Thyroid cancer

Thyroid cancer is a thyroid neoplasm that is malignant. It can be treated with radioactive iodine or surgical resection of the thyroid gland. Chemotherapy or radiotherapy may also be used.

Symptoms
Most often the first symptom of thyroid cancer is a nodule in the thyroid region of the neck. However, many adults have small nodules in their thyroids, but typically under 5% of these nodules are found to be malignant. 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 involvement of recurrent larygeal nerve.

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, and thus the potential for malignancy is far greater.

Diagnosis
After a thyroid nodule is found during a physical examination, a referral to an endocrinologist, a thyroidologist or otolaryngologist may occur. Most commonly an ultrasound is performed to confirm the presence of a nodule, and assess the status of the whole gland. Measurement of thyroid stimulating hormone and anti-thyroid antibodies will help decide if there is a functional thyroid disease such as Hashimoto's thyroiditis present, a known cause of a benign nodular goiter.

Classification
Thyroid cancers can be classified according to their histopathological characteristics. The following variants can be distinguished (distribution over various subtypes may show regional variation):
 * Papillary thyroid cancer (75% to 85% of cases ) – often in young females – excellent prognosis
 * Follicular thyroid cancer (10% to 20% of cases )
 * Medullary thyroid cancer (5% to 8% of cases)- cancer of the parafollicular cells, part of MEN-2.
 * Anaplastic thyroid cancer (Less than 5% ). It is not responsive to treatment and can cause pressure symptoms.
 * Others
 * Lymphoma
 * Squamous cell carcinoma, sarcoma

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.

Etiology
From the 1940s to 1960s, external, low-dose radiation to the head and neck during infancy and childhood was used to treat many benign diseases. This type of therapy has been shown to predispose persons to thyroid cancer. The younger the patient was at time of exposure, the higher the risk of developing cancer.

Another cause may be due to high-dose irradiation to the head and neck. Patients with Hodgkin lymphoma treated with mantlefield irradiation have an increased risk of developing thyroid cancer, although hypothyroidism is more likely.

Detection of metastases
Detection of any metastases of thyroid cancer can be performed with a full body scintigraphy using iodine-131.

Treatment
Thyroid cancer may require surgery. Common surgeries include thyroidectomy, lobectomy, and tracheostomy.

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 sunitinib, approved for other indications show promise for thyroid cancer and are being used for some patients who do not qualify for clinical trials. Numerous agents are in phase II clinical trials and XL184 has started a phase III trial.

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. 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 of 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 has 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. However, very few of the people with these accidentally discovered, symptom-free thyroid cancers will ever have any symptoms, and treatment in such patients has only the potential to harm them, not to help them.

By 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 manifest 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. Does the finding of a small medullary thyroid carcinoma (which may lie dormant) justify the performance of a total thyroidectomy (necessary to perform total thyroidectomy because the medullary thyroid carcinomas identified may be microscopic and not identified by imaging or evaluation of the thyroid gland at the time of surgery) with its attendant risk of permanent hypoparathyroidism (low calcium) and damage to the nerves innervating the vocal cords (causing permanent hoarsenesss in 2-4% of patients). 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 USA, 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 clearly 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. As such, physicians who manage thyroid cancer of any stage treat it with respect and recognize that a small percentage of patients with low risk thyroid cancer will progress to develop metastatic disease and die. Fortunately, for those with metastatic thyroid cancer, the last 5 years has brought about a renaissance in thyroid cancer treatment. 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.