How Do You Know if Your Child Has Neuroblastoma?

Neuroblastoma is a type of cancer that occurs most often in infants and young children and starts when some very early forms of nerve cells, most often found in an embryo or fetus, grow out of control.  

Neuroblastoma is the most common cancer in infants less than 1 year old and accounts for about 6% of all cancers in children. Nearly 90% of cases of neuroblastoma are diagnosed by the time a child is 5 years, and the disease is rare in people over the age of 10 years.

Neuroblastoma can cause different signs and symptoms in a child depending on where the tumor is, how large it is, how far it has spread (metastasized), and if the tumor produces hormones. 

Symptoms of neuroblastoma caused by the main tumor may include:

• Lump or swelling in the child's abdomen, pelvis, or neck that is not painful
• Not wanting to eat or feeling full
• Abdominal pain
• Swelling of the legs 
• Swelling of the scrotum in boys
• Problems with bowel movements or urination
• Enlarged abdomen 

Symptoms of neuroblastoma caused by tumors in the neck or chest may include:

• A hard, painless lump
• Swelling in the face, neck, arms, and upper chest (sometimes with a bluish-red skin color)
• Headaches
• Dizziness
• Changes in consciousness 
• Coughing 
• Trouble breathing or swallowing
• Drooping eyelid and small pupil in one eye
• Problems being able to feel or move parts of the body

Symptoms of neuroblastoma caused by cancer that has spread (metastasized) to other parts of the body may include:

• Enlarged lymph nodes, often felt as lumps under the skin, especially in the neck, above the collarbone, under the arm, or in the groin
• Bone pain
• Limping/refusal to walk
• Weakness, numbness, or paralysis in the arms or legs 
• Lumps or bumps in the skin that may appear blue 
• Bulging eyes 
• Bruising around the eyes
• Bumps under the scalp
• Weight loss 
• Low red blood cells, white blood cells, or blood platelets
• Tiredness
• Irritability
• Weakness
• Frequent infections
• Excess bruising or bleeding from small cuts or scrapes
• Loss of clotting factors in the blood that results in a high risk of serious bleeding (consumption coagulopathy) that can be life threatening
• Blue or purple bumps that look like small blueberries on the skin
• Enlarged liver felt as a mass on the right side of the belly 
• Difficulty breathing 

Symptoms of neuroblastoma caused by hormones from the tumor (called paraneoplastic syndromes) may include:

• Constant watery diarrhea
• Fever
• High blood pressure (causing irritability)
• Rapid heartbeat
• Reddening (flushing) of the skin
• Sweating
• “Dancing eyes, dancing feet” (called opsoclonus-myoclonus-ataxia syndrome) (rare)
• Irregular, rapid eye movements (opsoclonus)
• Twitch-like muscle spasms (myoclonus)
• Loss of coordination when standing or walking (ataxia)
• Trouble speaking

The causes of most neuroblastomas are unknown but they are believed to develop from an early form of a nerve cell (called a neuroblast), found in the fetus, that grows abnormally due to a genetic mutation. The cause of the genetic mutation is unknown.

In rare cases, neuroblastoma is caused by an inherited change in a specific gene (the ALK gene, a protein coding gene). Hereditary neuroblastoma accounts for only 1% to 2% of cases of neuroblastoma. 

Risk factors for developing neuroblastoma include: 

• Age
  • Most common in very young children, and very rare in people over the age of 10 years
• Heredity
  • While most neuroblastomas are not inherited, about 1% to 2% of children inherit an increased risk of developing neuroblastoma from a parent
• Having birth defects (congenital anomalies)

Neuroblastoma is diagnosed with a physical examination, patient history, and tests such as: 

• Blood and urine catecholamine tests
  • Blood cell counts
  • Liver and kidney function
  • Electrolyte
  • Urinalysis (urine test) 
• Imaging tests
  • Ultrasound (sonogram)
  • Magnetic resonance imaging (MRI) scan
  • Computed tomography (CT or CAT) scan
  • CT-guided needle biopsy
  • Meta-iodobenzylguanidine (MIBG) scan
  • Bone scan
  • Positron emission tomography (PET) scan
  • X-rays
• Biopsies
  • Incisional (open or surgical) biopsy
  • Needle (closed) biopsy 
  • Bone marrow aspiration and biopsy

Treatment for neuroblastoma may involve one or more of the following: 

• Surgery
  • Surgical (open) biopsy to get a sample of the tumor for diagnosis and to determine treatment
  • Removal the entire tumor if possible
  • Chemotherapy may be used before surgery to shrink the tumor and make it easier to remove (neoadjuvant chemotherapy) 
• Chemotherapy usually includes a combination of drugs such as:
  • Cyclophosphamide
  • Cisplatin or carboplatin
  • Vincristine
  • Doxorubicin (Adriamycin)
  • Etoposide
  • Topotecan
  • Busulfan and melphalan (sometimes used during stem cell transplant)
  • Thiotepa (sometimes used during stem cell transplant)
• Radiation therapy 
  • External beam radiation therapy
  • Radioisotope based radiation
• High-dose chemotherapy/radiation therapy and stem cell transplant
  • Often used in children with high-risk neuroblastoma who are unlikely to be cured with other treatments
  • Before the stem cell transplant 5 months of intense chemotherapy is given 
• Retinoid therapy 
  • 13-cis-retinoic acid (isotretinoin) is used to reduce the risk of the cancer recurring after high-dose chemotherapy and stem cell transplant
• Immunotherapy 
  • Anti-GD2 monoclonal antibodies
    • Dinutuximab (Unituxin) given together with cytokines (immune system hormones) such as GM-CSF and interleukin-2 (IL-2) 
    • Naxitamab (Danyelza) given together with the cytokine GM-CSF