title: Human herpesvirus 8+ polyclonal IgMλ B-cell lymphocytosis mimicking plasmablastic leukemia/lymphoma in HIV-infected patients.
abstract: OBJECTIVE
  Multicentric Castleman disease (MCD) is a distinct lymphoproliferative disorder characterized by inflammatory symptoms, lymphadenopathy, splenomegaly, and cytopenia. Kaposi's sarcoma-associated herpesvirus (KSHV), also called human herpesvirus-8 (HHV-8), is the cause of virtually all cases of MCD occurring in patients with HIV infection. MCD lesions characteristically contain HHV-8-infected polyclonal IgMλ plasmablasts. A high frequency of HHV-8-related non-Hodgkin lymphoma has been reported in these patients.
  
  
  METHODS
  We now report on three patients who presented with severe symptoms of MCD, extreme splenomegaly, and rapid expansion of B-cell lymphocytosis (44-81%) attributable to circulating HHV-8 positive plasmablasts.
  
  
  RESULTS
  The circulating plasmablastic cells shared the phenotype (IgMλ, CD19+, CD20- CD138-) of HHV-8-infected cells from MCD lesions, mimicking the leukemic phase of large B-cell lymphoma occurring in HHV-8-related MCD. These patients displayed a very high HHV-8 viral load in blood (>7 logs HHV-8 DNA copies/ml) and high levels of serum vIL-6, the viral homolog of human interleukin 6. Serum IL-6 and IL-10 were also abnormally elevated. HHV-8-infected cells were demonstrated by immunoglobulin gene rearrangement analysis, to be polyclonal and likely represent an expansion of HHV-8-infected cells similar to those found in MCD lesions.
  
  
  CONCLUSIONS
  Thus, the spectrum of HHV-8-related plasmablastic lymphoproliferative disorders in patients with HIV infection is expanded to include HHV-8+ polyclonal IgMλ B-cell lymphocytosis. At onset, this lymphoproliferative disorder may mimic plasmablastic leukemia/lymphoma. Recognizing this unusual complication may have important implications in treatment decision avoiding unnecessary toxicity to the patients.
authors.affiliation: Department of Clinical Immunology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Oksenhendler
authors.forename: David
authors.initials: D
authors.lastname: Boutboul
authors.forename: Kheira
authors.initials: K
authors.lastname: Beldjord
authors.forename: Véronique
authors.initials: V
authors.lastname: Meignin
authors.forename: Adrienne
authors.initials: A
authors.lastname: de Labarthe
authors.forename: Claire
authors.initials: C
authors.lastname: Fieschi
authors.forename: Antoine
authors.initials: A
authors.lastname: Dossier
authors.forename: Felix
authors.initials: F
authors.lastname: Agbalika
authors.forename: Carlo
authors.initials: C
authors.lastname: Parravicini
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tosato
authors.forename: Laurence
authors.initials: L
authors.lastname: Gérard
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D002999:Clone Cells / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D003937:Diagnosis, Differential; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D006566:Herpesviridae Infections / Q000276:immunology / Q000821:virology; D019288:Herpesvirus 8, Human / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000473:pathology; D018655:Lymphocyte Count; D008218:Lymphocytosis / Q000150:complications / Q000175:diagnosis* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D054219:Neoplasms, Plasma Cell / Q000175:diagnosis*; D010641:Phenotype
chemical_list: D016207:Cytokines; D007075:Immunoglobulin M
keywords: HIV; human herpesvirus-8; lymphoma; multicentric Castleman disease