P375 - ECE_3484 - Clinicopathological and molecular features of papillary thyroid microcarcinoma

Abstract

Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer, with a substantial proportion being microcarcinomas (uPTCs). Currently, there is no clear strategy for their treatment. This study focused on the most frequent pathogenic variant, V600E, of the BRAF gene. The aim was to correlate tumor size with clinicopathological characteristics and subsequent response to treatment. A total of 969 fresh-frozen tissue samples from primary PTC tumors were analyzed for the presence of the most prevalent genetic alterations in PTC, including BRAF, TERT, RAS, and 23 fusion genes (ALK, BRAF, GLIS3, NTRK1, NTRK3, PPARG, and RET). Of the total PTC cohort, 253 (26.1%) cases were uPTCs. For the correlation between tumor size and aggressiveness, only PTCs harboring the BRAF V600E mutation were included. Multifocal PTCs were classified as carcinomas or microcarcinomas based on the largest lesion and included in the statistical analysis accordingly. If a clinicopathological feature was present in only one lesion, it was considered valid. Samples were excluded if a genetic alteration other than BRAF V600E was detected even in another lesion. In uPTCs, the risks of lymph node or distant metastasis, angioinvasion, invasiveness, and extrathyroidal extension were 19.8%, 6.3%, 23.3%, and 13.4%, respectively. In PTCs larger than 10 mm (*PTCs) and uPTCs, respectively, BRAF mutations were detected in 439 and 148 patients, RAS mutations in 61 and 18 patients, TERT mutations in 58 and 6 patients, and fusion genes in 156 and 43 patients. Of the 515 PTCs harboring only the BRAF V600E mutation, 138 (26.8%) were uPTCs. The only statistically significant differences (P ≤ .05) between *PTCs and uPTCs were angioinvasion and tumor invasiveness with higher incidence in *PTCs. No statistically significant differences were observed in tumor metastasis or extrathyroidal extension. A 24-month follow-up was available for 196 (52.0%) *PTC patients and 64 (46.4%) uPTC patients. An excellent, indeterminate, structural incomplete, and biochemical incomplete response to treatment was observed in 62.8%, 23.0%, 8.2%, and 6.1% of *PTC patients and in 71.9%, 25.0%, 1.6%, and 1.6% of uPTC patients, respectively. The risk of aggressive behavior in uPTCs harboring the BRAF V600E mutation is not negligible. Therefore, uPTCs should be managed cautiously, and molecular testing should be incorporated into their diagnostic and therapeutic evaluation. Supported by AZV NU21-01-00448 and MH CZ RVO 00023761.