Papillary thyroid cancer

Synonyms

1

Overview

Papillary thyroid carcinoma is a form of  cancer that occurs due to abnormal and uncontrolled cell growth of certain cells (follicular cells) of the thyroid. Many people with papillary thyroid carcinoma have no signs or symptoms of the condition. When present, symptoms may include a small lump at the base of the neck, hoarseness, difficulty swallowing, trouble breathing, and pain in the neck or throat. The cause of papillary thyroid carcinoma is currently unknown. Risks for developing thyroid cancer include a history of  high-dose external radiation treatments to the neck and radiation exposure during nuclear plant disasters.  It is often well-differentiated, slow-growing, and localized, although it can metastasize.

Papillary thyroid cancer or papillary thyroid carcinoma is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases. It occurs more frequently in women and presents in the 20–55 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had previous radiation to the head and neck.

Symptoms

Thyroid cancer usually begins as a small bump (nodule) in the thyroid gland, which is located at the front of the neck. However, it should be emphasized that most thyroid bumps are harmless and noncancerous (benign).

Causes

About 75-85% of all thyroid cancers diagnosed in the United States are papillary carcinoma. It is more common in women than in men. It may occur in childhood, but is typically seen in people between ages 20 and 40. The cause of this cancer is unknown. A genetic defect may be involved. High-dose external radiation to the neck increases the risk of developing thyroid cancer.

Papillary thyroid cancer in children has also been linked to atomic bomb testing in the Marshall Islands and the 1986 Chernobyl nuclear disaster in the Ukraine. Radiation given through a vein during medical tests and treatments does NOT increase the risk of developing thyroid cancer.

Prevention

Doctors aren't sure what causes most cases of thyroid cancer, so there's no way to prevent thyroid cancer in people who have an average risk of the disease.

Prevention for people with a high risk:
Adults and children with an inherited gene mutation that increases the risk of thyroid cancer are often advised to have thyroid surgery to prevent cancer (prophylactic thyroidectomy). Discuss your options with a genetic counselor who can explain your risk of thyroid cancer and your treatment options.

Prevention for people near nuclear power plants:
Fallout from an accident at a nuclear power plant could cause thyroid cancer in people living nearby. If you live within 10 miles of a nuclear power plant in the United States, you may be eligible to receive a medication (potassium iodide) that blocks the effects of radiation on the thyroid. If an emergency were to occur, you and your family could take the potassium iodide tablets to help prevent thyroid cancer. Contact your state or local emergency management department for more information.

Diagnosis

  • Physical exam: Routine examination as an asymptomatic thyroid nodule 
  • Removing a sample of thyroid tissue:  through a fine needle aspiration biopsy (FNA) for biopsy
  • Blood tests. Blood tests help determine if the thyroid gland is functioning normally
  • Imaging tests.  Imaging tests may include computerized tomography (CT) scans, positron emission tomography (PET) or ultrasound.
  • Genetic testing

Markers:
Thyroglobulin can be used as a tumor marker for well-differentiated papillary thyroid cancer. HBME-1 staining may be useful for differentiating papillary carcinomas from follicular carcinomas; in papillary lesions it tends to be positive.

Reduced expression of ATP5E is significantly associated with the diagnosis of papillary thyroid cancer and may serve as an early tumor marker of the disease.

Prognosis

Depending on source, the overall 5-year survival rate for papillary thyroid cancer is 96 percent or 97 percent, with a 10-year survival rate of 93 percent.

Based on overall cancer staging into stages I to IV, papillary thyroid cancer has a 5-year survival rate of 100 percent for stages I and II, 93 percent for stage III and 51 percent for stage IV.

Treatment

Partial or total thyroidectomy. Thyroid lobectomy alone may be sufficient treatment for small (<1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas in the absence of prior head and neck irradiation or radiologically or clinically involved cervical nodal metastasis.

  • Minimal disease (diameter up to 1.0 centimeters) - hemithyroidectomy (or unilateral lobectomy) and isthmectomy may be sufficient. There is some discussion whether this is still preferable over total thyroidectomy for this group of patients.
  • Gross disease (diameter over 1.0 centimeters) - total thyroidectomy, and central compartment lymph node removal is the therapy of choice. Additional lateral neck nodes can be removed at the same time if an ultrasound guided FNA and thyrobulin TG cancer washing was positive on the pre-operative neck node ultrasound evaluation.

Arguments for total thyroidectomy are:

  • Reduced risk of recurrence, if central compartment nodes are removed at the original surgery.
  • 30-85% of papillary carcinoma is multifocal disease. Hemithyroidectomy may leave disease in the other lobe. However, multifocal disease in the remnant lobe may not necessarily become clinically significant or serve as detriment to patient survival.
  • Ease of monitoring with thyroglobulin (sensitivity for picking up recurrence is increased in presence of total thyroidectomy, and ablation of remnant normal thyroid by low dose radioiodine 131 after following a low iodine diet (LID).
  • Ease of detection of metastatic disease by thyroid and neck node ultrasound.
  • Post-operative complications at high-volume thyroid surgery centers with experienced surgeons are comparable to that of hemithyroidectomy.

Arguments for hemithyroidectomy:

  • Most patients have low-risk cancer with excellent prognosis, with similar survival outcomes in low-risk patients who undergo total thyroidectomy versus hemithyroidectomy.
  • Less likelihood of patient requiring lifelong thyroid hormone replacement after surgery.
     

Papillary tumors tend to be more aggressive in patients over age 45. In such cases it might be required to perform a more extensive resection including portions of the trachea. Also, the sternocleidomastoid muscle, jugular vein, and accessory nerve are to be removed if such procedure allows apparently complete tumor resection. If a significant amount of residual tumor is left in the neck, external radiotherapy has been indicated and has proven useful especially in those cases when residual tumor does not take up radioiodine.

After surgical thyroid removal, the patient waits around 4–6 weeks to then have radioiodine therapy. This therapy is intended to both detect and destroy any metastasis and residual tissue in the thyroid. The treatment may be repeated 6–12 months after initial treatment of metastatic disease where disease recurs or has not fully responded.

Patients are administered hormone replacement levothyroxine for life after surgery, especially after total thyroidectomy. 

Chemotherapy with cisplatin or doxorubicin has proven limited efficacy, however, it could be helpful for patients with bone metastases to improve their quality of life. Patients are also prescribed levothyroxine and radioiodine after surgery. Levothyroxine influences growth and maturation of tissues and it is involved in normal growth, metabolism, and development. In case of metastases, patients are prescribed antineoplastic agents which inhibit cell growth and proliferation and help in palliating symptoms in progressive disease.

Targeted drug therapy:

  • Lenvatinib (Lenvima) - FDA approved indication for the Treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine refractory differentiated thyroid cancer
  • Sorafenib (Nexavar) - FDA approved indication  Treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DCT) that is refractory to radioactive iodine treatment.
  • Cabozantinib ( Cometriq) - FDA approved for the  Treatment of follicular, medullary and anaplastic thyroid carcinoma and metastatic or locally advanced papillary thyroid cancer.