Identification of the Tumor Cells in Peripheral T-Cell Lymphomas by Combined Polymerase Chain Reaction-Based T-Cell Receptor β Spectrotyping and Immunohistological Detection with T-Cell Receptor β Chain Variable Region Segment-Specific Antibodies

Geissinger, Eva; Bonzheim, Irina; Krenács, László; Roth, Sabine; Ströbel, Philipp; Ott, German; Reimer, Peter; Wilhelm, Martin; Müller‐Hermelink, Hans Konrad; Rüdiger, Thomas

doi:10.1016/s1525-1578(10)60576-4

Cited by 17 publications

(14 citation statements)

References 65 publications

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“…The reasons for the discrepancies are not clear; however, factors such as lack of uniform treatment, statistical power, and difficulty in accurately identifying the correct phenotype in T-cell lymphomas using single-parameter IHC may play a role. 35 Certainly, validation of our findings should be carried out.…”

Section: Discussionmentioning

confidence: 80%

Diagnostic Accuracy of a Defined Immunophenotypic and Molecular Genetic Approach for Peripheral T/NK-cell Lymphomas

Hsi¹,

Said²,

Macon³

et al. 2014

American Journal of Surgical Pathology

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The diagnosis of peripheral T-cell and NK-cell lymphomas (PTNKCL) is difficult with few standards for required ancillary studies. We evaluated a series of PTNKCLs using a tiered approach to immunohistochemistry and molecular genetic characterization to document diagnostic accuracy and clinical relevance. Seven hematopathologists reviewed 374 cases that included PTNKCL and non-PTNKCL cases to mimic diagnostic practice. Cases received tier 0, 1, and 2 diagnoses by 3 independent pathologists, on the basis of hematoxylin and eosin stains and progressive immunohistochemistry panels. A tier 2b diagnosis was rendered when gene rearrangement data were available, and a final consensus diagnosis was rendered after discussion of each case. Across all 374 cases, consensus agreement was 92.5%. For PTNKCLs, World Health Organization subclassification was possible in 16.5%, 37.1%, 82.8%, and 85.9% of individual reviewer diagnoses at tier 0, 1, 2, and 2b, respectively. Gene rearrangement contributed to a change in diagnosis in 51 of 647 (8%) individual reviews. Following this algorithm may provide prognostic information on the basis of individual marker expression in common PTNKCL types (CD4 in peripheral T-cell lymphoma, not otherwise specified and PD-1 in angioimmunoblastic T-cell lymphoma). This evidence-based approach to the diagnosis of PTNKCL informs practicing pathologists, clinical trial designers, and policy-makers regarding required ancillary studies.

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Section: Discussionmentioning

confidence: 80%

Diagnostic Accuracy of a Defined Immunophenotypic and Molecular Genetic Approach for Peripheral T/NK-cell Lymphomas

Hsi¹,

Said²,

Macon³

et al. 2014

American Journal of Surgical Pathology

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“…24,[34][35][36][37][38] Indeed, flow cytometric analysis revealed that the majority of thymocytes and …”

Section: Clonal Expansion and Peripheral Infiltration Of Activated Ptmentioning

confidence: 99%

T-cell lymphomas in T-cell-specific Pten-deficient mice originate in the thymus

Hagenbeek

Spits

2007

Leukemia

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Phosphatase and tensin homolog deleted on chromosome 10 (Pten) is a tumor suppressor protein whose loss of lipid phosphatase activity is associated with lymphomagenesis. We made use of the Cre-loxP system to delete Pten expression in Lck-or CD4-expressing T-lineage cells. Mice initially showed modest thymic hyperplasia and subsequently developed expanding and infiltrating T-cell lymphomas, leading to a premature death within 5 to 23 weeks. Frequently, all thymocyte and peripheral T-cell populations displayed phenotypes characteristic for immature developing thymocyte precursors and shared elevated levels of clonally rearranged T-cell receptor (TCR) b chains. In concert, CD2, CD5, CD3e and CD44, proteins associated with increased expression and signaling capacity of both the immature pre-TCR and the mature abTCR, were more abundantly expressed, reflecting a constitutive state of activation. Although most T-cell lymphomas had acquired the capability to infiltrate the periphery, not all populations left the thymus and expanded clonally exclusively in the thymus. In line with this, only transplantation of thymocytes with infiltrating capacity gave rise to T-cell lymphoma in immunodeficient recipients. These results indicate that T-cell-specific Pten deletion during various stages of thymocyte development gives rise to clonally expanding T-cell lymphomas that frequently infiltrate the periphery, but originate in the thymus.

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“…We have therefore defined a method that identifies tumour cells within frozen sections by their clonally expressed TCR-V chain [61]. In a first step, the rearranged TCR-V gene segment is defined by PCR.…”

Section: Inflammatory Background In Nodal Ptclmentioning

confidence: 99%

‘Normal counterparts’ of nodal peripheral T‐cell lymphoma

Rüdiger

Geissinger

Müller‐Hermelink

2006

Hematological Oncology

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Peripheral T-cell lymphomas (PTCL) have been difficult to classify. A homogeneous principle of classification is still lacking, partly because lymph node compartments containing functionally distinct T-cell subsets have not been identified. A correlation to differentiated T-cell subsets, as CD4(+) or CD8(+) cells as well as cytotoxic populations has not revealed clinically meaningful entities. Upon antigen encounter, mature T-cells pass through distinct stages characterized by their surface molecule expression. Naïve T-cells are CD45RA(+)/CD45R0(-)/CD27(+)/CCR7(+), however, after antigen contact CD45RA expression is replaced by CD45R0. They differentiate to central memory cells, which retain CD27 and CCR7, or to effector-memory cells, which loose expression of both molecules depending on the strength of the antigen interaction. Immunohistological analysis of PTCL showed an effector or effector-memory cell phenotype (CD45RA(-)/CD45R0(+)/CD27(-)) for both angioimmunoblastic T-cell lymphoma (AILT) and anaplastic large cell lymphoma (ALCL), but different cytotoxic and activation markers expressed by these tumours. A subset of CD4(+) PTCL-not otherwise specified (PTCL-NOS) may correspond to a central memory cell phenotype (CD45RA(-)/CD45R0(+)/CD27(+)). Thus, a correlation of PTCL to stages of differentiation, rather than to the direction of differentiation, may reveal homogeneous categories. A comparison between the lymphomas and their normal counterparts may contribute to the understanding of the underlying transformation mechanisms.

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Identification of the Tumor Cells in Peripheral T-Cell Lymphomas by Combined Polymerase Chain Reaction-Based T-Cell Receptor β Spectrotyping and Immunohistological Detection with T-Cell Receptor β Chain Variable Region Segment-Specific Antibodies

Cited by 17 publications

References 65 publications

Diagnostic Accuracy of a Defined Immunophenotypic and Molecular Genetic Approach for Peripheral T/NK-cell Lymphomas

Diagnostic Accuracy of a Defined Immunophenotypic and Molecular Genetic Approach for Peripheral T/NK-cell Lymphomas

T-cell lymphomas in T-cell-specific Pten-deficient mice originate in the thymus

‘Normal counterparts’ of nodal peripheral T‐cell lymphoma

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