title: Hemophagocytic syndrome in five patients with Epstein-Barr virus negative B-cell lymphoma.
abstract: BACKGROUND
  The recent recognition of the association of Epstein-Barr virus (EBV) with T-cell/natural killer cell (T/NK-cell) lymphoma has documented that particular types of EBV-containing T/NK-cell lymphoma are frequently complicated by hemophagocytic syndrome (HPS). This observation suggests that both EBV and proliferating T/NK-lymphoma cells play significant roles in the development of HPS. Cytokines released from neoplastic T cells are presumed to account for the activation of macrophages, which is followed by a complex cascade of cytokine production, resulting in full-blown HPS. Five patients with B-cell lymphoma complicated by HPS were studied for elevated serum cytokines, the association of EBV, and CD25 expression of lymphoma cells; the aim of this study was to verify whether the mechanisms of HPS development hypothesized for T/NK-cell lymphoma also operate in B-cell lymphoma.
  
  
  METHODS
  Sera were analyzed for the presence of inflammatory and immunoregulatory cytokines. Flow cytometry, immunohistology (IH), in situ hybridization (ISH), polymerase chain reaction (PCR), and Southern blot analysis were performed using bone marrow aspirates, biopsy specimens, and autopsy specimens.
  
  
  RESULTS
  Immunophenotypic and Southern blot studies verified that the lymphoma cells of all five patients were of B-cell lineage. Bone marrow aspirates demonstrated histiocytosis with extensive hemophagocytic activity. Marked elevation of serum cytokines and expression of CD25 were observed in all five patients. However, the results of PCR, ISH using EBER1 probe, and IH for latent membrane protein indicated that these lymphoma cells were free of EBV infection.
  
  
  CONCLUSIONS
  In patients with B-cell lymphoma, EBV infection is not necessarily required for the initiation of HPS. In this article, the pathogenesis of HPS assumed to be operative in B-cell lymphoma is discussed with reference to T/NK-cell lymphoma complicated by HPS.
authors.affiliation: Department of Internal Medicine, Ohtsu Red Cross Hospital, Nagara, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohno
authors.forename: N
authors.initials: N
authors.lastname: Miyake
authors.forename: S
authors.initials: S
authors.lastname: Hada
authors.forename: Y
authors.initials: Y
authors.lastname: Hirose
authors.forename: A
authors.initials: A
authors.lastname: Imura
authors.forename: T
authors.initials: T
authors.lastname: Hori
authors.forename: T
authors.initials: T
authors.lastname: Uchiyama
authors.forename: T
authors.initials: T
authors.lastname: Saiga
authors.forename: T
authors.initials: T
authors.lastname: Mizumoto
authors.forename: H
authors.initials: H
authors.lastname: Furukawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000956:Antigens, Viral / Q000032:analysis; D019411:Clinical Laboratory Techniques; D016207:Cytokines / Q000097:blood; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D015616:Histiocytosis, Non-Langerhans-Cell / Q000150:complications / Q000821:virology*; D006801:Humans; D017403:In Situ Hybridization; D016393:Lymphoma, B-Cell / Q000150:complications / Q000821:virology*; D008297:Male; D008487:Medical History Taking; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D014763:Viral Matrix Proteins / Q000032:analysis
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C099537:Epstein-Barr virus encoded RNA 1; D012367:RNA, Viral; D015375:Receptors, Interleukin-2; D014763:Viral Matrix Proteins