Thyroid and Parathyroid Cancers

THYROID CANCER

Thyroid cancer is the most common endocrine cancer. The number of deaths from thyroid cancer projected for the year 2006 is 1,500, or 7% of all new thyroid cancer cases.

The prevalence rate for occult thyroid cancers found at autopsy is 5%–10%, except in Japan and Hawaii, where the rate can be as high as 28%. Autopsy rates do not correlate with clinical incidence.

The incidence of thyroid nodules in the general population is 4%–7%, with nodules being more common in females than males. The prevalence of thyroid cancer in a solitary nodule or in multinodular thyroid glands is 10%–20%; this increases with irradiation of the neck in children and older men (see section on “Etiology and risk factors”).

Tumor types

Thyroid cancer is classified into four main types according to its morphology and biologic behavior: papillary, follicular, medullary, and anaplastic. Differentiated (papillary and follicular) thyroid cancers account for > 90% of thyroid malignancies and constitute approximately 0.8% of all human malignancies. Medullary thyroid cancers represent 5%–10% of all thyroid neoplasms. About 80% of patients with medullary cancer have a sporadic form of the disease, whereas the remaining 20% have inherited disease. Anaplastic carcinoma represents ≤ 5% of all thyroid carcinomas.

Papillary thyroid carcinoma is the most common subtype and has an excellent prognosis. Most papillary carcinomas contain varying amounts of follicular tissue. When the predominant histology is papillary, the tumor is considered to be a papillary carcinoma. Because the mixed papillary-follicular variant tends to behave like a pure papillary cancer, it is treated in the same manner and has a similar prognosis.

Papillary tumors arise from thyroid follicular cells, are unilateral in most cases, and are often multifocal within a single thyroid lobe. They vary in size from microscopic to large cancers that may invade the thyroid capsule and infiltrate into contiguous structures. Papillary tumors tend to invade the lymphatics, but vascular invasion (and hematogenous spread) is uncommon.

Up to 40% of adults with papillary thyroid cancer may present with regional lymph node metastases, usually ipsilateral. Distant metastases occur, in decreasing order of frequency, in the lungs, bones, and other soft tissues. Older patients have a higher risk for locally invasive tumors and for distant metastases. Children may present with a solitary thyroid nodule, but cervical node involvement is more common in this age group; up to 10% of children and adolescents may have lung involvement at the time of diagnosis.

Follicular thyroid carcinoma is less common than papillary thyroid cancer, occurs in older age groups, and has a slightly worse prognosis. Follicular thyroid cancer can metastasize to the lungs and bones, often retaining the ability to accumulate radioactive iodine (which can be used for therapy). Metastases may be appreciated many years after the initial diagnosis.

Follicular tumors, although frequently encapsulated, commonly exhibit microscopic vascular and capsular invasion. Microscopically, the nuclei tend to be large and have atypical mitotic figures. There is usually no lymph node involvement.

Follicular carcinoma can be difficult to distinguish from its benign counterpart, follicular adenoma. This distinction is based on the presence or absence of capsular or vascular invasion, which can be evaluated after surgical excision but not by fine-needle aspiration (FNA).

Thyroglobulin, normally synthesized in the follicular epithelium of the thyroid, is present in well-differentiated papillary and follicular carcinomas and infrequently in anaplastic carcinomas but not in medullary carcinomas. Therefore, thyroglobulin immunoreactivity is considered to be indicative of a follicular epithelial origin.

Hürthle cell carcinoma Hürthle cell, or oxyphil cell, carcinoma is a variant of follicular carcinoma. Hürthle cell carcinoma is composed of sheets of Hürthle cells and has the same criteria for malignancy as does follicular carcinoma. Hürthle cell carcinoma is thought to have a worse outcome than follicular carcinoma and is less apt to concentrate radioactive iodine.

Medullary thyroid carcinoma originates from the C cells (parafollicular cells) of the thyroid and secretes calcitonin. On gross examination, most tumors are firm, grayish, and gritty.

Sporadic medullary thyroid carcinoma usually presents as a solitary thyroid mass; metastases to cervical and mediastinal lymph nodes are found in half of patients and may be present at the time of initial presentation. Distant metastases to the lungs, liver, bones, and adrenal glands most commonly occur late in the course of the disease. Secretory diarrhea, related to calcitonin secretion, can be a clinical feature of advanced medullary thyroid carcinoma.

Familial medullary thyroid carcinoma presents as a bilateral, multifocal process. Histologically, familial medullary carcinoma of the thyroid does not differ from the sporadic form. However, the familial form is frequently multifocal, and it is common to find areas of C-cell hyperplasia in areas distant from the primary carcinoma. Another characteristic feature of familial medullary carcinoma is the presence of amyloid deposits.

Anaplastic carcinoma Anaplastic tumors are high-grade neoplasms characterized histologically by a high mitotic rate and lymphovascular invasion. Aggressive invasion of local structures is common, as are lymph node metastases. Distant metastases tend to occur in patients who do not succumb early to regional disease. Occasional cases of anaplastic carcinoma have been shown to arise from preexisting differentiated thyroid carcinoma or in a preexisting goiter.

Other tumor types Lymphomas of the thyroid account for < 5% of primary thyroid carcinomas. Other tumor types, such as teratomas, squamous cell carcinomas, and sarcomas, may also rarely cause primary thyroid cancers.

Genetic factors In addition to sporadic medullary thyroid cancer, which represents the majority of cases, there are three hereditary forms: familial medullary thyroid carcinoma; multiple endocrine neoplasia type 2A (MEN-2A), characterized by medullary thyroid cancer, pheochromocytomas, and hyperparathyroidism; and multiple endocrine neoplasia type 2B (MEN-2B), characterized by medullary thyroid cancer, marfanoid habitus, pheochromocytomas, and neuromas. These syndromes are associated with germ-line mutations of the RET proto-oncogene, which codes for a receptor tyrosine kinase (RTK). Familial medullary thyroid carcinoma is inherited as an autosomal-dominant trait with high penetrance and variable expression. (For a discussion of genetic testing to screen for RET mutations in MEN-2A kindreds, see section on “Staging and prognosis.”)