Clinicopathologic characteristics and A20 mutation in primary thyroid lymphoma.

Background Primary thyroid lymphoma (PTL) is a rare disease frequently arising against a background of autoimmune thyroiditis. It has recently been reported that the inactivation of the NF-κB negative regulator A20 by deletion and/or mutation could be involved in the pathogenesis of subsets of B-cell lymphomas. This study investigated the clinicopathologic characteristics and A20 mutation in PTL. Methods We analyzed the characteristics of 45 PTL patients (14 men and 31 women), with a median age of 71 (range, 35-90) years. A20 mutations were analyzed in DNA extracted from 20 samples consisting of 19 tumor tissues and 1 sample from Hashimoto's thyroiditis. Results Thirty-five patients (82%) had a history of Hashimoto's thyroiditis and 29 (64%) had diffuse large B-cell lymphoma (DLBCL), presenting with larger tumors including bulky mass, elevated soluble interleukin-2 receptor levels, and longer history of Hashimoto's thyroiditis compared with mucosa-associated lymphoid tissue (MALT) lymphoma patients (n=16). A20 mutations were identified in 3 of 19 PTL patients (16%), 2 of 10 (20%) with DLBCL, and 1 of 9 (11%) with MALT lymphoma. Interestingly, all patients with A20 mutations had Hashimoto's thyroiditis. Furthermore, they had a common missense variant in exon 3 (rs2230926 380T>G; F127C), which is known to reduce the ability of A20 to inhibit NF-kB signaling. Conclusion Our study demonstrated that the histological features of PTL affect clinical outcomes, and that A20 mutations could be related to PTL pathogenesis in some patients with Hashimoto's thyroiditis.