[1310] Notch 1 in Primary Effusion Lymphoma: A Clinicopathologic Study

HY Wang, F Fuda, NJ Karandikar. UT Southwestern Medical Center at Dallas, Dallas, TX

Background: Primary effusion lymphoma (PEL) is a human herpes virus 8 (HHV8) [also known as Kaposi-sarcoma associate herpes virus (KSHV)] -associated large cell lymphoma of body cavities. In vitro studies using PEL cell lines have defined the linkage between latent infection of HHV8 and the induction of oncogenesis through Notch1 (J Virol. 2006;80:6411-6419 and Virology. 2006;351:393-403). However, the potential pathogenic role of Notch1 has not been evaluated in ex vivo patient material.
Design: A total of 11 cases of PEL were retrieved from the Flow Cytometry database of the UT Southwestern Medical Center at Dallas from 1996-2007. Clinical, laboratory and other relevant demographic data were reviewed; detailed flow cytometric analysis was performed. Immunohistochemical staining of Notch1 (mN1A, Chemicon International), using the monoclonal antibody with a high affinity for the activated intracellular form of Notch1, was carried out on 6 cases from which cell blocks were available.
Results: HIV was positive at the time of diagnosis in 72.7% (8/11) of cases. Three HIV-negative PEL patients included a post heart transplantation patient, an elderly patient with asbestosis exposure, and an elderly patient with Hepatitis C. The longest follow-up was 113 months. Flow cytometry analysis detected the expression of following surface antigens (in descending order): CD38(100%), CD45(100%), CD71(100%), CD45RO(88%), HLA-DR(86%), CD30(82%), CD7(36%), CD4(18%), CD20(18%) and CD22(14%). HHV8 was detected in all 8 tested cases (100%) by either polymerase chain reaction (PCR), or in situ hybridization, or both. Notch1 was positive in 83.3% (5/6) of cases with both the nuclear and cytoplasmic staining pattern with the former stronger than the latter.
Conclusions: In consistent with in vitro studies using PEL cell lines, we found Notch1 expression in the vast majority of PEL specimens, corroborating the notion that it may play an important role in PEL pathogenesis. Other mechanism(s) in the setting of HHV8 should also be considered. As rarely reported, PEL can occur in HIV(-) but immuosuppressed as well as in non-immunosuppressed patients. In agreement with previous studies, PEL has high expression of cell surface activation markers (CD38, CD71, HLA-DR and CD30) with incomplete expression of B-cell antigens and aberrant expression of T-cell associated antigens.
Category: Hematopathology

Wednesday, March 11, 2009 9:30 AM

Poster Session V # 169, Wednesday Morning