Neuroblastoma is a rare cancer of the sympathetic nervous system, a nerve network throughout the body that carries messages from the brain.

Solid, cancerous tumors that manifest as a lump or mass in the abdomen or around the spinal cord in the chest, neck, or pelvis. This type of cancer is found almost exclusively in young children under 5 years old (approximately)

Neuroblastoma can form before the baby is born and can sometimes be detected during a prenatal ultrasound examination. Most often, however, Neuroblastoma are detected only after the cancer has spread to other parts of the body such as the lymph nodes, liver, lungs, bones, and bone marrow.

Spontaneous regression of neuroblastoma in infants under approximately 2 years old is still a rare phenomenon, but it is frequently observed and is still being studied and researched to fully understand why it happens, to hopefully find a cure.

As with most cancers, the cause of Neuroblastoma is unknown and despite successful treatments that have been developed, a cure is yet to be found

There are different types of Neuroblastoma, according to what areas and parts of the body and organs are affected and each type requires a different way to treat it.

When treatment has been successful in completely eliminating the Neuroblastoma or making it inactive we call this status NED - which stands for No Evidence of Disease. This is the equivalent of Remission. Unlike a lot of other types of cancer, where 3 years of remission makes the status All Clear, there is always the risk of Neuroblastoma relapse which has even occurred over 20 years after first diagnosis and successful treatment.

As with other cancers, Neuroblastoma is not infectious and cannot be passed on to other people.

Symptoms

Diagnosis of neuroblastoma can be complicated because its symptoms mimic so many other diseases.

Symptoms vary according to areas of the body affected. The child may have just a few symptoms, all or none.

• A lump or mass in the abdomen, chest, neck, or pelvis
• Protruding eyes and dark circles under the eyes,: black eyes, a droopy eyelid, vision problems, or changes in the colour of the iris
• Chest pain, difficulty breathing, or persistent cough
• Unexplained aches, pain or numbness in the back, pelvis or legs, limping, inability to stand, stumbling, clumbsiness
• Fever, anaemia, and high blood pressure, irritability, listlessness, lack of energy
• Loss of appetite, nausea, weight loss, stomach pain, constipation, difficulty urinating

Most malignant solid tumors, such as neuroblastoma, produce swelling or pain. The symptoms of neuroblastoma vary because the location of the tumor determines the symptoms. Most neuroblastomas are found in the abdomen. Parents may feel a lump or mass while dressing or bathing their child. A tumor in the abdomen may cause the child to feel "full", experience stomach pain, loss of appetite, constipation and difficulty urinating. Other primary sites can include the head/neck or chest. Tumors located in the head and neck may present as a mass. The child may have "black eyes", much like bruises, an eyelid that droops, or a pupil that doesn't constrict properly. Chest tumors may cause pain, difficulty breathing, or a persistent cough. Tumors that grow in spinal areas may cause the child to have pain, numbness of the lower extremities, constipation and difficulty urinating.

In the majority of cases 73, neuroblastoma has already spread to areas outside of the original site at the time of diagnosis.

Statistics

UK - Neuroblastoma is the third commonest tumour of childhood in the UK, having an incidence rate of 1 in 10 500. Incidence and mortality rates were calculated for the whole of the United Kingdom for a period of at least 10 years. The effects of age, stage and regional health authority at diagnosis, year of birth, year of diagnosis and sex on the incidence and mortality rates were determined. Incidence was found to vary with age and stage at diagnosis, and there was a significant interaction between age and stage. A difference in incidence between the sexes was also discovered. Mortality was found to vary with age and stage at diagnosis, athough no interaction was found.

USA - Neuroblastoma is the third most common type of childhood cancer in the United States, and accounts for 7.3% of all childhood cancers and 50% of cancers in infants. Approximately 650 new cases of Neuroblastoma are diagnosed each year in the United States. Almost 90% of Neuroblastoma are diagnosed by age 6. Overall, about 50% to 55% of children with Neuroblastoma can be cured, and 69% of children live at least five years after a Neuroblastoma diagnosis. The cure rate for children with high-risk cancer is less than 30%.

Diagnosis

Only a pathologist familiar with neuroblastoma can distinguish the difference (and neuroblastoma is rare). Other characteristics of the suspected neuroblastoma cells can be studied by immunohistochemistry and electron microscopy. In about 90% of cases of neuroblastoma, elevated levels of catecholamines or its metabolites are found in the urine or blood. Catecholamines and its metabolites include dopamine, homovanillic acid (HVA), and/or vanillylmandelic acid (VMA).

Another way to detect neuroblastoma is the MIBG scan (meta-iodobenzylguanidine), but it doesn't diagnose the disease in 100% of the cases.

It works like this: MIBG is taken up by sympathetic neurons, and is a functioning analog of the neurotransmitter norepinephrine. When it is radio-ionated with I-131 (a radioactive iodine), it is a very good radiopharmaceutical for diagnosis of this disease.

To make a definite diagnosis of neuroblastoma and enter a clinical trial, certain criteria have to be met. A pathologic diagnosis from actual tumour tissue OR bone marrow contains tumour cells AND urine contains increased urinary catecholamine metabolites. (HVA and VMA).

What? - The Histology and Cytogenetics (The Science Part!!)

Your child's cancer cells exhibit a defined "histology", or profile of molecular and biological characteristics. These features are often indicators of treatment success and some of them direct treatment decisions to more or less intensive protocols.

The characteristics below are known to be important in neuroblastoma:

N-myc amplification. N-myc is an oncogene, or a gene (DNA sequence) that turns on cell growth. Amplification means that more than one copy is found in the cell.

Hyperploidy. A normal cell has 46 chromosomes. Cancer cells often have extra chromosomes, and this is termed "hyperploidy".

VMA/HVA ratio. This is the ratio of catecholamine metabolites found in the urine.

NSE. Neuron-specific enolase, a serum marker. This is an enzyme specific to the sympathetic nervous cells from which the neuroblastoma derives.

Serum ferritin. An accurate estimate of the body's iron stores; a serum marker.

LDH. Lactate dehydrogenase (LDH) is a group of enzymes that have a similar biological activity; a serum marker.

Gd2. Presence of this serum marker (a sialic acid-containing glycosphingolipid) may play a role in faster tumour progression.

CD44 antigen. The presence of this antigen indicates a particular developmental stage of the neuroblastoma cells.

TRK-A protooncogene. Again, oncogenes turn on cell growth.

1p deletion. Deletion on chromosome 1.

Risk Factors

Neuroblastoma most commonly occurs in children without any family history of Neuroblastoma. The cause is not known. Uncommonly, a child who has one or more family members who developed the disease will be diagnosed with Neuroblastoma. Children with an inherited predisposition tend to develop the disease, on average, nine to 13 months earlier than children who develop non-inherited cases of Neuroblastoma. In children who have a family history of Neuroblastoma, the disease may occur in two or more organs. Neuroblastoma occurs more often in boys than in girls