Exploration of BRAFV600E as a diagnostic adjuvant in the non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)

The non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) are distinguished from classical papillary thyroid carcinoma with predominantly follicular architecture (CPTCPFA) by distinct histomorphologic and molecular features. CPTCPFA frequently harbor the oncogenic variant BRAFV600E while NIFTP and EFVPTC are largely RAS driven. CPTCPFA have rare papillae and intranuclear pseudoinclusions that may distinguish them from NIFTP or EFVPTC. We evaluated for BRAFV600E mutation using mutation-specific BRAF (VE1) antibody immunohistochemistry (BRAFVE) as part of an immunomorphologic tumor panel, often including HBME1, for follicular-patterned lesions with nuclear atypia. An archival search identified cases of NIFTP, CPTCPFA, or EFVPTC between 2015–2017, and demographic data, tumor characteristics, molecular data, and metastases were documented. Our search yielded 275 tumors across categories, and 208 were tested with BRAFVE. Sixty-one NIFTP and 31 sub-centimeter NIFTP were tested, and none (0/92) were positive for BRAFVE. Nineteen CPTCPFA and 14 sub-centimeter CPTCPFA were tested with 18 of 33 (54.5%) BRAFVE positive. Sixty-one EFVPTC and 21 sub-centimeter EFVPTC were tested, with 12 of 81 (14.8%) positive. Mean follow-up time was 1.5 years. Six (4.6%) patients with concurrent classical papillary thyroid carcinoma had local lymph node metastases at time of NIFTP diagnosis, as did 15 of 111 (13.5%) EFVPTC. Six of 34 (14.7%) CPTCPFA had local nodal metastases with five being considered the primary lesion. One EFVPTC (0.9%), BRAFVE negative, metastasized to femur. The findings indicate that BRAFVE used in conjunction with routine sampling of follicular-patterned tumors is a useful diagnostic adjuvant.