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Differentiated thyroid carcinoma
Differentiated thyroid carcinoma (DTC), also known as papillary or follicular thyroid carcinoma, is a slow-growing malignancy usually presenting in adults as an asymptomatic thyroid mass.
ORPHA:146Classification level: Disorder
DTC is the most common form of thyroid cancer and includes both papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Overall annual incidence is about 1/10,000, and the incidence appears to be increasing. The female to male ratio is about 3:1. About 90% of DTCs are PTC, and 10% are FTC.
The two forms of DTC have similar presentations. FTC is generally considered slightly more aggressive. The age at diagnosis is usually over 30 years. DTC usually presents as an asymptomatic nodule within the thyroid. Rare but worrisome presentations include hoarseness due to vocal cord paralysis and obstruction of the airway or esophagus. DTC grows slowly, and distant metastases are rare at the time of presentation. The most common metastatic site is cervical lymph nodes. Distant metastasis to lungs or bones is rare (about 5%).
Most DTCs are sporadic and without known cause. Ionizing radiation causes PTC. Iodine deficiency is associated with an increased risk of FTC. The sporadic molecular pathogenesis of these two malignancies is partially understood. The V600E BRAF mutation (7q34) is the single most common mutation in PTC. Multiple different fusion genes involving RET (10q11.2) are also relatively common. Activating RAS mutations occur in both PTC and FTC as well as in benign thyroid lesions. The PAX8/PPAR gamma fusion gene (2q13) is unique to follicular thyroid cancer. About 5% of PTCs have a familial predisposition.
Differentiated thyroid cancer usually presents on physical examination or ultrasound as an asymptomatic nodule within the thyroid gland and must be differentiated form benign thyroid nodules that are much more common. Serum concentrations of thyroid hormone are usually normal. Thyroid fine needle aspiration biopsy is most frequently used to distinguish between the benign and malignant nodules. Diagnosis is confirmed on pathology review following surgical resection. About 50% of PTCs are characterized by the presence of ''psammoma bodies'' which are deposits of calcium. Different histological subtypes have been described. Follicular variant of PTC has a prognosis identical to PTC; the tall cell variant (10%) of PTC is a more aggressive variant.
Differential diagnosis of thyroid nodules includes nodular goiter, thyroid cyst, follicular adenoma, other thyroid malignancies, as well as Hashimoto thyroiditis and thyroid lymphoma (see these terms).
Management and treatment
The treatment of DTC is prioritized. First, complete surgical resection is essential to cure. Second, thyroid hormone administration to suppress TSH helps prevent recurrence. Third, since most DTCs maintain the ability to take up iodine, 131-iodine therapy is useful in eradicating residual microscopic disease. For those few patients that do not respond to conventional therapy, external radiation and multikinase inhibitors are effective. Long-term follow-up is essential because of the cumulative risk of recurrence (about 20% at 20 years). Recurrences are detected by physical examination, neck ultrasound, iodine scans, and serum thyroglobulin measurements.
The two forms of DTC have similar outcomes: about 5% of cases are fatal. Prognosis is generally good in most patients. Those below 45 years and tumor size below 2 cm have a particularly good prognosis. Those with distant metastatic disease have a poorer prognosis. Occasional patients may progress to anaplastic thyroid cancer (see this term) that uniformly has a very poor prognosis.