KSHV/HHV8-negative Effusion-based Lymphoma, a Distinct Entity Associated With Fluid Overload States

Abstract

Human herpesvirus-8 (HHV8)-positive effusion-based lymphomas have been termed primary effusion lymphoma (PEL) in the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Kaposi sarcoma herpesvirus (KSHV)/ HHV8-negative effusion-based lymphomas (KSHV/HHV8-negative EBLs) resembling PELs have been reported in the literature and in many cases have been (mis)classified as PEL-like lymphomas. Herein, we present a series of cases and a review of KSHV/HHV8-negative EBLs. This lymphoma, although cytomorphologically resembling PEL, is a distinct entity with characteristic clinical and pathologic features. Patients are older, generally human immunodeficiency virus negative and not immunosuppressed, frequently hepatitis C positive compared with the population baseline, and often have an underlying medical condition leading to fluid overload. The lymphoma cells express pan-B-cell antigens in 86.7%, and CD20 is expressed in 71.1% of the cases. The lymphoma is often of germinal center B or mixed germinal center B/activated B-cell signature with the Hans classifier, and Epstein-Barr virus is positive in nearly 30% of cases. Rare T-cell lymphomas were also reported. Clinical outcomes and response to therapy, including isolated aspiration, are relatively favorable compared with cases of PEL. We suggest that HHV8-negative effusion-based lymphoma is a distinct entity associated with fluid overload states.

Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma in the pericardium: A case with latency type III Epstein–Barr virus infection showing good prognosis without chemotherapy

“…About 30% of PEL-like lymphomas are infected with EBV [17,21], a low rate as compared with 65.6% of PELs [21]. Although the pathogenesis of PEL-like lymphoma might be more complex, as in our case, EBV may be related.…”

“…LMP1 is not expressed in PEL [2]. In PEL-like lymphoma accompanied by EBV infection, latent infection types were indicated in none of 10 reports in the literature [5,7,9,[11][12][13][14][21][22][23]. Although the relevance to EBV infection is still unknown, it is possible that the revealed EBV latent infection genes differ between PEL and PEL-like lymphoma.…”

“…Because there are some differences in PEL and PEL-like lymphoma, these have been proposed to be distinct diseases [21].…”

A unique case of primary effusion lymphoma‐like lymphoma showing disappearance and recurrence of the body cavity effusion

“…To date, few papers have investigated the clinical features and the treatment of PEL‐LL patients who are generally elderly, express CD20 for pan‐B‐cell antigens, and have a slow prognosis for mortality 5, 6. PEL has a strong prognosis for mortality during the early phase, whereas the literature includes numerous reports of favorable responses to chemotherapy in patients with PEL‐LL 7.…”

Current status of treatment for primary effusion lymphoma

“…Recently classified HHV-8-negative PEL-like lymphoma shows similar clinical and laboratory features, except for being HHV-8/KSHV negative and CD20 positive (41), and the term "HHV-8/KSHV-negative effusion-based lymphoma" was proposed (42). This lymphoma also presents with lymphomatous effusion without detectable masses.…”