Thyroid cancer is fairly common, with an annual incidence ranging from 0.5 to 10 per 100,000 in various populations. Thyroid cancer is two to four times as frequent in women as in men. Main risk factors for thyroid cancer include exposure to radiation (a history of radiation therapy administered in infancy or childhood, exposure to nuclear fallout), family history of thyroid disease or multiple endocrine neoplasia (MEN) syndrome, RET gene mutation, and history of goiter.
Symptoms of thyroid cancer can include a painless lump or swelling in the front of the neck, longstanding unexplained hoarseness, and difficulty swallowing. Thyroid cancer can present with symptoms of disrupted endocrine functions due to the altered production of thyroid hormones.
Classification of thyroid tumors into several different subtypes is based on histological features. The most common form of thyroid cancer is papillary carcinoma (70-80%), followed by follicular carcinoma (10-20%), medullary carcinoma (5-10%), and anaplastic carcinoma (2-10%). Generally speaking, papillary and follicular thyroid carcinomas are well-differentiated tumors while anaplastic carcinomas lose the differentiation and are one of the most aggressive malignancies in human pathology. Poorly-differentiated thyroid carcinoma is defined by an increased mitotic rate, necrosis, and loss of characteristic nuclear features and is between these two categories when it comes to prognosis.
Papillary thyroid carcinoma is defined as a malignant epithelial tumor. Microscopically, the tumor shows evidence of follicular cell differentiation, typically with papillary and follicular structures as well as characteristic changes in tumor cell nuclei. The key to an accurate diagnosis are nuclear characteristics, including a ground-glass appearance, large size, pale staining, and irregular outline with deep grooves and pseudoinclusions. Papillary thyroid carcinoma grows slowly, with an excellent long-term prognosis, despite a propensity to invade locally and to spread metastatically to regional lymph nodes. Distant metastases are uncommon.
Follicular thyroid carcinoma shows follicular differentiation but lacks the diagnostic features of papillary carcinoma. The incidence of follicular carcinoma is higher in areas of endemic goiter and iodine deficiency appears to be the main contributing risk factor. In contrast to papillary carcinoma, the main mode of metastatic spread is hematogenous rather than through the lymphatic system. Follicular carcinoma is typically delimited by a fibrous capsule surrounding tightly packed follicles, trabeculae or solid sheets of tumor cells. Tumor cells are often cuboidal with dark or pale staining nuclei with inconspicuous nucleoli. Rare cases of follicular carcinomas may display nuclear pleomorphism.
For most thyroid tumors, diagnosis can be established by microscopic examination alone, although immunohistochemistry plays an important role in tumors exhibiting unusual morphological features. Antibodies used in diagnostics of thyroid tumors include thyroglobulin (TG), calcitonin (CALCA), and thyroid transcription factor (TTF1). Molecular investigations of genetic alterations in BRAF, RAS, and RET genes in different forms of thyroid cancer can have diagnostic value.
The main treatments of thyroid cancer depend on tumor type and stage. They include partial or complete surgical removal of the thyroid gland, treatment with radioactive iodine, radio- and chemotherapy. The prognosis is good for the major forms of thyroid cancer, with a 10-year relative survival rate of 99% for papillary carcinoma, 96% for follicular carcinoma, 89% for medullary carcinoma, and 7% for anaplastic carcinoma. Besides age, where young patients have a considerably better prognosis, the size of the primary tumor and the tumor stage are the most significant prognostic factors.