Primary Effusion Lymphoma: A Timely Review on the Association with HIV, HHV8, and EBV

Abstract

Primary effusion lymphoma (PEL) is defined by the WHO classification as a large B-cell neoplasm without detectable tumor masses. It is universally associated with HHV8, with most cases occurring in the setting of immunodeficiency such as HIV infection, and a poor prognosis. Morphologically, the neoplastic cells range from immunoblastic, plasmablastic, to anaplastic; and phenotypically, most cases express plasma cell but not B-cell markers, i.e., plasmablastic. During the past decade, primary HHV8-negative effusion lymphoma has been reported. Such cases were considered in the WHO classification scheme as effusion-based lymphoma. We performed a systemic review of 167 HHV8-negative effusion lymphomas from the literature and found that only 42% were associated with a fluid overload state, and with low rates of HIV (6%) or EBV (21%) infection. Furthermore, most patients are old (or immunosenescent) with underlying medical conditions/comorbidities, most neoplasms are of B-cell phenotype, and the outcome is more favorable than that of HHV8-positive PEL. These distinctive findings supported our prior proposal of designating these HHV8-negative cases as type II PEL, in contrast to the classic or type I PEL as defined by the WHO. Furthermore, we propose an algorithmic approach for the diagnosis of PEL and its mimickers.

Targeting VEGF with bevacizumab inhibits malignant effusion formation of primary human herpesvirus 8‐unrelated effusion large B‐cell lymphoma in vivo

“…During the past decade, primary effusion lymphomas lacking HHV8 have been documented, and terms such as PEL‐like lymphoma, HHV8‐unrelated PEL, and HHV8‐negative effusion‐based lymphoma (EBL) have been coined to describe these conditions. However, the terms ‘PEL’ and ‘EBL’ seem to have been used interchangeably in the literature 8 . The recent consensus opinion of an international group of hematopathologists is that the designation PEL should be restricted to cavity‐based lymphomas with neoplastic HHV8‐infected cells 24 .…”

“…Intriguingly, in these documented cases, patients of East Asian origin account for about 60% of cases of HHV8-unrelated ELBCLs. [5][6][7][8][25][26][27][28][29][30][31] Cell lines provide invaluable tools for research on rare diseases such as HHV8-unrelated ELBCL. To the best of our knowledge, to date, only three HHV8-unrelated ELBCL cell lines, STR-428, OGU1…”

“…In contrast to PEL, HHV8‐unrelated ELBCL cells express pan‐B‐cell markers and frequently display c‐MYC alterations. Studies have concluded that HHV8‐unrelated ELBCL is a clinical entity distinct from PEL 4–8 . However, because of the limited number of cases reported, there is no standard therapeutic regimen recommended for treatment of the HHV8‐unrelated ELBCL.…”

“…Most patients with HHV8‐unrelated ELBCL are older and HIV negative, and often have an underlying medical condition that leads to fluid overload. 4 , 5 , 6 , 7 , 8 In contrast to PEL, HHV8‐unrelated ELBCL cells express pan‐B‐cell markers and frequently display c‐MYC alterations. Studies have concluded that HHV8‐unrelated ELBCL is a clinical entity distinct from PEL.…”

“…Studies have concluded that HHV8‐unrelated ELBCL is a clinical entity distinct from PEL. 4 , 5 , 6 , 7 , 8 However, because of the limited number of cases reported, there is no standard therapeutic regimen recommended for treatment of the HHV8‐unrelated ELBCL. In these reported cases, most patients received intermediate systemic chemotherapy including CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) or a CHOP‐like regimen with or without rituximab, but some had an aggressive clinical course.…”