Papillary thyroid carcinoma tall cell variant.

Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Thyroid: official journal of the American Thyroid Association (Impact Factor: 3.84). 10/2008; 18(11):1179-81. DOI: 10.1089/thy.2008.0164
Source: PubMed

ABSTRACT 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 > or =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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. The Warthin-like variant of papillary thyroid (WLPTC) is a rare subtype of papillary thyroid carcinoma (PTC) resembling Warthin tumors of the salivary glands. Due to its rarity, the clinicopathologic and molecular features of WLPTC remain unclear. Methods. Of the 2,139 patients who underwent surgical treatment for PTC from 2012 to 2013, 40 patients with WLPTC were identified and compared to 200 consecutive patients with classic PTC. BRAF mutation was tested with pyrosequencing. Results. There were no significant differences in age, predilection for women, multifocality, extrathyroidal extension, or lymph node metastasis between WLPTC and classic PTC. However, WLPTCs were more commonly associated with Hashimoto’s thyroiditis than classic PTCs (93% versus 36%, resp., P < 0.001) and showed significantly lower rate of BRAF mutation when compared to classic PTCs (65% versus 84%, resp., P = 0.007). In classic PTC, the frequency of BRAF mutations was negatively correlated with coexisting Hashimoto’s thyroiditis. When we compared WLPTC and classic PTC in the patients with coexisting Hashimoto’s thyroiditis, there were no significant differences in clinicopathologic characteristics or the BRAF mutational rate between the two groups. Conclusions. Patients with WLPTC have similar demographic, clinical, pathologic, and molecular characteristics to those with classic PTC coexisting with Hashimoto’s thyroiditis.
    International Journal of Endocrinology 01/2015; 2015:1-8. DOI:10.1155/2015/456027 · 1.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Defining the histologic variant of thyroid carcinoma is an important clinical implication as their progression, recurrence, aggressiveness, and prognosis differ. Warthin-like variant is one of the rarest histologic variants of papillary thyroid cancer. A 36-year-old female sought consult for assessment of a painless right neck tumor. High-resolution neck ultrasound revealed a right hypoechoic, 1.71 × 1.05 cm thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy report was a Bethesda grade III. Thyroid function tests showed Hashimoto's thyroiditis. The patient underwent right hemithyroidectomy. Microscopically, the tumor was composed of papillae lined by cells with eosinophilic cytoplasm, nuclear chromatin clearing, grooves, and pseudoinclusions and a characteristic lymphoplasmacytic infiltrate of the papillae cores. Extension into the perithyroidal soft tissue and 3 ipsilateral lymph nodes was found to be positive for cancer. Warthin-like variant is an uncommon and relatively unknown variant of papillary thyroid carcinoma that has been usually associated with an excellent prognosis. Interestingly, BRAF mutations have been reported to be present in up to 75% of the patients. It is frequently associated with Hashimoto's thyroiditis and presents unique morphological features that make it recognizable on histologic examination. The cytological diagnosis is difficult to assess due to the overlap in its findings with the classical variant and Hashimoto's thyroiditis.
    01/2015; 2015:251898. DOI:10.1155/2015/251898
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A BRAF somatic mutation at residue 600 of the BRAF protein (BRAFV600E) is highly prevalent in papillary thyroid carcinomas (PTC). This mutation occurs in approximately 44% (from 29% to 83%) of PTC depending on the different studies. BRAFV600E is almost always found in PTC with a papillary or a mixed follicular/papillary architecture, being rarer in other subtypes of PTC. The discovery of the BRAFV600E mutation in tissue and fine-needle aspiration (FNA) is diagnostic for PTC and has been frequently associated with worse clinical prognosis. However, some studies failed to reveal this prognostic association. Transcriptional and post-transcriptional modulation of PTC with a BRAF mutation has been evaluated in some recent studies. Current therapeutic approaches targeting BRAF are being tested in clinical trials, particularly in more aggressive PTC. In this review, we will first discuss the diagnostic value of a BRAF mutation for PTC diagnosis. The prognostic role of a BRAFV600E mutation is then outlined and discussed in the context of other well-accepted clinicopathological prognostic parameters for PTC (age, gender, pTNM stage, histological subtype). Finally, the currently and potentially used treatments targeting BRAF in patients with PTC are presented.
    Current Medicinal Chemistry 03/2010; 17(17):1839-50. DOI:10.2174/092986710791111189 · 3.72 Impact Factor


Available from