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Thyroid neoplasm

 
Medical Encyclopedia: Thyroid Cancer

Definition

Thyroid cancer is a disease in which the cells of the thyroid gland become abnormal, grow uncontrollably, and form a mass of cells called a tumor.

Description

Thyroid cancer is grouped into four types based on how its cells appear under a microscope. The types are papillary, follicular, medullary and anaplastic thyroid cancers. They grow at different rates and can spread to other parts of the body if left untreated.

The thyroid is a hormone-producing butterfly-shaped gland located in the neck at the base of the throat. It has two lobes, the left and the right. The thyroid uses iodine, a mineral found in some foods, to make several of its hormones. Thyroid hormones regulate essential body processes such as heart rate, blood pressure, body temperature, metabolism; and affect the nervous system, muscles and other organs. These hormones also play an important role in regulating childhood growth and development.

Diseases of the thyroid gland affect millions of Americans. The most common diseases of the thyroid are either hyperthyroidism (Graves' disease) or hypothyroidism, an overactive or an underactive gland, respectively. Sometimes lumps or masses may develop in the thyroid, and although most (ninety-five percent) of these lumps or nodules are noncancerous (benign), all thyroid lumps should be taken seriously. The American Cancer Society estimates that the approximately 17,200 new cases of thyroid cancer that occur in the United States account for 1% of all cancers.

Women are three times more likely to develop thyroid cancer than men. Although the disease affects teenagers and young adults, most people that develop thyroid cancer are over 50 years of age.

— Kulbir Rangi, DO



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Oncology Encyclopedia: Thyroid Cancer
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Key Terms: Biopsy, Calcitonin, Chemotherapy, Hormone therapy, Hyperthyroidism, Hypothyroidism, Lobectomy, Radiation therapy.

Definition

Thyroid cancer is a disease in which the cells of the thyroid gland become abnormal, grow uncontrollably and form a mass of cells called a tumor.

Description

The thyroid is a hormone-producing, butterfly-shaped gland located in the neck at the base of the throat. It has two lobes, the left and the right. The thyroid uses iodine, a mineral found in some foods, to make several of its hormones. Thyroid hormones regulate essential body processes such as heart rate, blood pressure, body temperature, metabolism, and affect the nervous system, muscles and other organs. These hormones also play an important role in regulating childhood growth and development.

Types of Thyroid Cancer

Thyroid cancer is grouped into four types based on how its cells appears under a microscope. The types are papillary, follicular, medullary and anaplastic thyroid cancers. They grow at different rates and can spread to other parts of the body if left untreated.

Papillary

The papillary type (60%–80% of all thyroid cancers) is a slow-growing cancer that develops in the hormone-producing cells that contain iodine.

Follicular

The follicular type (30%–50% of thyroid cancers) also develops in the hormone-producing cells.

Medullary

The medullary type (5%–7% of all thyroid cancers) develops in the parafollicular cells (also known as the C cells) that produce calcitonin, a hormone that does not contain iodine.

Anaplastic

The fourth type of thyroid cancer, anaplastic (2% of all thyroid cancers), is the fastest growing, most aggressive thyroid cancer type.

Demographics

Diseases of the thyroid gland affect millions of Americans. The most common diseases of the thyroid are either hyperthyroidism (Grave's disease) or hypothyroidism, an overactive or an underactive gland, respectively. Sometimes lumps or masses may develop in the thyroid. Although most (95%) of these lumps or nodules are non-cancerous (benign), all thyroid lumps should be taken seriously. The American Cancer Society estimates that in 2001, approximately 19,500 new cases of thyroid cancer will have been diagnosed in the United States.

Women are three times more likely to develop thyroid cancer than men. Although the disease affects teenagers and young adults, most people who develop thyroid cancer are over 50 years of age. Caucasians are affected more often than African Americans.

Causes and Symptoms

The exact cause of thyroid cancer is not known but some risk factors have been identified. Radiation was used in the 1950s and 1960s to treat acne and to reduce swelling in infections of the tonsils, adenoids and lymph nodes. It has been proven that this exposure is a risk factor for thyroid cancer. In some areas of the world, diets are low in iodine. Papillary and follicular cancers occur more frequently in these areas. Iodine deficiency is not a large problem in the United States because iodine is added to table salt and other foods. Approximately 7% of thyroid cancers are caused by the alteration (mutation) of a gene called the RET oncogene, which can be inherited.

Symptoms are rare, and the lump is not usually painful. The symptoms of thyroid nodules are:

  • A lump or nodule that can be felt in the neck is the most frequent sign of thyroid cancer.
  • The lymph nodes may be swollen and the voice may become hoarse because the tumor presses on the nerves leading to the voice box.
  • Some patients experience a tight or full feeling in the neck and have difficulty breathing or swallowing.

Diagnosis

Physicians use several tests to confirm the suspicion of thyroid cancer, to identify the size and location of the lump and to determine whether the lump is non-cancerous (benign) or cancerous (malignant).

A blood test called the thyroid stimulating hormone (TSH) test checks thyroid function. The blood is drawn by a technician with a needle and the test takes a few minutes. The results take several days to be interpreted by a pathologist.

A test known as the calcitonin test may be ordered. Calcitonin is a hormone produced by the C cells (parafollicular cells) of the thyroid gland. The hormone is produced in excess when the parafollicular cells of the thyroid become cancerous. Blood calcitonin levels are used to confirm the diagnosis of medullary thyroid cancer if it is suspected.

Computed tomography scan (CT scan) or ultrasonography (an ultrasound scan) are imaging tests used to produce a picture of the thyroid. A radiologist usually interprets the results of these tests within 24 hours. In ultrasonography, high-frequency sound waves are bounced off the thyroid. The pattern of echoes that is produced by these waves is converted into a computerized image on a television screen. This test can determine whether the lumps found in the thyroid are benign fluid-filled cysts or solid malignant tumors.

A radioactive scan (a thyroid nuclear medicine scan) may take several hours and can be used to identify any abnormal areas in the thyroid. For this test, the patient is given a very small amount of radioactive iodine which can either be swallowed or injected. Since the thyroid is the only gland in the body that absorbs iodine, the radioactive iodine accumulates there. An x-ray image can then be taken or an instrument called a "scanner" can be used to identify areas in the thyroid that do not absorb iodine normally. These abnormal spots are called "cold spots" and further tests are performed to check whether the cold spots are benign or malignant tumors. If a significant amount of radioactive iodine is concentrated in the nodule, then it is termed "hot" and is usually benign. Again a radiologist interprets the results within a day.

The most accurate diagnostic tool for thyroid cancer is a biopsy. In this process, a sample of thyroid tissue is withdrawn and examined under a microscope by a pathologist. This usually takes a day or so. The tissue samples can be obtained either by drawing out a sample of tissue through a needle (needle biopsy) or by surgical removal of the nodule (surgical biopsy). A needle biopsy takes a few minutes and can be done by any trained physician, usually a radiologist. The surgical biopsy is done by a surgeon under general anesthesia with the help of an anesthesiologist and will take a few hours. If thyroid cancer is diagnosed, further tests may be done to learn about the stage of the disease and help doctors plan appropriate treatment.

Treatment Team

The types of healthcare providers often involved in the care of patients are surgeons, internal medicine specialists, pathologists, radiologists, endocrinologists, anesthesiologists, hematologist-oncologists (cancer specialists) and radiation-oncologists.

Clinical Staging, Treatment and Prognosis

Staging

The aggressiveness of each type of thyroid cancer is different. Cancer staging considers the size of the tumor, whether it has grown into surrounding lymph nodes and whether it has spread to distant parts of the body (metastasized). Age and general health status are also taken into account. The American Joint Commission on Cancer (AJCC) staging is summarized below for each thyroid cancer type.

Papillary and Follicular

In patients younger than 45 years:

  • Stage I refers to patients without evidence of cancer beyond the thyroid.
  • Stage II refers to patients with spread of cancer outside the thyroid gland.

In patients over 45:

  • Stage I: Tumors are smaller than one cm (0.3 in).
  • Stage II: Tumors have not broken through the capsule (covering) of the thyroid.
  • Stage III: Tumors have spread locally to the nearby lymph nodes.
  • Stage IV: Tumors have spread outside the thyroid area (distant metastases). In the case of Stage IV cancer, the places to which thyroid cancer often metastasizes are the lungs and bone.

Medullary

  • Stage I: Tumor is less than 1 cm (0.3 in) or is only detected by a provocative screening test.
  • Stage II: Tumor is between 1 and 4 cm (between 0.3 and 1.5 in).
  • Stage III: Nearby lymph nodes reveal cancer.
  • Stage IV: Evidence of distant metastases.

Anaplastic

All cases of anaplastic thyroid cancer are considered Stage IV, because this cancer is extremely aggressive.

Treatments

Papillary thyroid cancer can be treated successfully. Follicular thyroid cancer also has a good cure rate but may be difficult to control if the cancer invades blood vessels or grows into nearby structures in the neck. Medullary thyroid cancers are more difficult to control because they often spread to other parts of the body. Anaplastic thyroid cancer is the fastest growing and tends to respond poorly to all treatments.

Like most cancers, cancer of the thyroid is best treated when it is found early by a primary physician. Treatment depends on the type of cancer and its stage. Four types of treatment are used: surgical removal, radiation therapy, hormone therapy, and chemotherapy.

Surgery

Surgical removal is the usual treatment if the cancer has not spread to distant parts of the body. It is the primary treatment for earlier stage papillary, follicular, and medullary thyroid cancers. The surgeon may remove the side or lobe of the thyroid where the cancer is found (lobectomy) or all of it (total thyroidectomy). If the adjoining lymph nodes are affected, they may also be removed during surgery.

Radiation

For papillary and follicular thyroid cancers, radioactive iodine may be used in addition to surgery. In this treatment, the patient would be asked to swallow a drink containing radioactive iodine. Because the thyroid cells take up iodine, the radioactive iodine collects in any thyroid tissue remaining in the body and kills the cancer cells. External beam radiation may also be used if the radioactive iodine is unsuccessful.

For medullary cancers, radioactive iodine is not used. External beam radiation may be used as a palliative therapy. (A palliative therapy is one intended to make the patient more comfortable, not to cure the cancer.)

Hormone Therapy

When the thyroid gland is removed and levels of thyroid hormones decrease, the pituitary gland produces TSH that would normally stimulate the thyroid gland to make thyroid hormone. TSH also stimulates thyroid cells to grow, and it probably also promotes thyroid cancer growth. Hormone therapy uses hormones after surgery to stop this growth and the formation of new cancerous thyroid cells. To prevent cancerous growth, the natural hormones that are produced by the thyroid are taken in the form of a pill. Thus, their levels remain normal and inhibit the pituitary gland from making TSH. If the cancer has spread to other parts of the body and surgery is not possible, hormone treatment is aimed at killing or slowing the growth of cancer cells throughout the body.

CHEMOTHERAPY For advanced thyroid cancers for which surgery was not an option or that have not responded well to other treatments, chemotherapy may be tried. For advanced papillary, follicular, and anaplastic thyroid cancers, no chemotherapeutic regimen can be considered standard, and several clinical studies may be ongoing for which patients with these cancers may be eligible. For anaplastic thyroid cancer, some chemotherapeutic agents (doxorubicin, doxorubicin/cisplatin combination) have effected partial remission in some patients, but not on a large scale. Patients with anaplastic thyroid cancer may also be eligible for ongoing clinical trials.

Prognosis

More than 90% of patients who are treated for papillary or follicular cancer will live for 15 years or longer after the diagnosis of thyroid cancer. Eighty percent of patients with medullary thyroid cancer will live for at least 10 years after surgery. Three to seventeen percent of patients with anaplastic cancer survive for five years.

Alternative and Complementary Treatments

Alternative treatments are treatments used instead of conventional treatments. Complementary therapies are intended to supplement traditional therapies and usually have the objective of relieving symptoms or helping cancer patients cope with the disease or traditional treatments. Common complementary therapies that may be employed by cancer patients are aromatherapy, art therapy, journal therapy, massage, meditation, music therapy, prayer, t'ai chi, and yoga or other forms of exercise, which can reduce anxiety and increase a patient's feeling of well-being. A well-balanced diet can also enhance a patient's sense of well-being, and can help cancer patients better manage their treatments and the side effects of those treatments.

A powerful phytochemical (a chemical found in plants), lycopene, gives tomatoes their red color and appears to act as an antioxidant. Antioxidants such as lycopene help inhibit DNA oxidation (which can lead to certain forms of cancer), repair damaged cells, and scavenge free radicals. (Free radicals are the molecules thought to be responsible for most types of degenerative diseases and aging.) While it is not being suggested that thyroid cancer could be prevented with antioxidants, patients receiving plenty of antioxidants in their diets may feel healthier and more energetic. Lycopene is a normal constituent of human blood and tissues, where it is found in greater concentrations than beta-carotene or any other carotenoid. Tomatoes, including cooked or processed tomatoes, tomato juices, soups, sauces, paste and ketchup, contain more lycopene than any other food. Guava, rose hip, watermelon and grapefruit also contain lycopene.

Other antioxidants are: Vitamin E, Vitamin C, Beta carotene, Lutein, Pycnogenol, Green tea, Grape-seed extract, Alpha lipoic acid, N-acetylcysteine, and Selenium. Pregnant women should consult a physician before taking any medication, and all patients should discuss the complementary therapies and nutritional supplements they are considering with their physician. Some therapies may interfere with patients' prescribed treatments.

Coping With Cancer Treatment

After thyroid surgery, some patients experience:

To cope with difficult swallowing, once patients are able to eat after the surgery, many patients start with soft foods, like milkshakes, bananas, applesauce, yogurt, mashed potatoes, and pureed foods. A consultation before the surgery with a dietitian may be helpful, so that the patient can be prepared.

Hoarseness after surgery is usually temporary. Patients may have difficulty hitting high notes when singing, but, the voice change and hoarseness is usually not a major issue for most patients. (Professional singers are advised to discuss their surgery in great detail with their surgeons beforehand.)

If all four parathyroid glands are injured or damaged, it may be necessary for patients to take calcium supplements for a few weeks. Rarely, these supplements may be prescribed for longer periods of time, or even indefinitely.

After radioiodine treatment, some patients experience neck tenderness, nausea and stomach irritation, and dry mouth (xerostomia). These side effects are rare, but if they occur, patients can try to eat foods that are easy to digest, drink plenty of water to keep the mouth and throat moist, keep lips moist with lip balm, and patients can try sucking on hard candies to alleviate the dry mouth.

The side effects of chemotherapy are bone marrow suppression causing anemia and low platelets. This causes weakness or bleeding. Other problems are nausea and vomiting, hair loss (alopecia), and inflammation of the oral mucosa. The symptoms are improved with medications.

Depression, if it occurs, is often temporary and can be managed by counseling and family support. Medication is usually not necessary.

Clinical Trials

Seven clinical trials taking place for patients diagnosed with various types of thyroid cancer were studying the effectiveness of radioimmunotherapy and peripheral stem cell transplants, combination chemotherapy (using such drugs as paclitaxel, trastuzumab, and interleukin-12), and vaccine therapy. Information about current clinical trials is available through the National Institutes of Health.

Thyroid cancers
Cancer typeCharacteristicsPrognosis
Papillary60–80% of thyroid cancers Slow-growing cancer in hormone—producing cells90% of patients will live for 15 years or longer after diagnosis
Follicular30–50% of thyroid cancers Found in hormone—producing cells90% of patients will live for 15 years or longer after diagnosis
Medullary5–7% of Thyroid cancers Found in calcitonin—producing cells Difficult to control as it often spreads to other parts of the body80% of patients will live for at least 10 years after surgery
Anaplastic2% of Thyroid cancers Fastest growing Rapidly spreads to other parts of the body3–17% of patients will survive for five years

Prevention

Because most people with thyroid cancer have no known risk factor, it is not possible to prevent this disease completely. However, the risk for radiationrelated thyroid cancer can be reduced by avoiding radiation to the neck when possible, and inherited cases of medullary thyroid cancer can be prevented. If a family member has had this disease, the rest of the family can be tested and treated early. Carriers of the RET mutation may want to consider undergoing prophylactic thyroidectomy at an early age. The National Cancer Institute recommends that every one or two years, a doctor examine anyone who has received radiation to the head and neck during childhood. The neck and the thyroid should be carefully examined for any lumps or enlargement of the nearby lymph nodes. Ultrasound may also be used to screen for the disease in people at risk for thyroid cancer.

Questions to Ask the Doctor

  • What type of thyroid cancer do I have?
  • Has it spread?
  • Is my thyroid cancer hereditary? Should other members of my family be tested?
  • What treatment do you recommend? Do you recommend a clinical trial?
  • What are the advantages, disadvantages, and side effects of this treatment?
  • How much experience do you have treating thyroid cancer/performing thyroid surgery?

Special Concerns

Complications of surgery are very rare with experienced surgeons. Sometimes injury to the nerves in the neck can cause a husky voice or difficulty singing high notes. This can be improved with collagen injection after surgery. Occasionally there is bleeding after the surgery and the incision is reopened to evacuate the clot and stop the bleeding. Patients may have a slightly increased risk of developing another cancer (such as leukemia) in the future after undergoing radioiodine treatment, but this correlation has not been proven. Because thyroid cancers may grow slowly and may recur decades after treatment, follow-up care is important.

Resources

Books

Cameron, John L. Current Surgical Therapy. 6th ed. St. Louis: Mosby, Inc., 2001.

Organizations

American Cancer Society. Telephone: 1-800-ACS-2345. Web site: .

National Cancer Institute, Cancer Information Service. Telephone: 1-800-4-CANCER (1-800-422-6237). Deaf and hard of hearing callers with TTY equipment may call 1-800-332-8615. Web site: .

Other

Clinical Trials.gov. Web site: .

National Institutes of Health. Eating Hints for Cancer Patients: Before, During, and After Treatment. NIH Publication #98-2079. Revised July 1997. Also available at: .

—Lata Cherath, Ph.D.; Kulbir Rangi, DO

Wikipedia: Thyroid neoplasm
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Thyroid cancer
Classification and external resources

Micrograph (high power view) of papillary thyroid carcinoma demonstrating diagnostic features (nuclear clearing and overlapping nuclei). H&E stain.
ICD-10 C73.
ICD-9 193
eMedicine ent/646
MeSH D013964

Thyroid neoplasm or thyroid cancer usually refers to any of four kinds of malignant tumors of the thyroid gland: papillary, follicular, medullary or anaplastic.[1] Most patients are 25 to 65 years of age when first diagnosed; women are more affected than men.[1] Papillary and follicular tumors are the most common. They grow slowly and may recur, but are generally not fatal in patients under 45 years of age. Medullary tumors have a good prognosis if restricted to the thyroid gland and a poorer prognosis if metastasis occurs. Anaplastic tumors are fast-growing and respond poorly to therapy.

Thyroid nodules are diagnosed by ultrasound guided fine needle aspiration (USG/FNA) or frequently by thyroidectomy (surgical removal and subsequent histological examination). As thyroid cancer can take up iodine, radioactive iodine is commonly used to treat thyroid carcinomas, followed by TSH suppression by high-dose thyroxine therapy.

Contents

Symptoms

Most often the first symptom of thyroid cancer is a nodule in the thyroid region of the neck.[1] 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.

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.

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 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. [2]

Fine needle biopsy

One approach used to determine whether the nodule is malignant is the fine needle biopsy (FNB)[3], which some have described as the most cost-effective, sensitive and accurate test. [4]

[5] FNB or ultrasound-guided FNA usually yields sufficient thyroid cells to assess the risk of malignancy, although in some cases, the suspected nodule may need to be removed surgically for pathological examination.

Rarely, a biopsy is done using a large cutting needle, so that a piece of nodule capsule can be obtained.

Blood tests

Blood or imaging tests may be done prior to or in lieu of a biopsy. The possibility of a nodule which secretes thyroid hormone (which is less likely to be cancer) or hypothyroidism is investigated by measuring thyroid stimulating hormone (TSH), and the thyroid hormones thyroxine (T4) and triiodothyronine (T3).

Tests for serum thyroid autoantibodies are sometimes done as these may indicate autoimmune thyroid disease (which can mimic nodular disease).

Imaging

The blood assays may be accompanied by ultrasound imaging of the nodule to determine the position, size and texture, and to assess whether the nodule may be cystic (fluid filled). Also suspicious findings in a nodule are hypoechoic,[6] irregular borders, microcalcifications, or very high levels of blood flow within the nodule. Less suspicious findings in benign nodules include, hyperechoic, comet tail artifacts from colloid[clarification needed], no blood flow in the nodule and a halo, or smooth border.

Some clinicians will also request technetium (Tc) or radioactive iodine (I) imaging of the thyroid[citation needed]. An 123I scan showing a hot nodule, accompanied by a lower than normal TSH, is strong evidence that the nodule is not cancerous.

Classification

Thyroid cancers can be classified according to their pathological characteristics.[7][8] 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".[10] These types have a more favorable prognosis than the medullary and undifferentiated types.[11]


  • Papillary microcarcinoma is a subset of papillary thyroid cancer defined as measuring less than or equal to 1cm. [12]. 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 [13]. Michael Pakdaman et al. report the highest incidence in a retrospective surgical series at 49.9% of 860 cases [14]. 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 ≤ 1.5cm in diameter.[15]


Thyroid adenoma is a benign neoplasm of the thyroid.

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.[1]

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.[1]

Treatment

If the nodule is benign, patients may receive thyroxine therapy to supress thyroid-stimulating hormone and should be reevaluated in 6 months.[1]

If the nodule is malignant or has indeterminate cytologic features, it may require surgery. Common surgeries include thyroidectomy, lobectomy, and tracheostomy.[1]

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.[1]

External irradiation may be used when the cancer is unresectable, when it recurs after resection, or to relieve pain from bone metastasis.[1]

References

  1. ^ a b c d e f g h i Hu MI, Vassilopoulou-Sellin R, Lustig R, Lamont JP. "Thyroid and Parathyroid Cancers" in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach. 11 ed. 2008.
  2. ^ Bennedbaek FN, Perrild H, Hegedüs L (1999). "Diagnosis and treatment of the solitary thyroid nodule. Results of a European survey". Clin. Endocrinol. (Oxf) 50 (3): 357–63. doi:10.1046/j.1365-2265.1999.00663.x. PMID 10435062. http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0300-0664&date=1999&volume=50&issue=3&spage=357. 
  3. ^ Ravetto C, Colombo L, Dottorini ME (2000). "Usefulness of fine-needle aspiration in the diagnosis of thyroid carcinoma: a retrospective study in 37,895 patients". Cancer 90 (6): 357–63. doi:10.1002/1097-0142(20001225)90:6<357::AID-CNCR6>3.0.CO;2-4. PMID 11156519. 
  4. ^ Hamberger, B (1982). "Fine-needle aspiration biopsy of thyroid nodules. Impact on thyroid practice and cost of care". Am J Med 73: 381-384. PMID 7124765. 
  5. ^ Mazzaferri (1993). "Management of a Solitary Thyroid Nodule". N Engl J Med 328: 553-9. PMID 8426623. 
  6. ^ Wong KT, Ahuja AT (2005). "Ultrasound of thyroid cancer". Cancer Imaging 5: 157–66. doi:10.1102/1470-7330.2005.0110. PMID 16361145. 
  7. ^ "Thyroid Cancer Treatment - National Cancer Institute". http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/HealthProfessional/page2. Retrieved 2007-12-22. 
  8. ^ "Thyroid cancer". http://cancerweb.ncl.ac.uk/cancernet/101252.html#2_CELLULARCLASSIFICATION. Retrieved 2007-12-22. 
  9. ^ Schlumberger M, Carlomagno F, Baudin E, Bidart JM, Santoro M (2008). "New therapeutic approaches to treat medullary thyroid carcinoma". Nat Clin Pract Endocrinol Metab 4 (1): 22–32. doi:10.1038/ncpendmet0717. PMID 18084343. 
  10. ^ Nix P, Nicolaides A, Coatesworth AP (2005). "Thyroid cancer review 2: management of differentiated thyroid cancers". Int. J. Clin. Pract. 59 (12): 1459–63. doi:10.1111/j.1368-5031.2005.00672.x. PMID 16351679. http://www.medscape.com/viewarticle/518396. 
  11. ^ Nix PA, Nicolaides A, Coatesworth AP (2006). "Thyroid cancer review 3: management of medullary and undifferentiated thyroid cancer". Int. J. Clin. Pract. 60 (1): 80–4. doi:10.1111/j.1742-1241.2005.00673.x. PMID 16409432. http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=1368-5031&date=2006&volume=60&issue=1&spage=80. 
  12. ^ Shaha AR (2007). "TNM classification of thyroid carcinoma.". World J Surg 31 (5): 879–87. doi:10.1007/s00268-006-0864-0. PMID 17308849. 
  13. ^ Harach HR, Franssila KO, Wasenius VM (1985). "Occult papillary carcinoma of the thyroid. A "normal" finding in Finland. A systematic autopsy study.". Cancer 56 (3): 531–8. doi:10.1002/1097-0142(19850801)56:3<531::AID-CNCR2820560321>3.0.CO;2-3. PMID 2408737. 
  14. ^ Pakdaman MN, Rochon L, Gologan O, Tamilia M, Garfield N, Hier MP, Black MJ, Payne RJ (2008). "Incidence and histopathological behavior of papillary microcarcinomas: Study of 429 cases.". Otolaryngol Head Neck Surg 139 (5): 718–22. doi:10.1016/j.otohns.2008.08.014. PMID 18984270. 
  15. ^ LEWIS B. WOOLNER, M.D., MARK L. LEMMON, M.D.{dagger}, OLIVER H. BEAHRS, M.D., B. MARDEN BLACK, M.D. and F. RAYMOND KEATING, JR., M.D. OCCULT PAPILLARY CARCINOMA OF THE THYROID GLAND: A STUDY OF 140 CASES OBSERVED IN A 30-YEAR PERIOD* Journal of Clinical Endocrinology & Metabolism Vol. 20, No. 1 89-105 doi:10.1210/jcem-20-1-89 PMID: 13845950 [PubMed - OLDMEDLINE]

See also

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