The Frequency of B- and T-Cell Gene Rearrangements and Epstein-Barr Virus in T-Cell Lymphomas

Abstract

We report on a series of 58 cases of angioimmunoblastic T-cell lymphoma (AILT) and 59 cases of peripheral Tcell lymphoma, unspecified (PTCL-NOS). Subsets of cases from both diagnostic groups were complicated by associated B-cell proliferations, and we performed Band 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 TCR␥ 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.

Optimisation and validation of a PCR for antigen receptor rearrangement (PARR) assay to detect clonality in canine lymphoid malignancies

“…Two of three discordant samples had clonal rearrangements of both IgH and TCRγ, which has been documented previously in canine and human lymphoid tumours (Burnett et al, 2003, Tan et al, 2006, Valli et al, 2006, Bagg, 2006). In humans, the clonal rearrangements may arise from separate populations of cells.…”

“…In humans, the clonal rearrangements may arise from separate populations of cells. In T-cell tumours, a clonal B-cell population may arise secondary to immune dysfunction, usually in association with EBV infection (Luzzatto et al, 2005, Tan et al, 2006) and transform to produce a tumour containing malignant B- and T-cells (Zettl et al, 2002). In B-cell tumours, a restricted T-cell response may generate clonal TCR rearrangements (Sze, 2005).…”

Cerebellar EBV-associated diffuse large B cell lymphoma following angioimmunoblastic T cell lymphoma

“…Although clonal immunoglobulin gene rearrangement can be found in as many as 20–30 % of AITL cases [5, 12], the expanded B cell component is generally polytypic and regarded reactive in nature, while subsequent development of EBV-associated B cell lymphomas in patients with AITL is rare. To our knowledge, only 21 cases of AITL with histologic progression to EBV-associated B cell lymphoma, involving nodal (13/21) and extranodal (8/21) sites, have been described in English literature [14–22, 24].…”

“…AITL was previously considered an atypical reactive process termed angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), with propensity of progression to frank T cell lymphoma [2, 3]. However, subsequent genetic studies demonstrated presence of monoclonal T cell receptor gene rearrangements as well as clonal cytogenetic abnormalities in vast majority of the cases, supporting the neoplastic nature of the proliferation from the onset [4, 5]. Consequently, AITL is recognized as a distinct clinicopathologic entity in the current WHO classification [6].…”

Prevalence of bone marrow involvement in systemic anaplastic large cell lymphoma: are immunohistochemical studies necessary?

“…These multiplex PCRs are based on a European collaborative study (BIO-MED Concerted Action). The polymerase chain reaction (PCR) was performed according to the manufacturer's protocols and as previously reported [17]. Briefly, DNA was obtained from paraffin-embedded tissue blocks using a DNease tissue kit (Qiagen, Valencia, CA).…”