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Thyroid cancer is cancer that develops from the tissues of the thyroid gland.[1] It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body.[8][9] Symptoms can include swelling or a lump in the neck.[1] Cancer can also occur in the thyroid after spread from other locations, in which case it is not classified as thyroid cancer.[4]
Globally as of 2015, 3.2 million people have thyroid cancer.[6] In 2012, 298,000 new cases occurred.[11] It most commonly is diagnosed between the ages of 35 and 65.[5] Women are affected more often than men.[5] Those of Asian descent are more commonly affected;[4] with a higher rate of mortality among Filipino females.[12] Rates have increased in the last few decades, which is believed to be due to better detection.[11] In 2015, it resulted in 31,900 deaths.[7]
Signs and symptoms
Most often, the first symptom of thyroid cancer is a nodule in the thyroid region of the neck.[13] However, up to 65% of adults have small nodules in their thyroids, but typically under 10% of these nodules are found to be cancerous.[14] Sometimes, the first sign is an enlarged lymph node. Later symptoms that can be present are pain in the anterior region of the neck and changes in voice due to an involvement of the recurrent laryngeal nerve.[15]
Thyroid cancer is usually found in a euthyroid patient, but symptoms of hyperthyroidism or hypothyroidism may be associated with a large or metastatic, well-differentiated tumor. Thyroid nodules are of particular concern when they are found in those under the age of 20. The presentation of benign nodules at this age is less likely, thus the potential for malignancy is far greater.[citation needed]
Causes
Thyroid cancers are thought to be related to a number of environmental and genetic predisposing factors, but significant uncertainty remains regarding their causes.[16]
Environmental exposure to ionizing radiation from both natural background sources and artificial sources is suspected to play a significant role, and significantly increased rates of thyroid cancer occur in those exposed to mantlefield radiation for lymphoma, and those exposed to iodine-131 following the Chernobyl,[17]Fukushima, Kyshtym, and Windscale[18] nuclear disasters.[19]Thyroiditis and other thyroid diseases also predispose to thyroid cancer.[18][20]
After a thyroid nodule is found during a physical examination, a referral to an endocrinologist or a thyroidologist may occur. Most commonly, an ultrasound is performed to confirm the presence of a nodule and assess the status of the whole gland. Some ultrasound results may report a TI-RADS or TIRADS score to categorize the risk of malignancy.[22] Measurement of thyroid stimulating hormone, free and/or total triiodothyronine (T3) and thyroxine (T4) levels, and antithyroid antibodies will help decide if a functional thyroid disease such as Hashimoto's thyroiditis is present, a known cause of a benign nodular goiter.[23] a thyroid scan, performed often in conjunction with a radioactive iodine uptake test may be used to determine whether a nodule is "hot" or "cold"[24] which may help to make a decision whether to perform a biopsy of the nodule.[25] Measurement of calcitonin is necessary to exclude the presence of medullary thyroid cancer. Finally, to achieve a definitive diagnosis before deciding on treatment, a fine needle aspiration cytology test may be performed and reported according to the Bethesda system.[26]
After diagnosis, to understand potential for spread of disease, or for follow up monitoring after surgery, a whole body I-131 or I-123 radioactive iodine scan may be performed.[27]
In adults without symptoms, screening for thyroid cancer is not recommended.[28]
Classification
Pie chart of thyroid cancer types by incidence.[29]
Thyroid cancers can be classified according to their histopathological characteristics.[30][31] These variants can be distinguished (distribution over various subtypes may show regional variation):
Papillary thyroid cancer (75 to 85% of cases[32]) – is more often diagnosed in young females compared to other types of thyroid cancer and has an excellent prognosis. It may occur in women with familial adenomatous polyposis and in patients with Cowden syndrome. A follicular variant of papillary thyroid cancer also exists.[33]
The follicular and papillary types together can be classified as "differentiated thyroid cancer".[37] These types have a more favorable prognosis than the medullary and undifferentiated types.[38]
Papillary microcarcinoma is a subset of papillary thyroid cancer defined as a nodule measuring less than or equal to 1 cm.[39] 43% of all thyroid cancers and 50% of new cases of papillary thyroid carcinoma are papillary microcarcinoma.[40][41] Management strategies for incidental papillary microcarcinoma on ultrasound (and confirmed on FNAB) range from total thyroidectomy with radioactive iodine ablation to lobectomy or observation alone. Harach et al. suggest using the term "occult papillary tumor" to avoid giving patients distress over having cancer. Woolner et al. first arbitrarily coined the term "occult papillary carcinoma", in 1960, to describe papillary carcinomas ≤ 1.5 cm in diameter.[42]
Staging
Cancer staging is the process of determining the extent of the development of a cancer. The TNM staging system is usually used to classify stages of cancers, but not of the brain.[43]
Stage M1 thyroid cancer
Stage N1a thyroid cancer
Stage N1b thyroid cancer
Stage T1a thyroid cancer
Stage T1b thyroid cancer
Stage T2 thyroid cancer
Stage T3 thyroid cancer
Stage T4a thyroid cancer
Stage T4b thyroid cancer
Metastases
Detection of differentiated thyroid cancer metastases may be detected by performing a full-body scintigraphy using iodine-131.[44][45]
Spread
Thyroid cancer can spread directly, via lymphatics or blood. Direct spread occurs through infiltration of the surrounding tissues. The tumor infiltrates into infrahyoid muscles, trachea, oesophagus, recurrent laryngeal nerve, carotid sheath, etc. The tumor then becomes fixed. Anaplastic carcinoma spreads mostly by direct spread, while papillary carcinoma spreads so the least. Lymphatic spread is most common in papillary carcinoma. Cervical lymph nodes become palpable in papillary carcinoma even when the primary tumor is unpalpable. Deep cervical nodes, pretracheal, prelaryngeal, and paratracheal groups of lymph nodes are often affected. The lymph node affected is usually the same side as that of the location of the tumor. Blood spread is also possible in thyroid cancers, especially in follicular and anaplastic carcinoma. The tumor emboli do angioinvasion of lungs; end of long bones, skull, and vertebrae are affected. Pulsating metastases occur because of their increased vascularity.[46]
Treatment
Thyroidectomy and dissection of central neck compartment is the initial step in treatment of thyroid cancer in the majority of cases.[13] Thyroid-preserving operations may be applied in cases, when thyroid cancer exhibits low biological aggressiveness (e.g. well-differentiated cancer, no evidence of lymph-node metastases, low MIB-1 index, no major genetic alterations like BRAF mutations, RET/PTC rearrangements, p53 mutations etc.) in patients younger than 45 years.[47]
If the diagnosis of well-differentiated thyroid cancer (e.g. papillary thyroid cancer) is established or suspected by FNA, then surgery is indicated, whereas watchful waiting strategy is not recommended in any evidence-based guidelines.[47][48]Watchful waiting reduces overdiagnosis and overtreatment of thyroid cancer among old patients.[49]
Post surgical monitoring for recurrence or metastasis may include routine ultrasound, CT scans, FDG-PET/CT, radioactive iodine whole body scans, and routine laboratory blood tests for changes in thyrogolubin, thyroglobuilin antibodies, or calcitonin, depending on the variant of thyroid cancer.[50][51][52]
Radioactive iodine-131 is used in people with papillary or follicular thyroid cancer for ablation of residual thyroid tissue after surgery and for the treatment of thyroid cancer.[53] Patients with medullary, anaplastic, and most Hurthle-cell cancers do not benefit from this therapy.[13] External irradiation may be used when the cancer is unresectable, when it recurs after resection, or to relieve pain from bone metastasis.[13]
Sorafenib and lenvatinib are approved for advanced metastatic thyroid cancer.[54] Numerous agents are in phase II and III clinical trials.[54]
Prognosis
The prognosis of thyroid cancer is related to the type of cancer and the stage at the time of diagnosis. For the most common form of thyroid cancer, papillary, the overall prognosis is excellent. Indeed, the increased incidence of papillary thyroid carcinoma in recent years is likely related to increased and earlier diagnosis. One can look at the trend to earlier diagnosis in two ways. The first is that many of these cancers are small and not likely to develop into aggressive malignancies. A second perspective is that earlier diagnosis removes these cancers at a time when they are not likely to have spread beyond the thyroid gland, thereby improving the long-term outcome for the patient. No consensus exists at present on whether this trend toward earlier diagnosis is beneficial or unnecessary.
The argument against early diagnosis and treatment is based on the logic that many small thyroid cancers (mostly papillary) will not grow or metastasize. This view holds the overwhelming majority of thyroid cancers are overdiagnosed that is, will never cause any symptoms, illness, or death for the patient, even if nothing is ever done about the cancer. Including these overdiagnosed cases skews the statistics by lumping clinically significant cases in with apparently harmless cancers.[55] Thyroid cancer is incredibly common, with autopsy studies of people dying from other causes showing that more than one-third of older adults technically have thyroid cancer, which is causing them no harm.[55] Detecting nodules that might be cancerous is easy, simply by feeling the throat, which contributes to the level of overdiagnosis. Benign (noncancerous) nodules frequently co-exist with thyroid cancer; sometimes, a benign nodule is discovered, but surgery uncovers an incidental small thyroid cancer. Increasingly, small thyroid nodules are discovered as incidental findings on imaging (CT scan, MRI, ultrasound) performed for another purpose; very few of these people with accidentally discovered, symptom-free thyroid cancers will ever have any symptoms, and treatment in such patients has the potential to cause harm to them, not to help them.[55][56]
Thyroid cancer is three times more common in women than in men, but according to European statistics,[57] the overall relative 5-year survival rate for thyroid cancer is 85% for females and 74% for males.[58]
The table below highlights some of the challenges with decision making and prognostication in thyroid cancer. While general agreement exists that stage I or II papillary, follicular, or medullary cancer have good prognoses, when evaluating a small thyroid cancer to determine which ones will grow and metastasize and which will not is not possible. As a result, once a diagnosis of thyroid cancer has been established (most commonly by a fine needle aspiration), a total thyroidectomy likely will be performed.
This drive to earlier diagnosis has also manifested itself on the European continent by the use of serum calcitonin measurements in patients with goiter to identify patients with early abnormalities of the parafollicular or calcitonin-producing cells within the thyroid gland. As multiple studies have demonstrated, the finding of an elevated serum calcitonin is associated with the finding of a medullary thyroid carcinoma in as high as 20% of cases.
In Europe where the threshold for thyroid surgery is lower than in the United States, an elaborate strategy that incorporates serum calcitonin measurements and stimulatory tests for calcitonin has been incorporated into the decision to perform a thyroidectomy; thyroid experts in the United States, looking at the same data, have for the most part not incorporated calcitonin testing as a routine part of their evaluations, thereby eliminating a large number of thyroidectomies and the consequent morbidity. The European thyroid community has focused on prevention of metastasis from small medullary thyroid carcinomas; the North American thyroid community has focused more on prevention of complications associated with thyroidectomy (see American Thyroid Association guidelines below).
As demonstrated in the table below, individuals with stage III and IV disease have a significant risk of dying from thyroid cancer. While many present with widely metastatic disease, an equal number evolve over years and decades from stage I or II disease. Physicians who manage thyroid cancer of any stage recognize that a small percentage of patients with low-risk thyroid cancer will progress to metastatic disease.
Improvements have been made in thyroid cancer treatment during recent years. The identification of some of the molecular or DNA abnormalities has led to the development of therapies that target these molecular defects. The first of these agents to negotiate the approval process is vandetanib, a tyrosine kinase inhibitor that targets the RET proto-oncogene, two subtypes of the vascular endothelial growth factor receptor, and the epidermal growth factor receptor.[59] More of these compounds are under investigation and are likely to make it through the approval process. For differentiated thyroid carcinoma, strategies are evolving to use selected types of targeted therapy to increase radioactive iodine uptake in papillary thyroid carcinomas that have lost the ability to concentrate iodide. This strategy would make possible the use of radioactive iodine therapy to treat "resistant" thyroid cancers. Other targeted therapies are being evaluated, making life extension possible over the next 5–10 years for those with stage III and IV thyroid cancer.
Prognosis is better in younger people than older ones.[58]
Prognosis depends mainly on the type of cancer and cancer stage.
Thyroid cancer, in 2010, resulted in 36,000 deaths globally up from 24,000 in 1990.[65]Obesity may be associated with a higher incidence of thyroid cancer, but this relationship remains the subject of much debate.[66]
Thyroid cancer accounts for less than 1% of cancer cases and deaths in the UK. Around 2,700 people were diagnosed with thyroid cancer in the UK in 2011, and around 370 people died from the disease in 2012.[67]
However, in South Korea, thyroid cancer was the 5th most prevalent cancer, which accounted for 7.7% of new cancer cases in 2020.[68]
^ abcdHu MI, Vassilopoulou-Sellin R, Lustig R, Lamont JP, eds. (2008). "Thyroid and Parathyroid Cancers". Cancer Management: A Multidisciplinary Approach (11th ed.). Lawrence, Kansas: CMP Media. ISBN 978-1-891483-62-2. Archived from the original on 28 February 2010.
^Durante C, Grani G, Lamartina L, Filetti S, Mandel SJ, Cooper DS (March 2018). "The Diagnosis and Management of Thyroid Nodules: A Review". JAMA. 319 (9): 914–924. doi:10.1001/jama.2018.0898. PMID29509871. S2CID5042725.
^"Thyroid Cancer". Herbert Irving Comprehensive Cancer Center (HICCC) - New York. 1 February 2021. Archived from the original on 5 February 2023. Retrieved 5 February 2023.
^Bibbins-Domingo K, Grossman DC, Curry SJ, Barry MJ, Davidson KW, Doubeni CA, et al. (May 2017). "Screening for Thyroid Cancer: US Preventive Services Task Force Recommendation Statement". JAMA. 317 (18): 1882–1887. doi:10.1001/jama.2017.4011. PMID28492905. S2CID205091526.
^Malith V, Bombil I, Harran N, Luvhengo TE (September 2018). "Demographic and histological subtypes of Hurthle cell tumours of the thyroid in a South African setting". South African Journal of Surgery. Suid-Afrikaanse Tydskrif vir Chirurgie. 56 (3): 20–23. doi:10.17159/2078-5151/2018/v56n3a2557 (inactive 24 April 2024). PMID30264938.{{cite journal}}: CS1 maint: DOI inactive as of April 2024 (link)
^"Thyroid Cancer Treatment". National Cancer Institute. 1 January 1980. Archived from the original on 21 April 2008. Retrieved 22 December 2007.
^"Thyroid cancer". National Cancer Institute. Archived from the original on 20 December 2007. Retrieved 22 December 2007.
^ abcChapter 20 in: Mitchell RS, Kumar V, Abbas AK, Fausto N (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 978-1-4160-2973-1. 8th edition.
^Nix PA, Nicolaides A, Coatesworth AP (January 2006). "Thyroid cancer review 3: management of medullary and undifferentiated thyroid cancer". International Journal of Clinical Practice. 60 (1): 80–84. doi:10.1111/j.1742-1241.2005.00673.x. PMID16409432. S2CID11825588.
^Hughes DT, Haymart MR, Miller BS, Gauger PG, Doherty GM (March 2011). "The most commonly occurring papillary thyroid cancer in the United States is now a microcarcinoma in a patient older than 45 years". Thyroid. 21 (3): 231–236. doi:10.1089/thy.2010.0137. hdl:2027.42/90466. PMID21268762.
^Woolner LB, Lemmon ML, Beahrs OH, Black BM, Keating FR (January 1960). "Occult papillary carcinoma of the thyroid gland: a study of 140 cases observed in a 30-year period". The Journal of Clinical Endocrinology and Metabolism. 20: 89–105. doi:10.1210/jcem-20-1-89. PMID13845950.
^"Cancer Staging - NCI". www.cancer.gov. 9 March 2015. Archived from the original on 19 March 2015. Retrieved 5 February 2023.
^Schlumberger M, Arcangioli O, Piekarski JD, Tubiana M, Parmentier C (November 1988). "Detection and treatment of lung metastases of differentiated thyroid carcinoma in patients with normal chest X-rays". Journal of Nuclear Medicine. 29 (11): 1790–1794. PMID3183748.
^Das S (2008). A concise textbook of surgery (5th ed.). Calcutta: Dr S. Das. ISBN 978-8190568128.
^ abCooper DS, Doherty GM, Haugen BR, Hauger BR, Kloos RT, Lee SL, et al. (November 2009). "Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer". Thyroid. 19 (11): 1167–1214. doi:10.1089/thy.2009.0110. hdl:2027.42/78131. PMID19860577.
^ abcWelch HG, Schwartz L, Woloshin S (2011). Overdiagnosed: Making People Sick in the Pursuit of Health. [Malaysia?]: Beacon Press. pp. 61–34. ISBN 978-0-8070-2200-9.
^Hofman MS (September 2013). "Thyroid nodules: time to stop over-reporting normal findings and update consensus guidelines". BMJ. 347: f5742. doi:10.1136/bmj.f5742. PMID24068719. S2CID5660811.
^"Thyroid Cancer". MedicineNet.com. Archived from the original on 20 October 2011. Retrieved 26 October 2011.
^ abNumbers from EUROCARE, from Page 10Archived 13 May 2016 at the Wayback Machine in: Grünwald F, Biersack HJ (2005). Thyroid cancer. Berlin: Springer. ISBN 978-3-540-22309-2.
^ abcdefgNumbers from National Cancer Database in the US, from Page 10Archived 13 May 2016 at the Wayback Machine in: Grünwald F, Biersack HJ (2005). Thyroid cancer. Berlin: Springer. ISBN 978-3-540-22309-2. (Note:Book also states that the 14% 10-year survival for anaplastic thyroid cancer was overestimated)
^Rounded up to nearest natural number from 96.7% as given by Santacroce L, Gagliardi S, Kennedy AS (28 September 2010). "Thyroid, Papillary Carcinoma". eMedicine. Archived from the original on 28 July 2010.
^"Republic of Korea Cancer Rates"(PDF). Global Cancer Observatory (GCO). World Health Organization. 2020. Archived(PDF) from the original on 11 November 2022. Retrieved 5 February 2022.