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Published on: January 7, 2019
Restricted kappa/lambda light chain ratio by flow cytometry in germinal center B cells in Hashimoto thyroiditis
Henry I Chen1, Ikser Akpolat, Dina R Mody
1Department of Pathology, Baylor College of Medicine, Houston, TX, USA.
Insights
The kappa/lambda ratio in germinal center B cells is significantly higher in Hashimoto thyroiditis (HT) than previously reported for reactive lymph nodes. This finding in HT may prevent misdiagnosis of follicular lymphoma.
Area of Science:
- Immunology
- Pathology
- Oncology
Background:
- Hashimoto thyroiditis (HT) is an autoimmune thyroid disease.
- Distinguishing reactive B-cell changes from lymphoma in HT is crucial for accurate diagnosis.
Purpose of the Study:
- To investigate the diagnostic significance of the kappa/lambda ratio in germinal center (GC) B cells within Hashimoto thyroiditis (HT).
- To assess the potential for misdiagnosis of follicular lymphoma in HT patients.
Main Methods:
- Utilized 4-color flow cytometry to immunophenotype GC B cells (CD10+) in 27 HT samples.
- Analyzed B-cell clonality using polymerase chain reaction (PCR) for immunoglobulin heavy chain (IgH) and bcl-2/IgH fusion genes.
- Compared kappa/lambda ratios between CD10+ and CD10- B cells and against established limits for reactive lymph nodes.
Main Results:
- CD10+ GC B cells in HT exhibited a significantly higher mean kappa/lambda ratio (5.1 ± 3.3) compared to CD10- B cells (2.0 ± 0.8).
- In 67% of samples, the kappa/lambda ratio in CD10+ GC B cells exceeded the upper limit found in reactive lymph nodes (range, 3.2-14.4).
- PCR analysis revealed no evidence of clonal proliferation, and no patients developed lymphoma during 3-year follow-up.
Conclusions:
- The kappa/lambda ratio of CD10+ GC B cells in HT can be markedly skewed, often exceeding levels seen in reactive lymph nodes.
- Pathologists must recognize this phenomenon in HT to avoid misdiagnosing follicular lymphoma.
- This finding is frequent in HT and has significant diagnostic implications.
Abstract:
To determine the diagnostic significance of the kappa/lambda ratio in germinal center (GC) B cells in Hashimoto thyroiditis (HT), we used 4-color flow cytometry to immunophenotype 27 samples (21 patients) of well-characterized HT B-cell clonality was analyzed further by polymerase chain reaction (PCR) of the immunoglobulin heavy chain (IgH) and bcl-2/IgH fusion genes using DNA extracted from aspirate smears and/or paraffin-embedded tissues. By flow cytometric analysis, the CD10+ GC B cells had a higher mean +/- SD kappa/lambda ratio than the CD10- B cells (5.1 +/- 3.3 vs 2.0 +/- 0.8; P < .0001, Student t test). In 18 samples (67%), CD10+ GC B cells had a kappa/lambda ratio greater than 3.07 (the upper limit of kappa/lambda ratio reported in reactive nodes; range, 3.2-14.4 in the 18 cases). Cases tested by PCR showed no evidence of a clonal proliferation. None of 21 cases developed lymphoma during clinical follow-up of up to 3 years. The kappa/lambda ratio of CD10+ GC B cells in HT can be skewed markedly beyond that reported in reactive lymph nodes. This finding frequently is present in HT. Pathologists should be familiar with this phenomenon to prevent misdiagnosis of follicular lymphoma in patients with HT.
