-Original-

Clinicopathologic Characteristics and A20 Mutation in Primary Thyroid Lymphoma

Yasuko Kuribayashi-Hamada¹, Mariko Ishibashi², Atsushi Tatsuguchi³, Toshio Asayama¹, Namiko Takada-Okuyama¹, Asaka Onodera-Kondo¹, Keiichi Moriya¹, Takehito Igarashi⁴, Hiroyuki Onose⁵, Sakae Tanosaki⁶, Norio Yokose⁷, Hiroki Yamaguchi¹ and Hideto Tamura^1,8

¹Department of Hematology, Nippon Medical School, Tokyo, Japan
²Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan
³Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan
⁴Department of Endocrine Surgery, Nippon Medical School, Tokyo, Japan
⁵Division of Endocrinology, Kanaji Hospital, Tokyo, Japan
⁶Division of Hematology, The Fraternity Memorial Hospital, Tokyo, Japan
⁷Division of Hematology, Department of Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
⁸Division of Diabetes, Endocrinology and Hematology, Department of Internal Medicine, Dokkyo Medical University Saitama Medical Center, Saitama, Japan

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 patients with 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 tissue samples 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) and presented with larger tumors including bulky mass, elevated soluble interleukin-2 receptor levels, and a longer history of Hashimoto's thyroiditis than that of patients with mucosa-associated lymphoid tissue (MALT) lymphoma (n=16). A20 mutations were identified in 3 of 19 PTL patients (16%), in 2 of the 10 (20%) with DLBCL and in 1 of the 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 reduces the ability of A20 to inhibit NF-κB signaling.
Conclusion: Our study suggests that the histological features of PTL affect clinical outcomes and that A20 mutations are related to PTL pathogenesis in some patients with Hashimoto's thyroiditis.

J Nippon Med Sch 2022; 89: 301-308

Keywords
primary thyroid lymphoma, A20 mutation, mucosa-associated lymphoid tissue (MALT) lymphoma, Hashimoto's thyroiditis

Correspondence to
Hideto Tamura, MD, PhD, Department of Hematology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
tam@nms.ac.jp

Received, July 8, 2021
Accepted, October 4, 2021