Thyroid cancer

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Thyroid cancer
Thyroid papillary carcinoma histopathology (4).jpg
Micrograph of a papillary thyroid carcinoma demonstrating diagnostic features (nuclear clearing and overlapping nuclei).
Specialty Oncology
Symptoms Swelling or lump in the neck [1]
Risk factors Radiation exposure, enlarged thyroid, family history, [1] [2] obesity [3]
Diagnostic method Ultrasound, fine needle aspiration [1]
Differential diagnosis Thyroid nodule, metastatic disease [1] [4]
TreatmentSurgery, radiation therapy, chemotherapy, thyroid hormone, targeted therapy, watchful waiting [1]
Prognosis Five year survival rates 98% (US) [5]
Frequency3.2 million (2015) [6]
Deaths31,900 (2015) [7]

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]

Contents

Risk factors include radiation exposure at a young age, having an enlarged thyroid, family history and obesity. [1] [2] [3] The four main types are papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer, and anaplastic thyroid cancer. [4] Diagnosis is often based on ultrasound and fine needle aspiration. [1] Screening people without symptoms and at normal risk for the disease is not recommended as of 2017. [10]

Treatment options may include surgery, radiation therapy including radioactive iodine, chemotherapy, thyroid hormone, targeted therapy, and watchful waiting. [1] Surgery may involve removing part or all of the thyroid. [4] Five-year survival rates are 98% in the United States. [5]

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]

Genetic causes include multiple endocrine neoplasia type 2, which markedly increases rates, particularly of the rarer medullary form of the disease. [21]

Diagnosis

Micrograph of a lymph node with papillary thyroid carcinoma Lymph node with papillary thyroid carcinoma.jpg
Micrograph of a lymph node with papillary thyroid carcinoma

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. Pie chart of relative incidences of thyroid cancers.png
Pie chart of thyroid cancer types by incidence.

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):

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]

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]

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]

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. [50] 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. [51] Numerous agents are in phase II and III clinical trials. [51]

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. [52] [53] [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 type		 5-year survival 10-year survival
Stage IStage IIStage IIIStage IVOverallOverall
Papillary 100% [60] 100% [60] 93% [60] 51%51% [60] 96% [61] or 97% [62] 93% [61]
Follicular 100% [60] 100% [60] 71% [60] 50% [60] 91% [61] 85% [61]
Medullary 100% [60] 98% [60] 81% [60] 28% [60] 80%, [61] 83% [63] or 86% [64] 75% [61]
Anaplastic (always stage IV) [60] 7% [60] 7% [60] or 14% [61] (no data)

Epidemiology

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]

Notable cases

Related Research Articles

<span class="mw-page-title-main">Thyroid</span> Endocrine gland in the neck; secretes hormones that influence metabolism

The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the isthmus (pl.: isthmi). The thyroid gland is a butterfly-shaped gland located in the neck below the Adam's apple. Microscopically, the functional unit of the thyroid gland is the spherical thyroid follicle, lined with follicular cells (thyrocytes), and occasional parafollicular cells that surround a lumen containing colloid. The thyroid gland secretes three hormones: the two thyroid hormones – triiodothyronine (T3) and thyroxine (T4) – and a peptide hormone, calcitonin. The thyroid hormones influence the metabolic rate and protein synthesis and growth and development in children. Calcitonin plays a role in calcium homeostasis. Secretion of the two thyroid hormones is regulated by thyroid-stimulating hormone (TSH), which is secreted from the anterior pituitary gland. TSH is regulated by thyrotropin-releasing hormone (TRH), which is produced by the hypothalamus.

<span class="mw-page-title-main">Thyroid neoplasm</span> Medical condition

Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm, such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected than men. The estimated number of new cases of thyroid cancer in the United States in 2023 is 43,720 compared to only 2,120 deaths. Of all thyroid nodules discovered, only about 5 percent are cancerous, and under 3 percent of those result in fatalities.

<span class="mw-page-title-main">Thyroidectomy</span> Surgical procedure involving partial or complete removal of the thyroid

A thyroidectomy is an operation that involves the surgical removal of all or part of the thyroid gland. In general surgery, endocrine or head and neck surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other condition of the thyroid gland or goiter. Other indications for surgery include cosmetic, or symptomatic obstruction. Thyroidectomy is a common surgical procedure that has several potential complications or sequelae including: temporary or permanent change in voice, temporary or permanently low calcium, need for lifelong thyroid hormone replacement, bleeding, infection, and the remote possibility of airway obstruction due to bilateral vocal cord paralysis. Complications are uncommon when the procedure is performed by an experienced surgeon.

<span class="mw-page-title-main">Calcitonin</span> Amino acid peptide hormone secreted by the thyroid gland

Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH).

<span class="mw-page-title-main">Thyroglobulin</span> Protein produced and used by the thyroid

Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment of the thyroid follicles, accounting for approximately half of the protein content of the thyroid gland. Human TG (hTG) is a homodimer of subunits each containing 2768 amino acids as synthesized.

<span class="mw-page-title-main">Pentagastrin</span> Chemical compound

Pentagastrin is a synthetic polypeptide that has effects like gastrin when given parenterally. It stimulates the secretion of gastric acid, pepsin, and intrinsic factor, and has been used as a diagnostic aid as the pentagastrin-stimulated calcitonin test.

<span class="mw-page-title-main">Thyroid disease</span> Medical condition

Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning that it is an endocrine organ. These hormones normally act in the body to regulate energy use, infant development, and childhood development.

<span class="mw-page-title-main">Hürthle cell</span> Medical condition

A Hürthle cell is a cell in the thyroid that is often associated with Hashimoto's thyroiditis as well as benign and malignant tumors. This version is a relatively rare form of differentiated thyroid cancer, accounting for only 3-10% of all differentiated thyroid cancers. Oncocytes in the thyroid are often called Hürthle cells. Although the terms oncocyte, oxyphilic cell, and Hürthle cell are used interchangeably, Hürthle cell is used only to indicate cells of thyroid follicular origin.

<span class="mw-page-title-main">Toxic multinodular goitre</span> Medical condition

Toxic multinodular goiter (TMNG), also known as multinodular toxic goiter (MNTG), is an active multinodular goiter associated with hyperthyroidism.

<span class="mw-page-title-main">Hürthle cell neoplasm</span> Medical condition

Hürthle cell neoplasm is a rare tumor of the thyroid, typically seen in women between the ages of 70 and 80 years old. When benign, it is called a Hürthle cell adenoma, and when malignant it is called a Hürthle cell carcinoma. Hürthle cell adenoma is characterized by a mass of benign Hürthle cells. Typically such a mass is removed because it is not easy to predict whether it will transform into the malignant counterpart of Hürthle cell carcinoma, which is a subtype of follicular thyroid cancer.

<span class="mw-page-title-main">Anaplastic thyroid cancer</span> Medical condition

Anaplastic thyroid cancer (ATC), also known as anaplastic thyroid carcinoma, is an aggressive form of thyroid cancer characterized by uncontrolled growth of cells in the thyroid gland. This form of cancer generally carries a very poor prognosis due to its aggressive behavior and resistance to cancer treatments. The cells of anaplastic thyroid cancer are highly abnormal and usually no longer resemble the original thyroid cells and have poor differentiation.

<span class="mw-page-title-main">Papillary thyroid cancer</span> Medical condition

Papillary thyroid cancer 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. It is often well-differentiated, slow-growing, and localized, although it can metastasize.

<span class="mw-page-title-main">Thyroid nodule</span> Medical condition

Thyroid nodules are nodules which commonly arise within an otherwise normal thyroid gland. They may be hyperplastic or tumorous, but only a small percentage of thyroid tumors are malignant. Small, asymptomatic nodules are common, and often go unnoticed. Nodules that grow larger or produce symptoms may eventually need medical care. A goitre may have one nodule – uninodular, multiple nodules – multinodular, or be diffuse.

<span class="mw-page-title-main">Follicular thyroid cancer</span> Medical condition

Follicular thyroid cancer accounts for 15% of thyroid cancer and occurs more commonly in women over 50 years of age. Thyroglobulin (Tg) can be used as a tumor marker for well-differentiated follicular thyroid cancer. Thyroid follicular cells are the thyroid cells responsible for the production and secretion of thyroid hormones.

<span class="mw-page-title-main">Medullary thyroid cancer</span> Malignant thyroid neoplasm originating from C-cells

Medullary thyroid cancer is a form of thyroid carcinoma which originates from the parafollicular cells, which produce the hormone calcitonin. Medullary tumors are the third most common of all thyroid cancers and together make up about 3% of all thyroid cancer cases. MTC was first characterized in 1959.

<span class="mw-page-title-main">Multiple endocrine neoplasia type 2B</span> Medical condition

Multiple endocrine neoplasia type 2B is a genetic disease that causes multiple tumors on the mouth, eyes, and endocrine glands. It is the most severe type of multiple endocrine neoplasia, differentiated by the presence of benign oral and submucosal tumors in addition to endocrine malignancies. It was first described by Wagenmann in 1922, and was first recognized as a syndrome in 1965-1966 by E.D. Williams and D.J. Pollock. It is caused by the pathogenic variant p.Met918Thr in the RET gene. This variant can cause medullary thyroid cancer and Pheochromocytoma. Presentation can include a Marfanoid body, enlarged lips, and ganglionueuromas.

<span class="mw-page-title-main">Noninvasive follicular thyroid neoplasm with papillary-like nuclear features</span>

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an indolent thyroid tumor that was previously classified as an encapsulated follicular variant of papillary thyroid carcinoma, necessitating a new classification as it was recognized that encapsulated tumors without invasion have an indolent behavior, and may be over-treated if classified as a type of cancer.

In CT scan of the thyroid, focal and diffuse thyroid abnormalities are commonly encountered. These findings can often lead to a diagnostic dilemma, as the CT reflects nonspecific appearances. Ultrasound (US) examination has a superior spatial resolution and is considered the modality of choice for thyroid evaluation. Nevertheless, CT detects incidental thyroid nodules (ITNs) and plays an important role in the evaluation of thyroid cancer.

Dr. Yuri Nikiforov is an American scientist who revolutionized the understanding of thyroid cancer, most recently winning a two-year battle in which the World Health Organization has agreed in 2017 to reclassify non-invasive thyroid tumors to non-cancerogenic liaisons. Those tumors typically have some, but not all, characteristics of cancer. The WHO has agreed to change the term for the tumors from Encapsulated Follicular Variant of Papillary Thyroid Carcinoma to Noninvasive Follicular Thyroid Neoplasm With Papillary-like Nuclear Features, or NIFTP. About 45,000 people a year are diagnosed with NIFTP in the world. The decision led to a change in protocol of medical treatment, which no longer required removal of the whole thyroid gland from such patients as well as ended the use of radioactive iodine, extending their life expectancy and quality of life. The patients still undergo surgery, in which their thyroid tumors are removed, typically with half, but not all, of the thyroid gland.

Active surveillance is an observational management being increasingly accepted as an alternative over immediate surgery due to low-risk papillary thyroid microcarcinoma with no evidence of extension or metastatic spread. Patients on active surveillance are observed with periodical ultrasound examinations and thyroid function tests. If disease progression is detected, patients are treated with surgery. The chances of thyroid cancer increased during the past 3 decades in many countries, mostly due to increased detection of small papillary thyroid carcinoma, without associated increase in mortality from thyroid cancer.

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