Plasmablastic Lymphoma Arising in HHV8+ Multicentric Castleman Disease

Plasmablastic Lymphoma Arising in HHV8+ Multicentric Castleman Disease

L Jeffrey Medeiros, MD

Schematic of the pathogenesis of plasmablastic lymphoma (PBL) arising in human herpes virus 8 (HHV8) (+) multicentric Castleman disease (MCD). HHV8 initially infects polyclonal IgMλ(+) plasmablasts that reside in the mantle zones of lymphoid follicles. These plasmablasts are polyclonal, lack Ig somatic mutations, and correspond to naïve B-cells. Plasmablasts subsequently coalesce into microlymphomas that are IgMλ(+) but polyclonal. Microlymphomas further coalesce and progress to monotypic and monoclonal PBL. HHV8 infection drives this sequence of events, most likely combined with other genetic alterations. Plasma cells in the MCD component are polytypic and IgA or IgG(+).



  • Plasmablastic lymphoma (PBL) arising in HHV8(+) multicentric Castleman disease (MCD)


  • Large B-cell lymphoma arising in HHV8(+) MCD

    • Terminology of World Health Organization Classification, 2008

  • HHV8(+) plasmablastic lymphoma

  • KSHV(+) plasmablastic lymphoma


  • PBL-MCD is a monoclonal proliferation of HHV8(+) plasmablasts that express IgMλ and arise in MCD


Infectious Agents

  • Human herpes virus 8 (HHV8) is involved in pathogenesis

    • a.k.a. Kaposi sarcoma herpes virus (KSHV)

  • HHV8 initially infects singly scattered plasmablasts in mantle zones of follicles

    • These plasmablasts are naive B cells that express IgM

      • Plasmablasts express λ light chain but are polyclonal at molecular level

      • Plasmablasts lack evidence of immunoglobulin (Ig) somatic hypermutation

    • HHV8 encodes at least 10 homologues of cellular genes

      • Inhibit cell apoptosis, promote cell proliferation, and drive infected B cells to differentiate into plasmablasts

      • HHV8 encodes for viral homologue of IL-6, which is thought to induce many features of MCD

  • HHV8(+) plasmablasts expand to form so-called microlymphomas

    • Polyclonal or monoclonal associated with HHV8(-) polyclonal cells

  • HHV8(+) “microlymphomas” expand into histologically overt lymphoma

    • Cells in overt lymphoma are monoclonal

    • Analysis of HHV8 episomes shows virus is monoclonal

      • Indicates HHV8 is present prior to clonal expansion


  • Most patients with PBL-MCD have profound immunosuppression

    • HIV infection is very common

  • Patients with MCD and HIV have 15x increased risk of non-Hodgkin lymphoma



  • Incidence

    • Rare

  • Age

    • Depends in part on presence or absence of HIV infection

      • HIV(+): Age mirrors that of HIV(+) patients in general

      • HIV(-): Older patients

  • Ethnicity

    • In HIV(-) patients, PBL-MCD is more common in regions endemic for HHV8 infection

      • Mediterranean basin, Africa


  • Lymph nodes, spleen

  • Leukemic involvement as part of a terminal phase

  • Extranodal sites not (or rarely) involved


  • Evidence of profound immunosuppression

  • Lymphadenopathy; ± splenomegaly

  • ± Kaposi sarcoma


  • No consensus

  • Therapeutic choices often limited by marked immunosuppression


  • Poor; survival often < 1 year


General Features

  • Lymphadenopathy and splenomegaly are most common


Histologic Features

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Plasmablastic Lymphoma Arising in HHV8+ Multicentric Castleman Disease

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