Neuroblastoma

What is neuroblastoma?

From: MedlinePlus, National Library of Medicine

Neuroblastoma is a type of cancer that forms in nerve cells called neuroblasts. Neuroblasts are immature nerve tissue. They normally turn into working nerve cells. But in neuroblastoma, they form a tumor.

Neuroblastoma usually begins in the adrenal glands. You have two adrenal glands, one on top of each kidney. The adrenal glands make important hormones that help control heart rate, blood pressure, blood glucose (blood sugar), and the way the body reacts to stress. Neuroblastoma may also begin in the neck, chest or spinal cord.

What causes neuroblastoma?

From: MedlinePlus, National Library of Medicine

Neuroblastoma is caused by changes in your genes. Gene changes also called gene variants or mutations. In most cases, the cause of the mutation is unknown. In some other cases, the mutation is passed from the parent to the child.

What are the symptoms of neuroblastoma?

From: MedlinePlus, National Library of Medicine

Neuroblastoma often begins in early childhood. Sometimes it begins before a child is born.The most common symptoms are caused by the tumor pressing on nearby tissues as it grows or by cancer spreading to the bone.They include:

• A lump in the abdomen, neck, or chest
• Bulging eyes
• Dark circles around the eyes
• Bone pain
• Swollen stomach and trouble breathing in babies
• Painless, bluish lumps under the skin in babies
• Weakness or paralysis (loss of ability to move a body part)

How is neuroblastoma diagnosed?

From: MedlinePlus, National Library of Medicine

To diagnose neuroblastoma, your child's health care provider will do various tests and procedures, which may include:

• A medical history.
• A neurological exam.
• Imaging tests, such as x-rays, a CT scan, an ultrasound, an MRI, or an MIBG scan. In an MIBG scan, a small amount of a radioactive substance is injected into a vein. It travels through the bloodstream and attaches itself to any neuroblastoma cells. A scanner detects the cells.
• Blood and urine tests.
• Biopsy, in which a sample of tissue is removed and examined under a microscope.
• Bone marrow aspiration and biopsy, in which bone marrow, blood, and a small piece of bone are removed for testing.

What are the treatments for neuroblastoma?

From: MedlinePlus, National Library of Medicine

The treatments for neuroblastoma include:

• Observation, also called watchful waiting, is where the health care provider does not give any treatments until your child's signs or symptoms appear or change.
• Surgery
• Radiation therapy.
• Chemotherapy.
• High-dose chemotherapy and radiation therapy with stem cell rescue. Your child will get high doses of chemotherapy and radiation. This kills the cancer cells, but it also kills healthy cells. So your child will get a stem cell transplant, usually of his or her own cells collected earlier. This helps to replace the healthy cells that were lost.
• Iodine 131-MIBG therapy, a treatment with radioactive iodine. The radioactive iodine collects in neuroblastoma cells and kills them with the radiation that is given off.
• Targeted therapy, which uses drugs or other substances that attack specific cancer cells with less harm to normal cells.

Genetic causes described in the linked summary

From: MedlinePlus Genetics

Neuroblastoma and other cancers occur when a buildup of genetic mutations in critical genes—those that control cell growth and division (proliferation) or maturation (differentiation)—allow cells to grow and divide uncontrollably to form a tumor. In most cases, these genetic changes are acquired during a person's lifetime and are called somatic mutations. Somatic mutations are present only in certain cells and are not inherited. When neuroblastoma is associated with somatic mutations, it is called sporadic neuroblastoma. It is thought that somatic mutations in at least two genes are required to cause sporadic neuroblastoma. Less commonly, gene mutations that increase the risk of developing cancer can be inherited from a parent. When the mutation associated with neuroblastoma is inherited, the condition is called familial neuroblastoma. Mutations in the ALK and PHOX2B genes have been shown to increase the risk of developing sporadic and familial neuroblastoma. It is likely that there are other genes involved in the formation of neuroblastoma.

Several mutations in the ALK gene are involved in the development of sporadic and familial neuroblastoma. The ALK gene provides instructions for making a protein called ALK receptor tyrosine kinase. Although the specific function of this protein is unknown, it appears to play an important role in cell proliferation. Mutations in the ALK gene result in an abnormal version of ALK receptor tyrosine kinase that is constantly turned on (constitutively activated). Constitutively active ALK receptor tyrosine kinase may induce abnormal proliferation of immature nerve cells and lead to neuroblastoma.

Several mutations in the PHOX2B gene have been identified in sporadic and familial neuroblastoma. The PHOX2B gene is important for the formation and differentiation of nerve cells. Mutations in this gene are believed to interfere with the PHOX2B protein's role in promoting nerve cell differentiation. This disruption of differentiation results in an excess of immature nerve cells and leads to neuroblastoma.

Deletion of certain regions of chromosome 1 and chromosome 11 are associated with neuroblastoma. Researchers believe the deleted regions in these chromosomes could contain a gene that keeps cells from growing and dividing too quickly or in an uncontrolled way, called a tumor suppressor gene. When a tumor suppressor gene is deleted, cancer can occur. The KIF1B gene is a tumor suppressor gene located in the deleted region of chromosome 1, and mutations in this gene have been identified in some people with familial neuroblastoma, indicating it is involved in neuroblastoma development or progression. There are several other possible tumor suppressor genes in the deleted region of chromosome 1. No tumor suppressor genes have been identified in the deleted region of chromosome 11.

Another genetic change found in neuroblastoma is associated with the severity of the disease but not thought to cause it. About 25 percent of people with neuroblastoma have extra copies of the MYCN gene, a phenomenon called gene amplification. It is unknown how amplification of this gene contributes to the aggressive nature of neuroblastoma.

Inheritance described in the linked summary

From: MedlinePlus Genetics

Most people with neuroblastoma have sporadic neuroblastoma, meaning the condition arose from somatic mutations in the body's cells and was not inherited.

About 1 to 2 percent of affected individuals have familial neuroblastoma. This form of the condition has an autosomal dominant inheritance pattern, which means one copy of the altered gene in each cell increases the risk of developing the disorder. However, the inheritance is considered to have incomplete penetrance because not everyone who inherits the altered gene from a parent develops neuroblastoma. Having the altered gene predisposes an individual to develop neuroblastoma, but an additional somatic mutation is probably needed to cause the condition.

Which doctor should you see?

The suggested department for discussing Neuroblastoma is Oncology, with a oncologist and relevant organ specialist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics; Relevant organ specialist / Surgical Oncology as indicated.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Has the exact tumour type been confirmed, and is staging relevant?
• What is the goal of each proposed treatment option?
• How will side effects, daily function and supportive care be addressed?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.