Papillary Thyroid Carcinoma, Subtypes, and Related Tumors

Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid, in both adults and children, accounting for approximately 85% of all cancers at this site. PTC usually presents clinically as a thyroid nodule, often discovered incidentally on routine examination; less commonly, patients present with metastatic disease in the neck lymph nodes. PTC spreads via lymphatics to the regional lymph nodes and less frequently to the lungs. PTC is much more common in women and has a well-documented association with prior radiation exposure to the neck. It generally carries a good prognosis; death secondary to PTC is rare. Approximately five percent of all thyroid FNAs are diagnosed as malignant, and the majority of these are PTC. When a diagnosis of PTC is made by FNA, 94-96% prove to be PTC on histologic follow-up taking into consideration the reclassification of some follicular variant of PTC as NIFTP. Conventional PTCs are notable histologically for numerous papillae lined by cuboidal to low columnar neoplastic follicular cells with characteristic nuclear features. PTC has many histological subtypes, however, and these have a spectrum of corresponding cytomorphologic characteristics. At the molecular level, the most important event is activation of the MAPK pathway, resulting from activating mutations of RAS and BRAF or gene rearrangements such as RET fusions. The standard treatment is lobectomy or near-total thyroidectomy, sometimes followed by radioactive iodine, although active surveillance may be considered in select patients. In this chapter, conventional PTC and its subtypes are described separately to highlight some of the morphologic heterogeneity in this family of tumors. Some uncommon thyroid neoplasms which have been related to PTC in the past, including hyalinizing trabecular tumor and cribriform-morular thyroid carcinoma, are also discussed in this chapter since they share some cytomorphological features with PTC.