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Painless swelling in region of thyroid Thyroid function tests usually normal Past history of irradiation to head and neck region may be present Positive thyroid needle aspiration
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The incidence of papillary and follicular (differentiated) thyroid carcinomas increases with age The female:male ratio is 3:1 In the United States, thyroid cancer is diagnosed in nearly 26,000 people yearly, and about 1 in every 250 people eventually receives this diagnosis About 13% of persons in the United States are found to have microscopic thyroid cancer at autopsy Clearly, most thyroid cancers remain microscopic and indolent However, larger thyroid cancers (palpable or 1 cm in diameter) are more malignant and require treatment Papillary thyroid carcinoma is the most common thyroid malignancy (Table 26 7) Pure papillary or mixed papillaryfollicular carcinoma represents about 80% of all thyroid
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Table 26 7 Some characteristics of thyroid cancer
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Papillary Incidence Average age Females Deaths due to thyroid cancer Invasion Juxtanodal Blood vessels Distant sites Resemblance to normal thyroid
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Follicular Common 50 72% 24% + +++ +++ +++ ++++ ++ to +++
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Most common 42 70% 6% +++++ + + + + +
I uptake
Degree of malignancy
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develop a papillary thyroid carcinoma Papillary carcinoma can sometimes undergo a late anaplastic transformation into an aggressive carcinoma Generally speaking, papillary carcinoma is the least aggressive thyroid malignancy However, the tumor spreads via lymphatics within the thyroid, becoming multifocal in 60% of patients and involving both lobes in 30% of patients About 80% of patients have microscopic metastases to cervical lymph nodes; palpable lymph node involvement is present in 15% of adults and 60% of youths Unlike other forms of cancer, patients with papillary thyroid carcinoma who have palpable lymph node metastases do not have a particularly increased mortality rate; however, their risk of local recurrence is increased Occult metastases to the lung occur in 10 15% of differentiated thyroid cancer; such lung metastases may be first noted on the whole-body scan following 131I therapy About 70% of small lung metastases resolve following 131I therapy; however, larger pulmonary metastases have only a 10% remission rate Microscopic micropapillary carcinoma (invisible even on thyroid ultrasound) is a variant of normal, being found in 24% of thyroidectomies performed for benign thyroid disease when 2-mm sections were carefully examined It thus appears that the overwhelming majority of these microscopic foci never become clinically significant The surgical pathology report of such a tiny papillary carcinoma that is otherwise benign does not justify aggressive follow-up or treatment because a cancer diagnosis is unwarranted and harmful All that may be required is yearly follow-up with palpation of the neck and mild TSH suppression by thyroxine Follicular thyroid carcinoma results from certain gene mutations or translocations Aberrant DNA methylation, activation of the ras oncogene, and mutations of the MEN1 gene can result in benign follicular adenomas Loss of function of PPARg or the 3P tumor suppressor gene can lead to follicular carcinoma, and additional loss of the p53 tumor suppressor gene can produce anaplastic carcinoma Follicular thyroid carcinoma and adenomas develop in patients with Cowden s disease, a rare autosomal dominant familial syndrome caused by loss of a tumor suppressor gene; such patients tend to have macrocephaly, multiple hamartomas, early-onset breast cancer, intestinal polyps, facial papules, and other skin and mucosal lesions Follicular and H rthle cell carcinoma accounts for about 14% of thyroid malignancies and is generally more aggressive than papillary carcinoma Rarely, some follicular carcinomas secrete enough T4 to cause thyrotoxicosis if the tumor load becomes significant Metastases commonly are found in neck nodes, bone, and lungs Most follicular thyroid carcinomas avidly absorb iodine, making possible diagnostic scanning and treatment with 131I after total thyroidectomy Certain follicular histopathologic features are associated with a high risk of metastasis and recurrence: poorly differentiated and H rthle cell (oncocytic) variants The latter variants do not take up RAI Medullary thyroid carcinoma is often caused by an activating mutation of the ret oncogene on chromosome 10 Mutation analysis of the ret oncogene s exons 10, 11, 13, and 14 detects 95% of the mutations causing MEN 2A and 90% of the mutations causing familial medullary thyroid carci-
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