Contents
What is Neuroblastoma?
Neuroblastoma is a tumor that usually affects children up to 15 years of age. The tumor is solid and develops in the abdomen, chest or pelvis, although it originates in the adrenal glands. This type of cancer affects more than 7 out of 100 children under the age of 15.
In children under one year of age, this is the most common tumor, since almost 97% of neuroblastomas occur because they are embryonic malignancies of the nervous system.
As the disease is rare in children over 15 years old, when discovered, most of the time, it has already metastasized to other organs, bones and marrow in the body. Almost 70% of children are diagnosed with neuroblastoma up to 5 years of age, since, in most cases, the tumor has been present since birth.
Causes
It is not possible to state the initial cause of the genetic mutation in which the neuroblastoma occurs. However, it is known that this mutation allows cells to multiply and grow more and more, getting out of control, causing the tumor.
In the case of neuroblastoma, cancer begins in neuroblasts, immature cells that are part of the development of the fetus. These cells become nerve cells, fibrous and those that make up the adrenal glands. When the child is born, in most cases, neuroblasts are mature, but a part of them can be found in newborns. In most of these events, neuroblasts mature or disappear, but in others, it becomes a tumor or neuroblastoma.
Risk factors
Since there is no specific cause, it is difficult to determine any risk factor. But it is possible to state that when there is a family history of the disease, the risk of developing neuroblastoma becomes greater.
There are still other factors that can make us understand the disease more. In the United States, 650 cases of neuroblastoma are diagnosed each year. In developed countries with high incomes, such as those in Europe and North America, there is a higher incidence of occurrences than in underdeveloped countries.
Children are the most affected by the disease, about 83%. 55% of children between 1 and 5 years of age and 40% of children over 5 years of age. Boys have a slightly higher incidence of neuroblastoma than girls. The ratio is 1.2 boys for every 1 girl.
The survival rate of 5-year-old children increased from 24% (1960-1963) to 55% (1985-1994). This is due to better detection of tumors in nursing patients.
Symptoms
Symptoms usually vary according to the part of the body that has been affected with the disease.
Neuroblastoma no tórax
- Pains in the region;
- Wheezing in the chest;
- Eye changes, including drooping eyelids and uneven pupil sizes.
Neuroblastoma no abdômen
- Abdominal pain;
- Appearance of a hard mass under the skin;
- Swelling in the legs;
- Changes in bowel habits, such as frequent diarrhea.
Other known symptoms
- Fever;
- Back pain;
- Dark circles under the eyes;
- Pieces of tissue under the skin;
- Unexpected weight loss;
- Bone pain;
- Eyeballs that appear to be shifted forward.
Symptoms caused by the tumor
The main symptoms are bloating and weight loss due to the child’s lack of nutrition. Usually the swelling occurs in the belly and abdomen, but it can spread to the legs and testicles.
Urinary and intestinal problems can occur if the pressure of the tumor affects the urine or intestine due to pressure in the abdomen.
When the tumor is in the chest, the swelling can go up to the face, neck, arm and also in the upper part of the chest. Dizziness , headaches and doubts about awareness may arise. Coughing and difficulty in breathing can occur due to the pressure that happens in the throat and trachea.
The same pressure that occurs in the chest, can also pressure some nerves and cause the eyelid to dilate or fall.
Signs or symptoms caused by the spread of the tumor
Six out of ten cases of neuroblastoma have already spread the tumor to other organs when they were diagnosed.
If the tumor is spread to the lymph nodes, swelling can occur. Lymph nodes can be felt as nodules in the neck, armpit, groin and on top of the collarbone.
In most cases, the neuroblastoma reaches the bones, causing pain in the child, and in some of them, even walking becomes a problem. Weakness, numbness or paralysis in the upper or lower limbs can occur if the tumor presses on the spinal cord. If this happens, the production of white blood cells, platelets and red cells can be decreased, and symptoms such as bleeding from small cuts, irritability, scratches, weakness and tiredness can occur.
Signs or symptoms caused by hormones released by neuroblastoma
This is one of the few tumors in children capable of releasing hormones. They can cause problems in organs and tissues in which the disease is unrelated. This is known as paraneoplastic syndromes and its characteristics are:
- Fast heartbeat;
- Fever;
- Redness of the skin;
- Constant diarrhea;
- High blood pressure;
- Sweating.
Diagnosis
The specialist doctors to treat neuroblastoma are:
- Hematologist;
- Oncologist;
- Gastroenterologist;
- Pediatrician;
- Pulmonologist;
- Pediatric surgeon;
- Neurologist.
The best thing to do is that, as soon as the symptoms appear, the parents see the doctor so that he can analyze the changes in the body and in the behavior, in addition to the habits.
In order for the diagnosis to be made more quickly, parents may notice some symptoms that have been recurring, such as, for example, if there have been changes in the child’s routine.
For the doctor to be able to give the diagnosis, he needs to perform tests, such as:
- Physical exam;
- Urine analysis;
- Blood test;
- X-ray;
- Magnetic resonance imaging;
- Computed tomography;
- Ultrasound.
Stages of the disease
The stages of the disease are able to describe the type of cancer, where it is located, whether it affects other organs or not and the aspect it has. It is essential to have this information about the stages, so the doctor can diagnose the disease and indicate the treatment.
The result is given through exams, whether they are imaging, physical or biopsy of the tumor and its tissues.
The stages of neuroblastoma are carried out by the INSS (International Staging System for Neuroblastoma). Thus, the stages are characterized in:
Stage 1
It is the smallest stage of the disease and the tumor is in the same place where it originated. The cancer is visible and removed by surgery, and the lymph nodes that are in the tumor may or may not contain neuroblastoma cells. The lymph nodes present outside the tumor are not affected by the disease.
Stage 2A
The tumor is also in the same place where it originated, but because it is not fully visible, it may not be completely removed in surgery. The lymph nodes that are in the tumor may or may not contain neuroblastoma cells, but the lymph nodes present outside the tumor are not affected with the disease.
Stage 2B
The tumor is located on one side of the body and may or may not be completely removed during surgery. The lymph nodes outside the vicinity of the tumor contain neuroblastoma cells, but the cancer has not spread to other lymph nodes that are positioned further away.
Stage 3
The tumor is not spread to the other organs, but it can occur:
- The tumor may still be located where it originated and on only one side of the body. It has already spread to lymph nodes on the contralateral side of the body.
- The cancer is in the middle of the body and invades both sides and cannot be removed completely by surgery.
- The cancer cannot be completely removed by surgery and has already affected the spine, and may or may not spread to nearby lymph nodes.
Stage 4
The tumor was spread to other organs, bones, distant lymph nodes, to the skin and also to the bone marrow, but even so it is not yet characterized to be in the 4S stage.
Stage 4S
Children at this stage are less than 1 year old. The tumor is found on only one side, but it may have spread to the lymph nodes on that side. The cancer may have spread to the skin, bone marrow and liver. Despite this, less than 10% of the cells that make up the marrow are cancerous.
Relapse
Although not part of the stages of the disease, the term is used to characterize the return of the disease, which can occur in the same place where it started or in any other part of the human body.
INSS for the risk group
The INSS for the risk group is similar to the INSS, but it does not use the results of the surgery to define the stage of the disease, but the result of imaging tests, biopsies and others.
The INRGSS (International Neuroblastoma Staging System for Risk Groups) uses IDRFs (Image Defined Risk Factors) to discover how complex the removal of the tumor can become. This includes the growth of the tumor in the vicinity of a vital organ or around important blood vessels.
Neuroblastomas can be characterized in 4 stages by INGRSS:
M
A tumor that has spread to other organs, with the exception of tumors in the MS stage.
MS
Metastatic cancer in children under 1 and a half years old. The spread can be made to the skin, liver and / or bone marrow. Less than 10% of the marrow cells can be cancerous and MIBG scintigraphy (a form of diagnosis of neuroblastomas and heart disease) does not show the spread of the disease to the bone marrow and / or bones.
L1
The cancer did not grow in the originated site and the vital structures are not involved by the list of risk factors defined by image. The tumor is in only one location, such as the chest, abdomen or neck.
L2
The cancer did not grow far from where it originated, but it has at least one risk factor that could be defined by imaging.
Prognostic markers
These markers are characterized by identifying whether the child’s prognosis for curing the disease is better, or not, than would be predicted only by the first stages mentioned at the beginning of the topic. There are some factors that can influence these predictions, such as:
- Tumor histology;
- Age;
- Amplification of the MYCN gene;
- Ploidia do DNA.
Tumor histology
It is characterized by how the tumor cells are viewed under the microscope. Cancer, which can be visualized with the appearance of tissues and cells, has a better prognosis and a favorable histology. Tumors that are abnormal tend to have a worse prognosis.
Age
Children between a year and a year and a half are more likely to be cured than older children.
Amplification of the MYCN Gene
MYCN is an oncogene (a gene related to the appearance of tumors) that helps regulate cell growth. If there are changes in this oncogene, the cells can multiply and divide quickly, just like cancer cells. Children with neuroblastoma with this characteristic may have a worse diagnosis than other children.
Ploidia do DNA
The amount of DNA in each cell can be called the ploidy index and can be measured by special laboratory tests, such as image cytometry or flow cytometry. The cells with the highest amounts of DNA are called hyperdiploids. Those with normal cells are diploids. Children who have hyperdiploids can be associated with new stages of the disease, responding better to treatment and the prognosis is better than diploid cells.
Others
There are still other types of markers, which are not used to determine risk groups, but can influence the decision on how to treat neuroblastoma. They can be known as:
- Chromosomal changes;
- Neurotrophin receptors;
- Serum markers.
Chromosomal changes
The changes occur because chromosome 1 and 11 undergo changes, making the prognosis worse, and this is due to the fact that, in these lost parts of the chromosome, there could be suppression of the tumors. A part of chromosome 17 is related to a worse prognosis, probably because there is an oncogene in it.
Neurotrophin receptors
These receptors are substances that are on the surface of nerve cells and in some neuroblastoma cells. Generally, cells recognize neurotrophins (a chemical that helps nerve cells mature). Neuroblastomas with more than one type of neurotrophin receptor, especially the nerve growth factor receptor, called TRkA, may have a better prognosis.
Serum markers
The blood levels of some substances can be used to predict the prognosis. Children with a high level of ferritin possibly have a worse prognosis. Specific enolase is produced by some types of normal cells, such as neuroblastoma cells. The increase in the levels of these substances is related to a worse prognosis in children. A substance on the surface of certain nerve cells, known as ganglioside GD2, is usually increased in the blood of children with neuroblastoma. GD2 can also be important in the treatment of the disease.
Does Neuroblastoma have a cure?
Yes. However, for the cure to be complete, the patient will need to be in constant treatment until the disease is completely removed.
Neuroblastoma Treatment
There are some types of treatment that can be done. The specialist doctor will analyze which is the most suitable for you and for your stage of the disease. The most used by specialists are:
Chemotherapy
It is the indicated alternative for cancer cells to be eliminated through medication.
Radiotherapy
When radiation is used to kill cancer cells.
Surgery
In some cases, only the removal of the organ or a specific part of the body can be the solution for the child to live healthy.
Immunotherapy
When drugs are indicated to directly target neuroblastoma cells.
Bone marrow transplant
A cell transplant can be performed where the stem cells are collected, frozen and stored before chemotherapy, and are returned back to the patient after treatment.
Some side effects can appear even after years of treatment. Changes in kidney and heart function can arise, as well as problems with fertility and hearing.
Complications / Prognosis
There are three main complications that can occur in patients with neuroblastoma:
- Pain and even paralysis occur if there is compression of the spinal cord.
- The cancer can spread elsewhere in the body, to the bone marrow, liver, skin and lymph nodes.
- Paraneoplastic syndromes can also arise and irritate tissues that were previously healthy.
Patients who survive after a long time of treatment, two out of three, suffer effects caused by it. One of the biggest symptoms is hearing loss, thyroid disorder, learning difficulties, reduced growth and increased risk of secondary cancers.
Neuroblastoma prognosis / Living with the problem
Patients who live with the problem will have to be under constant treatment, until the disease is cured. Some of the patients will be undergoing chemotherapy, others in radiotherapy, this depends on the stage of the disease of each patient.
Prevention
There are no ways to prevent the disease, since it is a tumor and, in many cases, the baby is born with the disease.
It is necessary to be attentive, because even after the treatment and cure of the disease, it can recur later.
Reading and learning about health issues can be important to alleviate some symptoms or even improve the disease, but it is essential to consult the specialist doctor, as it is he who will give accuracy to your treatment.
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