(See also Overview of Thyroid Function Overview of Thyroid Function The thyroid gland, located in the anterior neck just below the cricoid cartilage, consists of 2 lobes connected by an isthmus. Follicular cells in the gland produce the 2 main thyroid hormones... read more .)
There are 4 general types of thyroid cancer: papillary, follicular, medullary, and anaplastic. Most thyroid cancers are papillary or follicular carcinomas and usually are not highly malignant and are seldom fatal. In contrast, anaplastic carcinoma is quite aggressive and has a poor prognosis, while patients with metastatic medullary carcinoma may live for many years but generally succumb to their cancer. Papillary and follicular carcinoma together are called differentiated thyroid cancer because of their histologic resemblance to normal thyroid tissue and because differentiated function (eg, thyroglobulin secretion) is preserved.
Most thyroid cancers manifest as asymptomatic nodules. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid cancers. Diagnosis is often by fine-needle aspiration biopsy but may involve other tests.
Treatment of well-differentiated thyroid cancers is surgical removal for lesions > 1.5 cm, often followed by ablation of residual tissue with radioactive iodine. Smaller lesions are treated with surgery or active surveillance.
Papillary Thyroid Carcinoma
Papillary carcinoma accounts for 80 to 90% of all thyroid cancers. The female:male ratio is 3:1. It may be familial in up to 5% of patients. Most patients present between ages 30 and 60. The tumor is often more aggressive in older patients. Many papillary carcinomas contain follicular elements Follicular Thyroid Carcinoma There are 4 general types of thyroid cancer. Most thyroid cancers manifest as asymptomatic nodules. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid... read more . One variant is called noninvasive follicular thyroid neoplasm with papillary-like nuclear features (previously known as noninvasive encapsulated follicular variant of papillary thyroid carcinoma) and is considered to be a benign lesion (1 Papillary thyroid carcinoma reference There are 4 general types of thyroid cancer. Most thyroid cancers manifest as asymptomatic nodules. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid... read more ).
The incidence of papillary thyroid carcinoma has risen over the last several decades, primarily due to the incidental discovery of small cancers in patients undergoing neck ultrasonography, MRI, CT scans, or PET scans that include the neck in the imaging field.
The tumor spreads via lymphatics to regional lymph nodes in one third of patients and may metastasize to the lungs. Patients < 55 years with small tumors confined to the thyroid have an excellent prognosis.
Tumors > 4 cm or that are diffusely spreading require total or near-total thyroidectomy with postoperative radioiodine ablation of residual thyroid tissue with appropriately large doses of iodine-131 administered when the patient is hypothyroid or after recombinant thyroid-stimulating hormone (TSH) injections. Treatment may be repeated after 6 to 12 months to ablate any remaining thyroid tissue.
TSH-suppressive doses of levothyroxine are given after treatment, and serum thyroglobulin levels are measured to help detect recurrent or persistent disease. Neck ultrasonography will detect recurrence in lymph nodes. About 20 to 30% of patients, mainly older patients, have recurrent or persistent disease.
Treatment for encapsulated tumors < 4 cm localized to one lobe is usually near-total thyroidectomy, although some experts recommend only lobectomy and isthmusectomy; surgery is almost always curative. Thyroid hormone in thyroid-stimulating hormone–suppressive doses is given to minimize chances of regrowth and cause regression of any microscopic remnants of papillary carcinoma. Active surveillance may be an alternative to surgery for papillary carcinomas < 1.5 cm with no evidence of lymph node or distant metastases (2 Papillary thyroid carcinoma reference There are 4 general types of thyroid cancer. Most thyroid cancers manifest as asymptomatic nodules. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid... read more ).
Papillary thyroid carcinoma reference
1. Nikiforov YE, Seethala RR, Tallini G, et al: Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: A paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol 2(8):1023–1029, 2016. doi:10.1001/jamaoncol.2016.0386
2. Saravana-Bawan B, Amandeep Bajwa A, Paterson J, et al: Active surveillance of low-risk papillary thyroid cancer: A meta-analysis. Surgery 167:46–55, 2020. doi: 10.1016/j.surg.2019.03.040
Follicular Thyroid Carcinoma
Follicular carcinoma, including the Hürthle cell variant, accounts for about 10% of thyroid cancers. It is more common among older patients and in regions of iodine deficiency. It is more malignant than papillary carcinoma Papillary Thyroid Carcinoma There are 4 general types of thyroid cancer. Most thyroid cancers manifest as asymptomatic nodules. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid... read more , spreading hematogenously with distant metastases.
Treatment requires near-total thyroidectomy with postoperative radioiodine ablation of residual thyroid tissue as in treatment for papillary carcinoma. Metastases are more responsive to radioiodine therapy than are those of papillary carcinoma. Thyroid-stimulating hormone–suppressive doses of levothyroxine are given after treatment. Serum thyroglobulin measurements and neck ultrasongraphy should be done periodically to detect recurrent or persistent disease.
Medullary Thyroid Carcinoma
Medullary carcinoma constitutes about 4% of thyroid cancers and is composed of parafollicular cells (C cells) that produce calcitonin. It may be sporadic (usually unilateral); however, it is often familial, caused by a mutation of the ret proto-oncogene. The familial form may occur in isolation or as a component of multiple endocrine neoplasia (MEN) syndrome type 2A Multiple Endocrine Neoplasia, Type 2A (MEN 2A) Multiple endocrine neoplasia, type 2A (MEN 2A) is a hereditary syndrome characterized by medullary carcinoma of the thyroid, pheochromocytoma, parathyroid hyperplasia or adenomas (causing hyperparathyroidism)... read more and MEN 2B Multiple Endocrine Neoplasia, Type 2B (MEN 2B) Multiple endocrine neoplasia, type 2B (MEN 2B) is an autosomal dominant syndrome characterized by medullary thyroid carcinoma, pheochromocytoma, multiple mucosal neuromas and intestinal ganglioneuromas... read more . Although calcitonin can lower serum calcium and phosphate levels, serum calcium is normal because the high level of calcitonin ultimately down-regulates its receptors. Characteristic amyloid deposits that stain with Congo red are also present in the tumor.
Metastases spread is via the lymphatic system to cervical and mediastinal nodes and sometimes to liver, lungs, and bone.
Patients typically present with an asymptomatic thyroid nodule, although many cases are now diagnosed during routine screening of affected kindreds with MEN 2A or MEN 2B before a palpable tumor develops.
Medullary carcinoma may have a dramatic biochemical presentation when associated with ectopic production of other hormones or peptides (eg, adrenocorticotropic hormone [ACTH], vasoactive intestinal polypeptide, prostaglandins, kallikreins, serotonin).
The best test is measurement of serum calcitonin, which is greatly elevated. A challenge with calcium (15 mg/kg IV over 4 hours) provokes excessive secretion of calcitonin.
X-rays or ultrasound may show a dense, homogenous, conglomerate calcification within the primary tumor.
All patients with medullary thyroid carcinoma should have genetic testing for mutations of the ret proto-oncogene; relatives of those with mutations should have genetic testing and measurement of basal and stimulated calcitonin levels.
Total thyroidectomy is indicated even if bilateral involvement is not obvious (1 Medullary thyroid carcinoma reference There are 4 general types of thyroid cancer. Most thyroid cancers manifest as asymptomatic nodules. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid... read more ). Lymph nodes are also dissected. If hyperparathyroidism is present, removal of hyperplastic or adenomatous parathyroids is required.
Pheochromocytoma Pheochromocytoma A pheochromocytoma is a catecholamine-secreting tumor of chromaffin cells typically located in the adrenals. It causes persistent or paroxysmal hypertension. Diagnosis is by measuring catecholamine... read more , if present, is usually bilateral. Pheochromocytomas should be identified and removed before thyroidectomy because of the danger of provoking hypertensive crisis during the operation.
Long-term survival is common in patients with medullary carcinoma and MEN 2A; more than two thirds of affected patients are alive at 10 years. Medullary carcinoma of the sporadic type and in MEN 2B has a worse prognosis.
Relatives with an elevated calcitonin level without a palpable thyroid abnormality should undergo thyroidectomy because there is a greater chance of cure at this stage. Some experts recommend surgery in relatives who have normal basal and stimulated serum calcitonin levels but who have the ret proto-oncogene mutation.
Medullary thyroid carcinoma reference
1. Wells Jr SA, Asa SL, Henning D, et al: Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma prepared by the American Thyroid Association Guidelines Task Force on Medullary Thyroid Carcinoma. Thyroid 25(6): 567–610, 2015. doi: 10.1089/thy.2014.0335
Anaplastic Thyroid Carcinoma
Anaplastic carcinoma is an undifferentiated cancer that accounts for about 1% of thyroid cancers. It occurs mostly in older patients and slightly more often in women. The tumor is characterized by rapid, painful enlargement. Rapid enlargement of the thyroid may also suggest thyroid lymphoma, particularly if found in association with Hashimoto thyroiditis Hashimoto Thyroiditis Hashimoto thyroiditis is chronic autoimmune inflammation of the thyroid with lymphocytic infiltration. Findings include painless thyroid enlargement and symptoms of hypothyroidism. Diagnosis... read more .
No effective therapy exists, and the disease is generally fatal. About 80% of patients die within 1 year of diagnosis. In a few patients with smaller tumors, thyroidectomy followed by external beam radiation therapy has been curative. Chemotherapy is mainly experimental. Up to 40% of these tumors harbor a BRAF V600E mutation. Targeted therapy with a combination of dabrafenib and trametinib has been shown to reduce tumor progression but has yet to been shown to improve long-term survival (1 Anaplastic thyroid carcinoma reference There are 4 general types of thyroid cancer. Most thyroid cancers manifest as asymptomatic nodules. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid... read more ).
Anaplastic thyroid carcinoma reference
1. Bible KC, Kebebew E, Brierley J, et al: 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. Thyroid 31(3):337–386, 2021. doi: 10.1089/thy.2020.0944
Radiation-Induced Thyroid Cancer
Thyroid tumors develop in people whose thyroid is exposed to large amounts of environmental radiation, as occurs as a result of atomic bomb blasts, nuclear reactor accidents, or incidental thyroid irradiation due to radiation therapy. Tumors may be detected 10 years after exposure, but risk remains increased for 30 to 40 years. Such tumors are usually benign; however, about 10% are papillary thyroid carcinoma Papillary Thyroid Carcinoma There are 4 general types of thyroid cancer. Most thyroid cancers manifest as asymptomatic nodules. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid... read more . The tumors are frequently multicentric or diffuse.
Patients who had thyroid irradiation should undergo yearly thyroid palpation and ultrasonography. A thyroid scan does not always reflect areas of involvement.
If ultrasonography reveals a nodule, fine-needle aspiration biopsy should be done. In the absence of suspicious or malignant lesions, many physicians recommend lifelong TSH-lowering doses of thyroid hormone to suppress thyroid function and thyrotropin secretion and possibly decrease the chance of developing a thyroid tumor.
Surgery is required if fine-needle aspiration biopsy suggests cancer. Near-total or total thyroidectomy is the treatment of choice, to be followed by radioiodine ablation of any residual thyroid tissue if a cancer is found (depending on the size, histology, and invasiveness).