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  • Title: B-cell posttransplant lymphoproliferative disorders in heart and/or lungs recipients: clinical and molecular-histogenetic study of 17 cases from a single institution.
    Author: Lucioni M, Capello D, Riboni R, Ippoliti G, Campana C, Bandiera L, Arcaini L, Rossi D, Cerri M, Dionigi P, Lazzarino M, Magrini U, Viganò M, Gaidano G, Paulli M.
    Journal: Transplantation; 2006 Oct 27; 82(8):1013-23. PubMed ID: 17060848.
    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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