Correlation between the BRAF V600E Mutation and Tumor Invasiveness in Papillary Thyroid Carcinomas Smaller than 20 Millimeters: Analysis of 1060 Cases

Context: Evaluation of the degree of neoplastic infiltration beyond the thyroid capsule remains a unique parameter that can be evaluated by histopathological examination to label a papillary thyroid carcinoma (PTC) of 20 mm or less in size as a pT1 or pT3 tumor. Objective: We correlated the BRAF V600E mutation with both clinical-pathological features and the degree of neoplastic infiltration to redefine the reliability of the actual system of risk stratification in a large selected group of PTCs smaller than 20 mm. Design: The presence of BRAF mutations was examined in 1060 PTCs less than 20 mm divided into four degrees of neoplastic infiltration: 1) totally encapsulated; 2) not encapsulated without thyroid capsule invasion; 3) thyroid capsule invasion; and 4) extrathyroidal extension. Results: The overall frequency of the BRAF V600E mutation was 44.6%. In both univariate and multivariate analyses, BRAF mutations showed a strong association with PTC variants (classical and tall cell), tumor size (11-20 mm), multifocality, absence of tumor capsule, extrathyroidal extension, lymph node metastasis, higher American Joint Commission on Cancer stage, and younger patient age. In PTCs staged as pT1 with thyroid capsule invasion, the frequency of BRAF mutations was significantly higher than in pT1 tumors that did not invade the thyroid capsule (67.3 vs. 31.8%, respectively; P < 0.0001). No statistically significant difference in BRAF alterations was found between pT1 tumors with thyroid capsule invasion and pT3 tumors (67.3 and 67.5%, respectively). Conclusion: We suggest that evaluation of BRAF status would be useful even in pT1 tumors to improve risk stratification and patient management, although follow-up data are necessary to confirm our speculations. (J Clin Endocrinol Metab 95: 4197-4205, 2010)