Clonal B cell populations in a minority of patients with Hashimoto’s thyroiditis

Abstract

Background: Hashimoto's thyroiditis (HT) is a risk factor for thyroid lymphoma, and clonal B cell populations in HT support this link. The literature on B cell clonality in HT is controversial. Aims: To identify clonal B cell populations in HT and to assess their usefulness in differentiating HT from mucosa associated lymphoid tissue (MALT) lymphoma and predicting future development of lymphoma. Methods: DNA from formalin fixed, paraffin wax embedded blocks of thyroid specimens from 10 patients with HT and two thyroid MALT lymphomas was analysed for B cell clonality by seminested polymerase chain reaction (PCR) using FRIII/LJH and FRIII/VLJH primers to amplify the IgH gene VDJ region. In one case, PCR products were sequenced. Immunohistochemistry was performed by labelled streptavidin-biotin technique using antibodies to: CD45, CD45RO, CD3, CD20, and cytokeratin. Results: The histopathological and clinical findings were characteristic of HT. Clonal bands were seen in three and a polyclonal smear pattern was seen in seven cases. The clonal bands in HT were associated with a background smear, and could not be reproduced from other blocks from the same case or from deeper sections of the same block. The clonal bands in thyroid lymphomas were not associated with a background smear and were reproducible. None of the patients with clonal B cells has developed malignant lymphoma during a follow up of 10-13 years. Conclusions: B cell clonal bands in HT have different features from those in lymphoma (non-pure and nonreproducible) and do not predict future development of lymphoma.

Non-Hodgkin's Lymphoma of Mucosa-Associated Lymphoid Tissue

“…Differentiating lowgrade lymphoma from Hashimoto's thyroiditis by cytology can be difficult, and open biopsy may be necessary [150]. Interestingly, clonal B-cell populations can be found in samples of thyroid tissue in patients with Hashimoto's thyroiditis, in the absence of lymphoma [151]. In one series, none of the three such patients developed lymphoma over a follow-up of 10-13 years.…”

What makes Lymphadenopathy in Patients with Autoimmune Thyroiditis Suspicious for Malignancy?

“…Several groups reported clonal B-cell populations within thyroid tissue samples of AIT patients in a vast minority of cases, but features are non-reproducible in multiple tissue samples [33][34][35]. Whether or not these monoclonal populations can evolve into a thyroid lymphoma remains unclear to date [33]. In our index case molecular analysis was a valuable tool to distinguish between a florid polyclonal lymphoid infiltrate and monoclonal lymphoma.…”

“…However, monoclonal rearrangement of B-cells can also occur in autoimmune diseases [32]. Several groups reported clonal B-cell populations within thyroid tissue samples of AIT patients in a vast minority of cases, but features are non-reproducible in multiple tissue samples [33][34][35]. Whether or not these monoclonal populations can evolve into a thyroid lymphoma remains unclear to date [33].…”

Autoimmune Disorders and Lymphomas

“…The lymphoid tissue present in HT thyroid gland share many features with MALT (Hyjek & Isaacson, 1988). The presence of clonal B-cell populations has been demonstrated in HT thyroid specimens also in patients without evidence of lymphoma development (Saxena et al, 2004). The clonal IgH gene rearrangements carried by thyroid lymphomas may already be evident in the oligoclonal rearrangements characterizing HT, and a fraction of thyroid lymphomas use the same IgH utilized by anti-thyroid auto-antibodies (Rossi, 2009, Moshynska & Saxena, 2008.…”