Papillary Thyroid Carcinoma With Rare Exon 15 BRAF Mutation Has Indolent Behavior: A Single-Institution Experience

Abstract

Context: Approximately 40% of papillary thyroid carcinomas (PTCs) harbor the BRAF V600E mutation, which is significantly associated with the advanced clinicopathological features of PTC at diagnosis, a higher recurrence rate, and disease-related mortality. BRAF alterations other than V600E are less common in PTC, and their clinical significance remains to be established.

Objective: The aim of the study was to describe a large cohort of rare exon 15 BRAF alterations (r-BRAF) and the clinicopathological features of PTC harboring these alterations and to clarify their clinical significance.

Methods: A total of 2961 PTCs were collected from 2006 to 2013 and screened for exon 15 BRAF alterations.

Results: Exon 15 BRAF alterations were found in 1186 of 2961 PTC cases (40.0%). In particular, we found the BRAF V600E mutation in 95.3% (1131 of 1186) and r-BRAF in 4.7% (55 of 1186) of the cases. r-BRAF were found in 18 microcarcinomas, 33 follicular variants, one classic variant, and one trabecular/solid variant. The most frequent r-BRAF was BRAF K601E (35 of 55; 63.6%), followed by BRAF V600_K601delinsE (seven of 55; 12.7%) and BRAF T599I-V600_R603del (two of 55; 3.6%). The remaining 11 alterations were found in one case only. The large majority of these tumors were unifocal (34 of 55; 61.8%), completely encapsulated (46 of 55; 83.6%), and intrathyroidal (53 of 55; 96.4%) with a low prevalence of lymph node metastases (one of 55; 1.8%) and a less advanced tumor stage at diagnosis (American Joint Commission on Cancer stage I/II, 51 of 55; 92.7%).

Conclusions: r-BRAF are very uncommon in PTC and are found almost exclusively in PTC with low-risk clinicopathological features.