Primary Effusion Lymphoma: A Clinicopathological Study of 70 Cases

Abstract

Primary effusion lymphoma (PEL) is a rare type of large B-cell lymphoma associated with human herpesvirus 8 (HHV8) infection. Patients with PEL usually present with an effusion, but occasionally with an extracavitary mass. In this study, we reported a cohort of 70 patients with PEL: 67 men and 3 women with a median age of 46 years (range 26–91). Of these, 56 (80%) patients had human immunodeficiency virus (HIV) infection, eight were HIV-negative, and six had unknown HIV status. Nineteen (27%) patients had Kaposi sarcoma. Thirty-five (50%) patients presented with effusion only, 27 (39%) had an extracavitary mass or masses only, and eight (11%) had both effusion and extracavitary disease. The lymphoma cells showed plasmablastic, immunoblastic, or anaplastic morphology. All 70 (100%) cases were positive for HHV8. Compared with effusion-only PEL, patients with extracavitary-only PEL were younger (median age, 42 vs 52 years, p = 0.001), more likely to be HIV-positive (88.9% vs 68.6%, p = 0.06) and EBV-positive (76.9% vs 51.9%, p = 0.06), and less often positive for CD45 (69.2% vs 96.2%, p = 0.01), EMA (26.7% vs 100%, p = 0.0005), and CD30 (60% vs 81.5%, p = 0.09). Of 52 (50%) patients with clinical follow-up, 26 died after a median follow-up time of 40.0 months (range 0–96), and the median overall survival was 42.5 months. The median OS for patients with effusion-only and with extracavitary-only PEL were 30.0 and 37.9 months, respectively (p = 0.34), and patients with extracavitary-only PEL had a lower mortality rate at the time of last follow-up (35% vs 61.5%, p = 0.07). The median OS for HIV-positive and HIV-negative patients were 42.5 and 6.8 months, respectively (p = 0.57), and they had a similar mortality rate of 50% at last follow-up. In conclusion, patients presenting with effusion-only versus extracavitary-only disease are associated with different clinicopathologic features. PEL is an aggressive lymphoma with a poor prognosis, regardless of extracavitary presentation or HIV status.

Clinical and Therapeutic Implications of Epstein–Barr Virus in HIV-Related Lymphomas

“…Primary effusion lymphoma is a rare and aggressive NHL appearing mainly in HIV-infected patients in the form of body cavity effusion, although there are also solid forms. The lymphoma cells have a plasma cell phenotype and are positive for HHV-8 [ 29 ], and elevated percentage of cases are also positive for EBV ( Figure 1 ) [ 11 , 29 , 35 , 137 , 138 ]. The presence of EBV in the cells is a useful diagnostic tool to differentiate this lymphoma from HHV-8-positive DLBCL, not otherwise specified (NOS), a similar entity that overlaps histological features, since this entity is EBV-negative [ 29 ].…”

“…This lymphoma occurs mainly in men (90%) with a median age of 50–55 years and advanced AIDS disease. Two-thirds of the patients are HIV-infected (representing 3–5% of HIV-NHLs), and in this group the median age is 40–45 years, and around 70 years in HIV-negative individuals [ 29 , 138 , 139 , 140 ]. In addition, it is also closely related to EBV, which accounts for 70–100% of HIV-PEL [ 11 , 29 , 35 , 137 , 138 ].…”

“…In addition, most individuals with PEL are also coinfected by EBV. Latency I, with expression of EBNA1 and EBERs, is the most frequent subtype (90–92%), although it is possible to detect latency II (8%) with LMP1 expression in some cases ( Table 1 ) [ 11 , 15 , 138 , 140 ]. The role of EBV in the pathogenesis of PEL remains unclear; however, the MAPK signaling pathway seems to differentiate EBV-positive and EBV-negative PEL, and together with HHV-8, could contribute to the proliferation and evasion of programmed cell death [ 10 , 57 ].…”

“…By definition, all cases with this presentation (effusion) are at stage IV [ 139 , 140 , 153 , 154 ]. In addition, these patients usually present advanced AIDS disease with low CD4+ lymphocyte counts (median 98–133 cells/µL) ( Table 1 ) [ 137 , 138 , 139 , 155 ]. Patients present with symptoms related to the affected cavity, with the pleura being the most frequent, followed by peritoneal and pericardial.…”

“…Patients present with symptoms related to the affected cavity, with the pleura being the most frequent, followed by peritoneal and pericardial. Solid forms of PEL present with symptoms related to the affected organ, with the gastrointestinal tract being the most frequent [ 137 , 138 ].…”