Most adenomas of the thyroid manifest as painless nodules, often discovered during a routine physical examination. Larger masses may produce local symptoms such as difficulty in swallowing. Individuals with toxic adenomas may present with features of thyrotoxicosis. After injection of radioactive iodine, most adenomas take up iodine less avidly than normal thyroid parenchyma. On radionuclide scanning, therefore, adenomas appear as cold nodules relative to the adjacent normal thyroid gland. Toxic adenomas, however, appear as warm or hot nodules in the scan. As many as 10% of cold nodules eventually prove to be malignant. By contrast, malignancy is uncommon in hot nodules. Essential techniques used in the preoperative evaluation of suspected adenomas are ultrasonography and fine-needle aspiration biopsy. Because of the need for evaluating capsular integrity, the definitive diagnosis of thyroid adenoma can be made only after careful microscopic examination of the resected specimen. Suspected adenomas of the thyroid are therefore removed surgically to exclude malignancy. Thyroid adenomas carry an excellent prognosis and do not recur or metastasize.
The detection of small , clinically asymptomatic cancerous nodules of the thyroid gland has increased dramatically in the United States over the last few years, largely due to the increasing use of thyroid ultrasound and other imaging studies. Nonetheless, deaths from thyroid cancer have remained relatively stable during this period, underscoring the favorable outcome for such incidentally detected thyroid carcinomas (and also raising questions about the value of detecting clinically insignificant cancers). A female predominance has been noted among patients who develop thyroid carcinoma in the early and middle adult years. By contrast, cases seen in childhood and late adult life are distributed equally between males and females. Most thyroid carcinomas (except medullary carcinomas) are derived from the thyroid follicular epithelium, and of these, the vast majority are well-differentiated lesions. The major subtypes of thyroid carcinoma and their relative frequencies are as follows:
Papillary carcinoma (accounting for more than 85% of cases)
Follicular carcinoma (5% to 15% of cases)
Anaplastic (undifferentiated) carcinoma (<5% of cases)
Medullary carcinoma (5% of cases)
Because of the unique clinical and biologic features associated with each type of thyroid carcinoma, these are described separately. Presented next is an overview of the molecular pathogenesis of all thyroid cancers.
Distinct molecular events are involved in the pathogenesis of the four major variants of thyroid cancer. Genetic alterations in the three follicular cell–derived malignancies are clustered along two oncogenic pathways that lie downstream of growth factor receptors and RAS—the mitogen-activated protein (MAP) kinase pathway and the phosphatidylinositol-3-kinase (PI-3K)/AKT pathway
Fig.20.13Hürthlecelladenoma.Onthishigh-powerview,thetumoriscomposedofcellswithabundanteosinophiliccytoplasmandsmallregularnuclei.(Courtesy of Dr. Mary Sunday, Brigham and Women’s Hospital, Boston, Massachusetts.) http://ebooksmedicine.net
PAX8:PPARG
Fig. 20.14 ). In normal cells, these pathways are transiently activated by binding of growth factors to receptor tyrosine kinases, which results in signal transduction. In thyroid carcinomas, as with many solid cancers (Chapter 6), gain-of-function mutations in components of these pathways lead to constitutive activation, even in the absence of growth factors, thus promoting carcinogenesis.