Thyroid Cancer Overview

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Thyroid cancer is the most common form of endocrine malignancy and accounts for more than 3% of all annually diagnosed cancers worldwide.1 Thyroid cancers are categorized into 5 main histological types that include papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), Hürthle-cell thyroid cancers (HTCs), anaplastic thyroid cancer, and medullary thyroid cancer.1,2 PTC, FTC, and HTCs are also referred to as differentiated thyroid cancer, while anaplastic is also referred to as poorly differentiated thyroid cancer, which is the most aggressive form. Medullary thyroid cancer is the only type that develops from thyroid C-cells.1 Differentiated thyroid cancers account for the majority (85%) of thyroid cancers (PTCs, 75%; FTCs, approximately 15%; HTCs, <19%).2 There are many elements that contribute to the significant complexity in the development of a tumor from cancer cells. Beyond the heterogeneity in histopathology types, heterogeneity results from additional factors, such as variation in several genetic and/or nongenetic alterations, the number of interactions between a tumor and the surrounding microenvironment, and interpatient differences.1

In the United States, the incidence of thyroid cancer has increased significantly over the past 4 decades.3 Between 1974 and 2013, the estimated incidence of thyroid cancer increased 3.6% per year on average. From 1974 to 1977, the estimated incidence was 4.56 per 100,000 person-years, while from 2010 to 2013, the estimated incidence was 14.42 per 100,000 person-years. The overall increase in incidence was driven in larger part by an annual increase of 4.4% for PTC diagnoses. However, the annual percent change in incidence-based mortality was lower than the incidence of thyroid cancer. Between 1994 and 2013, the estimated incidence-based mortality increased 1.1% per year. From 1994 to 1997, the estimated incidence-based mortality was 0.40 per 100,000 person-years and 0.46 per 100,000 person-years from 2010 to 2013.3

Thyroid cancers most frequently present as painless nodules found upon routine palpation.3 According to the American Thyroid Association guidelines, only thyroid nodules >1 cm should be evaluated, as they have a higher potential of being clinically significant cancers.4 However, in the presence of clinical symptoms or associated lymphadenopathy, nodules <1 cm may require further evaluation. The initial evaluation of a thyroid nodule should include a serum thyrotropin measurement. A radionuclide thyroid scan should be performed if the serum thyrotropin is subnormal.4

In addition, a complete history and physical examination should be performed with a focus on the thyroid gland and adjacent cervical lymph nodes. Patient history predictive of malignancy includes history of head and neck radiation therapy in childhood, total body radiation therapy for bone marrow transplantation, pediatric exposure to ionizing radiation from fallout, familial thyroid carcinoma, or thyroid cancer syndrome in a first-degree relative, rapid nodule growth, and hoarseness.4

Physical findings indicative of malignancy include vocal cord paralysis, cervical lymphadenopathy, and fixation of the nodule to surrounding tissue. In all patients with known or suspected thyroid nodules, a thyroid sonography with survey of the cervical lymph nodes should be performed. Thyroid nodule diagnostic fine needle aspiration is recommended for nodules >1 cm with high and intermediate suspicion sonographic pattern and nodules ≥1.5 cm with low suspicion sonographic pattern. Finally, the American Thyroid Association recommends that thyroid nodule fine needle aspiration cytology be reported using the diagnostic groups as outlined in the Bethesda System for Reporting Thyroid Cytopathology.4


  1. Chmielik E, Rusinek D, Oczko-Wojciechowska, et al. Heterogeneity of thyroid cancer. Pathobiology. 2018;85:117-129.
  2. Cabanillas ME, Ryder M, Jimenez C. Targeted therapy for advanced thyroid cancer: kinase inhibitors and beyond. Endocr Rev. 2019;40:1573-1604.
  3. Lim H, Devesa SS, Sosa JA, et al. Trends in thyroid cancer incidence and mortality in the United States, 1974-2013. JAMA. 2017;17:1338-1348.
  4. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26:1-33.

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