Frequent Coexpression of HHV-8 and EBV in HIV-Associated Multicentric Castleman Disease
D Peker, R Poppiti, H Yaziji, A Martinez. Mount Sinai Medical Center, Miami Beach; Vitro Molecular Laboratories, Miami
Background: HHV-8 associated lymphoproliferative disorders in HIV+ patients are heterogenous and include plasmablastic multicentric Castleman disease (MCD), including plasmablastic microlymphoma and lymphoma, primary effusion lymphoma and HHV-8+/Epstein-Barr virus (EBV)+ germinotropic lymphoproliferative disorder. We sought to characterize the cell types using immunohistochemistry (IHC) and EBV status by ISH (EBER) in seven cases of MCD, plasmablastic type, including one case with microlymphoma and one plasmablastic lymphoma in seven HIV+ patients.
Design: All patients presented with diffuse lymphadenopathy, splenomegaly, high HIV viral load and low CD4 count. Lymph node excisions were evaluated for each case, and autopsy was performed on one patient. The IHC stains included CD20, PAX-5, CD21, CD138, CD30, CD56, MUM-1, ALK, LMO2 and HHV-8. EBV status was available on 6 cases by ISH. Flow cytometry was performed on all cases.
Results: All lymph nodes showed variable features of CD, predominantly plasma cell type, including variably present regressed follicles with onion-skinning pattern of mantle cells, variable numbers of plasmablasts in the mantle zones. Two cases had Kaposi's sarcoma in the same node. In one case with microlymphoma nodular aggregates of large cells replacing germinal centers was seen. Another case showed lymphoma with architectural effacement by sheets of plasmablasts. Plasmablasts were positive with HHV-8 and MUM-1 in all cases. In the majority of the cases, plasmablasts CD138 positive and CD20 negative. CD30 was expressed in one case. None of the cases showed PAX-5, ALK or CD56 expression. CD21 showed dendritic cell meshworks in the follicles surrounded by the plasmablasts. LMO2 highlighted reactive germinal centers in six cases, and in the case with microlymphoma was reactive in plasmablasts coexpressing CD138. By flow cytometry, six cases showed no clonality, with lambda light chain restriction in one case. Six cases tested showed co-infection with EBV.
Conclusions: We demonstrated a majority of plasmablasts with an activated immunophenotype, as previously described in the literature; however, EBV coinfection was demonstrated in six of seven cases by EBER. A single case of microlymphoma showed coexpression of HHV-8 and EBV, and expressed the germinal center marker LMO2, suggesting transformation occurring at the germinal center. Further characterization of plasmablasts in MCD is necessary to further understand the pathogenesis, with potential therapeutic implications.
Monday, March 22, 2010 1:45 PM
Platform Session: Section B, Monday Afternoon