Combined analysis of T cell receptor γ and immunoglobulin heavy chain gene rearrangements at the single‐cell level in lymphomas with dual genotype

Vergier, Béatrice; Dubus, Pierre; Kutschmar, Anke; Parrens, Marie; Ferrer, Jacky; Mascarel, A. De; Merlio, Jean-Philippe

doi:10.1002/path.1192

Cited by 25 publications

(25 citation statements)

References 34 publications

(57 reference statements)

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“…Under these blinded conditions, we detected IGH clones in only 6 of 74 (8%) PTCL cases, consistent with previous reports on large series of PTCL (9 to 16%). [2][3][4][5][6] By contrast, we detected IGH clones in 23 of 24 (96%) pre-B-ALL cases, and similarly high rates of detection have been reported for pre-B-ALL. 18 -20 In regard to PTCL, the frequency of IGH clonality differed significantly from our previous report, in which we detected IGH clones in 33% of AILT cases and 35% of PTCL-U cases (P Ͻ 0.004).…”

Section: Discussionsupporting

confidence: 80%

“…Proof of lineage infidelity requires single cell analysis, which others have achieved by performing PCR on single cells isolated by microdissection. 6,24 However, the technical complexity of these experiments limits the number of cases that can be studied, and although evaluation for lineage infidelity is beyond the scope of this report, it remains a possible cause of IGH clonality. Several studies have shown that a single germinal center isolated by microdissection can yield an IGH clone by PCR.…”

Section: Discussionmentioning

confidence: 99%

“…Although PCR-based assays for TRG typically detect clones in 80 to 90% of PTCL cases, several studies have shown that IGH clones are also detected relatively frequently (9 to 16%). [2][3][4][5][6] The detection of an IGH clone, with or without a concurrent TRG clone, complicates an already challenging diagnosis.…”

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confidence: 99%

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The Frequency of Immunoglobulin Heavy Chain Gene and T-Cell Receptor γ-Chain Gene Rearrangements and Epstein-Barr Virus in ALK+ and ALK− Anaplastic Large Cell Lymphoma and Other Peripheral T-Cell Lymphomas

Tan

Seo

Warnke

et al. 2008

The Journal of Molecular Diagnostics

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We previously identified a relatively high frequency of B-cell proliferations along with simultaneous T-cell receptor ␥-chain gene (TRG) and immunoglobulin heavy chain gene (IGH) rearrangements in a seriesPeripheral T-cell lymphoma (PTCL) is an uncommon malignancy that accounts for less than 10% of non-Hodgkin lymphomas worldwide. By current World Health Organization criteria, the diagnosis and classification of PTCL is based on the combination of clinical, histologic, immunophenotypic, and genetic findings.1 However, the diagnosis of PTCL is difficult even for experienced pathologists, given the infrequency of cases, the often unusual histologic features, and perhaps most importantly, the lack of good immunophenotypic markers to assess for clonality in T-lineage neoplasms.In cases of suspected PTCL, pathologists often evaluate for clonality and assess for lineage by performing PCR-based assays for clonal rearrangement in both the T-cell receptor ␥-chain gene (TRG) and the immunoglobulin heavy chain gene (IGH). Although PCR-based assays for TRG typically detect clones in 80 to 90% of PTCL cases, several studies have shown that IGH clones are also detected relatively frequently (9 to 16%).2-6 The detection of an IGH clone, with or without a concurrent TRG clone, complicates an already challenging diagnosis.Recently, we investigated the etiology of IGH clones in PTCL by studying a large series of two of the most common subtypes of PTCL, angioimmunoblastic T-cell lymphoma (AILT) and PTCL-unspecified (PTCL-U).7 A subset of cases were complicated by associated B-cell proliferations, a finding that we and others have described as an atypical infiltrate of B cells that is often associated with Epstein-Barr virus (EBV). 8 -11 Using multiplex PCRs developed in a European collaborative study (BIOMED-2), we detected TRG clones in approximately 80% of cases and IGH clones in approximately 35% of cases, with the majority of IGH clones detected along with simultaneous TRG clones.Interestingly, a positive IGH clone correlated, at least in part, with the presence of a B-cell proliferation, suggesting that B-cell proliferations contribute to IGH clonality. However, alternate explanations for the detection of simultaneous TRG and IGH clones include those that are technical in nature and so-called lineage infidelity. In this context, lineage infidelity refers to recombination of both TRG and IGH in the same clone. However, this phenomenon is more common in immature hematolymphoid neoplasms and occurs only rarely (Ͻ5%) in mature B-and T-cell non-Hodgkin lymphomas. [12][13][14][15] Supported by the Stanford Department of Pathology.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

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The Frequency of Immunoglobulin Heavy Chain Gene and T-Cell Receptor γ-Chain Gene Rearrangements and Epstein-Barr Virus in ALK+ and ALK− Anaplastic Large Cell Lymphoma and Other Peripheral T-Cell Lymphomas

Tan

Seo

Warnke

et al. 2008

The Journal of Molecular Diagnostics

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“…Nevertheless, we considered that the muscle-infiltrated lymphocytes were clonal Tcells because a T-cell phenotype was shown by the immunohistochemical analysis. In addition, the frequency of dual genotypes of T-and B-cells in T-cell lymphomas was 11% in a previous study (4). Therefore, an additional diagnosis of Although combination chemotherapy with dexamethasone, etoposide, ifosfamide and carboplatin (DeVIC) normalized the serum CK levels, liver dysfunction and further elevation of the serum sIL-2R level were observed.…”

Section: ×10mentioning

confidence: 83%

Polymyositis as a Paraneoplastic Syndrome in Cytotoxic Molecule-positive and Epstein-Barr Virus-associated Peripheral T-cell Lymphoma, Not Otherwise Specified

et al. 2013

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We encountered a rare case of cytotoxic molecule-positive and Epstein-Barr virus (EBV)-associated peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), which was clinically preceded by polymyositis. A 50-year-old woman with a 4-year history of steroid-refractory polymyositis developed ulcerative skin swelling on her left arm. A diagnosis of cytotoxic molecule (TIA-1)-positive and EBV-associated PTCL-NOS was made on the basis of immunohistochemical and molecular examinations of the biopsied brachial muscle. Combination chemotherapies were ineffective, with a fatal outcome. Reassessment of the biopsy specimens of the muscle taken at the age of 46 years showed that the PTCL was already present, indicating that the polymyositis was likely a paraneoplastic manifestation.

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“…In phenotypically equivocal cases, therefore, molecular investigation of immunoglobulin heavy chain (IgH)-and T-cell receptor gene rearrangements to establish the B-or T-cell histogenesis should also be considered, although cases with concurrent rearrangement of IgH-and T-cell receptor genes are reported with a frequency of approximately 10% for both B-and T-cell lymphomas, respectively. 21,22 Thus, lymphoma lineage determination should be based on a multimodal approach that considers morpho-, pheno-and genotypic characteristics.…”

mentioning

confidence: 99%

Rare expression of BSAP (PAX-5) in mature T-cell lymphomas

et al. 2007

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Lineage determination in lymphomas is based on the assessment of lineage-specific markers, such as the B-cell-specific activator protein of the paired box family (BSAP, PAX-5) for the B-cell lineage. BSAP is thought to be expressed exclusively in B cells from the pro-B-to the mature B-cell stage and then silenced in plasma cells. BSAP has oncogenic potential and experimental evidence shows that the T-cell lineage is prone to this effect. Herein, we report on a BSAP-positive peripheral T-cell lymphoma with monoclonal T-cell receptor c-gene rearrangement. To assess the relative frequency of BSAP expression in mature T-cell lymphomas, we constructed and examined a tissue microarray consisting of 43 angioimmunoblastic T-cell lymphomas and peripheral T-cell lymphomas and detected no additional BSAP-positive cases. To conclude, BSAP can probably contribute to T-cell lymphomagenesis not only in vitro, but also in vivo. It is rarely expressed in peripheral T-cell lymphoma, thus its detection on lymphoid malignancies cannot be considered definitively lineage specific.

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Combined analysis of T cell receptor γ and immunoglobulin heavy chain gene rearrangements at the single‐cell level in lymphomas with dual genotype

Cited by 25 publications

References 34 publications

The Frequency of Immunoglobulin Heavy Chain Gene and T-Cell Receptor γ-Chain Gene Rearrangements and Epstein-Barr Virus in ALK+ and ALK− Anaplastic Large Cell Lymphoma and Other Peripheral T-Cell Lymphomas

The Frequency of Immunoglobulin Heavy Chain Gene and T-Cell Receptor γ-Chain Gene Rearrangements and Epstein-Barr Virus in ALK+ and ALK− Anaplastic Large Cell Lymphoma and Other Peripheral T-Cell Lymphomas

Polymyositis as a Paraneoplastic Syndrome in Cytotoxic Molecule-positive and Epstein-Barr Virus-associated Peripheral T-cell Lymphoma, Not Otherwise Specified

Rare expression of BSAP (PAX-5) in mature T-cell lymphomas

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