Plasmablastic Lymphoma Arising in HHV8+ Multicentric Castleman Disease



Plasmablastic Lymphoma Arising in HHV8+ Multicentric Castleman Disease


L Jeffrey Medeiros, MD





Key Facts


Terminology



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


Etiology/Pathogenesis



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


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


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


  • Most patients with PBL-MCD have profound immunosuppression


Clinical Issues



  • Lymph nodes, spleen


  • Leukemic involvement as part of a terminal phase


  • Poor; survival often < 1 year


Microscopic Pathology



  • Plasmablastic lymphoma



    • Sheets of plasmablasts (or immunoblasts)


    • Mitotic figures common


Ancillary Tests



  • HHV8(+), IgM(+), λ(+)


  • CD45/LCA(+/-), CD20(-/+), CD79a(-), EBV(-)


  • Single-cell PCR studies show monoclonal IgH rearrangements in PBL


Top Differential Diagnoses



  • Primary effusion lymphoma (PEL)


  • Extracavitary PEL


  • HHV8(+) germinotropic lymphoproliferative disorder







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(+).


TERMINOLOGY


Abbreviations



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


Synonyms



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



    • Terminology of World Health Organization Classification, 2008


  • HHV8(+) plasmablastic lymphoma


  • KSHV(+) plasmablastic lymphoma


Definitions



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


ETIOLOGY/PATHOGENESIS


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


Immunosuppression



  • 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


CLINICAL ISSUES


Epidemiology



  • 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


Site



  • Lymph nodes, spleen


  • Leukemic involvement as part of a terminal phase


  • Extranodal sites not (or rarely) involved


Presentation



  • Evidence of profound immunosuppression


  • Lymphadenopathy; ± splenomegaly


  • ± Kaposi sarcoma


Treatment



  • No consensus


  • Therapeutic choices often limited by marked immunosuppression


Prognosis



  • Poor; survival often < 1 year


IMAGE FINDINGS


General Features



  • Lymphadenopathy and splenomegaly are most common


MICROSCOPIC PATHOLOGY


Histologic Features

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

Full access? Get Clinical Tree
Get Clinical Tree app for offline access