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Published on: November 8, 2011
Plasmablastic microlymphoma occurring in human herpesvirus 8 (HHV-8)-positive multicentric Castleman's disease and
Jean-Louis Dargent1, Laurence Lespagnard, Nicolas Sirtaine
1Department of Pathology, ULB-Institut Jules Bordet/CHU Saint-Pierre, Brussels, Belgium.
Abstract:
Plasmablastic microlymphoma (PML) is defined as the accumulation of monotypic but polyclonal plasmablasts in lymphoid tissues involved in human herpes virus 8 (HHV-8)-positive multicentric Castleman's disease (MCD). So far, the nature of this very rare condition remains poorly determined. In this study, we describe a human immunodeficiency virus (HIV)-seropositive patient who developed a PML in the setting of HHV-8-positive MCD. In contrast to the cases previously reported, most of the plasmablasts in our patient were localized within the germinal center (GC) of lymphoid follicles. These plasmablasts expressed the multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4) protein as well as IgMlambda in a monotypic fashion. They did not show any immunoreactivity with antibodies directed against Pax-5, CD20, CD79a, CD10, CD30, CD23, CD138, epithelial membrane antigen (EMA) or BCL-6. These cells exhibited a high proliferation rate, expressed the HHV-8 latent nuclear antigen-1, and secreted the HHV-8 viral homologue of human interleukin-6. Polymerase chain reaction analysis did not demonstrate any clonal rearrangement of the genes coding for the heavy chain of the immunoglobulin. Moreover, no Epstein-Barr virus (EBV) RNA transcript could be found, using in situ hybridization. The present case illustrates that PML may arise within the GC of lymphoid follicles in the absence of EBV coinfection. In our opinion, PML occurring in MCD likely represents a variant of HHV-8-positive MCD in which lytic HHV-8 replication is particularly prominent, due to a local or systemic immune imbalance.
Insights
Plasmablastic microlymphoma (PML) is a rare condition associated with human herpes virus 8 (HHV-8)-positive multicentric Castleman
Area of Science:
- Hematopathology
- Virology
- Immunology
Background:
- Plasmablastic microlymphoma (PML) is a rare condition characterized by plasmablast accumulation in human herpes virus 8 (HHV-8)-positive multicentric Castleman's disease (MCD).
- The precise nature and pathogenesis of PML remain poorly understood, particularly its relationship with HHV-8 and Epstein-Barr virus (EBV).
Observation:
- This study details a case of PML in a human immunodeficiency virus (HIV)-seropositive patient with HHV-8-positive MCD.
- Unlike previously reported cases, the plasmablasts in this patient were predominantly located within germinal centers (GCs) of lymphoid follicles.
- These cells expressed MUM1/IRF4 and IgMlambda monotypically, lacked B-cell markers (Pax-5, CD20, CD79a, CD10, CD23), and did not express CD30, CD138, or EMA.
Findings:
- The observed plasmablasts demonstrated high proliferation, expressed HHV-8 latent nuclear antigen-1, and secreted HHV-8 viral IL-6.
- Genetic analysis revealed no clonal immunoglobulin heavy chain gene rearrangement, and in situ hybridization excluded EBV coinfection.
- PML can arise within GCs in HHV-8-positive MCD without EBV involvement.
Implications:
- This case suggests PML in MCD may represent a variant of HHV-8-positive MCD with prominent viral replication.
- Immune dysregulation, potentially local or systemic, may drive this phenomenon.
- Further research is needed to elucidate the pathogenesis and clinical significance of PML in the context of MCD.
