Pediatric neuroblastoma

- 3rd most common pediatric tumor after leukemia and primary brain

- originates from "neuroblasts" - essentially precursor neural crest cells, which make multipotential progenitor cells that give rise to the peripheral nervous system including dorsal root ganglia, the enteric nervous system, sympathetic chain, pigment cells, Schwann cells, adrenal medullary cells, cells of the craniofacial skeleton (including odontoblasts) -- within the brain, neural crest cells form nerve sheaths of cranial nerves 5/7/9/10, the optic vesicle (i.e. may eye structures like iris/cornea, as well as skeletal muscle that attach the eye to the skull), otic capsule/inner ear
- you can derive a neuroblastoma anywhere you have any of the above cells; most common is adrenal medulla in the abdomen, and along paraspinal sympathetic ganglia.
- depending on the degree of differentiation of the tumor stem cell, the resultant tumor will be  neuroblastoma, ganglioneuroblastoma, or ganglioneuroma in order of least to most differentiated. as you would expect, prognosis is better the more differentiated the origin cell line.
- paragangliomas i.e are tumors derived from chromaffin cells, which are differentiated neural crest

- 50-70% are metastatic by the time they are found - liver, lymph nodes, bone. This is because neural crest cells are undergo an epithelial to mesenchymal transition early on in their development,  and thus acquire enhanced migratory abilities and decreased requirements for intercellular contact. this allows the cells to leave the neural tube and go about the body.

- CNS mets are not very common, but when they happen, its nearly always to bone - calvaria and skull base. Especially at junction of lateral orbital wall and greater wing of sphenoid. They can also metastasize to dura and will typically expand along exterior aspect of dura between dura and bone. They have a characteristic "sunburst" appearance --- ddx also includes ewing's

- as treatment for neuroblastoma improves, the rate of CNS involvement is increasing - this is likely because kids are living longer with the disease, and the chemo that they get that achieves tumor control may not have good BBB penetration, which means the CNS may be a sanctuary site for the tumor. 

- very rarely will metastasize to brain parenchyma, into ventricles, or leptomeningeally - parenchymal mets often will bleed or be calcified, qualities which are rare among pediatric brain tumors 

- Imaging - they show a sunburst/hairlike projections of bone into tumor -- this is from rapid, aggressive growth of tumor causing a periosteal reaction. Other tumors that do the hair thing - ewing's sarcoma (used to be believed that they had a neuroblast origin cell - actually its a fusion gene expressed in mesenchymal stem cells), other sarcoma, lymphoma/solid leukemia

Helpful papers: 

https://www.ncbi.nlm.nih.gov/pubmed/19353343 - Calvarial lesions: a radiological approach to diagnosis.

https://www.ncbi.nlm.nih.gov/pubmed/20410407 - Imaging of metastatic CNS neuroblastoma.