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

• 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 syndrome (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 microscopic pathology 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)