Hashimoto Thyroiditis in Primary Thyroid Non-hodgkin Lymphoma

A Systematic Review and Meta-Analysis

Antonio Travaglino, MD; Mirella Pace, MD; Silvia Varricchio, BTD, PhD; Luigi Insabato, MD, PhD; Claudia Giordano, MD; Marco Picardi, MD, PhD; Fabrizio Pane, MD, PhD; Stefania Staibano, MD, PhD; Massimo Mascolo, MD, PhD


Am J Clin Pathol. 2020;153(2):156-164. 

In This Article

Abstract and Introduction


Objectives: To assess the prevalence of Hashimoto thyroiditis (HT) in primary thyroid lymphoma (PTL) and whether it differs between mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL).

Methods: Electronic databases were searched for studies assessing HT prevalence in PTL, based on antithyroid antibodies, clinical history, or pathology. Pooled prevalence of HT and its association with histotype (MALT or DLBCL) were calculated.

Results: Thirty-eight studies with 1,346 PTLs were included. Pooled prevalence results were 78.9% (any HT evidence), 65.3% (antithyroid antibodies), 41.7% (clinical history), and 64% (pathology). HT prevalence was significantly higher in MALT lymphoma than in DLBCL (P = .007) and in mixed DLBCL/MALT than in pure DLBCL (P = .002).

Conclusions: Overall, 78.9% of patients with PTL have any HT evidence, but only half of these had been clinically followed. The difference in HT prevalence suggests that a subset of DLBCL may not derive from MALT lymphoma.


Primary thyroid lymphoma (PTL) is a rare malignancy that accounts for 1% to 5% of all thyroid malignancies and 1% to 7% of all extranodal lymphomas.[1–4] PTL occurs preferentially in females, with an incidence peak in the seventh decade.[1,4,5] The most common clinical presentation of PTL is a palpable mass in the neck, which may cause dysphagia, dyspnea, and hoarseness. In addition, B symptoms (fever, night sweats, and weight loss of 10% and higher in the past 6 months) can be present.[1]

The most common histotypes are diffuse large B-cell lymphoma (DLBCL), which accounts for 50% to 70% of cases, and mucosa-associated lymphoid tissue (MALT) lymphoma, which accounts for 10% to 50% of cases.[6] Follicular lymphoma, small lymphocytic lymphoma, Burkitt lymphoma, mantle cell lymphoma, T-cell lymphoma, and Hodgkin lymphoma have been described less commonly.[1]

The most important risk factor for PTL is Hashimoto thyroiditis (HT), which causes a 40- to 80-fold increase in the risk of PTL.[3] However, it is unclear whether HT is a necessary condition for the development of PTL. In fact, while some authors suggested that all PTLs originate in an HT setting, other authors reported no evidence of HT in a series of patients with PTL.[2,3,7–9] Moreover, it is also unclear whether HT is associated with particular PTL histotypes more strongly than with other ones.

Aims of this study were (1) to define the prevalence of HT in patients with PTL, based on the several different diagnostic criteria adopted (eg, positive antithyroid antibodies, clinical history, histologic evidence) and (2) to assess the association of HT with PTL histotypes.