The Prediction of Sonographic features and BRAF Mutation for Central Lymph Node Metastasis in Papillary Thyroid Microcarcinoma: Reply.

Abstract

We appreciate the thoughtful and valuable comments by Dr. Coskun Ali from Turkey for our manuscript. Although papillary thyroid microcarcinoma (PTMC) has an indolent course, the central lymph node metastasis (CLNM) has been found with a high incidence in PTMCs at the time of diagnosis [1–3]. The role of therapeutic central lymph node dissection (CLND) for treatment of CLNM in PTMC is well accepted for cN1 disease by The American Thyroid Association (ATA) guidelines for differentiated thyroid cancer and 2014 updating version [4, 5]. However, given the undetermined effect on long-term survival and related morbidity in PTMC patients, the value of routinely prophylactic CLND for cN0 disease remains unclear. Therefore, we conducted a meta-analysis to investigate the clinicopathologic factors predictive of CLNM for guiding prophylactic CLND in PTMCs with risk factors. As noted from comments, the accurate preoperative imaging doesenable complete clearance of the primary tumor and affected lymph node in PTMC patients. Recently, Yeh et al. have published ‘‘American Thyroid Association Statement on Preoperative Imaging for Thyroid Cancer Surgery’’ and highlighted that ultrasonography (US) remained the most important imaging modality in the assessment for both the primary tumor and all associated cervical lymph node basins preoperatively [6]. Positive lymph nodes may be distinguished from normal nodes based upon size, shape, echogenicity, hypervascularity, loss of hilar architecture, and the presence of calcifications in US examination [6]. Actually, we had reviewed the clinicopathologic and imaging features in a total of 163 patients with thyroid micro-nodules, diagnosed as Bethesda classification V (44/163, 27.0 %) and VI (119/163, 73.0 %) for papillary carcinoma by preoperative cytology. All of them had received thyroidectomy, and PTMC was confirmed in 162 patients on histology. In the multivariate analysis, the US suspicious images for nodal metastasis (Figs. 1 and 2), as mentioned above, we reproved to be independent predictors for CLNM in PTMCs [7]. In addition, recent advances in research on thyroid carcinogenesis have yielded applications of diagnostic molecular biomarkers in the management of thyroid nodules [8]. Molecular markers have been reported to enhance the diagnostic sensitivity of fine-needle aspiration (FNA) cytology in detecting malignancy preoperatively [9], such as genetic alterations occur in the MAP kinase (MAPK) and PI3 K/AKT pathways, including BRAF and RAS point mutations, as well as translocations in the RET/PTC and PAX8/PPARc genes [8, 10]. In the latest 2014 ATA guidelines [5], it is pointed out that studies of the BRAF mutation have suggested an association between presence of the mutation and the risk of nodal disease [11–13]. However, BRAF mutation has a limited positive predictive value for recurrence and therefore BRAF mutation status in the primary tumor is not recommended on the decision for prophylactic CLND in the new guidelines [5]. We have reviewed the related studies and found that results across all patients on association between BRAF mutation status and the risk of & Qing-hai Ji jonathan_qn@163.com