Papillary Thyroid Carcinoma

Abstract

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, accounting for 80 % of thyroid carcinomas in adults and 90 % in children. PTC is a malignant epithelial tumor showing follicular differentiation and distinctive nuclear features. Patients usually are 20–50 years old, but those of any age may be affected. PTC is more common in women than men. Most PTCs are sporadic but may occur with syndromes such as Gardner syndrome, Cowden syndrome, and ataxia telangiectasia. PTC may arise in ectopic thyroid tissue such as struma ovarii, adrenal glands, and trachea. Radiation exposure is a risk factor for PTC. Histologic variants of PTC are important to recognize prognostically and for association with other diseases. Aggressive variants include tall cell, columnar cell, solid, and the recently described hobnail variant. The cribriform-morular variant often is associated with familial adenomatous polyposis. PTCs are positive for thyroglobulin, thyroid transcription factor 1 (TTF1), and keratins and are negative for calcitonin, chromogranin, and synaptophysin. Markers useful in confirming a diagnosis of PTC are HBME-1, keratin 19, galectin-3, and CITED1. BRAF mutations occur in about 60 % of PTCs, and RET/PTC rearrangements occur in 20–30 % of adult PTCs. BRAF mutation and RET/PTC rearrangement are mutually exclusive abnormalities in PTCs. RET/PTC1 is more common in papillary microcarcinomas and PTCs with classic architectural features, whereas RET/PTC3 is more common in the solid variant. BRAF mutations occur in classic, Warthin-like, and oncocytic PTCs; microcarcinomas; and aggressive variants such as tall cell, columnar, and hobnail PTCs. Poorly differentiated and anaplastic thyroid carcinomas also may show BRAF mutation, particularly if associated with or dedifferentiated from a PTC. BRAF mutation is not common in pediatric or radiation-associated PTCs. The follicular variant of PTC (FVPTC) is associated with RAS mutations (as are follicular neoplasms), thus RAS is not useful in separating FVPTC from follicular neoplasms. PTCs usually metastasize to cervical nodes, particularly ipsilateral nodes, before spreading to the lung and other sites. Unfavorable prognostic features are older age, male sex, large tumor size, multicentricity, angiolymphatic invasion, necrosis, mitoses, extrathyroid extension, distant metastases, high grade, marked nuclear atypia, and progression to poorly or undifferentiated carcinoma. PTCs are treated by thyroidectomy and removal of involved lymph nodes. Radioactive iodine may be used to ablate any remaining tumor, including metastatic sites. Overall, PTC has an excellent prognosis, with >90 % survival, and most patients survive even with metastatic disease.