Neuroblastoma is type of cancer that develops from immature nerve cells called neuroblasts. Neuroblasts are immature nerve cells found in unborn babies. When these immature nerve cells fail to grow as normal into maturity, they can change and start to grow out of control which will result into cancer specifically known as neuroblastoma.
Sometimes babies can be born with some clusters of immature nerve cells (neuroblasts) which will eventually mature into nerve cells. But if these clusters fail to mature and start to grow, they will result into development of tumor.
Neuroblastoma originates from nerve cells outside the brain in infants and young children. It can develop from nerve tissues near the spine but it often develop from the adrenal glands. Anatomically, the adrenal glands are on top of kidneys. These glands produce hormones that help to control body functions, such as blood pressure and heart rate.
Normally neuroblastoma affect infants and children of less than 5years. It is not common among children of more than 10 years. Number of boys who develop this type of cancer is slightly higher than that of girls. It can develop before baby is born and be detected before birth but in most cases it is found while it has already spread to other organs in the body.
Risk factors for neuroblastoma
For other cancer that affects adults, cancers are normally linked with their environmental factors and life style such as exposure to harmful chemicals and being obese. Developing cancer due to such factors, it takes a lot of time (years), But this is not the case for neuroblastoma because an infant or unborn child has not been exposed to such environment for long period and some are not even exposed to such environment but they develop neuroblastoma. The risk factor for neuroblastoma includes the following;
• Family history of the disease. Although at very low percentage, some neuroblastoma cases are in families with the history of the disease. This is linked to the inheritance of gene mutations that increase the probability of developing neuroblastoma. Some researches indicate that, neuroblastoma have been found in families with parent having congenital central hypoventilation syndrome (CCHS), which is a unique breathing disorder.
• Genetic mutation without family history of the disease. There are some cases of neuroblastoma that result from some genetic mutationthat occur to unborn baby during development and these mutations may influence development of neuroblastoma. Division and growth of cells is controlled by DNA inside the cell, so if DNA is destructed, it can lead to development of abnormal cells that may lead to cancer. When this happens to neuroblasts, it can result to development of neuroblastoma.
• Age. Since neuroblastoma affects infants and young children, then being at that age increases possibility of being affected.
Prevention of neuroblastoma
To prevent something you need to know the specific cause of it. For neuroblastoma, there is no known specific cause of the disease so preventing neuroblastoma is currently very difficult. If the risk factors of this type of cancer could be environmental related or lifestyle related, it could have been possible to reduce the risk of developing the disease, but since even risk factors cannot be avoided (controlled), then even reducing the risk of developing the disease is not possible.
Early detection and screening
Screening is the process of running some tests to someone with no signs or symptoms of a certain disease with the intention verifying presence or absence of that disease. One of the importance of screening is detection of the disease while still at an early stage so as to improve the outcome of treatment of the disease.
For neuroblastoma, screening has not proved to be helping because at some point screening may result to early detection of tumors that wouldn’t have normally been harmful. Most of these tumors would probably not cause any harm to health than their respective early treatment options. But due to such early detection, it can frighten parents and can lead to unnecessary tests and surgery in children whose tumors would have gone away or matured on their own if left alone.
That is why many experts do not recommend screening to children who are not under increased risk. But to those at high risk of developing of neuroblastoma, screening can be done by using urine tests and ultrasound.
Ultrasound is also used detect common birth defects before birth (prenatal) and during these tests, sometimes even cancer can be detected.
Signs and symptoms of neuroblastoma
Signs and symptoms of neuroblastoma vary depending on size of tumor, location of tumor and how far has the cancer spread. Many of the signs and symptoms of neuroblastoma resemble to those caused by other health reasons so the only way to find out is to take your child to your doctor. Signs and symptoms of neuroblastoma include the following;
• A lump in the abdomen. If a tumor is in the abdomen, you may feel there is swelling in the abdomen. And if a child can speak she/he will complain of feeling full most of the time.
• Bone pain. This normally happen if tumor has spread to the bones.
• Changes in eyes. This may include eyes barging out, constriction of pupil and change in iris colour, having droopy eyelids and having dark circles under the eye.
• Tumors in the chest can cause chest pain. This may also affect breathing and having persistent cough.
• Having back pain. Tumor near vertebral column and spinal cord can cause back pain, numbness, weakness and paralysis to the legs.
• Anaemia, excessive breeding and prone to infection. This may happen if tumor has spread to bones responsible for production of blood cells hence there is low red blood cells which lead to anaemia, platelets which cause excessive bleeding when injured and prone to infection due to low white blood count.
• Abnormal heart rate and blood pressure. This may happen if cancer has affected adrenal gland.
• Effects from hormones released by tumor. These effects include fever, diarrhea, high blood pressure, sweating, and rapid heartbeat.
Those are some of the signs and symptoms, when a parent finds any abnormal swelling under the skin it is important to see a doctor for more checkup and not to just ignore.
Diagnosis of neuroblastoma
Medical diagnosis simply means identification of nature of an illness by elimination of the symptoms. Normally people don`t go to hospital knowing they have cancer but during diagnostic procedures is when doctors detect the disease.
Following suspicion of the disease, doctors normally run combination of tests to determine whether there are cancerous cells in the body or not and if there are cancer cells, how far have they spread. Along with thorough medical history and physical examination, doctors normally use combination of the following tests to diagnose cancer.
Laboratory tests are important in ruling out other conditions and confirming diagnosis. For cancer diagnosis laboratory tests normally include blood tests, urine tests, tumor markers and other body fluids tests.
• Blood tests. Blood tests help to reveal level of different substances in the blood which will help doctors to know if there is anything wrong in the body. From blood tests doctors can see complete blood count which indicates number, size and maturity of blood cells. Also from the blood tests doctors can analyze if kidney and liver are working properly.
• Urine tests. Urine tests (urinalysis) involve laboratory examination of urine to check presence of blood, proteins, and other substances such as drugs. For instance blood in the urine may be an indication of benign condition, infection or other health problem.
• Tumor markers. These are biomarkers (proteins) that can be produced by both cancer cells and normal body cells in response to cancer. Tumor markers are released into the blood or urine. Although studies are still conducted to determine role of these markers in diagnosing cancer because sometimes people with benign condition will have elevated level of these proteins. Also not all tumors have their markers and some markers are not specific to one type of tumor.
• Other body fluids. Despite being rarely used, sometimes body fluids can be tested in the lab during diagnosis of cancer. For instance the use of cerebral spinal fluid (CSF) and pleural fluid. CSF is used in diagnosis of brain tumors while pleural fluid for lung cancer.
Diagnostic imagings involve tests that create pictures of inside the body that help the doctor to see if there is tumor or not. There are several imaging tests used in cancer diagnosis depending on the type and location of cancer suspected. These imaging tests include;
• Computed tomography (CT) scan. CT scan machine is a donut-shaped scanner that uses x-rays to create series of pictures of body organs from different angles. This machine is linked to a computer where those series of pictures taken will be combined to create a 3D- image of inside the body. During the scanning process patient will lie still on the table which will slide into the scanner. In order to get a clear image, sometimes the doctor will inject the patient with a contrast material before scanning. From the images the doctor will be able to differentiate between healthy and unhealthy tissues.
• Magnetic resonance imaging (MRI). MRI is an imaging technique that uses powerful magnet and radio waves to take series of pictures of body organs and create a 3D image in a computer linked to a machine. Just like in CT, during MRI procedure the patient will lie on a table that will slide into a long round chamber. Also during this procedure the doctor may inject the patient with a contrast material for clear image view.
• X-ray. This is an imaging technique that is uses low dose of radiation to create pictures of inside your body. Technician will position the patient and direct the x-ray beam to the intended part of the body.
• Ultrasound. Ultrasound is a diagnostic imaging procedure that uses high energy sound waves to produce images of organs inside the body. During the examination, a patient will lie on the table while the technician will slowly move a device called transducer on the skin over the part of the body that is being examined.
• PET scan. Positron emission tomography (PET) scan is an imaging test that uses radioactive glucose to create 3-D images of areas inside the body. Radioactive glucose is used for this test because cancer cells tend to absorb more glucose than normal body cells, so the scan will show which areas of the body has more glucose than others. Before the scan, doctor will inject the patient with tracer called radioactive glucose then during imaging the patient will be asked to lie on the table that will be moving back and forth through the scanner.
• Bone scan. Bone scan is used to examine bones. When it comes to cancer, bone scan is used for diagnosis of bone cancer or cancer that has metastasized into the bones. Before the test, patient will be injected with small amount of radioactive material that tends to collect more on abnormal parts of the bones. Then pictures that will be taken by a scan will indicate the distribution of those radioactive materials in the bones throughout the body.
Biopsy is a diagnostic procedure that involves removing a tissue sample from the body and examines it under microscope in the laboratory. Examination in the laboratory is normally done by a pathologist who will check if the cells in the tissue are cancerous or not. In most cancer cases, biopsy is considered to be the confirmatory test. Depending on the location and type of cancer, biopsy can be obtained in different ways. Some of them include;
• Using needle. By using a thin needle, doctors can draw same tissue or fluid for examination under microscope. This method can be used to draw some fluid (spinal tap), bone marrow (bone marrow aspiration), blood or small amount of tumor from the suspected organ such as liver and breast (fine needle aspiration).
• Surgery. Abnormal tissue samples are obtained while the doctor is performing the surgery. Tissues are then sent to the lab for examination during the surgery. If the surgeon removes just a portion of abnormal area it is called incisional biopsy while when the entire tumor (abnormal site) is removed it is called excisional biopsy.
• Using endoscope. Endoscope is a thin, lighted tube with a camera (focusing telescope) at the end. It is used for viewing inside the body through natural openings like mouth and anus. During an examination if the doctor sees any abnormal tissue, then endoscope can also be used to take sample for that tissue. There are different kinds of endoscopy exams depending on the site of the body being examined. Some of the exams include colonoscopy (for rectum and colon), bronchoscopy (for trachea, bronchi and lungs) and esophagogastroduodenoscopy EGD (for esophagus, stomach and duodenum)
In addition to physical examination and medical history, some of the tests involved in diagnosing neuroblastoma include, urine tests where doctors look for presence of homovalinic acid (HVA), ultrasound, MRI scan, X-ray, CT- Scan, biopsy, bone marrow aspiration, bone scan and MIBG scan.
Meta-iodobenzylguanine (MIBG) is a chemical with small amount of radioactive iodine. This chemical is injected into the body and travel around the body through blood. This chemical has ability to attach at neuroblastoma at any part of the body. After certain time interval, picture will be taken by using a special camera to see where this radioactive iodine picks up. This test is preferred by most doctors as standard test for neuroblastoma.
Staging of neuroblastoma
Staging is a way that doctors use to describe the size, location and the extent of spread of cancer. Diagnostic results help doctors to stage cancer into different groupings. By knowing your stage, doctors are able to determine which treatment option is more beneficial for you.
For neuroblastoma there are different staging systems that are used worldwide but in Tanzania the most used system is international neuroblastoma staging system (INSS). The INSS is a clinical, radiographic, and surgical appraisal of children with neuroblastoma.
The system combines many of the most important diagnostic criteria from each of the staging systems and includes initial distribution (spread) and surgical resectability of the tumor. Stages of INSS can be described as follows;
• Stage 1.Characterized by a localized tumor that can be removed completely by surgery. Lymph nodes attached to the tumor and removed together with primary tumor may be affected by cancer, (test cancer positive.
• Stage 2A. Characterized by localized tumor that cannot be removed completely by surgery. Nearby lymph nodes are not involved (test negative).
• Stage 2B.Characterized by a localized tumor that may or may not be completely removed by surgery. Nearby lymph nodes are involved (affected by cancer).
• Stage 3. Tumor cannot be removed by surgery. There is reginal lymph node involvement. Tumor has spread to other areas near the tumor but no other parts of the body involved.
• Stage 4. Tumor has spread to distant lymph nodes. There is involvement of other organs such as liver, bones, bone morrow, skin and/or other organs.
• Stage 4s. Characterized by localized tumor (as in stage 1,2A and 2B) with spread limited to only liver, skin and /or bone marrow. This stage is only for infants under the 12 months.
Children cancers are not common, so even their management is normally slightly different from the way adult cancers are managed. This is why children cancers are treated in a specialized centers that deals with management of children cancers.
Children with cancers and their families have special needs different to those of adults. To meet those needs they are treated in specialized centers (children cancer centers). The centers have teams of specialists for children cancers who understand the differences between cancers in adults and children
Making treatment decision
Since a person with cancer is a child then treatment decision has to be made by parents. With the help of a child`s doctor, parents have to take time to understand about the condition their child, treatment options and possible outcome of treatment. Parents are free to ask if there is anything they do not understand clearly for example any possible side effects of treatments.
Normally when making treatment plan, when it comes to treatment options, doctors normally provide treatment options basing on the following;
• Stage of the disease
• General health condition of a child
• Possible side effects
• Parent`s preference
Taking part in clinical trial
Clinical trials are new drugs or modified mode of treatment or new treatment combination for cases like yours that are to be tested if they are effective to be used as standard care treatment option or not. Your child`s doctor or nurse will discuss with you if you want your child to take part in clinical trial.
Over the years, trials have improved treatments and led to better outcomes to children cancers. It may be helpful to talk with another specialist to get second opinion before letting your child take part in clinical trials. And if your child decides to take part, he/she can also withdraw at any time.
Treatment of neuroblastoma requires team of doctors, nurses and other health care professionals.Also pediatric cancer centers normally have additional support services for children and their families, such as dietitians, child life specialists, physical and occupational therapists, social workers, and counselors. Treatment options for neuroblastoma include the following;
Surgery is the treatment option that involves removing tumor and surrounding soft tissues by operation. Surgery is performed by pediatric surgical oncologist. Neuroblastoma case which is localized (not spread to other areas and parts of the body), surgery can remove the entire tumor. But in case tumor has spread, surgery is will be for removing the tumor as much as possible.
Side effects of surgery
Side effects of surgery will depend on the site where surgery has been performed and extent of surgery. Some of the common side effects include the following;
• Excess bleeding
• Risk of infection
• Reaction from anesthesia
Chemotherapy is the use of drugs to destroy cancer cells or stop its growth. This treatment option is given by specialized doctor known as pediatric oncologist. Chemotherapy is the most often used treatment option because most cases of neuroblastoma are diagnosed while they have already spread. Drugs can be given through injections into veins (intravenously) or muscles or may be given orally as pills or capsule.
Chemotherapy can also be used in combination with surgery (before surgery in order to shrink tumor or after surgery so as to remove remaining cancer cells after surgery).
Side effects of chemotherapy
Side effects of chemotherapy depend on type of drug used and amount of dose given. Most of these side effects go away on their own following completion of treatment although they can also be relieved by medication if they become too severe.
• Hair loss
• Loss of appetite
• Nausea and vomiting
• Easily bruising and bleeding
• Increased risk of infection
• Mouth sores
Radiation therapy is the use of high energy X-rays or other radiation particles to destroy cancer cells. A doctor who has specialized in treatment of children cancers by using radiation therapy is called pediatric radiation oncologist.
Neuroblastoma is normally treated by using external beam radiation therapy that involve directing beam of radiation to the treatment site from the machine outside the body.
Side effects of radiation therapy
Side effects of radiation therapy of neuroblastoma depend on the location of tumor and dose given. Some of the possible side effects include the following;
• Skin reactions
• Loose bowel movement
• Loss of hair