Differentiated Thyroid Cancer | The Children's Hospital of Philadelphia

Pediatric Thyroid Center

Differentiated Thyroid Cancer

Before you begin reading about differentiated thyroid cancer, please read a description of the thyroid gland for a basic understanding of its structure and function.

What is differentiated thyroid cancer?


Differentiated thyroid cancer (DTC) includes papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). PTC is the most common form of thyroid cancer in both adults and children, representing about 85 to 90 percent of diagnoses. FTC accounts for only 5 to 10 percent of pediatric patients with differentiated thyroid cancer.

Compared to papillary thyroid cancer, follicular thyroid cancer is usually found as a solitary thyroid nodule and has a lower frequency of spreading to lymph nodes in the neck. However, because follicular thyroid cancer may invade into blood vessels, there may be a higher chance of spread to distant sites, such as the lungs and bones. This may occur even without spread to lymph nodes in the neck.

The following is general information about DTC, including both PTC and FTC. Families are encouraged to talk with their healthcare providers about differences in the management of PTC and FTC.

What causes differentiated thyroid cancer?

Several genes have been associated with the development of DTC. Unfortunately, at this time, knowing the specific gene mutation does not allow us to predict the behavior, response to therapy or prognosis of thyroid cancer in children and adolescents. One of the most active research areas of the Pediatric Thyroid Center at CHOP is to identify specific molecular markers, growth factors and proteins that would give us this type of information and capability.



Does differentiated thyroid cancer in children and adolescents behave the same as in adult patients?

The simple answer is no. Even with thyroid cancer that has spread, children and adolescents appear to have much better outcomes compared to adults. At the time of diagnosis, approximately 40 to 60 percent of children and adolescents will have thyroid cancer that has spread to the lymph nodes, and approximately 15 percent will have thyroid cancer that has spread to the lungs. In adults, a high degree of metastasis (spread) is associated with worse outcome; however, as a group, no matter the degree of metastasis, pediatric patients with DTC have a greater than 95 percent survival rate over 20 to 30 years of follow-up. In other words, when properly evaluated and treated, the vast majority of pediatric patients with thyroid cancer go on to lead productive and rewarding lives. The challenges of treatment for adults with significant metastasis are much greater and the outcomes are not as promising.


Are there risk factors for developing thyroid cancer?

The following factors are associated with an increased risk of developing differentiated thyroid cancer:

Ionizing radiation

A previous exposure to ionizing radiation has been identified as a risk factor for developing thyroid cancer. Fortunately, only a very small percentage of pediatric patients have a history of this risk factor. What this means is that for the remainder of our patients, we usually do not find an identifiable reason for why they developed thyroid cancer.

Outside of rare environmental exposure, such as the Chernobyl nuclear reactor accident in 1986, exposure to ionizing radiation is most often associated with treatment of another cancer. Examples of previous medical treatments include head and neck radiation for brain or facial tumors, treatment of Hodgkin’s lymphoma, and total body irradiation in preparation for bone marrow transplant. Younger age at the time of exposure, lower doses of radiation and female gender are all associated with an increased risk of developing thyroid nodules and thyroid cancer. These lesions rarely develop within the first three to five years after exposure but may develop as late as three to four decades after exposure. Because of this, we recommend that survivors of a non-thyroid malignancy who received head-and-neck or total-body exposure to radiation have regular thyroid physical exams starting within a year of their original diagnosis, and surveillance thyroid ultrasound (US) exams starting within three to five years of diagnosis.

In addition to thyroid nodules and thyroid cancer, patients exposed to ionizing radiation are at risk of developing hypothyroidism or hyperthyroidism. Thyroid function tests should be a regular part of screening for these patients.

Age and gender

Adolescent girls between the ages of 15 and 18 have the highest rate of developing papillary thyroid cancer (PTC). There are many potential reasons; however, none fully explains the observed risk for this subgroup of patients.

Autoimmune thyroid disease

The second group at increased risk of developing thyroid nodules and thyroid cancer are patients with autoimmune thyroid disease, most frequently Hashimoto’s thyroiditis, also called chronic lymphocytic thyroiditis (CLT) (see autoimmune hypothyroidism).

This is another area with significant controversy, complicated by the fact that in patients with autoimmune thyroid disease, the appearance of abnormal thyroid tissue and enlarged lymph nodes on ultrasound might be unrelated to thyroid cancer. Therefore, if a thyroid ultrasound is performed, the results must be interpreted with these known associations in mind.

Because of these complicating features, we recommend that ultrasounds only be considered for patients with autoimmune thyroid disease (hypothyroidism or hyperthyroidism) that have a very irregular thyroid gland, palpable (able to be touched or felt) thyroid nodule(s) or abnormal lymph nodes on physical exam.

Family history of thyroid cancer

Once a family member is diagnosed with either papillary or follicular thyroid cancer, there appears to be a small, but significant risk for other family members developing the same type of cancer. The risk may be isolated to the development of thyroid cancer or may be associated with an increased risk of developing other forms of cancers or medical conditions.

Your child’s doctor will discuss the risks in more details with you and your family and answer any questions you might have.


What are the symptoms of thyroid cancer?

The majority of patients do not have any symptoms associated with their thyroid cancer. Most frequently, a nodule is discovered during a physical exam or through a non-thyroid-related head and neck radiologic study.

When symptoms are present, they may include:


How is thyroid cancer treated at CHOP?

Thyroid cancer is treated with surgery and radioactive iodine. Going to the right surgeon in the right setting ensures the greatest chance of achieving remission (see below for definition) and the lowest risk of complications.

A dedicated program, like the Pediatric Thyroid Center at CHOP, has the experience, expertise and resources to fully evaluate and prepare your child if or when he needs radioactive iodine. The expertise of the thyroid program you choose is also a critical factor in achieving remission and preventing recurrence of the cancer.

The medical team should have all treatment options available, and have the expertise to determine whether a patient needs more or less extensive surgery, and a single or repeated doses of radioactive iodine. These decisions can reduce complication rates and optimize immediate and long-term quality of life.

Treatment schedule

Around the time of surgery, each patient receives specific education and instructions about what to do before, during and after treatment. This “roadmap” includes specific dates for starting a low-iodine diet and stopping thyroid hormone therapy, as well as scheduling of radioactive iodine (RAI) whole body scans and treatment.

Thyroid surgery

The extent of thyroid surgery is based on the results of the fine-needle aspiration biopsy (FNA) and pre-operative staging. During an FNA, a very thin needle is used to extract a sample of cells from a thyroid nodule(s) and/or lymph nodes to be analyzed. At a minimum, pre-operative staging should include a thyroid and neck ultrasound. Additional tests may include a neck MRI. Chest X-ray and chest CT scan are rarely needed as their findings usually do not affect the surgical approach.

For patients who have an FNA result that is “indeterminate,” including follicular lesions of undetermined significance (FLUS) or follicular neoplasms (FN), the usual surgery of choice is to remove half the thyroid gland, a procedure known as a lobectomy. Surgically removing the nodule allows the pathologist to more completely evaluate the tissue to determine the appearance and behavior of the cells. In fact, the diagnosis of a benign follicular adenoma (FA) vs. a follicular thyroid cancer (FTC) can only be made by examining the tissue after surgery. In adults, there are several additional tests that can be performed on the FNA sample to help determine if "indeterminate" cells are benign (not cancerous) or malignant (cancerous) prior to surgery, but these tests have not been studied in children. This is another area of research for our Pediatric Thyroid Center.

If there are indeterminate nodules in both sides of the thyroid gland or if the patient has an increased risk of thyroid cancer based on personal or family history, complete removal of the thyroid gland, a procedure called a total thyroidectomy, is recommended.

The most common post-surgical diagnosis and actions include:

Diagnosis Action
Benign (follicular adenoma) Clinical follow-up
Follicular thyroid cancer (FTC)
Minimal invasion Clinical follow-up or total thyroidectomy*
Invasive Total thyroidectomy*
Papillary thyroid cancer (PTC) Total thyroidectomy*
Follicular variant of PTC (fvPTC) Total thyroidectomy*
* Total thyroidectomy: surgical removal of the entire thyroid gland

Risks of thyroid surgery

The two most common risks of thyroidectomy include damage to the parathyroid glands or the recurrent laryngeal nerves, structures that are directly attached to the thyroid gland.


The risks of thyroid surgery can be decreased by having the operation performed by an experienced surgeon who performs at least 30 thyroid surgeries per year, like the surgeons at the Pediatric Thyroid Center at CHOP.

What to expect after surgery

The majority of patients should plan on spending two to three days in the hospital after surgery. This time allows for recovery, control of pain and monitoring for the potential risks of low calcium and RLN damage.

The pain from surgery usually goes away within the first few days, although patients may experience some stinging or a burning sensation on the skin for several weeks to months as the nerves in the skin heal. The scar is usually 2 to 4 cm in length, situated in a skin fold. Absorbable sutures (stitches) and Steri-Strips are used so there is no need to have stitches removed. Most patients can go back to school, work and activities in a short time. Your surgeon can give you more details.

Treatment outcomes

The overall disease-specific outcomes for differentiated thyroid cancer among all ages of pediatric patients are excellent. This is true for patients who enter remission (see below for definition) after the first treatment as well as for patients who require more than one surgery and/or multiple doses of RAI therapy. patients who require more than one surgery and those who need multiple doses of radioactive iodine (RAI) to achieve remission. Prognosis is even excellent for patients who do not achieve remission but develop stable, persistent disease.

For the subset of patients that achieve remission, there is still an approximate 30 percent risk of recurrence (return of the cancer) that may occur decades after remission was achieved. Even then, the majority will experience an excellent outcome. However, because of the high risk of recurrence, and due to the long-term concerns associated with the use of RAI, all patients will need lifelong follow-up. The exams and surveillance frequency will decrease over time, but transition to adult care and regular follow-up with a primary care manager and adult endocrinologist are extremely important.

The vast majority of pediatric patients with differentiated thyroid cancer are able to live productive and rewarding lives.


How are patients followed after thyroid surgery?

Hormone replacement therapy

With the thyroid gland removed patients are no longer able to make thyroid hormone on their own. Your child will need to take thyroid hormone in order to get the thyroxine hormone (T4) and the thyroid-stimulating hormone (TSH) in the normal range.

Thyroid hormone suppression

For thyroid cancer patients, we prescribe higher doses of hormone replacement therapy with the goal of making the T4 high-normal or even just above the normal limit with the TSH below the normal limit. This is called suppressive therapy and is used because TSH can stimulate normal as well as thyroid cancer cells to grow. Using a suppressive therapy helps to decrease the risk that any remaining cancer cells will grow.

With the higher doses of thyroid hormone replacements, patients may experience mild symptoms of hyperthyroidism, including:

You should contact your healthcare team to determine if the dose can be adjusted if these symptoms are affecting your child's daily activities.


All children and adolescents are followed at the Pediatric Thyroid Center with repeated physical exams and laboratory tests every three to six months.

Your healthcare team will customize a follow-up plan based on your child’s condition and outcome.


The strictest definition for the absence of persistent disease includes all of the following:

  1. No clinical evidence of disease
  2. No imaging evidence of disease
  3. No evidence of disease through laboratory testing


Persistent or recurrent thyroid disease

Persistent disease is defined as evidence of disease by physical exam, laboratory testing and/or imaging six to 12 months after initial treatment. Recurrent disease is defined as a return of clinical disease after a patient was considered free of disease for six months or more.

Despite an extremely favorable outcome for pediatric patients with DTC, recurrence is more common in children than adults. Specific groups that appear to be at highest risk include:

Fortunately, the outcome in children with recurrent disease is much better than in adults.

Treatment of recurrent PTC

Recurrent papillary thyroid cancer (PTC) develops in 30 percent of children, most commonly in the lymph nodes in the anterior and lateral part of the neck. In most cases, recurrent PTC can be treated with repeat surgery. Surgical complications are more common with re-exploration of the neck, but can be minimized when performed by an experienced surgeon who performs at least 30 thyroid procedures per year.

Treatment of children with pulmonary metastasis

PTC may spread to the lungs in up to 20 percent of pediatric patients. The finding of significant metastasis in the neck is a marker of increased risk for spread to the lungs. In contrast to adults, when PTC spreads to the lungs in a child or adolescent it usually retains the ability to absorb iodine, a status called "iodine avid" disease.

While RAI may be more effective, care will be taken to select a dose and treatment frequency that will avoid adverse effects. More than half of patients will respond to RAI and ultimately achieve remission. However, up to 33 percent of patients will develop stable, persistent disease. For these patients, repeat RAI is not effective and only increases the risk of side effects. Pulmonary function testing should be performed on a regular basis, and the decision to treat with repeated doses of RAI must be individualized based on documented response to prior treatment.

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