Primary Effusion (Body Cavity) Lymphoma

6/12/00 (Doyle)

Group: Monday Residents

RE: A 31 year old African American HIV+ male with abdominal pain.

Question: What are the characteristics of body cavity lymphoma?

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Unique Identifier: 97367981

Authors: Karcher DS. Alkan S.

Institution: Department of Pathology, the George Washington University Medical Center, Washington, DC 20037, USA.

Abstract: Human immunodeficiency virus (HIV)-related body cavity-based lymphomas (BCBLs) are known to exhibit unusual: clinical, immunophenotypic, and genotypic features, and have recently been found to harbor DNA sequences of a new: human herpesvirus, designated Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8).: The authors have encountered eight cases of HHV-8-associated BCBL in HIV-infected patients. A literature search: revealed an additional 50 reported cases of HIV-related BCBL, as well as reports of several other disorders associated: with HHV-8 DNA. Comprehensive analysis of the clinical and pathobiological features of all 58 known cases of: HIV-related BCBL shows it to be a unique B-cell neoplasm with a strong propensity for body-cavity involvement: without mass lesions and with little or no dissemination, poor prognosis, high grade usually immunoblastic morphology,: late B-cell phenotype and genotype, no associated c-myc gene rearrangement, frequent presence of Epstein-Barr virus: (EBV) genome, and uniform association with HHV-8 DNA. Considering these features in the context of other disorders: associated with HHV-8 DNA, HHV-8 appears to play a causal role in BCBL, possibly in concert with EBV, and may: induce this lymphoma through dysregulation of cytokines, particularly interleukin-6, or infection of an unusual B-cell: subset. The characteristics of HHV-8-associated BCBL suggest a possible role for antiherpes or anticytokine agents in: the treatment of this lymphoma. [References: 47]

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Unique Identifier: 20204461

Authors: Gaidano G. Capello D. Fassone L. Gloghini A. Cilia AM. Ariatti C. Buonaiuto D. Vivenza D. Gallicchio M. Avanzi GC.: Prat M. Carbone A.

Institution: Division of Internal Medicine, Department of Medical Sciences, Amedeo Avogadro University of Eastern Piedmont, Via: Solaroli 17, 28100, Novara, Italy. gaidano@med.unipmn.it

Abstract: BACKGROUND: Primary effusion lymphoma (PEL) associates with HHV-8 infection, preferentially develops in: immunodeficient patients and grows in the serous body cavities. PEL derives from post-germinal center, pre-terminally: differentiated B-cells. The pathogenesis of PEL is unclear and the sole identified genetic lesions are human herpesvirus: type-8 (HHV-8) infection in all cases and EBV infection in 70% of cases. Epstein-Barr virus (EBV) infection in PEL: displays a latency I phenotype. OBJECTIVES: To clarify the pathogenesis and histogenesis of PEL by investigating (1): the lymphoma karyotype; (2) the expression status of the Met tyrosine kinase receptor and of its ligand hepatocyte: growth factor (HGF); (3) the molecular profile of EBV, with particular focus on mutations of EBNA-1 genes, which are: thought to affect viral tumorigenicity in EBV-infected neoplasms displaying the latency I phenotype. STUDY DESIGN:: Twenty-four PEL (nine cell lines and 15 primary specimens) formed the basis of the study. Karyotypes were: investigated by conventional cytogenetics and fluorescent in situ hybridization (FISH) in selected cases. The expression: status of Met and HGF was defined by multiple techniques, including RT-PCR, FACS analysis, immunocytochemistry,: Western blot studies and ELISA. The molecular profile of EBNA-1 genes of EBV were investigated by DNA direct: sequencing. RESULTS: Trisomy 7, trisomy 12 and breaks at 1q21-q25 are recurrently associated with PEL. PEL: consistently co-express Met and HGF both at the mRNA and protein level. Among aggressive B-cell lymphomas,: Met/HGF co-expression appears to be relatively specific for PEL. The EBNA-1 gene of EBV displays a high degree of: genetic heterogeneity in PEL, with no preferential association with one specific variant. CONCLUSIONS: PEL: associates with recurrent chromosomal alterations, suggesting that viral infection is not sufficient for tumor development: and that lesions of cellular genes may be required. The expression of Met/HGF by PEL cells may bear implications for: the lymphoma proliferation and growth pattern, since Met/HGF interactions influence cell mitogenesis and motogenesis.: EBV infection in PEL displays a latency I phenotype and fails to associate with specific EBNA-1 variants, suggesting: that the role of EBV in PEL is not mediated by the major transforming pathways currently known in EBV positive: lymphomas.