title: Cytotoxic Epstein-Barr virus-positive large B cell lymphoma: a regulatory B cell-derived neoplasia?
abstract: OBJECTIVE
  A new subtype of granzyme B (GrB)-producing regulatory B cells (Bregs) has been described recently; these peculiar cytotoxic B cells are increased significantly in interleukin (IL)-21-rich settings, and in particular during HIV and Epstein-Barr virus (EBV) infection. Our aim is to report a unique case of an EBV-positive diffuse large B cell lymphoma (DLBCL) with cytotoxic features arisen in an HIV+patient, and to understand if this lesion may represent a proliferation of neoplastic cytotoxic Bregs.
  
  
  RESULTS
  We describe a 66-year-old male patient who presented with cervical lymph node enlargement and B symptoms; subsequently, HIV infection was diagnosed. Histopathological, immunohistochemical and molecular studies were performed, and revealed an EBV-positive DLBCL with cytotoxic features. Considering the immunological setting and unconventional phenotype observed, we tried to evaluate further the expression of GrB and IL-21 in another 150 aggressive B cell lymphomas (17 of 150 EBV+, two of 150 EBV+/HIV+). Minimal dot-like expression of GrB was found in seven lymphomas (in fewer than 1% of tumour cells), three of which were EBV-positive.
  
  
  CONCLUSIONS
  Bregorigin has never been reported in B cell lymphomas. We describe an exceptional case of EBV-positive DLBCL with aberrant expression of cytotoxic markers in a patient with a previously unknown HIV infection. We propose cytotoxic Bregsas a possible normal counterpart for this unusual tumour.
authors: Unit of Haematopathology, European Institute of Oncology, Milan, Italy.
authors: Valentina
authors: V
authors: Tabanelli
authors: Department of Pathology, University of Antioquia, Medellin, Colombia.
authors: Vanessa
authors: V
authors: Santiago-Pacheco
authors: III Division of Infectious Diseases, Luigi Sacco Hospital, Milan, Italy.
authors: Mario
authors: M
authors: Corbellino
authors: Unit of Haematopathology, European Institute of Oncology, Milan, Italy.
authors: Angelica
authors: A
authors: Calleri
authors: Department of Experimental Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors: Claudio
authors: C
authors: Agostinelli
authors: Section of Infectious Diseases and Immunopathology, Luigi Sacco Hospital, Milan, Italy.
authors: Carlo
authors: C
authors: Parravicini
authors: Unit of Haematopathology, European Institute of Oncology, Milan, Italy.|Bologna University School of Medicine, Bologna, Italy.
authors: Stefano A
authors: SA
authors: Pileri
mesh_terms: D000368:Aged; D060151:B-Lymphocytes, Regulatory / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D060085:Coinfection; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology / Q000473:pathology*; D053804:Granzymes / Q000096:biosynthesis; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D017403:In Situ Hybridization; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications / Q000276:immunology / Q000473:pathology*; D008297:Male; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D053804:Granzymes
keywords: 
  DLBCL
  ; 
  EBV
  ; 
  HIV
  ; Breg; cytotoxic; granzyme B