Rare Classroom: Differentiated Thyroid Cancer

Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The rare disease that we will be learning about today is:

Differentiated Thyroid Cancer

What is Differentiated Thyroid Cancer?

  • Thyroid cancer is a cancer that starts in the thyroid gland 
  • The type of cancer is important because it affects how serious the cancer is and what type of treatment is needed 
  • The term “differentiated” is used because the cancer cells look and act in some respects like normal thyroid cells
  • The National Cancer Institute estimates 62,450 new cases of thyroid cancer in the US in 2015 (all types)​
  • Estimated to be 1,950 deaths from thyroid cancer in 2015​
  • The most rapidly increasing cancer in the US​
  • About 2% of thyroid cancers occur in children and teen​s​
  • Mean age at diagnosis is 40-45 years for papillary tumors (PTC) and 50-55 years for follicular tumors (FTC)​
  • Differentiated thyroid cancer vs Other thyroid cancer:
    • Other types:
      • Less common
      • Examples: medullary thyroid carcinoma, anaplastic carcinoma, thyroid lymphoma, thyroid sarcoma
    • Differentiated:
      • Most common
      • Originate from follicular cells
      • ​Examples: follicular carcinoma, papillary carcinoma, Hürthle (Hurthle) cell carcinoma
      • Hürthle (Hurthle) cell carcinoma
        • Account for 2-3% of all thyroid malignancies​
        • Often considered a variant of follicular carcinoma​
        • Occur more commonly in women than in men, typically in the 5th decade of life​
        • Prognosis not quite as good as it is difficult to find and treat​
      • Papillary carcinoma
        • Most common thyroid cancer​
        • Represents 80% of thyroid cancers​
        • Developed by women 3 times more frequently than men​
        • Mean age at presentation is 34-40 years old​
        • Grow slowly, but often spread to lymph nodes in neck​
        • Are often treated successfully and are rarely fatal​
      • Follicular carcinoma
        • 2nd most common thyroid cancer​
        • Represents 10% of thyroid cancers​
        • More seen where dietary intake of iodine is low​
        • Mean age range at diagnosis is late in the fourth to sixth decades​
        • Usually don’t spread to lymph nodes, but can spread to lungs and bones​
        • Prognosis not quite as good as papillary, but still very good ​
  • Different types of thyroid cancer develop from each kind of thyroid gland cell
    • C​ cells
      • Make calcitonin, a hormone that helps control how the body uses calcium
    • Follicular cells
      • Use iodine from the blood to make thyroid hormones that control the body’s heart rate, blood pressure, temperature, and the rate at which food is turned into energy (metabolism)

How Do You Get It?

  • In most cases, the cause is unknown
  • Papillary thyroid cancer – Several acquired DNA mutations found:​
    • RET gene mutation​
      • Many papillary cancers have specific changes in this gene​
      • The altered form of the RET gene is called the PTC oncogene​
      • The PTC oncogene is found in  10-30% of papillary cancers​
    • BRAF gene mutation ​
      • These cancers tend to grow and spread to other parts of the body more quickly​
    • Also tied to papillary thyroid cancer​
    • MET gene​
    • NTRK1 gene​
  • Follicular thyroid cancer
    • Some caused by acquired changes in the RAS oncogene
  • Risk factors
    • Radiation exposure
      • Sources include certain medical treatments and radiation fallout from power plant accidents or nuclear weapons
    • Low-iodine diet
      • Follicular thyroid cancers are more common in areas of the world where people’s diets are low in iodine​
      • Papillary cancer risk is increased with low iodine diet if there is also radiation exposure​
    • Family history of colon growths
      • Papillary carcinoma may occur in some people with a family history of multiple growths in the colon, such as with familial adenomatous polyposis (FAP)
    • Gender
      • Women are at three times the risk of men
    • Genetic risk factors
      • Some rare genetic diseases associated with increased risk

What Are The Symptoms?

  • In many cases, patients may be asymptomatic, at least at first
  • Symptoms can include:
    • A lump in the throat​
    • Cough​
    • Hoarseness​
    • Pain in the throat and neck​
    • Difficulty swallowing​
    • Swollen lymph nodes in the neck​
    • Trouble breathing​

How Is It Treated?

  • Treatment of most patients with DTC includes surgery, thyroid hormone therapy, and selective use of radioactive iodine​
  • For some patients, the DTC progresses despite treatment with radioactive iodine.  These cases are referred to as radioactive iodine-refractory DTC.
  • Those with radioactive iodine-refractory DTC represent about 15% of those with DTC​
  • Treatment for this group is challenging – conventional cytotoxic chemotherapy does not show good response rates and has significant toxicity​
  • “For symptomatic, nonresectable, RAI-refractory metastases that have been treated or cannot be treated with EBRT, National Comprehensive Cancer Network and American Thyroid Association guidelines recommend consideration of participation in a clinical trial or the use of small-molecule tyrosine kinase inhibitors (TKIs)”​
  • The decision whether to start a TKI should be based on clinical presentation of the patient, as well as imaging studies. Those patients who are asymptomatic may not be a candidate for TKI therapy​
  • Surgery
    • The primary and typically first treatment for thyroid cancer​
    • Types: ​
      • Lobectomy – used to treat cancers that are small and show no signs of spread​
      • Thyroidectomy – Most common surgery. Called a total thyroidectomy if completely removed and a sub-total if not.​
  • Radioactive iodine ablation
    • Radioactive iodine (RAI) (I-131) is taken into the thyroid gland and destroys any thyroid tissue not destroyed by surgery. Also treats thyroid cancer that has spread to lymph nodes and other parts of the body​
  • Thyroid hormone replacement therapy
    • Replaces the loss of the natural thyroid hormone following surgery. Can also reduce risk of recurrence in high-risk cancers​
  • External beam radiation
    • Delivered from a machine outside the body. Uses high-energy particles to destroy cancer cells or slow their growth​
  • Chemotherapy
    • Not needed in most cases. Sometimes used for advanced cancers that no longer respond to other treatments​
  • Targeted therapies
    • There are two targeted drugs used to treat papillary or follicular thyroid cancer: sorafenib (Nexavar) and lenvatinib (Lenvima™ )
    • Both drugs are considered kinase inhibitors​
    • Kinase inhibitors work by:​
      • Blocking tumors from forming new blood vessels​
      • Targeting some of the proteins made by cancer cells that normally help them grow​
    • Both drugs help stop cancer growth for a time when given to patients with differentiated thyroid cancer whose cancers no longer respond to treatment with radioactive iodine.​
    • Other targeted drugs, such as such as, sunitinib (Sutent), pazopanib (Votrient), and vandetanib (Caprelsa) are not approved to treat papillary and follicular thyroid cancer, but have shown some early promise and may be helpful for some patients​
  • Treatment for differentiated thyroid cancer by stage:
  • Stage I or II
    • Surgical removal via a lobectomy or near-total/total thyroidectomy. A near-total/total thyroidectomy is more common than a lobectomy.​
    • A central compartment neck dissection may also be done. This means surgical removal of lymph nodes next to the thyroid.​
    • In the lowest-risk patients, surgery may be the only treatment. The cure rate for lowest-risk patients with only surgery is excellent.​
    • Some patients receive radioactive iodine (RAI) treatment after the thyroidectomy. The patient’s age and other factors affect the decision about radioactive iodine.​
    • The MD will prescribe thyroid hormone replacement therapy after thyroidectomy, with a dosage appropriate for a lower-risk patient​
  • Stage III and IV
    • Surgical removal is usually a near-total/total thyroidectomy, plus a central compartment neck dissection (surgical removal of lymph nodes next to the thyroid). If the cancer has spread to other lymph nodes in the neck, a modified radical neck dissection is often done. This is a more extensive surgical removal of lymph nodes from the neck.​
    • Radioactive iodine treatment is generally given to eliminate any remaining thyroid tissue after surgery and to treat any undetectable cancer remaining in the neck or elsewhere in the body that takes up iodine.​
    • Some patients may receive external beam radiation. Some may receive chemotherapy in a clinical trial for metastatic differentiated thyroid cancer that does not take up iodine.​
    • According to the 2009 ATA Guidelines for Differentiated Thyroid Cancer, patient’s should receive thyroid hormone therapy, with the dosage high enough to suppress the blood level of TSH (thyroid stimulating hormone) well below the level that is the normal range for someone without thyroid cancer.​
  • For recurring/relapsing cancer:
    • Cancer that comes back on the neck
      • An ultrasound-guided biopsy is first done to confirm that it is really cancer. Then, if the tumor appears to be removable surgery is often used.
    • Cancer appears on a radioiodine scan
      • Radioactive iodine (RAI) therapy may be used, either alone or with surgery
    • Cancer detected on MRI or PET scan
      • External radiation
    • Targeted therapy or chemotherapy may be tried if the cancer has spread to several places and RAI and other treatments are not helpful

Where Can I Learn More???

  • Check out our cornerstone on this disease here.

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