeorge syndrome
- Hirschsprung disease

# Gross Pathology
- On gross pathology, a  well defined, bulky, and tan colored mass is a characteristic finding of neuroblastoma.
- 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:
- 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: schwannian stroma rich group and a schwannian stroma poor group as illustrated below:
- 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:
- Undifferentiated neruoblastoma
- Poorly differentiated neuroblastoma
- Differentiating neuroblastoma
- The table below summarizes the differnces between the three histological subtypes of neurublastoma:

# Gallery
- Illustrated below is a series of microscopic images demonstrating neuroblastoma:
- Adrenal neuroblastoma
- Adrenal neuroblastoma
- Adrenal neuroblastoma
- Adrenal neuroblastoma
- Adrenal neuroblastoma
- Adrenal neuroblastoma
- Adrenal neuroblastoma
- Adrenal neuroblastoma
- Adrenal neuroblastoma
-  Jump up to: 1.0 1.1 1.2 Neuroblastoma. Wikipedia(2015)  Accessed on October, 5 2015
-  Jump up to: 2.0 2.1 2.2 2.3 Neuroblastoma. Radiopaedia(2015)  Accessed on October, 5 2015
-  Jump up to: 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11  Neuroblastoma. Libre Pathology(2015) #Neuroblastoma Accessed on October, 5 2015
-  Jump up to: 4.0 4.1 4.2 Neuroblastoma, Ganglioneuroblastoma and Ganglioneuroma. Stanford Medicine Surgical Pathology Criteria(2015) / 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): 245161. PMID 11745303.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}