Pediatric Thyroid Cancer
Gland - Guide for parents

BASIC POINTS

• Pediatric thyroid cancer is a disease in which malignant (cancerous) cells form in the thyroid gland.
• Thyroid nodules can be benign or malignant (cancerous).
• Thyroid nodules can be found during a routine medical examination and are usually not cancerous.
• Pediatric thyroid cancer increases in incidence when exposed to radiation or certain genetic syndromes.
• Myeloid thyroid cancer is sometimes caused by a change in a gene that is passed from parent to child.
• Signs of thyroid cancer include swelling or the appearance of a swollen throat.
• For the diagnosis and stage of thyroid cancer are used tests that control the thyroid, the presence of abnormal lymph nodes in the throat and blood tests.
• Certain factors affect the prognosis (chance of recurrence).

Pediatric thyroid cancer is a disease in which malignant (cancerous) cells grow in the thyroid.

The thyroid is a gland located in the lower part of the neck, on its front surface and surrounds the trachea. It has a butterfly shape, with 2 lobes, the right and the left lobe. The isthmus is the part that connects the two lobes. Usually the thyroid gland is not visible when we look at someone’s throat.

Anatomy of the thyroid and parathyroid gland. The thyroid gland is located at the base of the neck and surrounds the trachea. It has a butterfly shape, with the right lobe and left lobe connected by a thin piece of tissue called the isthmus.

The thyroid uses iodine, a metal that is absorbed through food to make hormones. Thyroid hormones do the following:

• They control the physical and mental development of the baby
• They control all the functions of the human body
• They control heart rate, body temperature, how quickly food is converted into energy (metabolism), etc..

Thyroid nodules in children can be adenomas or carcinomas.

Pediatric thyroid cancer – rates of malignancy

There are two types of thyroid nodules:

• Adenomas: Adenomas can grow very large in size and can sometimes produce thyroid hormones. Adenomas are not cancerous, but they can rarely become malignant (cancer). They can then metastasize to the lymph nodes in the throat or lungs.
• Cancerous: There are three main types of thyroid cancer in children
  • Papillary: Papillary thyroid carcinoma is the most common type of thyroid cancer in children. It occurs more often in adolescents. Papillary thyroid carcinoma often consists of more than one nodule in both thyroid lobes. It often spreads to the lymph nodes in the throat and can also spread to the lungs. The prognosis for most patients is very good.
  • Follicular: Follicular carcinoma of the thyroid usually consists of a nodule. It often spreads to the bones and lungs, but rarely spreads to the lymph nodes in the throat. The prognosis for most patients is very good.
  • Myeloid: Myeloid carcinoma of the thyroid is formed by C cells in the thyroid. It is usually associated with an inherited mutation in the RET gene and type 2 multiple endocrine neoplasm syndrome (MEN 2). It occurs most often in children aged 4 years and under and may have spread to other parts of the body at the time of diagnosis. Children with MEN 2 syndrome may also be at risk for pheochromocytoma or hyperparathyroidism.

    Papillary and follicular cancer are sometimes called differentiated thyroid cancer. Myeloid and regenerative thyroid cancer are sometimes called poorly differentiated or undifferentiated thyroid cancer. Regenerative thyroid cancer is very rare in children and is not discussed in this guide.

Thyroid nodules can be found during a routine medical examination and are usually not cancerous.

Your child’s doctor may find a thyroid nodule during a routine medical examination. A nodule can also be found with another test, such as an ultrasound of the child for another reason. Thyroid nodule is an abnormal growth of cells within the thyroid. These nodules may be solid or contain fluid.

When a nodule is found in the thyroid, an ultrasound is performed on the thyroid and lymph nodes in the throat. A fine needle aspiration (FNA) biopsy may be needed to check for signs of cancer. Blood tests can also be done to check the levels of thyroid hormones and anti-thyroid antibodies in the blood. This is done to control other types of thyroid disease.

Thyroid nodules usually do not cause symptoms or need treatment. Sometimes thyroid nodules become so large that it is difficult to swallow or breathe and more tests and treatment are needed. Only one in five thyroid nodules becomes cancerous.

Pediatric thyroid cancer increases in incidence when exposed to radiation or certain genetic syndromes.

Risk factors for childhood thyroid cancer

Anything that increases the risk of developing a disease is called a risk factor. Having a risk factor does not mean that you will develop cancer. Not having risk factors does not mean that you will not get cancer. Talk to your doctor if you think your child may be at risk.

Pediatric thyroid cancer has the following risk factors:

• It is exposed to radiation either from tests or due to some treatment or from the environment.
• Existence of certain genetic syndromes, such as the following:
  • Multiple endocrine neoplasm syndrome type 2A (ΜΕΝ2Α)
  • Multiple endocrine neoplasm syndrome type 2B (MEN2B)
• Existence of a family history of thyroid cancer.
• Existence of thyroiditis (inflammation of the thyroid gland).

Myeloid childhood thyroid cancer is sometimes caused by a change in a gene that is passed from parent to child.

Genes in cells carry hereditary information from parent to child. A specific change in the RET gene that is passed from parent to child (inherited) can cause myeloid thyroid cancer.

There is a genetic test used to check for a mutated gene. The patient is first examined to see if the gene has changed. If the patient has it, other family members should also be tested to see if they also have an increased risk of developing myeloid thyroid cancer. Family members, including young children, who have the altered gene may need to undergo prophylactic thyroidectomy (surgery to remove the thyroid). This can reduce the chance of developing myeloid thyroid cancer.

Pediatric thyroid cancer can have the following signs and symptoms.

Signs and symptoms of childhood thyroid cancer

Thyroid nodules in children usually do not cause symptoms. Sometimes childhood thyroid cancer has no signs or symptoms. These and other signs and symptoms can be caused by either thyroid cancer or other conditions.

Contact your child’s doctor if your child has any of the following:

• A lump in the throat.
• BREATHING PROBLEMS.
• Swallowing problem.
• Hoarseness or change in voice.

Pediatric thyroid cancer is diagnosed and staged with tests that check the thyroid, throat and blood

Diagnostic tests in pediatric thyroid cancer

Pediatric thyroid cancer is diagnosed by testing. After the cancer is diagnosed, more tests are done to see if the cancer cells have spread to nearby areas or other parts of the body. This process is called staging. The test that is done to see if the cancer cells have spread before the tumor is removed by surgery is called preoperative staging. It is important to know if childhood thyroid cancer has spread in order to plan the best treatment.

The following procedures and tests may be performed:

Clinical examination

• Clinical examination and history taking: A physical examination of the child for a general health check-up, including check-ups for signs of illness, such as bumps or swelling in the throat and lymph nodes, and anything else that seems unusual. A history will also be taken of the patient’s health but also of old illnesses and treatments.

Laboratory Tests

• Thyroid function tests: Blood is checked for abnormal levels of thyroid stimulating hormone (TSH). TSH stimulates the release of thyroid hormone and controls how fast thyroid cells grow. Blood can also be tested for high levels of calcitonin (a hormone produced by the thyroid that controls the amount of calcium in the blood).
• Thyroglobulin test: The blood is checked for the amount of thyroglobulin, this is a protein produced by the thyroid gland. Thyroglobulin levels are low or absent when there is normal thyroid function, but may be higher in the presence of thyroid cancer or other conditions.
• RET gene test: A blood or tissue sample is tested for certain changes in the RET gene. This test is done for children who may have myeloid thyroid cancer.
  Illustrative

• Ultrasound: This test can show the size, morphology of a thyroid nodule and whether it is solid or full of fluid (bladder). Ultrasound can also be used to guide a thin suction needle for biopsy. Before each surgery, a complete neck examination is performed with an ultrasound.
• Thyroid scintillation: A small amount of radioactive drug is injected or swallowed. The radioactive element is absorbed by the cells of the thyroid gland. A special camera connected to a computer detects the radiation emitted and takes pictures that show how the thyroid looks and works. It also shows if the cancer has spread beyond the thyroid gland.
• Computed tomography: An examination that shows images that show organs or tissues more clearly and provides more information about their morphology. The child is lying on a table passing through the C / T scanner, which takes x-ray images of the inside of the head and neck.

Axial for thyroid cancer in a child

Gadolinium MRI (MRI): An examination that takes a series of detailed images of areas inside the body, such as the neck and chest. A substance called gadolinium is injected into a vein. Gadolinium is collected around cancer cells so that they appear brighter in the image.

• Chest X-ray: X-ray of the organs and bones inside the chest. X-ray makes an image of the organs inside the body.

Invasive

• Fine needle aspiration biopsy: Using a fine needle we take a sample from the thyroid for examination. The needle is inserted through the skin into the thyroid. Several sections of tissue are removed from different parts of the thyroid. A pathologist examines tissue samples under a microscope to look for cancer cells. Because the type of thyroid cancer can be difficult to diagnose, patients should ask to have the tissue samples checked by a pathologist who has experience in diagnosing thyroid cancer.
• Surgical biopsy: It is the taking of part or all of a thyroid nodule or a thyroid lobe through surgery. This is no longer done often. The material obtained is examined under a microscope by the pathologist to check for signs of cancer. Because the type of thyroid cancer can be difficult to diagnose, patients should ask for biopsy specimens to be checked by a pathologist who has experience in diagnosing thyroid cancer.

Certain factors affect the prognosis of thyroid cancer in children.

The prognosis depends on the following:

• The age of the child at the time of diagnosis.
• The type of thyroid cancer.
• The size of the cancer.
• Whether the tumor has spread to lymph nodes or other parts of the body at the time of diagnosis.
• From whether the cancer was completely removed with surgery.
• The general health of the child.

Pediatric Thyroid Cancer – Stages

BASIC POINTS

• After the cancer is removed with surgery, tests are done to see if the cancer cells remain in the body.
• There are three ways in which cancer spreads throughout the body.
• Cancer can spread from where it started to other parts of the body.

Pediatric thyroid cancer, when removed with surgery, tests are done to see if cancer cells remain in the body.

Tests are done after the thyroid is removed to see if cancer cells remain and to determine if additional treatment is needed. This is called postoperative staging.

The following tests may be done about 12 weeks after surgery:

• Ultrasound
• Thyroglobulin blood test: Thyroglobulin is a protein produced only by the thyroid gland. So when its price goes up it means there is a problem.
• Scintigraphy: Measures the remnant of thyroid tissue that remained after surgical removal of the thyroid gland. It is important that this residue is almost zero. It is an examination that shows how good the operation was.

There are three ways in which childhood thyroid cancer spreads throughout the body.

Cancer can spread through the surrounding tissues, through the lymphatic system and through the blood:

• Neighboring tissues. The cancer has spread from where it started, infecting neighboring organs.
• Lymphatic system. The cancer spreads from where it started entering the lymphatic system. Cancer travels through the lymphatics to other parts of the body.
• Blood. Cancer spreads from where it started to enter the bloodstream. Cancer travels through blood vessels to other parts of the body.

Metastases of thyroid cancer

Pediatric thyroid cancer can spread from where it appeared to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells move away from where they started and travel through the lymphatic system or blood.

• Lymphatic system. The cancer enters the lymphatic system, travels through the lymph vessels and forms a tumor called metastatic, in another part of the body.
• Blood. The cancer enters the bloodstream, travels through the blood vessels and forms a tumor (metastatic tumor) in another part of the body.

Metastatic tumor is the same type of cancer as primary tumor. For example, if thyroid cancer spreads to the lungs, the cancer cells in the lungs are actually thyroid cancer cells. The disease is metastatic thyroid cancer and not lung cancer.

Many cancer deaths occur when the cancer moves from the original tumor and spreads to other tissues and organs. This is called metastatic cancer.

Pediatric thyroid cancer in children – Treatment options

BASIC POINTS

• There are several types of treatment for thyroid cancer patients.
• Children with thyroid cancer should have their treatment planned by a team of doctors who specialize in treating childhood cancer.
• Four types of treatment are used:
  • Surgery
  • Treatment with radioactive iodine
  • Targeted treatment
  • Hormone replacement therapy
• New types of treatment are being tested in clinical trials.
• Treatment for childhood thyroid cancer can cause side effects.
• Patients may want to consider taking part in a clinical trial.
• Patients may undergo clinical examinations before, during or after the start of cancer treatment.
• Follow-up tests may be needed.

There are several treatments for children with thyroid cancer.

Types of treatment for thyroid cancer in children

The main treatment is surgery, this is total thyroidectomy. Sometimes, however, additional treatment is needed. Total thyroidectomy removes the cancer locally, from the point of occurrence. Complementary therapy removes cancer from the whole body. Some treatments are standard (the current treatment used) and some are being tested in clinical trials. A clinical treatment trial is a research study that aims to improve current treatments. However, it also helps to obtain information about new treatments for patients with thyroid cancer. When clinical trials show that a new treatment is better than standard treatment, the new treatment can become standard treatment.

Because cancer in children is rare, participation in a clinical trial should be considered. Some clinical trials are only open to patients who have not started treatment.

Pediatric thyroid cancer should be treated by a team of doctors who specialize in treating childhood cancer.

Pediatric thyroid cancer is treated by a team of doctors

Treatment should be supervised by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other doctors who specialize in treating children with cancer and who specialize in other areas of medicine. This may include the following doctors and other health professionals:

• Pediatrician
• Radiotherapist oncologist
• Oncologist
• Social Worker
• Rehabilitation specialist
• Psychologist

Four types of standard treatment are used in children with thyroid cancer:

Pediatric thyroid cancer – surgery

Pediatric thyroid cancer – minimally invasive thyroidectomy

Surgery is the most common but also the main treatment for thyroid cancer. One of the following types of surgery can be used:

• Total thyroidectomy: Removal of the entire thyroid gland with almost zero residue.
• Almost total thyroidectomy: Removal of the entire gland except for a very small part of the thyroid. In children, total thyroidectomy is usually performed.
• Total thyroidectomy with lymph node dissection: The thyroid gland and lymph nodes are removed from the throat.

Quality of surgery – total thyroidectomy

The patient’s prognosis largely depends on the quality of the surgery. The quality of life of the child also depends on the thyroidectomy. It is very important that the thyroidectomy is EXCELLENT. This means removing the entire thyroid and leaving almost no residue. The cervical lymph nodes should also be removed when needed. Oncology surgeries have inviolable rules. It all depends on the initial operation. These surgeries are demanding and require the specialization and extensive experience of the surgeon. Reoperations bother patients and have a high risk of complications.

All other treatments are complementary. These are done to complete the surgery. They are not made to replace it or to correct it. Radioactive iodine, for example, will destroy any cells that remain after surgery. It is not right to leave a large residue on the grounds that the residue will be destroyed by radioactive iodine. Because if the residue is large then a large dose of radioactive iodine will be needed. If it is even larger, it will take several sessions. While if it is even bigger it will need reoperation. Reoperations bother patients and have a high risk of complications.

Treatment with radioactive iodine

Radioactive Iodine Treatment in Thyroid Cancer

Papillary and follicular thyroid cancer are sometimes treated with radioactive iodine (RAI) therapy. RAI therapy can be given to children after surgery to kill any thyroid cancer cells that have not been removed or to children whose tumor cannot be removed by surgery. RAI therapy is taken orally and the drug is absorbed from any remaining thyroid tissue, including thyroid cancer cells that have spread to other parts of the body. Because only thyroid tissue receives RAI, it destroys only the remaining thyroid tissue and thyroid cancer cells without damaging other tissues. Prior to administration of radioactive iodine therapy, a small test dose is given to determine if the tumor is absorbing iodine.

Targeted treatment

Targeted treatment of thyroid cancer in children

Targeted therapy is a type of treatment that uses drugs or other substances that will attack cancer cells. Targeted treatments usually cause less damage to normal cells than those caused by chemotherapy and radiation.

Tyrosine kinase inhibitor (TKI) therapy is a type of targeted therapy that blocks the signals needed for tumor growth. Larotrectinib is a TKI used to treat children with papillary and follicular cancer. Vandetanib is a TKI used to treat children with advanced myeloid.

Targeted therapy is being studied to treat recurrent childhood thyroid cancer (relapse).

Hormone replacement therapy

Hormones are substances that are essential for the functioning of the human body. These are produced by the endocrine glands and circulate in the bloodstream to regulate various functions. After treatment for thyroid cancer (thyroidectomy), the thyroid is removed, so the body does not have thyroid hormones. These patients are given hormone replacement pills produced by the thyroid gland. They will receive these for the rest of their lives.

New types of treatment are being tested in clinical trials.
Treatment for childhood thyroid cancer can cause side effects.

Cancer side effects that start during or after treatment and can last for months or years. Delayed effects of treating childhood thyroid cancer may include:

• Problems such as changes in the salivary glands, infection or difficulty breathing.
• Changes in mood, emotions, thinking, learning or memory.
• Emergence of other cancers (new types of cancer).

Children with thyroid cancer may want to consider taking part in a clinical trial.

For some patients, participating in a clinical trial may be the best treatment option. Clinical trials are part of the cancer research process. Clinical trials are underway to see if new cancer treatments are safe and effective or better than standard treatments.

Many of the current standard treatments for cancer are based on previous clinical trials. Patients participating in a clinical trial may receive standard treatment or be among the first to receive new treatment.

Patients participating in clinical trials are also helping to improve the way cancer is treated in the future. Even when clinical trials do not lead to effective new therapies, they often answer important questions and help advance research.

Pediatric thyroid cancer can be treated by including the child in clinical trials before, during, or after starting cancer treatment.

Some patients who have not yet been treated take part in some clinical trials. Other trials are looking at treatments for patients whose cancer has not improved. There are also clinical trials where new ways are being tried to stop cancer from recurring or to reduce the side effects of cancer treatment.

Follow-up examinations will be required.

It is not uncommon for thyroid cancer to recur, especially in children under the age of 10 and in people with lymph node cancer. Ultrasound, whole-body scintigraphy, and thyroglobulin measurements can be done from time to time to check if the cancer has come back. Lifelong monitoring of thyroid hormone levels in the blood is required to ensure that the correct dose of hormone replacement is given. Talk to your child’s doctor to find out how often these tests should be done.

Treatment of papillary and follicular thyroid cancer in children

Treatment of newly diagnosed papillary and follicular thyroid cancer in children may include the following:

• Surgery to remove the thyroid gland. Sometimes thyroidectomy is supplemented by removal of the cervical lymph nodes.
• Sometimes radioactive iodine treatment is needed to destroy the thyroid residue.
• Thyroid hormone replacement therapy is given since the thyroid gland is no longer present.

Within 12 weeks of surgery, tests are done to see if thyroid cancer remains in the body. These may include thyroglobulin tests and scintigraphy. Whole-body scintigraphy is done to find areas in the body where thyroid cancer cells have not been removed during surgery and can multiply rapidly.

• Targeted treatment with tyrosine kinase inhibitor (larotrectinib)

Treatment of childhood myeloid thyroid cancer

Treatment for newly diagnosed myeloid thyroid cancer in children may include the following:

• Surgery to remove the cancer. This is usually thyroidectomy and removal of cervical lymph nodes from the central compartment of the cervix, at least.
• Targeted treatment with a tyrosine kinase inhibitor (vandetanib) for cancer that is advanced or has spread to other organs.

Treatment of progressive or recurrent thyroid cancer in childhood

Signs of relapse of thyroid cancer in childhood

It is the cancer that did not respond to the initial treatment or the one that recurred, both in the thyroid and in other organs, after the treatment.

Treatment for papillary or follicular includes:

• Treatment with radioactive iodine
• A targeted treatment clinical trial after examining the tumor for a type of gene change

Treatment for recurrent myeloid thyroid cancer in children includes:

• A clinical trial that checks a sample of a patient’s tumor for certain gene changes. The type of targeted treatment that will be given to the patient depends on the type of gene change.