Preoperative BRAFV600E mutation detection in thyroid carcinoma by immunocytochemistry.

The BRAFV600E (BRAF) mutation is present in 40-50% of papillary thyroid carcinomas (PTC) and has been associated with more aggressive clinicopathological characteristics of PTC. The aim of this study was to evaluate different methods for preoperative identification of the BRAF mutation in PTC using cytological and histological specimens. Prospectively collected preoperative cytological clots from patients with suspected PTC were tested with BRAF immunocytochemistry (ICC) and the Cobas Test (PCR). In addition, histological specimens were tested with BRAF immunohistochemistry (IHC) and the Cobas Test. All nodules were histologically examined. Fifty-three patients were included in the study. Complete mutation testing was available in 32 patients. The main reason for exclusion was insufficient cell content in the cytological specimen. Twenty-seven nodules were histologically diagnosed as PTC, and 41% (n = 11) of PTCs were BRAF ICC positive. All non-PTC nodules were negative by BRAF ICC. In 26 nodules, all four BRAF tests were concordant, while discordant test results were found in six nodules. ICC was in accordance with the consensus BRAF status in five of these nodules, while BRAF status was undetermined in one nodule. BRAF ICC showed high concordance with the Cobas Test and a low rate of false negative stain. These results indicate that BRAF ICC may be a feasible method for preoperative detection of the BRAFV600E mutation in patients with PTC.

Risk-stratification of thyroid nodules examined by 18FDG-PET/CT while ensuring congruity between imaging and histopathological localization.

PURPOSE: The risk of malignancy (ROM) in FDG-avid thyroid incidentalomas varies between studies, which may be contributed by discordance between the anatomical localization depicted on 18FDG-PET/CT and by histopathological examination. The purpose was to ensure anatomical congruity between the index tumour identified by 18FDG-PET/CT and the histopathological examination, in order to assess the risk of malignancy (ROM) in PET-positive and PET-negative thyroid nodules. Further, preoperative characteristics indicative of thyroid malignancy were identified. METHODS: Thirty-two patients referred to thyroid surgery were prospectively included. 18FDG-PET/CT, fine-needle aspiration biopsy and thyroid ultrasonography examination were performed in all participants. The exact anatomical localization of the index nodule was established by histopathological examination to ensure concordance with the 18FDG-PET/CT finding. RESULTS: Forty thyroid nodules were included. Malignancy was identified in 10 of 28 PET-positive nodules and in 1 of 12 PET-negative nodules, resulting in a ROM of 36% and 8%, respectively. A Hurtle cell neoplasm was found in 50% of patients with a benign nodule and a PET-positive scan. One PET-negative nodule represented a papillary microcarcinoma. In PET-positive nodules, hypoechogenicity, irregular margins, and pathological lymph nodes on thyroid ultrasonography were characteristics associated with malignancy. CONCLUSIONS: In this study-ensuring anatomical congruity between PET-findings and the histopathological examination-the risk of malignancy in PET-positive thyroid nodules was 36%. A low ROM was seen in thyroid nodules without suspicious ultrasonographic findings, independent of the 18FDG-PET/CT result. TRIAL REGISTRATION NUMBER: NCT02150772 registered 14th of April 2014.

Reappraisal of shear wave elastography as a diagnostic tool for identifying thyroid carcinoma.

Thyroid nodular disease is common, but predicting the risk of malignancy can be difficult. In this prospective study, we aimed to assess the diagnostic accuracy of shear wave elastography (SWE) in predicting thyroid malignancy. Patients with thyroid nodules were enrolled from a surgical tertiary unit. Elasticity index (EI) measured by SWE was registered for seven EI outcomes assessing nodular stiffness and heterogeneity. The diagnosis was determined histologically. In total, 329 patients (mean age: 55 ± 13 years) with 413 thyroid nodules (mean size: 32 ± 13 mm, 88 malignant) were enrolled. Values of SWE region of interest (ROI) for malignant and benign nodules were highly overlapping (ranges for SWE-ROImean: malignant 3-100 kPa; benign 4-182 kPa), and no difference between malignant and benign nodules was found for any other EI outcome investigated (P = 0.13-0.96). There was no association between EI and the histological diagnosis by receiver operating characteristics analysis (area under the curve: 0.51-0.56). Consequently, defining a cut-off point of EI for the prediction of malignancy was not clinically meaningful. Testing our data on previously proposed cut-off points revealed a low accuracy of SWE (56-80%). By regression analysis, factors affecting EI included nodule size >30 mm, heterogeneous echogenicity, micro- or macrocalcifications and solitary nodule. In conclusion, EI, measured by SWE, showed huge overlap between malignant and benign nodules, and low diagnostic accuracy in the prediction of thyroid malignancy. Our study supports that firmness of thyroid nodules, as assessed by SWE, should not be a key feature in the evaluation of such lesions.

Is serum TSH a biomarker of thyroid carcinoma in patients residing in a mildly iodine-deficient area?

PURPOSE: To investigate the association between the pre-operative serum TSH (s-TSH) level and differentiated thyroid carcinoma (DTC) in a mildly iodine-deficient area. METHODS: Patients undergoing surgery for thyroid nodular disease (TND) were included from three tertiary surgical departments. Data were collected from a national thyroid surgery database (THYKIR) and from patient charts. Individuals with overtly coexisting thyroid disorders were excluded for subgroup analyses. Patients were compared with the Danish background population, employing previous data from DanThyr, a study initiated to monitor the iodine fortification program in Denmark. RESULTS: Nine-hundred ninety-eight patients [cases/controls: 265/733; female/male: 794/204; age (mean ± SD): 51 ± 15 years] were included. S-TSH was significantly higher in the DTC group [median (IQR): 1.3 (0.9-1.9 mIU/L)] compared with the benign TND group [0.9 (0.6-1.5 mIU/L)] (p < 0.0001). The median s-TSH in the background population was similar to that found among DTC patients (p = 1.00), but markedly higher than the s-TSH level in the benign TND group (p < 0.0001). There was no association between s-TSH and DTC disease stage (p = 0.08-0.87). CONCLUSIONS: s-TSH was significantly higher in patients with DTC than in those with benign TND. However, this difference can be explained by abnormally lower s-TSH level in the latter group, probably caused by subtle nodular functional autonomy. Due to the huge overlap and the small difference in median s-TSH between patients with benign and malignant TND, s-TSH is not suitable as a biomarker of DTC in a clinical setting.

Is the reproducibility of shear wave elastography of thyroid nodules high enough for clinical use? A methodological study.

OBJECTIVE: To systematically assess the reproducibility of thyroid ultrasonographic shear wave elastography (SWE). CONTEXT: SWE has been suggested as a potential tool for thyroid nodule evaluation, but assessment of its reproducibility has been insufficiently addressed. DESIGN: SWE examinations were performed prospectively by two investigators. PATIENTS: Seventy-two patients (male/female: 19/53; mean age: 53 ± 14 years; malignant/benign 17/55) undergoing thyroid surgery were enrolled in the study. MEASUREMENTS: Repeated and blinded measurements of elasticity index (EI) in predefined regions of interest (ROI) were collected. The inter- and intrarater agreement, along with the day-to-day agreement, was evaluated in terms of the 95% limits of agreement (LOA). Results are presented as a ratio, by which 1·0 indicates perfect agreement. RESULTS: The interrater, intrarater and day-to-day LOA showed ratios between repeated measurements of 1·7-3·6, 1·8-3·7 and 2·2-2·9, respectively. These values reflect a low to moderate degree of agreement for all EI outcomes. The interrater LOA was higher for malignant nodules compared with benign nodules for six of seven EI outcomes (P < 0·001-0·03). The proportion of agreement calculated from the optimum cutoff point for differentiating malignant from benign nodules was 63-88% for the investigated EI outcomes. CONCLUSIONS: In this methodological study, EI measured by thyroid SWE seems suboptimal for clinical use, due to a low inter- and intrarater agreement. That EI varies from day to day furthermore jeopardizes the validity of the method. Although the proportion of agreement was acceptable for some EI parameters, it is questionable whether EI assessments can reliably differentiate malignant from benign nodules in the individual patient.