BRAFV600E mutation test on fine-needle aspiration specimens of thyroid nodules: Clinical correlations for 4600 patients.

BACKGROUND: The BRAFV600E mutation is valuable for the diagnosis, prognosis, and therapy of papillary thyroid cancer (PTC). However, studies related to this mutation have involved only a small number of patients. Therefore, we performed a large-scale analysis from a single institute to evaluate the accuracy of combined fine-needle aspiration (FNA) and BRAFV600E mutation tests for PTC diagnosis. METHODS: A total of 4600 patients with thyroid nodules who underwent both FNA cytology and BRAFV600E mutation analysis on FNA specimens were enrolled. The association between the BRAFV600E mutation and clinicopathological features was analyzed. A separate analysis was performed for the 311 patients who underwent repeated FNA for comparison of cytological evaluation and BRAFV600E mutation results. The diagnostic efficacy of the BRAFV600E mutation test and cytologic diagnoses was evaluated for 516 patients who underwent preoperative FNA tests in comparison with conclusive postoperative histopathologic results. RESULTS: The cytology results of all 4600 FNA samples were categorized according to The Bethesda System for Reporting Thyroid Cytology (TBSRTC) stages I-VI, which accounted for 11.76%, 60.02%, 6.46%, 3.61%, 6.71%, and 11.43% of the samples, respectively. The BRAFV600E mutation was detected in 762 (16.57%) FNA samples, with rates of 1.48%, 0.87%, 20.20%, 3.01%, 66.02%, and 87.81% for TBSRTC I-VI lesions, respectively. Among the 311 repeat FNA cases, 81.0% of the BRAFV600E -positive and 4.3% of the BRAFV600E -negative specimens with an initial indication of cytological non-malignancy were ultimately diagnosed as malignant by repeat FNA (p < 0.001). Among the 516 patients who underwent thyroidectomy, the sensitivity and specificity of the BRAFV600E mutation test alone for PTC diagnosis were 76.71% and 100.0%, respectively, which increased to 96.62% and 88.03%, respectively, when combining the BRAFV600E mutation test with cytology. BRAFV600E mutation was significantly associated with lymph node metastasis (p < 0.001), but not with age, gender, or tumor size. CONCLUSIONS: The BRAFV600E mutation test in FNA samples has potential to reduce false negatives in PTC diagnosis, and therefore plays an important role in the diagnosis of thyroid nodules, especially those with an indeterminate or nondiagnostic cytology, which should be considered for repeat FNA.

Combination of Lymphatic and Intravenous Contrast-Enhanced Ultrasound for Evaluation of Cervical Lymph Node Metastasis from Papillary Thyroid Carcinoma: A Preliminary Study.

The aim of this prospective study was to evaluate the value of the combination of lymphatic contrast-enhanced ultrasound (LCEUS) and intravenous contrast-enhanced ultrasound (IVCEUS) for the identification of cervical lymph node metastasis (CLNM) from papillary thyroid carcinoma (PTC). From November 2018 to March 2019, 24 consecutive patients with PTC were evaluated. All patients underwent routine US, LCEUS and IVCEUS. Pathology was used as the gold standard. After injection of a contrast agent into the thyroid parenchyma, lymphatic vessels and lymph nodes (LNs) could be exclusively displayed as hyper-enhancement on LCEUS. Benign LNs displayed a complete bright ring (100%) and homogeneous perfusion (88.9%) on LCEUS, while displaying centrifugal perfusion (66.7%) and homogenous enhancement (88.9%) on IVCEUS. Perfusion defects (94.9%) and interruption of the bright ring (71.8%) were the two characteristic LCEUS signs for diagnosing CLNM. On IVCEUS, CLNM appeared as centripetal perfusion (59.0%) and heterogeneous enhancement (59.0%). After comparison with pathology, perfusion defect was correlated to the metastatic foci in the medulla and interruption of the bright ring to the tumor seeding in the marginal sinus (all p values <0.05). LCEUS had more value (area under the receiver operating characteristic curve [AUC] = 0.850, 95% confidence interval [CI]: 0.682-1.000) in diagnosing CLNM than IVCEUS (AUC = 0.692, 95% CI: 0.494-0.890) and routine US (AUC = 0.581, 95% CI: 0.367-0.796). The combination of LCEUS and IVCEUS has the highest diagnostic value (AUC = 0.863, 95% CI: 0.696-1.000). LCEUS had higher diagnostic value than IVCEUS and US for CLNM from PTC. The combination of LCEUS and IVCEUS has the highest diagnostic value for CLNM.

[The prognostic impact of preoperative PET-CT on postoperative recurrence for completely resected stage I non-small cell lung cancer].

OBJECTIVE: To analyze the prognostic impact of preoperative (18)F-fluorodeoxyglucose (FDG) PET-CT on postoperative recurrence in patients with completely resected stage I non-small cell lung cancer (NSCLC). METHODS: The clinic data of 182 patients with stage I NSCLC who underwent (18)F-FDG PET-CT scan before surgical resection between June 2005 and June 2012 were reviewed retrospectively. There were 121 male and 61 female patients, with an average age of 68 years (range from 34 to 85 years). The pathological stage was I A in 98 patients, I B in 84 patients; the histology were adenocarcinoma in 137 patients, squamous cell carcinoma in 35 patients, and others in 10 patients. Clinicopathological factors including gender, age, smoking history, SUV(max), surgical procedure, pathological features and adjuvant chemotherapy were evaluated to identify the independent factors predicting postoperative recurrences by univariate and multivariate analysis. The survivals were calculated by the Kaplan-Meier method and differences in variables were analyzed by the Log-rank test. RESULTS: The postoperative recurrence rate was 15.9%. The univariate analysis identified that the SUV(max) (t=3.278, P<0.001), p-stage (χ² =5.204, P=0.026), blood vessel invasion (χ² =5.333, P=0.027) and visceral pleural invasion (χ² =7.697, P=0.009) are factors for predicting postoperative recurrence. Only SUV(max) was found to be a significant independent factor according to multivariate analysis (HR=1.068, 95%CI: 1.015 to 1.123, P=0.001). The study population was stratified into three groups by SUV(max), patients with SUV(max) > 5.0 had significantly higher risk of recurrence (23.9%) than those with 2.5 < SUV(max) ≤ 5.0 (15.0%) and SUV(max) ≤ 2.5 (7.3%) (P=0.043); patients with SUV(max) ≤ 2.5 had significantly better 5-year recurrence-free survival rate (90.9%) than those with 2.5 < SUV(max) ≤ 5.0 (82.7%) and SUV(max) ≤ 2.5 (71.0%) (P=0.030). There was a trend toward higher probability of blood vessel invasion (χ² =20.267, P < 0.001), visceral pleural invasion (χ² =6.185, P=0.045) and pathological stage I B (χ² =13.589, P=0.001) with increased SUV(max). CONCLUSIONS: Preoperative SUV(max) of primary tumor is a predictor of postoperative relapse for stage I NSCLC after surgical resection. Therefore, it can contribute to the risk stratification for patients with the same pathological stage and selecting the optimal postoperative follow-up and therapeutic strategy.