Papillary Thyroid Carcinoma Tall Cell Variant

Background: The most common of the aggressive variant of papillary thyroid carcinoma (PTC) is the tall cell variant (TCV). Because there are serious prognostic and management implications to a diagnosis of TCV, we review the entity to inform clinicians about the many facets of TCV. Summary: The TCV of PTC is characterized by cells having the nuclear features of PTC and whose height is at least twice or thrice their width. There is disagreement regarding the proportion of tall cells and the cell height required to diagnose TCV. In view of its blurred definition and rarity, studies have shown that TCV is still underdiagnosed. We propose that PTC be diagnosed as TCV if it is composed of >= 50% tall cells. The latter should have a height that is at least twice their width, an eosinophilic cytoplasm, and the nuclear features of PTC. Whatever its definition, there is a consensus that TCV has a higher recurrence and death rate than classical PTC. Most authorities believe that TCV's worse prognosis is related to its older age at presentation, larger tumor size, and high frequency of extrathyroid extension (ETE). However, in a recent article, TCV without ETE was shown to have a more aggressive behavior than classical PTC without ETE independent of age, gender, and tumor size. The aggressive behavior of TCV could be related to the high expression of Muc1 and matrix metalloproteinase and to the higher prevalence of B-RAF mutations when compared to classical PTC. The importance of TCV is accentuated by the fact that it is overrepresented in those fluorodeoxyglucose positron-emission tomogram (FDG-PET)-positive thyroid carcinomas that are refractory to radioactive iodine (RAI) therapy constituting 20% of these incurable tumors. Conclusion: TCV is a biologically and clinically aggressive form of PTC that is still underdiagnosed. TCV is overrepresented in patients with RAI refractory disease. It has a high prevalence of B-RAF mutations making the latter an attractive target in RAI refractory cases. Imaging modalities that can detect RAI refractory disease such as FDG-PET scanning are needed in many patients and a requirement in those with extensive ETE. More studies are needed to identify those TCV that become RAI refractory and develop effective target therapies against these incurable carcinomas.