A Feasible Flowchart to Screen EBV-Positive Diffuse Large B Cell Lymphoma of the elderly: A Molecular Approach

  • Simona Ferrari Unit of Anatomical Pathology, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy
  • Luca Caschera Unit of Radiology, University of Milan, via Festa del Perdono, 7, 20122, Milan, Italy.
  • Giuseppe Deda Unit of Anatomical Pathology, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy
  • Michelina Maria Carla Amato Unit of Anatomical Pathology, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy
  • Ombretta Annibali Unit of Hematology, Stem Cell Transplantation, Transfusion Medicine and Cellular Therapy, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy.
  • Carla Rabitti Unit of Anatomical Pathology, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy
  • Anna Crescenzi Unit of Anatomical Pathology, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy
  • Tommasangelo Petitti Unit of Hygiene Public Health and Statistics, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy.
  • Giuseppe Avvisati Unit of Hematology, Stem Cell Transplantation, Transfusion Medicine and Cellular Therapy, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy.
  • Andrea Onetti Muda Unit of Anatomical Pathology, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy
  • Francesca Zalfa Unit of Microscopic and Ultrastructural Anatomy, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy.
  • Antonella Bianchi Unit of Anatomical Pathology, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Rome, Italy
Keywords: Epstein-Barr virus (EBV), EBV-positive diffuse large B cell lymphoma of the elderly, Diffuse large B cell lymphoma (DLBCL), EBER in situ hybridization (EBER-ISH), Quantitative real time PCR (Q-PCR).

Abstract

Background: Epstein Barr Virus-positive diffuse large B cell lymphoma of the elderly (DLBCL-EBV+-e), initially described in 2003, is a provisional entity in the 4th edition of the World Health Organization (WHO) Classification of tumors of hematopoietic and lymphoid tissues and is defined as an EBV+ monoclonal large B cell proliferation that occurs in patients >50 years of age and in whom there is no known immunodeficiency or history of lymphoma. It is associated with a poor prognosis but could be treated with the association of novel therapeutic approaches. EBER in situ hybridization (EBER-ISH)  is the gold standard assay for defining a tumor as EBV-related, however there are no uniform criteria for the percentage of EBV-positive cells in DLBCL-EBV+-e.Methods: We applied to Formalin Fixed Paraffin Embedded (FFPE) tissue of 43 novel DLBCL over 50 years Q-PCR for the detection of viral DNA in concert with EBER-ISH.Result: Only one case was defined as true DLBCL-EBV+-e being Q-PCR positive  with a value of log EBV DNA/105 cells ≥ 6 and EBER-ISH positive.Conclusion: In the current study we applied to FFPE tissue of DLBCL-EBV+-e a reliable and feasible Q-PCR/EBER-ISH combined protocol for the screening of EBV status. Our protocol could help to better identify the DLBCL-EBV+-e patients eligible for novel therapeutic approaches.

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Published
2016-08-09
Section
Original Article