title: B-cell posttransplant lymphoproliferative disorders in heart and/or lungs recipients: clinical and molecular-histogenetic study of 17 cases from a single institution.
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.
authors.affiliation: Anatomic Pathology Section, Department of Human Pathology, University of Pavia, IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lucioni
authors.forename: Daniela
authors.initials: D
authors.lastname: Capello
authors.forename: Roberta
authors.initials: R
authors.lastname: Riboni
authors.forename: Giovanbattista
authors.initials: G
authors.lastname: Ippoliti
authors.forename: Carlo
authors.initials: C
authors.lastname: Campana
authors.forename: Laura
authors.initials: L
authors.lastname: Bandiera
authors.forename: Luca
authors.initials: L
authors.lastname: Arcaini
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Michaela
authors.initials: M
authors.lastname: Cerri
authors.forename: Paolo
authors.initials: P
authors.lastname: Dionigi
authors.forename: Mario
authors.initials: M
authors.lastname: Lazzarino
authors.forename: Umberto
authors.initials: U
authors.lastname: Magrini
authors.forename: Mario
authors.initials: M
authors.lastname: Viganò
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Marco
authors.initials: M
authors.lastname: Paulli
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001402:B-Lymphocytes / Q000166:cytology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007150:Immunohistochemistry; D016040:Lung Transplantation / Q000009:adverse effects*; D008232:Lymphoproliferative Disorders / Q000175:diagnosis* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D007135:Immunoglobulin Variable Region