BRAF, when mutated at V600E, is a well-known potent early oncogenic driver in papillary thyroid carcinoma (PTC), with potential prognostic and therapeutic implications. Non-V600E mutations are less co Show more
BRAF, when mutated at V600E, is a well-known potent early oncogenic driver in papillary thyroid carcinoma (PTC), with potential prognostic and therapeutic implications. Non-V600E mutations are less common and without clear functional or therapeutic significance. One class of non-V600E mutations is BRAF gene fusions, which typically involve the C-terminal kinase domain of BRAF joined to a wide repertoire of potential N-terminal fusion partners. The aim of this study was to employ a sequential algorithmic approach to identify patients with BRAF fusions based on an integrated analysis of histologic, immunohistochemistry (IHC), and molecular (NGS) features of BRAF-rearranged PTCs. Nine patients with PTC previously scrutinized as BRAF V600E negative by IHC were analyzed by NGS. The studied 9 cases showed conventional PTC growth; 2 cases displayed a minor high-grade component (tall cell and hobnailing, < 20%), 1 case qualified as high-grade differentiated thyroid carcinoma (presence of necrosis and mitotic activity > 5 MF/ 2 mm Show less