Neuroblastoma is the most common solid tumor, other than brain tumors, in children.  The great majority of cases affect young children before school age, with some cases beginning before birth and unusual cases first arising as late as adolescence.  No environmental factors are known to cause neuroblastoma, and neuroblastoma rarely runs in families.

Neuroblastoma tends to behave quite differently in infants as compared to children over 12 – 18 months.  Infants usually develop a form of neuroblastoma that is less aggressive and can mature into a benign tumor.  Children over 12 – 18 months usually develop a more aggressive form of neuroblastoma that often invades vital structures and may spread throughout the body.

Neuroblastoma Symptoms

• Abdominal swelling
• An abdominal mass
• A neck mass
• Horner’s syndrome (unequal pupils, a drooping eyelid, and decreased sweating on one side of the face) associated with a chest mass.
• Back pain with bowel and bladder dysfunction
• A bulging eye with bruising
• Bone pain
• Anemia and bleeding
• Bluish skin nodules (in infants)
• Severe and persistent diarrhea
• Dancing eyes and uncontrollable muscle twitching

Neuroblastoma Diagnostic Testing and Surgery

After a careful history and physical examination, we typically obtain:

• CT scan of the body
• MRI scan if there is concern about the spine
• Nuclear medicine scans
• Urine testing for substances produced by neuroblastoma cells
• Blood counts and tests of kidney and liver function
• Bone marrow tests
• Cardiac echo and EKG, as a baseline
• Consultation with a surgeon and a radiation oncologist

The surgeon may be able to remove the tumor immediately.  However, if the tumor is invading vital structures, the surgeon will initially take only enough tissue from the tumor to make the diagnosis and test the biology of the tumor.  Surgery to remove the tumor would then be delayed until chemotherapy can be given to shrink the tumor.

To manage neuroblastoma, it is important both to see the appearance under the microscope and to assess molecular features of the tumor.  In addition to the histology, amplification of the MYCN gene, DNA content, chromosomal changes, and expression of certain master genes affect the behavior of the tumor and how we treat it.

Neuroblastoma Staging

There is an international staging system for neuroblastoma:

• Stage 1 – A single tumor that is removed without any visible tumor remaining
• Stage 2A – A single tumor that is not completely removed, but has not spread to lymph nodes
• Stage 2B – A single tumor that has spread to regional lymph nodes on the same side of the body
• Stage 3 – An unresectable tumor that crosses the midline of the body or involving lymph nodes on the other side of the body
• Stage 4 – A tumor with distant spread
• Stage 4S – A special category for infants under 1 year old with primary tumors that do not cross the midline, with spread limited to skin, liver, and limited marrow involvement

Neuroblastoma Therapy and Prognosis

Neuroblastoma is classified as low, intermediate, or high risk on the basis of age, stage, and tumor biologic features.
For low-risk neuroblastoma, resection alone may be the only treatment needed.  For intermediate-risk neuroblastoma, a moderate course of chemotherapy would be given in addition to surgery.  For high-risk neuroblastoma, the treatment includes aggressive chemotherapy, resection, high-dose chemotherapy with stem cell rescue (autologous bone marrow transplantation), treatment with cis-retinoic acid (Accutane) to cause maturation of the tumor, and immunotherapy.  Radiation therapy is often helpful in addition to chemotherapy and surgery.

Treatment of neuroblastoma is an area of very active clinical research.  Goals include reducing side effects of treatment of intermediate-risk disease and increasing the cure rate of high-risk disease.

Therapy for Relapse

If neuroblastoma recurs after resection only, or after modest initial therapy, treatment may again involve surgery, radiation therapy, and chemotherapy, perhaps including autologous stem cell rescue.

Treatment of recurrent neuroblastoma is an important area of investigation.  New chemotherapy agents, molecules that deliver radiation to the tumor, and immune therapies are being considered.

Long-term Evaluation

After treatment is complete, patients are followed for signs or symptoms of recurrent neuroblastoma and for late effects of their particular treatment.  The aggressive treatment for high-risk disease can affect growth, hearing, heart and kidney function, and fertility. Patients are also at risk to develop other forms of cancer later.  Detecting and treating potential problems early is important to maximize health and the quality of survivorship.