The frequency of B- and T-cell gene rearrangements and epstein-barr virus in T-cell lymphomas: a comparison between angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified with and without associated B-cell proliferations

Abstract

We report on a series of 58 cases of angioimmunoblastic T-cell lymphoma (AILT) and 59 cases of peripheral T-cell lymphoma, unspecified (PTCL-NOS). Subsets of cases from both diagnostic groups were complicated by associated B-cell proliferations, and we performed B- and T-cell clonality studies and in situ hybridization for Epstein-Barr virus (EBV) to investigate the relationship between B-cell proliferation, B-cell clonality, and EBV. Using multiplex polymerase chain reaction assays based on the BIOMED-2 collaborative study, we detected TCRgamma T-cell clones in 78 and 81% of AILT and PTCL-NOS cases, respectively, and IGH B-cell clones in 34 and 35% of AILT and PTCL-NOS cases, respectively. The majority of cases contained EBV-positive cells, including 50% of AILT and 57% of PTCL-NOS cases, and cases with B-cell proliferations were more often EBV-positive. Although a relatively high rate of B-cell clonality has been shown for AILT, our findings for PTCL-NOS differ from previous reports in that B-cell clonality was relatively frequent. Overall, a positive B-cell clone correlated, in part, with the presence of a B-cell proliferation but not with EBV. Our findings demonstrate that B-cell clonality is a common finding in AILT and PTCL-NOS, and its presence should not negate the diagnosis established by morphologic, immunophenotypic, and clinical findings.

Figure 1

Histology of representative AILT and PTCL-NOS cases. All panels shown at identical magnification. A–F: AILT with EBV-associated large B-cell proliferation stained with H&E (A), immunohistochemistry with anti-CD5 (B), anti-CD20 (C), in situ hybridization for EBV (D), anti-CD21 (E), or anti-CD10 (F). G and H: PTCL-NOS stained with H&E (G) or examined by in situ hybridization for EBV (H). Images were captured with a Nikon Eclipse E1000 microscope (Nikon, Tokyo, Japan) using a ×20/0.75 objective lens (Nikon) and a Spot CCD camera (Diagnostic Instruments, McHenry, IL) with Spot software version 4.0.5 for image acquisition.

Figure 2

Electropherogram of PCR for TCRγ rearrangements. The x axis indicates DNA length in nucleotides. The y axis indicates relative fluorescence units. Shown is electrophoresis of products from one multiplex tube, which contains primers to amplify V_γ1-8 and/or V_γ10 rearrangements, with expected product sizes above the x axis. The case was interpreted as positive with a clonal peak detected by V_γ10 primers (arrow) and polyclonal signals detected by V_γ1-8 primers.

Figure 3

Electropherograms of PCRs for IGH rearrangements. The x axis indicates DNA length in nucleotides. The y axis indicates relative fluorescence units. Shown are electrophoresis of products from three multiplex tubes, which contain primers targeting the FR1 (A), FR2 (B), and FR3 regions (C), with expected product sizes above the x axis. The case was interpreted as positive with clonal peaks detected by FR1 and FR2 primers (arrows) and polyclonal signals detected by FR3 primers.