Thyroid Cancer

The thyroid gland and its relations. Source: Gray's Anatomy, 1918.

Thyroid cancer is a disease in which abnormal cells form in the tissues of the thyroid gland. The gland sits at the base of the throat near the trachea. The thyroid gland uses iodine, a mineral found in some foods and in iodized salt, to help make several hormones. The thyroid hormones help to control the heart rate, body temperature, blood pressure and weight. Calcitonin is made by C cells in the thyroid. It plays a small role in keeping a healthy level of calcium in the body.

Types

There are four main types of thyroid cancer:

Papillary

The most common type of thyroid cancer in the United States, this type begins in the follicular cells of the thyroid and grows slowly. If diagnosed early, most people with papillary thyroid cancer can be cured. Papillary cancer is most common in women who are between 30 and 50 years of age.

Follicular

This type makes up about 15% of all thyroid cancers. It begins in the follicular cells and also tends to grows slowly. It tends to affect an older population than papillary cancer. If diagnosed early, most people with follicular thyroid cancer can be treated successfully. This type of cancer does not tend to spread but may invade the blood vessels nearby.

Medullary

This type, which represents less than 5% of thyroid cancers in the United States, begins in the C cells of the thyroid. Cancer that starts in the C cells can make abnormally high levels of calcitonin. It also produces a protein called carcinoembryonic antigen (CEA). Both substances can be detected in the blood when medullary cancer is present. This type of thyroid cancer tends to grow slowly and is easier to treat if detected before it spreads to other parts of the body.

There are three types of medullary cancer.

• Sporadic medullary cancer affects a middle-aged population and is not inherited.
• Multiple endocrine neoplasia, type II (MEN 2) tumors are inherited and tend to affect a younger population. These patients tend to have tumors in other locations as well.
• Familial medullary cancers are also inherited but tend to occur in men and to affect only the thyroid gland.

Anaplastic

This less common type of thyroid cancer begins in the follicular cells of the thyroid. It is also referred to as undifferentiated cancer because it looks very different from normal thyroid tissue under a microscope. The cells of anaplastic thyroid cancer tend to grow and spread very quickly. This type is also difficult to treat (does not respond well to radiation or chemotherapy).

Recurrent

Recurrent thyroid cancer is cancer that has recurred (come back) after it has been treated. Thyroid cancer may come back in the thyroid or in other parts of the body.

Signs and Symptoms

Thyroid cancer may not cause early symptoms. It is sometimes found during a routine physical exam. Symptoms may occur as the tumor gets bigger and may include:

• A lump in the neck
• Trouble breathing
• Difficulty swallowing
• Hoarseness

Causes

The thyroid has two parts (lobes). A thin piece of tissue (the isthmus) separates the lobes. The thyroid produces thyroid hormone and calcitonin. Four or more tiny parathyroid glands are situated behind the thyroid on its surface. These glands make parathyroid hormone, which plays a large role in helping the body maintain a healthy level of calcium.

The thyroid contains two main types of cells. Follicle cells make the thyroid protein thyroglobulin and produce and store thyroxine and triiodothyronine. Other cells, called C cells (parafollicular cells), produce calcitonin. The different types of thyroid cancer develop in each of these types of cells.

Healthy cells grow and divide in an organized, orderly manner. DNA — the genetic blueprint of the body, controls the growth and division of cells. When there is damage to the DNA, cells may begin to grow out of control and eventually form a mass or tumor and may also spread to other parts of the body. The DNA damage that leads to thyroid cancer be a result of exposure to environmental contaminants such as radiation, from the aging process or, can be inherited.

Diagnosis

Exams and tests

The following tests and procedures may be used to detect (find) and diagnose thyroid cancer:

• Physical exam and history assist in identying signs of disease, such as lumps or swelling in the neck, voice box, and lymph nodes, and anything else that seems unusual.
• Laryngoscopy is a procedure in which the doctor checks the larynx (voice box) with a mirror or with a laryngoscope. A laryngoscope is a thin, tube-like instrument with a light and a lens for viewing. A thyroid tumor may press on vocal cords. The laryngoscopy is done to see if the vocal cords are moving normally.
• Blood tests measure the amounts of certain hormones released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. The blood may be checked for abnormal levels of thyroid-stimulating hormone (TSH). TSH is made by the pituitary gland in the brain. It stimulates the release of thyroid hormone and controls how fast follicular thyroid cells grow. The blood may also be checked for high levels of the hormone calcitonin or for the protein CEA.
• Radioactive iodine scan (RAI scan) is a procedure to find areas in the body where thyroid cancer cells may be dividing quickly. Radioactive iodine (RAI) is used because only thyroid cells take up iodine. A very small amount of RAI is swallowed, travels through the blood, and collects in thyroid tissue and thyroid cancer cells anywhere in the body. Abnormal thyroid cells take up less iodine than normal thyroid tissue. Areas that do not absorb the iodine normally (cold spots) show up lighter in the picture made by the scan. Cold spots can be either benign (not cancer) or malignant, so a biopsy is done to find out if they are cancerous.
• Thyroid ultrasound shows the size of a thyroid tumor and whether it is solid or a fluid -filled cyst. Ultrasound may be used to guide a fine-needle aspiration biopsy.
• Computed tomography (CT) scan of the head and neck
• Magnetic resonance imaging (MRI)
• Positron emission tomography (PET) scan in which malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
• Fine-needle aspiration of the thyroid involves the removal of thyroid tissue using a thin needle. A pathologist views the tissue samples under a microscope to look for cancer cells.
• Surgical biopsy involves the removal of the thyroid nodule or one lobe of the thyroid during surgery so the cells and tissues can be viewed under a microscope by a pathologist to check for signs of cancer.

Staging thyroid cancer

After thyroid cancer has been diagnosed, tests are done to find out if cancer cells have spread within the thyroid or to other parts of the body.

The process used to find out if cancer has spread within the thyroid or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. In addition to the tests described for diagnosis of thyroid cancer, the following tests may give additional information:

• Lymph node biopsy: The removal of all or part of a lymph node. A pathologist views the tissue under a microscope to look for cancer cells.
• Bone scan: A procedure to check if there are rapidly dividing cells, such as cancer cells, in the bone. A very small amount of radioactive material is injected into a vein and travels through the bloodstream. The radioactive material collects in the bones and is detected by a scanner.
• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

Staging papillary and follicular cancer

The following stages are used for papillary and follicular thyroid cancer in patients younger than 45 years of age:

• In stage I papillary and follicular thyroid cancer, the tumor is any size, may be in the thyroid, or may have spread to nearby tissues and lymph nodes. Cancer has not spread to other parts of the body.
• In stage II papillary and follicular thyroid cancer, cancer has spread from the thyroid to other parts of the body, such as the lungs or bone.

The following stages are used for papillary and follicular thyroid cancer in patients 45 years of age and older:

In stage I papillary and follicular thyroid cancer, cancer is found only in the thyroid and the tumor is 2 cm or smaller.

In stage II papillary and follicular thyroid cancer, cancer is only in the thyroid and the tumor is larger than 2 cm but not larger than 4 cm.

In stage III papillary and follicular thyroid cancer, either of the following is found:

• the tumor is larger than 4 cm or the tumor is any size and cancer has spread to tissues just outside the thyroid, but not to lymph nodes; or
• the tumor is any size and cancer may have spread to tissues just outside the thyroid and has spread to lymph nodes near the trachea or the larynx (voice box).

Stage IV papillary and follicular thyroid cancer is divided into stages IVA, IVB, and IVC.

• In stage IVA, either of the following is found:
  • the tumor is any size and cancer has spread outside the thyroid to tissues under the skin, the trachea, the esophagus, the larynx (voice box), and/or the recurrent laryngeal nerve (a nerve with two branches that go to the larynx); cancer may have spread to lymph nodes; or
  • the tumor is any size and cancer may have spread to tissues just outside the thyroid. Cancer has spread to lymph nodes on one or both sides of the neck or between the lungs.
• In stage IVB, cancer has spread to tissue in front of the spinal column or has surrounded the carotid artery or the blood vessels in the area between the lungs.
• In stage IVC, cancer has spread to other parts of the body, such as the lungs and bones.

Staging medullary cancer

The following stages are used for medullary thyroid cancer:

Stage 0 medullary thyroid cancer is found only with a special screening test. No tumor can be found in the thyroid.

Stage I medullary thyroid cancer is found only in the thyroid and is 2 cm or smaller.

Stage II medullary thyroid cancer is only in the thyroid and is larger than 2 cm but not larger than 4 cm.

In stage III medullary thyroid cancer:

• the tumor is larger than 4 cm or cancer has spread to tissues just outside the thyroid, but not to lymph nodes; or
• the tumor is any size and cancer may have spread to tissues just outside the thyroid and has spread to lymph nodes near the trachea or the larynx (voice box).

Stage IV medullary thyroid cancer is divided into stages IVA, IVB, and IVC.

• In stage IVA, it may be possible to remove the tumor by surgery; either of the following is found:
  • cancer has spread out of the thyroid to tissues under the skin, the trachea, the esophagus, the larynx (voice box), and/or the recurrent laryngeal nerve (a nerve with two branches that go to the larynx); cancer may have spread to lymph nodes; or
  • cancer may have spread to tissues just outside the thyroid and has spread to lymph nodes on one or both sides of the neck or between the lungs.
• In stage IVB, the tumor cannot be removed by surgery; cancer has spread to tissue in front of the spinal column or has surrounded the carotid artery or the blood vessels in the area between the lungs. Cancer may have spread to lymph nodes.
• In stage IVC, cancer has spread to other parts of the body, such as the lungs and bones.

Staging anaplastic cancer

There is no traditional staging system for anaplastic thyroid cancer. All patients with this type of cancer are considered to have stage IV thyroid cancer because of its rapid spread.

Stage IV anaplastic thyroid cancer is divided into stages IVA, IVB, and IVC.

• In stage IVA, cancer is found in the thyroid and may have spread to lymph nodes. The cancer can be removed by surgery.
• In stage IVB, cancer has spread outside the thyroid and may have spread to lymph nodes. The cancer cannot be removed by surgery.
• In stage IVC, cancer has spread to other parts of the body, such as the lungs and bones.

Treatment

Four types of standard treatment are used to treat thyroid cancer:

Surgery

Surgery is the most common treatment of thyroid cancer. One of the following procedures may be used:

• Lobectomy: Removal of the lobe in which thyroid cancer is found. Biopsies of lymph nodes in the area may be done to see if they contain cancer.
• Near-total thyroidectomy: Removal of all but a very small part of the thyroid.
• Total thyroidectomy: Removal of the whole thyroid.
• Lymphadenectomy: Removal of lymph nodes in the neck that contain cancer.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Radiation therapy may be given after surgery to kill any thyroid cancer cells that were not removed. Follicular and papillary thyroid cancers are sometimes treated with radioactive iodine (RAI) therapy. Higher doses than the amounts used to diagnose thyroid cancer are used. RAI is taken by mouth and collects in any remaining thyroid tissue, including thyroid cancer cells that have spread to other places in the body. Since only thyroid tissue takes up iodine, the RAI destroys thyroid tissue and thyroid cancer cells without harming other tissue. Before a full treatment dose of RAI is given, a small test-dose is given to see if the tumor takes up the iodine.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Thyroid hormone therapy

Hormone therapy is a cancer treatment that removes hormones or blocks their action and stops cancer cells from growing. Hormones are substances made by glands in the body and circulated in the bloodstream. In the treatment of thyroid cancer, drugs may be given to prevent the body from making thyroid-stimulating hormone (TSH), a hormone that can increase the chance that thyroid cancer will grow or recur.

Also, because thyroid cancer treatment kills thyroid cells, the thyroid is not able to make enough thyroid hormone. Patients are given thyroid hormone replacement pills.

Treatment by Stage

Stage I and II papillary and follicular cancer

Stage I and II papillary and follicular thyroid cancer treatment may include the following:

• Total or near-total thyroidectomy, with or without radioactive iodine therapy.
• Lobectomy and removal of lymph nodes that contain cancer, followed by hormone therapy. Radioactive iodine therapy may be given following surgery.

Stage III papillary and follicular cancer

Treatment of stage III papillary and follicular thyroid cancer is usually total thyroidectomy. Cancer that has spread outside the thyroid, as well as any lymph nodes that have cancer in them, will also be removed. Radioactive iodine therapy or external radiation therapy may be given after surgery.

Stage IV papillary and follicular cancer

Treatment of stage IV papillary and follicular thyroid cancer that has spread only to the lymph nodes can often be cured. When cancer has spread to other places in the body, such as the lungs and bone, treatment usually does not cure the cancer, but can relieve symptoms and improve the quality of life. Treatment may include the following:

• Radioactive iodine therapy.
• External-beam radiation therapy.
• Surgery to remove cancer from areas where it has spread.
• Hormone therapy.
• A clinical trial of chemotherapy.

Medullary cancer

Treatment may include the following:

• Total thyroidectomy if the cancer has not spread to other parts of the body.
• Removal of lymph nodes that contain cancer.
• External radiation therapy as palliative therapy to relieve symptoms and improve the quality of life for patients whose cancer has recurred in the thyroid.
• Chemotherapy as palliative therapy to relieve symptoms and improve the quality of life for patients whose cancer has spread to other parts of the body.

Anaplastic cancer

Treatment may include the following:

• Tracheostomy as palliative therapy to relieve symptoms and improve the quality of life.
• Total thyroidectomy as palliative therapy to relieve symptoms and improve the quality of life for patients whose cancer has not spread away from the thyroid.
• External radiation therapy.
• Chemotherapy.
• A clinical trial of total thyroidectomy followed by chemotherapy and radiation therapy.

Recurrent thyroid cancer

Treatment of recurrent thyroid cancer may include the following:

• Surgery with or without radioactive iodine therapy
• Radioactive iodine therapy when the cancer can be found only by a thyroid scan and cannot be felt during a physical exam
• External radiation therapy or intraoperative radiation therapy as palliative therapy to relieve symptoms and improve the quality of life
• Chemotherapy

Chances of Developing Thyroid Cancer

Risk factors

Risk factors for thyroid cancer include the following:

• Being between 25 and 65 years old.
• Female gender
• Being exposed to radiation to the head and neck as a child or being exposed to atomic bomb radiation. The cancer may occur as soon as 5 years after exposure.
• History of goiter (enlarged thyroid).
• Family history of thyroid disease or thyroid cancer.
• Having certain genetic conditions such as familial medullary thyroid cancer (FMTC), multiple endocrine neoplasia type 2A syndrome, and multiple endocrine neoplasia type 2B syndrome.
• Asian race

Genetics

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

The genes in cells carry hereditary information from parent to child. A certain change in a gene that is passed from parent to child (inherited) may cause medullary thyroid cancer. A test has been developed that can find the changed gene before medullary thyroid cancer appears. The patient is tested first to see if he or she has the changed gene. If the patient has it, other family members may also be tested. Family members, including young children, who have the changed gene can decrease the chance of developing medullary thyroid cancer by having a thyroidectomy (surgery to remove the thyroid).

Clinical Trials

A list of ongoing clinical trials is available at ClinicalTrials.gov: thyroid cancer trials

Research

Recent discoveries

• Motesanib diphosphate, a drug that inhibits vascular endothelial growth factor, was found to be an effective treatment for advanced or metastatic differentiated thyroid cancer. ^[1]
• The use of ultrasound appears to be the most useful technology to detect recurrent thyroid cancer. ^[2]

Current research

• A case control, pilot study is ongoing to evaluate the relationship between vitamin D levels and thyroid nodules, thyroid cancer in remission, and active thyroid cancer. ^[3]
• A randomized, double-blind study is underway to demonstrate an improvement in progression-free survival with ZD6474 (vandetanib) as compared to placebo in subjects with unresectable locally advanced or metastatic medullary thyroid cancer . ^[4]
• The usefullness of the drug thalidomide in treating thyroid cancer is being studied. ^[5]
• Celexocib is being evaluated as a possible treatment option for progressive metastatic differentiated thyroid cancer. ^[6]

Expected Outcome

Certain factors affect prognosis (chance of recovery) and treatment options.

• The age of the patient.
• The type of thyroid cancer.
• The stage of the cancer.
• The patient's general health.
• Whether the patient has multiple endocrine neoplasia type 2B (MEN 2B).
• Whether the cancer has just been diagnosed or has recurred (come back).

References

1. ↑ Sherman SI, Wirth LJ, Droz JP, et al. Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med. 2008 Jul 3;359(1):31-42. Abstract
2. ↑ Langer JE, Mandel SJ. Sonographic imaging of cervical lymph nodes in patients with thyroid cancer. Neuroimaging Clin N Am. 2008 Aug;18(3):479-89. Abstract
3. ↑ ClinicalTrials.gov. Vitamin D and Thyroid Cancer
4. ↑ ClinicalTrials.gov. An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer
5. ↑ ClinicalTrials.gov. Thalidomide in Treating Patients With Thyroid Cancer
6. ↑ ClinicalTrials.gov. Celecoxib in Treating Patients With Progressive Metastatic Differentiated Thyroid Cancer

External Links

American Cancer Society

ThyCa: Thyroid cancer survivor's association (US)

Thyryvors.org: Canadian thyroid cancer support group