Thyroid Cancers ?>

Thyroid Cancers

Thyroid Cancers

The 4 general types of thyroid cancer are papillary, follicular, medullary, and anaplastic. 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 present 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. Except for anaplastic and metastatic medullary carcinoma, most thyroid cancers are not highly malignant and are seldom fatal. Treatment is surgical removal, usually followed by ablation of residual tissue with radioactive iodine.

Papillary Carcinoma

Papillary carcinoma accounts for 70 to 80% of all thyroid cancers. The female-to-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 elderly patients. Many papillary carcinomas contain follicular elements.

The tumor spreads via lymphatics to regional lymph nodes in 1/3 of patients and may metastasize to the lungs. Patients < 45 yr with small tumors confined to the thyroid have an excellent prognosis.


Treatment for encapsulated tumors < 1.5 cm localized to one lobe is usually near-total thyroidectomy, although some experts recommend only lobectomy and isthmectomy; surgery is almost always curative. Thyroid hormone in thyroid-stimulating hormone (TSH)–suppressive doses is given to minimize chances of regrowth and cause regression of any microscopic remnants of papillary carcinoma.

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 131I administered when the patient is hypothyroid or after recombinant TSH injections. Treatment may be repeated q 6 to 12 mo to ablate any remaining thyroid tissue. TSH-suppressive doses of l-thyroxine are given after treatment, and serum thyroglobulin levels help detect recurrent or persistent disease. About 20 to 30% of patients, mainly older patients, have recurrent or persistent disease.

Follicular Carcinoma

Follicular carcinoma, including the Hurthle cell variant, accounts for about 15% of thyroid cancers. It is more common among older patients and in regions of iodine deficiency. It is more malignant than papillary carcinoma, 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. TSH-suppressive doses of l-thyroxine are given after treatment. Serum thyroglobulin should be monitored to detect recurrent or persistent disease.

Medullary Carcinoma

Medullary (solid) carcinoma constitutes about 3% 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) syndromes types IIA and IIB (see Multiple Endocrine Neoplasia (MEN) Syndromes: Multiple Endocrine Neoplasia, Type 2A (MEN 2A); see Multiple Endocrine Neoplasia (MEN) Syndromes: Multiple Endocrine Neoplasia, Type 2B (MEN 2B)). Although calcitonin can lower serum Ca and phosphate, serum Ca is normal because the high level of calcitonin ultimately down-regulates its receptors. Characteristic amyloid deposits that stain with Congo red are also present.

Metastases spread via the lymphatic system to cervical and mediastinal nodes and sometimes to liver, lungs, and bone.

Symptoms and Signs

Patients typically present with an asymptomatic thyroid nodule, although many cases are now diagnosed during routine screening of affected kindreds with MEN-IIA or IIB before a palpable tumor develops.

Medullary carcinoma may have a dramatic biochemical presentation when associated with ectopic production of other hormones or peptides (eg, ACTH, vasoactive intestinal polypeptide, prostaglandins, kallikreins, serotonin).


The best test is measurement of serum calcitonin, which is greatly elevated. A challenge with Ca (15 mg/kg IV over 4 h) provokes excessive secretion of calcitonin. X-rays may show a dense, homogenous, conglomerate calcification.

All patients with medullary carcinoma should have genetic testing; 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. Lymph nodes are also dissected. If hyperparathyroidism is present, removal of hyperplastic or adenomatous parathyroids is required. Pheochromocytoma, 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-IIA; > 2⁄3 of affected patients are alive at 10 yr. Medullary carcinoma of the sporadic type 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.

Anaplastic Carcinoma

Anaplastic carcinoma is an undifferentiated cancer that accounts for about 2% of thyroid cancers. It occurs mostly in elderly 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’s thyroiditis.

No effective therapy exists, and the disease is generally fatal. About 80% of patients die within 1 yr of diagnosis. In a few patients with smaller tumors, thyroidectomy followed by external radiation has been curative. Chemotherapy is mainly experimental.

Radiation-Induced Thyroid Cancer

Thyroid tumors develop in people exposed to large amounts of environmental thyroid radiation, as occurs from atomic bomb blasts, nuclear reactor accidents, or incidental thyroid irradiation due to radiation therapy. Tumors may be detected 10 yr after exposure, but risk remains increased for 30 to 40 yr. Such tumors are usually benign; however, about 10% are papillary thyroid carcinoma. The tumors are frequently multicentric or diffuse.

Patients who had thyroid irradiation should undergo yearly thyroid palpation, ultrasonography, and measurement of thyroid autoantibodies (to exclude Hashimoto’s thyroiditis). 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).

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