The utility of the Bethesda category and its association with BRAF mutation in the prediction of papillary thyroid cancer stage.

PURPOSE: This study aims to determine the utility of the Bethesda category and its association with BRAF mutation in prediction of the papillary thyroid cancer (PTC) stage. METHODS: A prospective study analyzed patients who had ultrasound-suspicious thyroid nodules, underwent FNA and cytological examination, and were classified according to the Bethesda system. Patients from Undetermined Significance Or Follicular Lesion Of Undetermined Significance (AUS/FLUS), Follicular Neoplasm or Suspicious for a Follicular Neoplasm (FN/SFN), Suspicious for Malignant Cells (SMC), and Positive for Malignant Cells (PMC) groups were examined for the BRAF mutation and had a thyroid surgery. Demographical and histological features and stage of the disease were evaluated for PTC patients in accordance with the Bethesda category and its association with BRAF mutation. RESULTS: Three hundred eight of all patients underwent operation. One hundred forty-three (46.4%) of them were diagnosed with PTC. In 14 (9.8%) PTC cases, FNA biopsies were classified as AUS/FLUS, 23 (16.1%) as FN/SFN, 41 (28.7%) as SMC, and 65 (45.5%) as PMC. I-II stages of PTC were diagnosed for 88 (61.5%) patients and III-IVA for 55 (38.5%). Patients from the SMC and PMC groups had larger tumors, higher incidence of lymph node metastases, classical PTC type, B-type Raf (BRAF) positive, and III-IVA stage cancer, than patients from the AUS/FLUS and FN/SFN groups. When comparing 27 (18.9%) BRAF-negative patients from the AUS/FLUS and FN/SFN groups with 116 (81.1%) BRAF-negative patients from the SMC and PMC groups and all BRAF-positive patients, the prediction of more aggressive histological features and stage was slightly improved. CONCLUSIONS: Higher Bethesda categories are associated with higher stages of PTC. Association of the Bethesda category with BRAF mutation can slightly improve the value of stage prediction.

Significance of BRAF V600E Mutation and Cytomorphological Features for the Optimization of Papillary Thyroid Cancer Diagnostics in Cytologically Indeterminate Thyroid Nodules.

BACKGROUND: Ultrasound guided fine needle aspiration biopsy with cytologic analysis is an initial step in diagnostic of thyroid nodules. Unfortunately, up to 30% of biopsies are indeterminate and diagnostic surgery is required. The aim of this study was to estimate the diagnostic value of BRAF V600E mutation status combined with cytomorphological features for diagnosis of papillary thyroid cancer (PTC) in cytologically indeterminate thyroid nodules. METHODS: A prospective study analyzed patients who had ultrasound suspicious thyroid nodules, underwent fine needle aspiration and cytological examination, and were classified according to the Bethesda system. Patients from indeterminate diagnostic categories were examined for BRAF V600E mutation and 22 cytomorphological features, and underwent thyroid surgery. A binary logistic regression model was used to evaluate the diagnostic utility. RESULTS: A total of 219 patients met study criteria. After histological examination, 77 (35.2%) patients were diagnosed with PTC and 142 (64.8%) with benign nodular thyroid disease. According to logistic regression model, significant features for PTC diagnosis were: liquid colloid consistency, papillary structures, eosinophilic colloid bodies, and BRAF V600E mutation. Risk groups classified by this model have sensitivity of 80.5% (95% CI: 69.9 to 88.7), specificity of 99.3% (95% CI: 96.1 to 100), positive predictive value of 98.4% (95% CI: 89.8 to 99.8), negative predictive value of 90.4% (95% CI: 85.7 to 93.7), and accuracy of 92.7% (95% CI: 88.4 to 95.8) for PTC diagnosis. CONCLUSIONS: Evaluation of BRAF V600E mutation status combined with cytomorphological features for diagnosis of PTC in cytologically indeterminate thyroid nodules can significantly improve diagnostic accuracy and reduce the number of diagnostic operations (calculator available at www.ptc-calc.we2host.lt).

The value of the repeated examination of BRAF V600E mutation status in diagnostics of papillary thyroid cancer.

INTRODUCTION: Nodular thyroid disease is one of the most frequently diagnosed pathologies of the adult population in iodine-deficient regions. Approximately 30% of thyroid aspirates are classified as nondiagnostic/unsatisfactory or indeterminate. However, patients with indeterminate cytology still undergo surgery. The object of this study was to determine the diagnostic value of re-examining the BRAF V600E mutation in papillary thyroid carcinoma patients. MATERIAL AND METHODS: All patients underwent ultrasound guided fine-needle aspiration of a thyroid nodule. They were assigned to one of the four groups (indeterminate or positive for malignant cells) of the Bethesda System for Reporting Thyroid Cytopathology. Genetic investigation of the BRAF V600E mutation was performed for all of the fine-needle aspiration cytology specimens. All of the patients underwent surgery. Subsequently, histological investigation of the removed tissues was performed. Additional analysis of the BRAF V600E mutation from the histology specimen was then performed for the initially BRAF-negative cases. RESULTS: Two hundred and fourteen patients were involved in the study. One hundred and six (49.53%) patients were diagnosed with thyroid cancer. Of these 106 patients, 95 (89.62%) patients were diagnosed with papillary thyroid cancer. The BRAF V600E mutation was positive in 62 (65.26%) and negative in 33 (34.74%) histologically confirmed papillary thyroid cancer cases. After the genetic investigation, a total of 74 (77.89%) papillary thyroid cancer cases were positive for the BRAF V600E mutation and 21 (22.11%) were negative. CONCLUSIONS: Repeated examination of the BRAF V600E mutation status in the fine-needle aspiration may potentially increase the sensitivity of papillary thyroid cancer diagnostics.