Globally as of 2015 3.2 million people have thyroid cancer. In 2012, 298,000 new cases occurred. It most commonly occurs between the ages of 35 and 65. Women are affected more often than men. Those of Asian descent are more commonly affected. Rates have increased in the last few decades which is believed to be due to better detection. In 2015 it resulted in 31,900 deaths.
Most often the first symptom of thyroid cancer is a nodule in the thyroid region of the neck. However, up to 65% of adults have small nodules in their thyroids, but typically under 10% of these nodules are found to be cancerous. 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.
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, and thus the potential for malignancy is far greater.
Thyroid cancers are thought to be related to a number of environmental and genetic predisposing factors, but significant uncertainty remains regarding their causes.
In adults without symptoms screening for thyroid cancer is not recommended.
Thyroid cancers can be classified according to their histopathological characteristics. The following 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". These types have a more favorable prognosis than the medullary and undifferentiated types.
Papillary microcarcinoma is a subset of papillary thyroid cancer defined as measuring less than or equal to 1 cm. The highest incidence of papillary thyroid microcarcinoma in autopsy series was reported by Harach et al. in 1985, who found 36 of 101 consecutive autopsies were found to have an incidental microcarcinoma. Michael Pakdaman et al. report the highest incidence in a retrospective surgical series at 49.9% of 860 cases. Management strategies for incidental papillary microcarcinoma on ultrasound (and confirmed on FNAB) range from total thyroidectomy with radioactive iodine ablation to observation alone. Harach et al. suggest using the term "occult papillary tumor" to avoid giving patients distress over having cancer. It was Woolner et al. who first arbitrarily coined the term "occult papillary carcinoma" in 1960, to describe papillary carcinomas ≤ 1.5 cm in diameter.
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.
Thyroid cancer can spread directly, via lymphatics or via 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 does angioinvasion and lungs, end of long bones, skull and vertebrae are affected. Pulsating metastases occur because of their increased vascularity.
Thyroidectomy and dissection of central neck compartment is initial step in treatment of thyroid cancer in majority of cases. Thyroid-preserving operation 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.
If the diagnosis of well-differentiated thyroid cancer (e.g. papillary thyroid cancer) is established or suspected by FNA the surgery is indicated, whereas watchful waiting strategy is not recommended in any evidence-based guidelines.Watchful waiting reduces overdiagnosis and overtreatment of thyroid cancer among old patients.
Radioactive Iodine-131 is used in patients with papillary or follicular thyroid cancer for ablation of residual thyroid tissue after surgery and for the treatment of thyroid cancer. Patients with medullary, anaplastic, and most Hurthle cell cancers do not benefit from this therapy.
External irradiation may be used when the cancer is unresectable, when it recurs after resection, or to relieve pain from bone metastasis.
Sorafenib and lenvatinib, are approved for advanced metastatic thyroid cancer. Numerous agents are in phase II and III clinical trials.
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. There is no consensus 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 viewpoint 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. 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. It is easy to detect nodules that might be cancerous, simply by feeling the throat, which contributes to the level of overdiagnosis. Benign (non-cancerous) nodules frequently co-exist with thyroid cancer; sometimes, it is a benign nodule that 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.
Thyroid cancer is three times more common in women than in men, but according to European statistics, the overall relative 5-year survival rate for thyroid cancer is 85% for females and 74% for males.
The table below highlights some of the challenges with decision making and prognostication in thyroid cancer. While there is general agreement that stage I or II papillary, follicular or medullary cancer have a good prognosis, it is not possible when evaluating a small thyroid cancer to determine which ones will grow and metastasize and which will not. As a result, once a diagnosis of thyroid cancer has been established (most commonly by a fine needle aspiration), it is likely that a total thyroidectomy 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 sets have, for the most part, not incorporated calcitonin testing as a routine part of their evaluation, 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). It is not clear at this time who is correct.
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 for thyroid cancer 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, 2 subtypes of the vascular endothelial growth factor receptor, and the epidermal growth factor receptor. 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 it possible to use radioactive iodine therapy to treat "resistant" thyroid cancers. Other targeted therapies are being evaluated, making it possible that life will be extended over the next 5–10 years for those with stage III and IV thyroid cancer.
Prognosis is better in younger people than older ones.
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.Obesity may be associated with a higher incidence of thyroid cancer, but this relationship remains the subject of much debate.
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.
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^By 100% minus cause-specific mortality of 17% at 5 yr, as given by Barbet J, Campion L, Kraeber-Bodéré F, Chatal JF (2005). "Prognostic Impact of Serum Calcitonin and Carcinoembryonic Antigen Doubling-Times in Patients with Medullary Thyroid Carcinoma". Journal of Clinical Endocrinology & Metabolism. 90 (11): 6077–84. doi:10.1210/jc.2005-0044. PMID16091497.
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