What is neuroblastoma?

Neuroblastoma, one of the most common solid tumors in childhood, is the tumor most often found in children with opsoclonus-myoclonus syndrome (OMS).

Who gets neuroblastoma?

The average age of children with neuroblastoma is about 18 months, but young infants, even newborns can have the tumor. About two-thirds of all cases occur before the age of 5 years. Neuroblastoma grows in the abdomen or chest, either in the adrenal glands or near the spinal cord. It can also be found in the pelvis or neck. There is also a second peak of tumor incidence that affects older children.

The number of new cases of neuroblastoma each year has been estimated at 1100. Only a few percent, possibly 100 to 200 children, exhibit a paraneoplastic syndrome affecting the nervous system. Neuroblastoma may be much more common than realized because it is often small and difficult to detect and also has a tendency to involute and regress on its own with the help of the immune system.

Is there more than one type of neuroblastoma?

The pathologist determines whether the tumor is a neuroblastoma, ganglioneuroblastoma, or ganglioneuroma. Some tumors are a composite of these different types. Ganglioneuroblastomas are more commonly found in the chest. Tumors from children with OMS contain more white blood cells (TILs) than tumors without associated OMS, suggesting the immune system is more active in those cases.

Is neuroblastoma genetic?

Tumor chromosomal abnormalities, such as the delection of the short arm of chromosome 1 (1p) and gain in the long arm of chromosome 17 (71q) occur in some neuroblastomas. Tumor DNA may be decreased (aneuploidy) and the N-myc oncogene (a cancer gene) may be amplified (increased in expression). Each of these features, which children with OMS usually lack, carries a poorer prognosis. Beyond the tumor genetics, we cannot yet predict which child will have a neuroblastoma or develop OMS. In a small subgroup of patients, neuroblastoma is familial.

What comes first, the tumor or OMS?

Usually the tumor is detected because of the OMS, so detection may occur earlier in children with OMS than without it. Sometimes the tumor is found before the OMS, so OMS remains a possibility in any child who has had neuroblastoma surgery.

How can the tumor be detected?

Body scans, such as CT, MRI, and MIBG, Octreoscan, allow neuroblastoma to be detected. To prevent false negative results, more than one type of scan should be done.

The above photograph shows a normal MIBG scan. Presence of the tracer (dark areas) in the liver and bladder is normal. The child has been given a drug to prevent uptake by the thyroid gland, which otherwise occurs. The photo below is taken from an abnormal MIBG scan. Note the uptake by the tumor near the adrenal gland.

(Figure coming soon)

Elevated urinary catecholamines (chemicals secreted by the tumor) and serum ferritin and neuron-specific enolase, and the finding of certain autoantibodies in the blood or spinal fluid should prompt a thorough investigation for neuroblastoma. If a tumor is not found, we often repeat the search at 6 month intervals for a year or more in the presence of these positive markers or if the child is doing poorly and not responding as expected to treatment. Because calcium is often deposited in the tumor, the finding of a fleck of calcium on the scan can alert the radiologist to the possibility of a tumor.

The above photo from a scan through the chest shows a large neuroblastoma on the left and over the the spine. The child's back is at the bottom of the photo and the front of the chest would be above the top of the photo.

What is the prognosis for survival?

In children with OMS, the prognosis for survival is excellent. Tumors associated with OMS tend to be more mature--the cells bear more similarity to brain cells--and less inclined to be aggressive or invasive. Metastatic disease is rare in pediatric OMS.

In the absence of OMS, 70 % of neuroblastomas are metastatic at the time of diagnosis. Prognosis depends on the child's age at diagnosis, clinical stage of disease, and regional lymph node involvement. Children with localized tumor and infants younger than 1 year of age generally have a good prognosis for survival. Neuroblastoma in adolescents carries a worse long-term prognosis.

How is the tumor "staged"?

Staging refers to identifying if the tumor has spread to other parts of the body. There are at least three different staging systems (Children's Cancer Group, Pediatric Oncology Group, International Staging). In the International Neuroblastoma Staging System (INSS), the classification is:

  • Stage I--localized and surgically respectable, no spread
  • Stage II--localized but not completely resectable
    A--no tumor in nearby lymph node microscopically examined
    B--tumor in nearby lymph node microscopically examined
  • Stage III--regional spread to surrounding tissue or lymphs nodes
  • Stage IV--disseminated to lymph nodes or bone, liver, skin, or other organs
  • Stage IVS--"special"situation treated differently: the tumor has spread only to the liver, skin, or bone marrow (minimal involvement), but is in the place where it began

How can the tumor be treated?

Treatment for neuroblastoma depends on the stage of the tumor and other factors, such as patient age. The four types of treatment to remove, shrink, or kill the tumor are:

  • Surgery (remove by one or more operations)
  • Chemotherapy (anti-cancer drugs given as pills or into a vein)
  • Radiation therapy (high-dose x-rays)
  • Bone marrow transplantation (after very high doses of radiation or chemotherapy)

They are usually used in combination involving two or three approaches. More invasive tumors may require bone marrow transplantation. When tumor removal is unfeasible because of size or location, radiation therapy and chemotherapy can be used to shrink the tumor. Tumor biopsy is helpful in these cases to determine how aggressive the tumor is. However, for children with OMS, surgery plus chemotherapy is usually sufficient in eradicating the tumor.

How soon should treatment begin?

Treatment of OMS should not be delayed. As soon as OMS is diagnosed, immunotherapy should be given, even before tumor removal. Surgical resection of the tumor may not help the symptoms of OMS; other treatment is usually necessary. Because chemotherapy is also immunotherapy, it should work to treat the tumor and the OMS.

Once the tumor is removed, parents often trade one set of worries for another. The problem of OMS grows in importance. To optimize and expedite therapy, both a pediatric neurologist and oncologist should be involved in the care. We also need to keep the primary care provider in the loop early, as there are many long-term care issues. The goal of treatment should always be to determine how close to normal the child can be.


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