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 cells can 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

[10bout 1–2% of cases run in families and have been linked to specific gene mutations. Familial neuroblastoma in some cases is caused by rare germline mutations in the anaplastic lymphoma kinase (ALK) gene.[13] Germline mutations in the PHOX2A or KIF1B gene have been implicated in familial neuroblastoma as well. MYCN oncogene amplification within the tumor is a common finding in neuroblastoma. The degree of amplification shows a bimodal distribution: either 3- to 10-fold, or 100- to 300-fold. The presence of this mutation is highly correlated to advanced stages of disease.[14] Duplicated segments of the LMO1 gene within neuroblastoma tumor cells have been shown to increase the risk of developing an aggressive form of the cancer.[15] Neuroblastoma has been linked to copy-number variation within the NBPF10 gene, which results in the 1q21.1 deletion syndrome or 1q21.1 duplication syndrome.[16]