Thyroid Cancer Treatment (Adult) (PDQ®)–Health Professional Version

General Information About Thyroid Cancer

Thyroid cancer includes the following four main types:

  • Papillary.
  • Follicular.
  • Medullary.
  • Anaplastic.

For clinical management of the patient, thyroid cancer is generally divided into the following two categories:[1]

  1. Differentiated thyroid cancer, which includes well-differentiated tumors, poorly differentiated tumors, and undifferentiated tumors (papillary, follicular, or anaplastic).
  2. Medullary thyroid cancer.

Well-differentiated tumors (papillary and follicular thyroid cancer) are highly treatable and usually curable. Poorly differentiated and undifferentiated thyroid tumors (anaplastic thyroid cancer) are less common, aggressive, metastasize early, and have a poorer prognosis. Medullary thyroid cancer is a neuroendocrine cancer that has an intermediate prognosis.

The thyroid gland may occasionally be the site of other primary tumors, including sarcomas, lymphomas, epidermoid carcinomas, and teratomas. The thyroid may also be the site of metastasis from other cancers, particularly of the lung, breast, and kidney.

Incidence and Mortality

Estimated new cases and deaths from thyroid cancer in the United States in 2018:[2]

  • New cases: 53,990.
  • Deaths: 2,060.

Thyroid cancer affects women more often than men and usually occurs in people aged 25 to 65 years. The incidence of this malignancy has been increasing over the last decade. Thyroid cancer commonly presents as a so-called cold nodule. It is detected as a palpable thyroid gland during a physical exam and evaluated with iodine I 131 scans; scintigraphy shows that the isotope is not taken up in an area of the gland. The overall incidence of cancer in a cold nodule is 12% to 15%, but it is higher in people younger than 40 years and in people with calcifications present on preoperative ultrasonography.[3,4]

Anatomy

Thyroid gland tissue envelops the upper trachea just below the thyroid and cricoid cartilages that make up the larynx. The gland has an isthmus and often asymmetric right and left lobes; usually four parathyroid glands lie posteriorly. When swallowing, the thyroid may be felt to rise with the larynx—most commonly in the presence of a disease process.

ENLARGEAnatomy of the thyroid and parathyroid glands; drawing shows the thyroid gland at the base of the throat near the trachea. An inset shows the front and back views. The front view shows that the thyroid is shaped like a butterfly, with the right lobe and left lobe connected by a thin piece of tissue called the isthmus. The back view shows the four pea-sized parathyroid glands. The larynx is also shown.
Anatomy of the thyroid and parathyroid glands.

Risk Factors

Patients with a history of radiation therapy administered in infancy or childhood for benign conditions of the head and neck (such as enlarged thymus, tonsils, or adenoids; or acne) have an increased risk of cancer and other abnormalities of the thyroid gland. In this group of patients, malignancies of the thyroid gland appear as early as 5 years after radiation therapy and may appear 20 or more years later.[5] Radiation exposure as a consequence of nuclear fallout has also been associated with a high risk of thyroid cancer, especially in children.[6-8]

Other risk factors for thyroid cancer include the following:[9]

  • Family history of thyroid disease or multiple endocrine neoplasia (MEN) syndrome.
  • RET gene mutation.[10,11]
  • A history of goiter.
  • Female gender.
  • Asian race.

Diagnostic and Staging Evaluation

The following tests and procedures may be used in the diagnosis and staging of thyroid cancer:

  • Physical exam and history.
  • Laryngoscopy.
  • Blood hormone studies.
  • Blood chemistry studies.
  • Ultrasound exam.
  • Computed tomography scan.
  • Fine-needle aspiration biopsy of the thyroid.
  • Surgical excision.

Prognostic Factors for Well-differentiated Thyroid Cancer

Age appears to be the single most important prognostic factor.[12] The prognosis for differentiated carcinoma (papillary or follicular) without extracapsular extension or vascular invasion is better for patients younger than 40 years.[12-16]

Patients considered at low risk according to age, metastases, extent, and size risk criteria include women younger than 50 years and men younger than 40 years without evidence of distant metastases. The low-risk group also includes older patients with primary papillary tumors smaller than 5 cm without evidence of gross extrathyroid invasion, and older patients with follicular cancer without major capsular invasion or blood vessel invasion.[14] Using these criteria, a retrospective study of 1,019 patients showed that the 20-year survival rate was 98% for low-risk patients and 50% for high-risk patients.[14]

A retrospective surgical series of 931 previously untreated patients with differentiated thyroid cancer found that age older than 45 years, follicular histology, primary tumor larger than 4 cm (T2–T3), extrathyroid extension (T4), and distant metastases were adverse prognostic factors.[17,18] Favorable prognostic factors included female gender, multifocality, and regional lymph node involvement.[17] Other studies, however, have shown that regional lymph node involvement had no effect [19,20] or had an adverse effect on survival.[15,16,21]

Another retrospective series of 1,807 patients found that the presence of distant metastases was most predictive of survival, followed by age.[22] An age cutoff of 55 years was identified as most predictive of survival. This led to an international multi-institutional validation of age 55 years as a cutoff for risk stratification in the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system for well-differentiated thyroid cancer. This analysis of 9,484 patients was responsible for the change in age cutoff from 45 years to 55 years in the AJCC Cancer Staging Manual, 8th edition, using AJCC/UICC staging for well-differentiated thyroid cancer.[23]

The prognostic significance of lymph node status is controversial. Use of sentinel lymph node biopsy may aid in identifying patients with occult metastases who might benefit from central neck dissection.[24]

Diffuse, intense immunostaining for vascular endothelial growth factor in patients with papillary cancer has been associated with a high rate of local recurrence and distant metastases.[25] An elevated serum thyroglobulin level correlates strongly with recurrent tumor when found in patients with differentiated thyroid cancer during postoperative evaluations.[26,27] Serum thyroglobulin levels are most sensitive when patients are hypothyroid and have elevated serum thyroid-stimulating hormone levels.[28] Expression of the tumor suppressor gene p53 has also been associated with an adverse prognosis for patients with thyroid cancer.[29]

(Refer to the Clinical Features and Prognosis section of the Medullary Thyroid Cancer section and the Clinical Features and Prognosis section of the Anaplastic Thyroid Cancer section of this summary for more information about prognosis.)

Related Summaries

Other PDQ summaries containing information related to thyroid cancer include the following:

  • Genetics of Endocrine and Neuroendocrine Neoplasias
  • Childhood Thyroid Cancer Treatment
  • Unusual Cancers of Childhood (including multiple endocrine neoplasia (MEN) syndrome and Carney Complex)
References
  1. LiVolsi VA: Pathology of thyroid disease. In: Falk SA: Thyroid Disease: Endocrinology, Surgery, Nuclear Medicine, and Radiotherapy. Philadelphia, Pa: Lippincott-Raven, 1997, pp 127-175.
  2. American Cancer Society: Cancer Facts and Figures 2018. Atlanta, Ga: American Cancer Society, 2018. Available online. Last accessed August 3, 2018.
  3. Tennvall J, Biörklund A, Möller T, et al.: Is the EORTC prognostic index of thyroid cancer valid in differentiated thyroid carcinoma? Retrospective multivariate analysis of differentiated thyroid carcinoma with long follow-up. Cancer 57 (7): 1405-14, 1986. [PUBMED Abstract]
  4. Khoo ML, Asa SL, Witterick IJ, et al.: Thyroid calcification and its association with thyroid carcinoma. Head Neck 24 (7): 651-5, 2002. [PUBMED Abstract]
  5. Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1457-72.
  6. Pacini F, Vorontsova T, Molinaro E, et al.: Prevalence of thyroid autoantibodies in children and adolescents from Belarus exposed to the Chernobyl radioactive fallout. Lancet 352 (9130): 763-6, 1998. [PUBMED Abstract]
  7. Cardis E, Kesminiene A, Ivanov V, et al.: Risk of thyroid cancer after exposure to 131I in childhood. J Natl Cancer Inst 97 (10): 724-32, 2005. [PUBMED Abstract]
  8. Tronko MD, Howe GR, Bogdanova TI, et al.: A cohort study of thyroid cancer and other thyroid diseases after the chornobyl accident: thyroid cancer in Ukraine detected during first screening. J Natl Cancer Inst 98 (13): 897-903, 2006. [PUBMED Abstract]
  9. Iribarren C, Haselkorn T, Tekawa IS, et al.: Cohort study of thyroid cancer in a San Francisco Bay area population. Int J Cancer 93 (5): 745-50, 2001. [PUBMED Abstract]
  10. American Cancer Society: Cancer Facts and Figures 2015. Atlanta, Ga: American Cancer Society, 2015. Available online. Last accessed September 21, 2018.
  11. Salvatore G, Giannini R, Faviana P, et al.: Analysis of BRAF point mutation and RET/PTC rearrangement refines the fine-needle aspiration diagnosis of papillary thyroid carcinoma. J Clin Endocrinol Metab 89 (10): 5175-80, 2004. [PUBMED Abstract]
  12. Mazzaferri EL: Treating differentiated thyroid carcinoma: where do we draw the line? Mayo Clin Proc 66 (1): 105-11, 1991. [PUBMED Abstract]
  13. Grant CS, Hay ID, Gough IR, et al.: Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 104 (6): 954-62, 1988. [PUBMED Abstract]
  14. Sanders LE, Cady B: Differentiated thyroid cancer: reexamination of risk groups and outcome of treatment. Arch Surg 133 (4): 419-25, 1998. [PUBMED Abstract]
  15. Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. Eur J Surg Oncol 20 (6): 613-21, 1994. [PUBMED Abstract]
  16. Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994. [PUBMED Abstract]
  17. Shah JP, Loree TR, Dharker D, et al.: Prognostic factors in differentiated carcinoma of the thyroid gland. Am J Surg 164 (6): 658-61, 1992. [PUBMED Abstract]
  18. Andersen PE, Kinsella J, Loree TR, et al.: Differentiated carcinoma of the thyroid with extrathyroidal extension. Am J Surg 170 (5): 467-70, 1995. [PUBMED Abstract]
  19. Coburn MC, Wanebo HJ: Prognostic factors and management considerations in patients with cervical metastases of thyroid cancer. Am J Surg 164 (6): 671-6, 1992. [PUBMED Abstract]
  20. Voutilainen PE, Multanen MM, Leppäniemi AK, et al.: Prognosis after lymph node recurrence in papillary thyroid carcinoma depends on age. Thyroid 11 (10): 953-7, 2001. [PUBMED Abstract]
  21. Sellers M, Beenken S, Blankenship A, et al.: Prognostic significance of cervical lymph node metastases in differentiated thyroid cancer. Am J Surg 164 (6): 578-81, 1992. [PUBMED Abstract]
  22. Nixon IJ, Kuk D, Wreesmann V, et al.: Defining a Valid Age Cutoff in Staging of Well-Differentiated Thyroid Cancer. Ann Surg Oncol 23 (2): 410-5, 2016. [PUBMED Abstract]
  23. Nixon IJ, Wang LY, Migliacci JC, et al.: An International Multi-Institutional Validation of Age 55 Years as a Cutoff for Risk Stratification in the AJCC/UICC Staging System for Well-Differentiated Thyroid Cancer. Thyroid 26 (3): 373-80, 2016. [PUBMED Abstract]
  24. Cunningham DK, Yao KA, Turner RR, et al.: Sentinel lymph node biopsy for papillary thyroid cancer: 12 years of experience at a single institution. Ann Surg Oncol 17 (11): 2970-5, 2010. [PUBMED Abstract]
  25. Lennard CM, Patel A, Wilson J, et al.: Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer. Surgery 129 (5): 552-8, 2001. [PUBMED Abstract]
  26. van Herle AJ, van Herle KA: Thyroglobulin in benign and malignant thyroid disease. In: Falk SA: Thyroid Disease: Endocrinology, Surgery, Nuclear Medicine, and Radiotherapy. Philadelphia, Pa: Lippincott-Raven, 1997, pp 601-618.
  27. Ruiz-Garcia J, Ruiz de Almodóvar JM, Olea N, et al.: Thyroglobulin level as a predictive factor of tumoral recurrence in differentiated thyroid cancer. J Nucl Med 32 (3): 395-8, 1991. [PUBMED Abstract]
  28. Duren M, Siperstein AE, Shen W, et al.: Value of stimulated serum thyroglobulin levels for detecting persistent or recurrent differentiated thyroid cancer in high- and low-risk patients. Surgery 126 (1): 13-9, 1999. [PUBMED Abstract]
  29. Godballe C, Asschenfeldt P, Jørgensen KE, et al.: Prognostic factors in papillary and follicular thyroid carcinomas: p53 expression is a significant indicator of prognosis. Laryngoscope 108 (2): 243-9, 1998. [PUBMED Abstract]