Endocrine malignancies, although relatively uncommon, are often difficult to diagnose and treat effectively. According to American Cancer Society (ACS) estimates, more than 39,000 new cases of endocrine neoplasms will be diagnosed in the United States in 2009, and approximately 2,470 deaths will result from these cancers. This chapter will focus on thyroid and parathyroid cancers. (A discussion of carcinoid tumors, insulinomas, gastrinomas, and other gastrointestinal neuroendocrine tumors, as well as adrenocortical cancer, can be found in chapter 11.)
THYROID CANCER
Thyroid cancer is the most common endocrine cancer. The number of deaths from thyroid cancer estimated for 2009 is 1,630, or 4.3% of all new thyroid cancer cases.
The prevalence rate for occult thyroid cancers found at autopsy is 5% to 10%, except in Japan and Hawaii, where the rate can be as high as 28%. Autopsy rates do not correlate with clinical incidence.
The prevalence of thyroid nodules in the general population is 4% to 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% to 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 3% to 5% of all thyroid neoplasms. About 75% of patients with medullary cancer have a sporadic form of the disease, whereas the remaining 25% have inherited disease. Anaplastic carcinoma represents < 3% 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 hematogeneous 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, 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.
