Phenotypic and genotypic heterogeneity of peripheral T-cell lymphoma

Smith, Joan K.; Haegert, David G.; Hodges, Elizabeth; Stacey, Glyn; Howell, W. M.; Wright, Dennis H.; Jones, David B.

doi:10.1038/bjc.1988.297

Cited by 28 publications

(12 citation statements)

References 35 publications

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“…Although some cases with large cell morphology are composed of an almost pure proliferation of tumor cells, most PTCL-NOS-in contrast to B-cell lymphomas-comprise a heterogeneous cellular population [16,22,42]. Apart from the tumor cells, there were abundant histiocytes, eosinophils, plasma cells, B-lymphocytes, and reactive T-lymphocytes.…”

Section: Lineage Of Ptclmentioning

confidence: 97%

“…This heterogeneity might result from technical problems because, in addition to the neoplastic cells, PTCL also comprises varying numbers of reactive T-lymphocytes [16,22,27,42]. Since most of these studies were performed, methods have become available to assess the morphology in immunostained slides and to double stain cells on paraffin sections.…”

Section: Introductionmentioning

confidence: 98%

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Nodal peripheral T-cell lymphomas and, in particular, their lymphoepithelioid (Lennert?s) variant are often derived from CD8+ cytotoxic T-cells

Geissinger

Odenwald²,

Lee³

et al. 2004

Virchows Arch

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Nodal peripheral T-cell lymphomas are not well understood, and most of them are classified in the "not otherwise specified group" (PTCL-NOS). Data on their normal cellular derivation are ambiguous. Most peripheral T-cell lymphomas are composed of tumor cells and a (sometimes dominant) reactive background, which also includes resting and activated T-lymphocytes. We defined the phenotype of the tumor cells in 101 PTCL-NOS based on their cytological atypia and using immunohistochemical double stains on paraffin sections with CD4/Ki67 and CD8/Ki67. The results were correlated to clinical presentation and outcome. Lineage could be defined in 98 cases (97%). Tumor cells were CD4(+) in 43 cases and CD8(+) in 38. These presented at a younger age but a higher clinical stage compared with the CD4(+) lymphomas. In 15 cases, the atypical cells were CD4(-)CD8(-); two cases were CD4(+)CD8(+). Of 17 lymphoepithelioid (Lennert's) lymphomas, 15 expressed CD8, one each was CD4(+) and CD4(-)CD8(-).

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Section: Lineage Of Ptclmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

Nodal peripheral T-cell lymphomas and, in particular, their lymphoepithelioid (Lennert?s) variant are often derived from CD8+ cytotoxic T-cells

Geissinger

Odenwald²,

Lee³

et al. 2004

Virchows Arch

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“…In previous studies, we found it difficult to reliably distinguish neoplastic T-cells from reactive bystander T-cells in PTCL [15,42], because cytologic atypia may be subtle and cannot be readily identified in immunostained slides. As reactive T-cells may be abundant in PTCL [43][44][45], they may impede the definition of the tumour cell phenotype. This might be one reason for the great variation in published phenotypes for AILT [7,12,[46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] and PTCL-NOS [7][8][9][10][11][12][13][14].…”

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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“…For Southern blot analysis, high molecular weight DNA was extracted from the biopsies by routine methods, digested with 3/4 restriction enzymes, Southern blotted, and probed with 32 P-labeled TCR and Ig probes as previously described. 20 …”

Section: Genotypic Studiesmentioning

confidence: 99%

Frequent T and B Cell Oligoclones in Histologically and Immunophenotypically Characterized Angioimmunoblastic Lymphadenopathy

Smith¹,

Hodges²,

Quin³

et al. 2000

The American Journal of Pathology

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The identification of clonal rearrangements of T cell receptor (TCR) genes is central to the diagnosis of T cell lymphomas. However, in angioimmunoblastic lymphadenopathy (AILD), first described as a nonneoplastic proliferation associated with immunodeficiency, the heterogeneity of TCR and IgH gene rearrangements suggest that some cases may harbor multiple lymphoid clones. In this study we have isolated DNA from archival paraffin biopsy material from 22 cases of AILD identified on the basis of classical histological and immunohistochemical features with the aim of establishing the occurrence of clones and oligoclones, the frequency of TCR and immunoglobulin heavy chain (IgH) variable (v) gene use, and the relationship of these findings to the presence of Epstein-Barr virus. DNA extracted from the biopsies was amplified using the polymerase chain reaction (PCR) and sequenced to detect functional and nonfunctional gene rearrangements. Epstein-Barr virusencoded short RNA species (EBERs) were detected using in situ hybridization combined with immunochemistry to identify the phenotype of the EpsteinBarr virus-infected cells. Fifty-seven clonal products were found in 20/22 patients: TCR␥ clonal products were identified in 16/22, TCR␤ clonal products in 16/22 and IgH clonal products in 6/22 cases. Oligoclonal PCR products were seen for TCR in 3/22 and for IgH in 3/22 cases. In one biopsy PCR products from all reactions were polyclonal. Sequence analysis revealed functional TCR␥, TCR␤, and IgH sequences in 6/12, 9/11, and 8/8 cases, respectively. Functional TCR and/or IgH oligoclones were detected in 6/20 (30%) cases. In addition, nonfunctional TCR and IgH sequences were found in 11 cases. EBERs were identified in 18/20 cases varying from occasional to 25 to 30% nuclei staining and were associated with both T and B cells, although the majority were of indetermi- Early reports of AILD stressed the nonneoplastic nature of this disease, 1,2 noting that neither the cytology nor the pattern of infiltration seen in biopsies or autopsies was that of a neoplasm. The disease was thought to be due to abnormal immune regulation, the majority of patients dying of infections, often with opportunistic organisms.2 An association with lymphoma was, however, noted by Lukes and Tindle, 3 who reported the development of immunoblastic lymphoma in 3 of their 32 patients. Subsequently, there has been controversy over the separation of AILD from AILD with immunoblastic lymphoma (IBL) based on histological features such as atypical clear cells, which has contributed to the variation in the reported incidence of lymphoma in AILD from 0 to 35%. 4 -6 In addition, both groups show clonality or lack of clonality. 4,7 Frizzera et al 8 has proposed that three AILDrelated disorders can be recognized as AILD, AILD-like dysplasia, and AILD-like peripheral T cell lymphoma (PTCL) based on a combination of morphology, phenotype, clonal-

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Phenotypic and genotypic heterogeneity of peripheral T-cell lymphoma

Cited by 28 publications

References 35 publications

Nodal peripheral T-cell lymphomas and, in particular, their lymphoepithelioid (Lennert?s) variant are often derived from CD8+ cytotoxic T-cells

Nodal peripheral T-cell lymphomas and, in particular, their lymphoepithelioid (Lennert?s) variant are often derived from CD8+ cytotoxic T-cells

‘Normal counterparts’ of nodal peripheral T‐cell lymphoma

Frequent T and B Cell Oligoclones in Histologically and Immunophenotypically Characterized Angioimmunoblastic Lymphadenopathy

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