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Differentiated Thyroid Cancer

What is Differentiated Thyroid Cancer?

Compared to adults, thyroid nodules are much less common in children and adolescents. However, childhood thyroid nodules are more likely to be malignant. In some cases, pediatric thyroid cancer may have spread to nearby lymph nodes and distant sites (lung) at diagnosis. It is also more likely to recur. Despite the greater tendency for spread in children compared to adults, differentiated thyroid cancer has an excellent outcome, with greater than 95% survival rate.

Most thyroid cancers in children are differentiated thyroid cancers (DTC), which arise from follicular cells in the thyroid gland. There are two types of differentiated thyroid cancers: papillary and follicular. Approximately 90% of pediatric thyroid cancers are papillary thyroid cancer.

Papillary thyroid cancer can often present with more than one nodule and involve both lobes of the thyroid (bilateral). In many cases, it has spread outside the thyroid to regional (cervical) lymph nodes at diagnosis. Follicular thyroid cancer is usually localized in the neck but is more likely to spread to lungs and bones.

Differentiated thyroid carcinomas are iodine-avid. This means that they take up iodine. This feature is important for screening and treatment with radioactive iodine.

Graphic of an adult female body with layover of organs visible and the thyroid gland is highlighted and labeled.

The thyroid gland is a butterfly-shaped organ located at the base of the throat in the front of the neck. It is arranged in two lobes, one on the right side and one on the left side.

Risk Factors and Causes of Differentiated Thyroid Cancer

Differentiated thyroid cancer occurs most often in older children and teens. Adolescents are 10 times more likely to develop thyroid cancer compared to younger children. These cancers are more common in females than males. Certain genetic factors may increase risk, and the tendency to develop thyroid and other cancers may be passed down in families. Children with differentiated thyroid cancer often have gene rearrangements of the RET gene.

Genetic syndromes associated with differentiated thyroid cancers

Genetic Syndrome
Familial Adenomatous Polyposis (FAP)
PTEN Hamartoma Tumor Syndrome
DICER1 Syndrome
Carney Complex

Ionizing radiation

Patients treated with radiation as a medical therapy are at increased risk of developing thyroid cancer. Environmental exposure to radiation such as radioactivity from nuclear disasters also increases risk. Higher doses of radiation and younger age during exposure are associated with higher risk.

Signs and Symptoms of Differentiated Thyroid Cancer

The main sign of thyroid cancer is a nodule, or lump, in the thyroid gland. Sometimes, lymph nodes in the neck will appear swollen. In rare cases, symptoms might include problems breathing, difficulty or pain swallowing, and hoarseness.

However, often thyroid cancer does not cause any symptoms and may be found as part of a routine exam.

Diagnosis of Differentiated Thyroid Cancer

  • A health history and physical exam helps doctors learn about symptoms, general health, past illness, and risk factors. Family history is important to find out whether there may be an inherited risk. With certain forms of thyroid cancer, genetic testing and genetic counseling is recommended for the child and family. Doctors will test for certain gene changes (mutations) that increase risk for cancer.
  • Lab studies will look at substances in the blood that give information about the thyroid and tumor. These tests include measures of:
    • Hormones that indicate thyroid function including thyroid stimulating hormone (TSH), T3, and free T4 (thyroxine). Usually, blood tests that measure thyroid function are normal.
    • Tumor markers including thyroglobulin (Tg). Thyroglobulin is a protein made in the thyroid gland. After surgery to remove the thyroid gland (thyroidectomy), abnormally high levels of Tg can help indicate presence or recurrence of differentiated thyroid cancers (papillary and follicular).
  • Imaging tests help identify the tumor, see how big the tumor is, and find out if it has spread to other places.
    • Ultrasound uses sound waves to create an image of the organs and tissues within the body. A neck ultrasound is one of the main tests doctors use to see if there is a tumor in the thyroid gland. Imaging of both sides of the neck is used to check for abnormally enlarged lymph glands. A high quality ultrasound by an experienced sonographer is important for evaluation of thyroid nodules and neck lymph glands. This information will be used to plan the next steps for diagnosis and treatment.
    • Computed tomography (CT scan) uses X-rays to create cross-sectional images of the organs and tissues inside the body. The machine takes many pictures to make a very detailed image. The images are taken as a series of “slices” of the body and are saved to a computer. These slices or sections can allow very small tumors to be seen. In more advanced cases, a CT scan may be used to help doctors get a better view of the tumor and plan treatment. An initial chest X-ray, or in special cases, a chest CT scan may be used to look for spread of the cancer to the lungs. Many times, the neck and thyroid ultrasound is the main imaging used prior to surgery.
  • Biopsy of the some of the tissue from the suspected tumor to check for signs of cancer in the cells and learn more about the histology. A pathologist looks at the tissue samples using a microscope to see if there are cancer cells. The way cells look under a microscope is important to make a diagnosis. The tissue sample is usually obtained by an ultrasound guided fine needle aspiration. In this procedure, doctors take a sample of thyroid tissue and/or enlarged lymph gland(s) from the neck, using a thin needle inserted through the skin. In some cases, an open biopsy, which involves surgical removal of the nodule, is needed to make a diagnosis.

Staging of Differentiated Thyroid Cancer

The stage, or extent of disease, depends on whether the cancer has spread. Stage of thyroid cancer is based on the characteristics of the thyroid nodules as well as spread of disease to lymph nodes and other parts of the body (lungs).

Patients who have no spread of disease outside the neck are considered Stage I.
Patients with distant spread of disease outside the neck are considered Stage II.

Post-operative staging is used to classify patients into risk groups. For all pediatric thyroid cancer patients, the risk of death is very low. However, some patients may be at higher risk for continued disease or spread of disease (metastases) after surgery.

Risk Spread of disease
Low Risk Cancer is only in the thyroid gland with little or no spread to lymph nodes
Intermediate Risk Some spread of cancer to nearby lymph nodes
High Risk Significant spread of cancer to nearby lymph nodes, invading tissues outside the thyroid, or distant spread (to lungs)

Prognosis for Differentiated Thyroid Cancer

Thyroid cancer has a >95% survival rate in pediatric patients. Recurrence is more likely in children under 10 years of age and patients who have regional lymph node involvement at diagnosis. However, even with risk of recurrence, chance of survival is very good.

Factors that influence prognosis include:

  • Extent of initial surgery
  • Whether the disease has spread to other places such as the lungs or bones
  • Gene mutations or hereditary factors that increase risk for other cancers

Treatment of Differentiated Thyroid Cancer

Care by a multidisciplinary pediatric team is important to manage assessment, treatment, and long-term monitoring of patients with pediatric thyroid cancer. Care decisions are focused on balancing risk of continued disease and harm due to treatment side effects. Because of the risk of recurrence and other considerations (e.g., hormone function, genetic predisposition), ongoing follow-up is needed for all patients.

Life After Differentiated Thyroid Cancer

Monitoring for recurrence and follow-up care

Patients treated for thyroid cancer need lifelong monitoring and follow-up care by an interdisciplinary medical team. Specific recommendations for frequency and types of tests differ according to patient needs and thyroid cancer type and stage.

In differentiated thyroid cancer, thyroglobulin levels can serve as tumor markers to assist in monitoring. Additional considerations include support for adherence to medications including thyroid hormone replacement therapy and TSH suppression.

Key aspects of long-term care:

  • Regular physical exams to check thyroid and lymph nodes
  • Neck/thyroid ultrasound imaging
  • TSH suppression and post-thyroidectomy hormone replacement therapy (levothyroxine), with support for medication adherence
  • Monitoring blood thyroglobulin (Tg) and Tg antibodies

Recurrence of thyroid cancer can occur many years after treatment. Ongoing monitoring can help with early detection of late recurrences.

Care after thyroid and neck surgery

Patients can benefit from psychosocial support during treatment and survivorship. Care team members representing Psychology, Child Life, Social Work, and other disciplines can assist with coping and adherence to treatments that may affect quality of life. Possible issues include adjustment to daily medication use, body image concerns due to surgical scars, and other adjustment needs.

Patients may also need physical therapy after surgery to assist with neck mobility and range of motion.

Adjusting to a thyroid cancer diagnosis can be challenging for families. Although the prognosis is generally very good, the disease requires lifelong management through medication and monitoring. Support needs may increase during life transitions such as adolescence and young adulthood as patients gain independence. Adjustment challenges may also be greater for patients who experience thyroid cancer a second cancer.

Late effects of therapy

Patients receiving radioactive iodine therapy should be followed for potential long-term and late effects of treatment. Special considerations include:

  • Follow-up care for salivary gland dysfunction and increased risk of tooth decay associated with dry mouth
  • Monitoring for effects on reproductive organs and fertility
  • Monitoring lung function in patients with lung involvement
  • Monitoring for second primary malignancies

For general health and disease prevention, all cancer survivors should adopt healthy lifestyle and eating habits, as well as continue to have regular physical checkups and screenings by a primary physician. Survivors should discuss their medical histories with their health care providers including all cancer therapies.

Reviewed: June 2018