Update on clinically important variants of papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, as well as the most common endocrine malignancy. Universally, PTC has an excellent clinical prognosis, even with local lymph node involvement at initial surgery. Over the past 20 years, numerous morphologic variants of PTC have been defined. These variants demonstrate a range of biologic aggressiveness, despite an overall favourable outcome for all variants. Molecular changes in PTC have been recognized for some time, most notably BRAF (V600E) mutations, but also mutations in KRAS, HRAS, NRAS, as well as RET/PTC rearrangements. Detection of these genetic anomalies may have diagnostic significance and possibly prognostic significance, since some of the more typically thought of aggressive variants have a higher rate of BRAF mutations. However, there is still a great deal of uncertainty as to which PTC will truly have aggressive biologic behaviour. In this article, we review clinically significant PTC variants, in terms of those with differences in biologic potential and clinical behaviour.