Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma

Abstract

It has been reported that papillary thyroid carcinoma (PTC) with chronic lymphocytic thyroiditis (CLT) is less associated with extrathyroidal extension (ETE), advanced tumor stage and lymph node (LN) metastasis. Other studies have suggested that concurrent CLT could antagonize PTC progression, even in BRAF-positive patients. Since the clinical significance of the BRAF mutation has been particularly associated with conventional PTC, the purpose of this study was to determine the clinical significance of CLT according to BRAF mutation status in conventional PTC patients. We retrospectively reviewed the medical records of 3332 conventional PTC patients who underwent total thyroidectomy with bilateral central neck dissection at the Thyroid Cancer Center of Samsung Medical Center between January 2008 and June 2015. In this study, the prevalence of BRAF mutation was significantly less frequent in conventional PTC patients with CLT (76.9% vs 86.6%). CLT was an independent predictor for low prevalence of ETE in both BRAF-negative (ORZ0.662, PZ0.023) and BRAF-positive (ORZ0.817, PZ0.027) conventional PTC patients. In addition, CLT was an independent predictor for low prevalence of CLNM in both BRAF-negative (ORZ0.675, PZ0.044) and BRAF-positive (ORZ0.817, PZ0.030) conventional PTC patients. In conclusion, BRAF mutation was significantly less frequent in conventional PTC patients with CLT. However, CLT was an independent predictor for less aggressiveness in conventional PTC patients regardless of BRAF mutation status. Key Words" BRAF mutation " papillary thyroid carcinoma " chronic lymphocytic thyroiditis " central lymph node metastasis " extrathyroidal extension

Nomogram for predicting central node metastasis in papillary thyroid carcinoma

“…Therefore, we did not separately Journal of Surgical Oncology present ETE as microscopic and gross. And previous studies have shown that the coexistence of CLT is negatively associated with ETE, advanced stage, LN metastasis, and recurrence in PTC patients [19,[32][33][34]. Because this study was a retrospective study, the analyses were conducted based on pathologic reports.…”

Thyroid Autoimmunity and Cancer

“…Accordingly, only few studies reported a worse prognosis of PTC associated with CLTI, but the great majority agree with the hypothesis that the presence of CTLI may lead to a better prognosis or not influence the clinical outcome of PTC [6,13,17,23]. Kim et al, in a study aimed to define the role of CLTI according to BRAF V600E mutation status in a cohort of PTC patients, concluded that CLTI was an independent predictor for low prevalence of both extra-thyroidal extension and central compartment nodal metastases, regardless BRAF mutation status [24]. Nevertheless, higher prevalence of multifocal or bilateral lesions was reported in TC patients with coexisting CLTI [24] and recently Iliadou el al [25] showed that children and adolescents with CLTI presented more frequently familial PTC, even if no differences in outcome were found with respect to the presence of CLTI.…”

“…Kim et al, in a study aimed to define the role of CLTI according to BRAF V600E mutation status in a cohort of PTC patients, concluded that CLTI was an independent predictor for low prevalence of both extra-thyroidal extension and central compartment nodal metastases, regardless BRAF mutation status [24]. Nevertheless, higher prevalence of multifocal or bilateral lesions was reported in TC patients with coexisting CLTI [24] and recently Iliadou el al [25] showed that children and adolescents with CLTI presented more frequently familial PTC, even if no differences in outcome were found with respect to the presence of CLTI. In this regard, it should finally be noted that TC histotypes with a worse prognosis (PDTC, ATC) are characterized by a very reduced lymphocyte infiltration [26].…”

“…Either in PTC and in AITDs prominent leukocytic infiltration of thyroid tissue is present [24]. In HT the first step is infiltration of dendritic cells (DCs) and then of leucocytes.…”

Hypothyroidism-Associated Autoimmune Thyroiditis and Papillary Thyroid Cancer

“…Whether thyroid autoimmunity represents a risk factor for cancer is still a matter of debate [10,11]. Some authors suggest that chronic thyroiditis might protect againts aggressive forms of papillary carcinoma (including BRAF positive patients since the mutation is frequently found in typically papillary forms) [12]. Others suggested that the inflammatory environment induced by the immune process is a trigger for genetic aberrations as seen in hOGG1 loss of heterozygosity (the gene repairs the DNA from free radical-induced oxidative stress) [13].…”