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J Nippon Med Sch ; 89(3): 301-308, 2022 Jun 28.
Article in English | MEDLINE | ID: mdl-34840214

ABSTRACT

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.


Subject(s)
Hashimoto Disease , Lymphoma, B-Cell, Marginal Zone , Lymphoma, Large B-Cell, Diffuse , Thyroid Neoplasms , Thyroiditis, Autoimmune , Tumor Necrosis Factor alpha-Induced Protein 3 , Adult , Aged , Aged, 80 and over , Female , Hashimoto Disease/complications , Hashimoto Disease/genetics , Hashimoto Disease/pathology , Humans , Lymphoma, B-Cell, Marginal Zone/genetics , Lymphoma, B-Cell, Marginal Zone/pathology , Lymphoma, Large B-Cell, Diffuse/complications , Male , Middle Aged , Mutation , NF-kappa B/genetics , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Thyroiditis, Autoimmune/complications , Thyroiditis, Autoimmune/genetics , Thyroiditis, Autoimmune/pathology , Tumor Necrosis Factor alpha-Induced Protein 3/genetics
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