Primary Body Cavity-Based AIDS-Related Lymphomas

Abstract

Five patients with advanced AIDS developed a unique type of high grade primary body cavity-based non-Hodgkin's lymphoma (NHL). The lymphomas were exclusively in serous effusions with no detectable mass disease in the body cavities and no lymphadenopathy or organomegaly. All of the lymphomas exhibited virtually identical morphology, which could not be precisely classified, but appeared to bridge features of large cell immunoblastic and anaplastic large cell lymphomas. Immunophenotypically the lymphoma cells lacked expression of any B- or T-lymphocyte antigens, but expressed CD45 and the activation antigens CD30, CD38, CD71, and HLA-DR. Clonally rearranged immunoglobulin heavy chain and kappa light chain genes were identified by Southern blot analysis. Molecular studies also revealed Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) genomes and germline configuration of the c-myc protooncogene. In two cases studied cytogenetically, the lymphoma cells manifested complex chromosome abnormalities. These lymphomas are clinically and biologically unique and found predominantly in patients with advanced AIDS, in many cases with pre-existing Kaposi's sarcoma.

Combined chemotherapy including high‐dose methotrexate in KSHV/HHV8‐associated primary effusion lymphoma

“…Most patients have not been treated with high-dose systemic chemotherapy probably because of low T CD4 + cell count and/or poor performance status [1][2][3][4][5]. PEL has been rarely observed in HIV-negative patients, and the relatively old age of these patients and/or the presence of visceral failures hampered the use of cytotoxic drugs [11,12].…”

“…PEL has been rarely observed in HIV-negative patients, and the relatively old age of these patients and/or the presence of visceral failures hampered the use of cytotoxic drugs [11,12]. CHOP has been the most frequently used chemotherapy regimen [2,4,6,7,[13][14][15]. Low-dose m-BACOD [4,6] and COP [16] have been occasionally administered.…”

“…In the context of AIDS, most cases are associated with other KSHV/ HHV8-related diseases such as Kaposi's sarcoma (KS) or multicentric Castleman's disease (MCD). The prognosis of PEL is poor, as the median survival in the previously published series does not exceed 3 months [1][2][3][4][5][6][7].…”

Lymphoma cell lines: in vitro models for the study of HHV-8+ primary effusion lymphomas (body cavity-based lymphomas)

“…1,3 The clinical outcome of AIDS-PEL is very poor as median survival ranged from 2 to 6 months; most patients have advanced AIDS and are poor candidates for aggressive chemotherapy. 8,9 Kaposi's sarcoma-associated herpesvirus -human herpesvirus -8 One of the unique features of PEL cells is their consistent infection with a new type of human virus. Kaposi's sarcomaassociated herpesvirus (KSHV) was first discovered in 1994 by Chang et al 10 in a search for an infectious agent in AIDSassociated Kaposi's sarcoma.…”

True

“…29 The poor clinical outcome of PEL in AIDS-related patients is commonly ascribed to the on-going immunosuppressive state of patients, which limits the applicability of potentially curative intensive chemotherapy programs. 25 However, many biologic characteristics of tumor cells influence the efficacy of treatment and in the last years particular attention has been dedicated to mechanisms associated with multidrug resistance. 23,30 We demonstrate in PEL cells both the expression of PGP and LRP as well as functional evidence of multidrug resistance when cells were exposed to pharmacological doses of different anthracyclines.…”