Role of EBV Expression in Diagnosis of Plasmablastic Plasmsa Cell Myeloma
DV Alapat, G Post, Z Singh. University of Arkansas, Little Rock, AR
Background: Plasmablastic morphology in plasma cell myeloma is associated with poor prognosis. Cytomorphologic and immunophenotypic features of plasmablastic plasma cell myeloma(PBM) are nearly identical to plasmablastic lymphoma (PBL), however, treatment strategies are different. The presence of a serum monoclonal protein and radiographic evidence of lytic lesions favors the diagnosis of plasma cell myeloma over PBL. Epstein–Barr virus (EBV) infection is strongly associated with PBL (∼70-100% of cases are positive for EBER by in situ hybridization) but not with PBM. However, rare cases of EBV+ plasmablastic myeloma have been reported, and the use of EBER to differentiate these two malignancies is controversial. We investigated the association of EBV infection via EBER or LMP1 expression in osseous and extraosseous PBM.
Design: All cases of plasmablastic plasma cell myeloma were diagnosed at UAMS during the period of 2004 – 2009. Clinical, immuophenotypic, cytogenetic and radiological findings were also reviewed. EBV infection status in these cases was studied using in situ hybridization for EBER and immunohistochemistry for LMP-1.
Results: A total of 12 cases were reviewed. All patients were HIV negative and had evidence of serum paraprotein, lytic bone lesions or a myeloma signature karyotype. Plasmablastic morphology (Grade III) was characterized by high N:C ratio, prominent nucleoli and fine chromatin. Six of the cases were extramedullary and 6 were bone marrow specimens. All of the cases were negative for EBER. As positive controls. EBER expression was detected in 3 cases of PBL.
Conclusions: We did not detect EBVinfection in osseous and non osseous PBM by either ISH or IHC. The results supports recent observations in an In vitro analysis that showed that the EBV infection in the terminally differentiated B-cells, like plasma cells lead to down regulation of plasma cell markers such as CD138, Blimp1, and MUM1, and expression of HLADR, CIITA and TCL1, which are normally not expressed in plasma cells1. A concurrent infection rather than a causal role for EBV in the few reported EBV positive PBM needs further exploration. An unequivocal expression of EBV in a plasmablstic neoplasm, especially in an extramedullary location should raise the concern for PBL. The association of lymphoma-specific karyotypic aberrations (for e.g 3q27) would exclude PBM in these challenging cases. A detailed immunophenotypic analysis including ISH for EBER and along with extensive clinical, radiographic and cytogenetic correlation is necessary to distinguish PBM from PBL. 1. Cancer Letters 284.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 207, Tuesday Morning