B-cell posttransplant lymphoproliferative disorders in heart and/or lungs recipients: Clinical and molecular-histogenetic study of 17 cases from a single institution

Marco Lucioni, Daniela Capello, Roberta Riboni, Giovanbattista Ippoliti, Carlo Campana, Laura Bandiera, Luca Arcaini, Davide Rossi, Michaela Cerri, Paolo Dionigi, Mario Lazzarino, Umberto Magrini, Mario Viganò, Gianluca Gaidano, Marco Paulli

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Posttransplantation lymphoproliferative disorders (PTLDs) are heterogeneous lymphoid proliferations representing a major complication of solid organ transplant. This study details the clinicopathological and molecular features of 17 B-cell PTLDs observed in a single center series of 988 heart and/or lung transplant recipients. METHODS. Cases were classified according to World Health Organization lymphoma classification and tested for Epstein-Barr Virus (EBV), clonality, histogenetic phenotypic (CD10, Bcl-6, MUM1, CD138), and genotypic (immunoglobulin and BCL-6 genes somatic hypermutation) markers. RESULTS. This series of 17 PTLDs included: two B-cell monoclonal polymorphic PTLDs and 15 B-cell monomorphic PTLDs (13 diffuse large B-cell lymphomas [DLBCL] and 2 Burkitt lymphomas [BL]). EBV was detected in 9/17 cases. A monoclonal immunoglobulin variable (IGV) genes rearrangement was documented in 17/17 cases; IGV somatic hypermutation was found in 88% of cases, indicating a prevalent origin from germinal center (GC)-experienced B cells. Using immunophenotypic markers, three histogenetic profiles were identified: a) CD10/bcl-6/MUM1/CD138, mimicking GC B-cells; b) CD10-/bcl-6+/MUM1+/CD138-, reminiscent of B-cells at the latest phases of GC reaction; and c) CD10-/bcl-6-/MUM1+/CD138±, consistent with preterminally differentiated B-cells. CONCLUSIONS. Correlation between morphology, histogenesis, and EBV status demonstrated a high degree of homogeneity in the two GC-related groups, mostly including EBV-negative cases with BL and DLBCL-centroblastic features; the third group, consisting of post GC EBV-positive cases, was histologically less homogeneous, as it included polymorphic PTLDs and DLBCL with immunoblastic and anaplastic features. The EBV-negative cases with GC histogenetic phenotype showed a slightly better outcome; however, such less aggressive prognostic trend was not confirmed by statistical analysis.

Original languageEnglish
Pages (from-to)1013-1023
Number of pages11
JournalTransplantation
Volume82
Issue number8
DOIs
Publication statusPublished - Oct 2006

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Lymphoproliferative Disorders
Germinal Center
Human Herpesvirus 4
B-Lymphocytes
Lung
Lymphoma, Large B-Cell, Diffuse
Burkitt Lymphoma
Immunoglobulin Somatic Hypermutation
Immunoglobulin Genes
Gene Rearrangement
Immunoglobulins
Lymphoma
Transplants
Phenotype
Genes

Keywords

  • Immunohistochemistry
  • Lymphoma
  • Molecular biology
  • Transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

B-cell posttransplant lymphoproliferative disorders in heart and/or lungs recipients : Clinical and molecular-histogenetic study of 17 cases from a single institution. / Lucioni, Marco; Capello, Daniela; Riboni, Roberta; Ippoliti, Giovanbattista; Campana, Carlo; Bandiera, Laura; Arcaini, Luca; Rossi, Davide; Cerri, Michaela; Dionigi, Paolo; Lazzarino, Mario; Magrini, Umberto; Viganò, Mario; Gaidano, Gianluca; Paulli, Marco.

In: Transplantation, Vol. 82, No. 8, 10.2006, p. 1013-1023.

Research output: Contribution to journalArticle

Lucioni, Marco ; Capello, Daniela ; Riboni, Roberta ; Ippoliti, Giovanbattista ; Campana, Carlo ; Bandiera, Laura ; Arcaini, Luca ; Rossi, Davide ; Cerri, Michaela ; Dionigi, Paolo ; Lazzarino, Mario ; Magrini, Umberto ; Viganò, Mario ; Gaidano, Gianluca ; Paulli, Marco. / B-cell posttransplant lymphoproliferative disorders in heart and/or lungs recipients : Clinical and molecular-histogenetic study of 17 cases from a single institution. In: Transplantation. 2006 ; Vol. 82, No. 8. pp. 1013-1023.
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abstract = "BACKGROUND. Posttransplantation lymphoproliferative disorders (PTLDs) are heterogeneous lymphoid proliferations representing a major complication of solid organ transplant. This study details the clinicopathological and molecular features of 17 B-cell PTLDs observed in a single center series of 988 heart and/or lung transplant recipients. METHODS. Cases were classified according to World Health Organization lymphoma classification and tested for Epstein-Barr Virus (EBV), clonality, histogenetic phenotypic (CD10, Bcl-6, MUM1, CD138), and genotypic (immunoglobulin and BCL-6 genes somatic hypermutation) markers. RESULTS. This series of 17 PTLDs included: two B-cell monoclonal polymorphic PTLDs and 15 B-cell monomorphic PTLDs (13 diffuse large B-cell lymphomas [DLBCL] and 2 Burkitt lymphomas [BL]). EBV was detected in 9/17 cases. A monoclonal immunoglobulin variable (IGV) genes rearrangement was documented in 17/17 cases; IGV somatic hypermutation was found in 88{\%} of cases, indicating a prevalent origin from germinal center (GC)-experienced B cells. Using immunophenotypic markers, three histogenetic profiles were identified: a) CD10/bcl-6/MUM1/CD138, mimicking GC B-cells; b) CD10-/bcl-6+/MUM1+/CD138-, reminiscent of B-cells at the latest phases of GC reaction; and c) CD10-/bcl-6-/MUM1+/CD138±, consistent with preterminally differentiated B-cells. CONCLUSIONS. Correlation between morphology, histogenesis, and EBV status demonstrated a high degree of homogeneity in the two GC-related groups, mostly including EBV-negative cases with BL and DLBCL-centroblastic features; the third group, consisting of post GC EBV-positive cases, was histologically less homogeneous, as it included polymorphic PTLDs and DLBCL with immunoblastic and anaplastic features. The EBV-negative cases with GC histogenetic phenotype showed a slightly better outcome; however, such less aggressive prognostic trend was not confirmed by statistical analysis.",
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T2 - Clinical and molecular-histogenetic study of 17 cases from a single institution

AU - Lucioni, Marco

AU - Capello, Daniela

AU - Riboni, Roberta

AU - Ippoliti, Giovanbattista

AU - Campana, Carlo

AU - Bandiera, Laura

AU - Arcaini, Luca

AU - Rossi, Davide

AU - Cerri, Michaela

AU - Dionigi, Paolo

AU - Lazzarino, Mario

AU - Magrini, Umberto

AU - Viganò, Mario

AU - Gaidano, Gianluca

AU - Paulli, Marco

PY - 2006/10

Y1 - 2006/10

N2 - BACKGROUND. Posttransplantation lymphoproliferative disorders (PTLDs) are heterogeneous lymphoid proliferations representing a major complication of solid organ transplant. This study details the clinicopathological and molecular features of 17 B-cell PTLDs observed in a single center series of 988 heart and/or lung transplant recipients. METHODS. Cases were classified according to World Health Organization lymphoma classification and tested for Epstein-Barr Virus (EBV), clonality, histogenetic phenotypic (CD10, Bcl-6, MUM1, CD138), and genotypic (immunoglobulin and BCL-6 genes somatic hypermutation) markers. RESULTS. This series of 17 PTLDs included: two B-cell monoclonal polymorphic PTLDs and 15 B-cell monomorphic PTLDs (13 diffuse large B-cell lymphomas [DLBCL] and 2 Burkitt lymphomas [BL]). EBV was detected in 9/17 cases. A monoclonal immunoglobulin variable (IGV) genes rearrangement was documented in 17/17 cases; IGV somatic hypermutation was found in 88% of cases, indicating a prevalent origin from germinal center (GC)-experienced B cells. Using immunophenotypic markers, three histogenetic profiles were identified: a) CD10/bcl-6/MUM1/CD138, mimicking GC B-cells; b) CD10-/bcl-6+/MUM1+/CD138-, reminiscent of B-cells at the latest phases of GC reaction; and c) CD10-/bcl-6-/MUM1+/CD138±, consistent with preterminally differentiated B-cells. CONCLUSIONS. Correlation between morphology, histogenesis, and EBV status demonstrated a high degree of homogeneity in the two GC-related groups, mostly including EBV-negative cases with BL and DLBCL-centroblastic features; the third group, consisting of post GC EBV-positive cases, was histologically less homogeneous, as it included polymorphic PTLDs and DLBCL with immunoblastic and anaplastic features. The EBV-negative cases with GC histogenetic phenotype showed a slightly better outcome; however, such less aggressive prognostic trend was not confirmed by statistical analysis.

AB - BACKGROUND. Posttransplantation lymphoproliferative disorders (PTLDs) are heterogeneous lymphoid proliferations representing a major complication of solid organ transplant. This study details the clinicopathological and molecular features of 17 B-cell PTLDs observed in a single center series of 988 heart and/or lung transplant recipients. METHODS. Cases were classified according to World Health Organization lymphoma classification and tested for Epstein-Barr Virus (EBV), clonality, histogenetic phenotypic (CD10, Bcl-6, MUM1, CD138), and genotypic (immunoglobulin and BCL-6 genes somatic hypermutation) markers. RESULTS. This series of 17 PTLDs included: two B-cell monoclonal polymorphic PTLDs and 15 B-cell monomorphic PTLDs (13 diffuse large B-cell lymphomas [DLBCL] and 2 Burkitt lymphomas [BL]). EBV was detected in 9/17 cases. A monoclonal immunoglobulin variable (IGV) genes rearrangement was documented in 17/17 cases; IGV somatic hypermutation was found in 88% of cases, indicating a prevalent origin from germinal center (GC)-experienced B cells. Using immunophenotypic markers, three histogenetic profiles were identified: a) CD10/bcl-6/MUM1/CD138, mimicking GC B-cells; b) CD10-/bcl-6+/MUM1+/CD138-, reminiscent of B-cells at the latest phases of GC reaction; and c) CD10-/bcl-6-/MUM1+/CD138±, consistent with preterminally differentiated B-cells. CONCLUSIONS. Correlation between morphology, histogenesis, and EBV status demonstrated a high degree of homogeneity in the two GC-related groups, mostly including EBV-negative cases with BL and DLBCL-centroblastic features; the third group, consisting of post GC EBV-positive cases, was histologically less homogeneous, as it included polymorphic PTLDs and DLBCL with immunoblastic and anaplastic features. The EBV-negative cases with GC histogenetic phenotype showed a slightly better outcome; however, such less aggressive prognostic trend was not confirmed by statistical analysis.

KW - Immunohistochemistry

KW - Lymphoma

KW - Molecular biology

KW - Transplantation

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