Neuroblastoma is the most common malignant (cancerous) extracranial (outside the cranium) solid tumor of childhood. It develops from the tissues that form the sympathetic nervous system. This system controls involuntary body functions (such as breathing, heart rate, digestion, blood pressure, eye reflexes).

The tumor usually begins in the nerve tissues of the adrenal gland (above the kidney). It may also start in nerve tissues of the neck, chest or pelvis.

Although often present at birth, it generally isn’t found until the tumor grows and compresses (squeezes) surrounding organs.

Cancer cells can metastasize (spread) quickly to other areas of the body, such as lymph nodes, liver, lungs, bones, the central nervous system and bone marrow. The cells will spread in almost 70% of children diagnosed with neuroblastoma. There can be more than one tumor present. The primary tumor is the first that develops and is usually the source from which the tumor spreads to other locations.

About 650 children in the United States are diagnosed with this tumor each year, mostly before age 5. Neuroblastoma occurs slightly more often in males than in females.

Neuroblastoma Causes

Most neuroblastoma cells have abnormalities involving a particular chromosome (chromosome number 1). The more malignant tumors often have multiple copies of the oncogene MYCN, a tumor-specific protein found in the tumor cells. A number of other genetic abnormalities may also be present.

The chance of the disease being present in a sibling of a child with neuroblastoma is about 1%.

Research is ongoing to learn if maternal exposure to toxic substances during pregnancy, environmental pollutants or radiation could be linked to the development of the disease.

Neuroblastoma Symptoms

The symptoms of neuroblastoma are very different depending on the size, location and spread of the tumor. The most common symptoms include:

• An abdominal (belly) mass, either felt during an exam or seen as a swollen abdomen
• Uncontrolled eye movement such as rapid eye movements or crossed eyes
• Swelling and bruising around the eyes
• Changes in peeing due to the tumor squeezing the kidney or bladder
• Pain, limping or weakness
• Easy bleeding or bruising if bone marrow is involved
• Paralysis and weakness
• Diarrhea
• Fever
• Dizziness, lightheadedness
• Shortness of breath
• Fatigue
• High blood pressure on exam
• Increased heart rate on exam

Neuroblastoma Diagnosis

In some cases, a fetal ultrasound can detect neuroblastoma before birth. A medical and physical examination must be done, and a number of diagnostic tests and procedures must be performed. These may include:

• Blood tests -- These should include a complete blood count, blood chemistries and kidney and liver function tests.
• Test of urine (pee) and plasma catecholamine excretion levels -- These levels are usually higher than normal due to tumor production.
• Multiple imaging studies -- Imaging can see the tumor and show the extent and location of any spread.
• Ultrasonography -- This imaging technique uses high-frequency sound waves and a computer to create images of blood vessels, tissues and organs. It looks at internal organs as they function and assesses blood flow through various vessels. It is often the first test to screen for the presence of an abdominal tumor.
• Computerized tomography scan (also called CT or CAT scan) -- This procedure combines X-rays and computer technology to produce cross-sectional images of the body. A CT scan shows details on any part of the body, including bones, muscles, fat and organs. CT scans are more detailed than standard X-rays.
• Magnetic resonance imaging (MRI) -- This provides detailed images of soft tissues to help identify and stage the tumor.
• Bone scans -- These are X-rays of the bone that are taken after an injected dye is absorbed by bone tissue. Bone scans are used to detect tumors and bone abnormalities.
• MIBG scans -- This scan highlights the location of the tumors in a person’s body using a special substance.
• Bone marrow biopsy and / or aspiration -- Experts can look at the number, size and maturity of blood cells and / or abnormal cells.
• Biopsy of primary tumor and / or metastatic lesions.

Neuroblastoma Stages

Diagnosing neuroblastoma involves staging and classifying the disease so treatment can be determined and a prognosis can be made. The stages of neuroblastoma, according to the International Neuroblastoma Staging System (INSS), are described below:

• Stage 1 involves a tumor that does not cross the midline of the body. The tumor is completely resected (removed) and has not spread to other areas of the body. The lymph nodes on the same side of the body as the tumor do not have cancer cells present.
• Stage 2A involves a tumor that does not cross the midline of the body. Though all visible tumor is removed, tumor removal is incomplete. This stage of tumor has not spread to other areas of the body. Lymph nodes on the same side as the tumor do not have tumor cells present.
• Stage 2B involves a tumor that may or may not be completely removed, and it has not spread to other areas of the body. Lymph nodes on the same side as the tumor have tumor cells present. Those on the opposite side do not.
• Stage 3 involves a tumor that crosses the midline of the body and is not completely removed. Lymph nodes may or may not have tumor cells present. This stage also includes a tumor that does not cross the midline but has lymph nodes on the opposite side of the body with tumor cells.
• Stage 4 involves a tumor that has spread to lymph nodes far from the primary tumor, bone marrow, liver, skin, and/or other organs (except as defined in stage 4S).
• Stage 4S involves a tumor that has metastasized (spread) to the liver, skin and/or bone marrow. It has not spread to the bones. This stage generally occurs in children younger than 1 year of age.

Neuroblastoma Treatment

Decisions about treatment plans should be made by parents and the child's providers together. The treatment chosen should consider a number of factors:

• The child's age, medical history, and overall health
• Extent of the disease
• The child's tolerance for specific medications, procedures, or therapies

Treatment includes a wide range of approaches. Depending on each child’s situation, one or more of these approaches may be used:

• Surgery to remove the primary tumor (the main or first tumor, if there are more than one)
• Chemotherapy
• Radiation therapy
• Blood and marrow transplant
• Immunotherapy

Each treatment has both benefits and side effects. The child’s doctors will closely monitor side effects and give supportive care. Antibiotics may be prescribed to prevent or treat infections.

New methods are continually being discovered to improve treatment approaches and decrease side effects.

Surgical Treatment of Neuroblastoma

The goal of surgery is to remove as much of the tumor as possible. However, partial removal may be needed if the tumor is unable to be separated from vital structures (such as blood vessels or nerves). The remaining tumor can then be treated through other methods like chemotherapy or radiation. Determining whether surgery is the best treatment option versus other treatments like chemotherapy depends on several factors. These include:

Information About the Tumor

• Location—Where is it in the body? Is it in the abdomen, chest, neck, or somewhere else?
• Size—How big is the tumor? Larger tumors might be more challenging to remove.
• Nearby organs—Is it close to organs or blood vessels?

How Far the Cancer has Spread

• Cancer stage—Has it stayed in one place (localized) or spread to other areas (advanced)?
• Other tumors—Are there additional tumors in other parts of the body that might need attention?

The Child's Health

• Overall condition—How strong and healthy is the child? Can they safely undergo a major surgery?
• Age—Very young children might need special considerations during surgery.
• Previous treatments—If the child had chemotherapy first, how did they respond? This can influence the timing and approach of surgery.

The Overall Treatment Plan

• Timing—When is the best time for surgery in relation to other treatments like chemotherapy or radiation?
• Goals—Is the aim to remove the entire tumor or take a sample for further testing?
• Future treatments—How might surgery affect or be affected by planned follow-up care?

What Happens During Surgery?

Before surgery begins, your child will be placed under general anesthesia. This means they’ll be asleep throughout the procedure and not feel pain. Once the anesthesia takes effect, the surgeon will make an incision (cut) to access the tumor.

The type of incision will depend on the location of the neuroblastoma and the extent of the cancer. In some cases, a laparoscopic or robotic procedure may be used. Laparoscopic surgery involves making several small incisions instead of one large one. A thin tube with a camera and surgical instruments is put through these small incisions, allowing the surgeon to operate without making a large cut. A robotic procedure is like a laparoscopic procedure, but a robot is used by the surgeon to improve how well they can see all parts of the tumor.

Depending on the location of the tumor and the extent of the cancer, the surgeon may also need to remove nearby lymph nodes or other tissues. The incision may range from less than an inch to several inches, depending on how much of the tumor needs to be removed.

How Long Will the Surgery Take?

The length of the surgery typically lasts between three to six hours. This can vary based on how complicated the procedure is. The surgeon will give you a specific time frame based on your child’s case.

Hospital Stay and Recovery

After surgery, most children stay in the hospital for several days. The length of the stay depends on the extent of the surgery and how quickly they recover. During this time, the medical team will closely watch your child for signs of infection or complications such as bleeding or damage to nearby organs or nerves. Pain management will be provided to keep them as comfortable as possible.

Enhanced Recovery After Surgery (ERAS) Protocol

The recovery time after surgery will vary depending on the type of surgery, the tumor size, and the child's overall health. Enhanced Recovery After Surgery (ERAS) is a special set of steps taken to help patients recover faster. It includes things like getting them ready before surgery, using special techniques during surgery, and taking good care of them afterward. This plan can help patients feel better sooner and go home from the hospital faster. This has resulted in:

• Significant improvement in recovery time
• Reduced length of hospital stays
• Quicker return to normal eating habits

Neuroblastoma Prognosis

Prognosis and long-term survival can vary greatly. Prompt medical attention and aggressive therapy are key, and prognosis depends upon a wide range of issues:

• Extent of disease
• Size and location of the tumor
• Presence or absence of metastases (spread)
• Type of pathology
• Biological factors
• Response of the tumor to therapy
• Child's tolerance of specific medications, procedures and therapies

Depending on these factors, children are placed in a category of low, medium or high risk. Care and treatment differ for each risk group. With current therapies, low-risk patients (stages 1 and 2) have more than a 90% long-term survival rate, regardless of age.

In higher-risk patients with more advanced stages of disease, survival rates are much lower. Treatments include chemotherapy, radiotherapy and blood and marrow transplants. Despite treatment, the more advanced stages of neuroblastoma have a much less optimistic prognosis.

Follow-Up Care

Continuous follow-up care is crucial. Regular monitoring helps track a child’s response to treatment, potential effects, and any disease recurrence. Ongoing care allows healthcare providers to adjust treatment plans as needed.

Cincinnati Children's Commitment to Neuroblastoma Care

Cincinnati Children's is an international referral center for the treatment of children and young adults with high-risk and relapsed neuroblastoma. Our faculty members lead national efforts to develop new targeted therapies, immunological approaches and stem cell transplantation.

We have a number of active treatment regimens for relapsed neuroblastoma. Learn more about our research studies.