Primary Effusion Lymphoma: A Clinicopathologic Perspective

SIMPLE SUMMARY: Primary effusion lymphoma (PEL) is a rare B-cell lymphoma with a particularly aggressive course. This disease usually affects the variably immunocompromised and maintains a predilection for body cavities, leading to the development of malignant effusions. Pathogenesis suggests an association with HHV8 and EBV, although this is unclear. There are no definitive guidelines for the treatment of PEL, but commonly used initial regimens include those similar to DA-EPOCH and CHOP. The prognosis remains poor, even with advanced treatment. Newer therapies incorporate the use of axicabtagene ciloleucel, CAR-T cell therapies, and augmented EPOCH regimens. Further investigation into oncogenesis and targeted molecular pathways could provide insights into treatment targets. In this review, the authors would like to compare this disease with other similarly aggressive B-cell lymphomas, as well as highlight the unique epidemiology, pathogenesis, and current treatment options for patients diagnosed with PEL. ABSTRACT: Primary effusion lymphoma (PEL) is a rare, aggressive B-cell lymphoma that usually localizes to serous body cavities to subsequently form effusions in the absence of a discrete mass. Although some tumors can develop in extracavitary locations, the areas most often affected include the peritoneum, pleural space, and the pericardium. PEL is associated with the presence of human herpesvirus 8 (HHV8), also called the Kaposi sarcoma-associated herpesvirus (KSHV), with some variability in transformation potential suggested by frequent coinfection with the Epstein-Barr virus (EBV) (~80%), although the nature of the oncogenesis is unclear. Most patients suffering with this disease are to some degree immunocompromised (e.g., Human immunodeficiency virus (HIV) infection or post-solid organ transplantation) and, even with aggressive treatment, prognosis remains poor. There is no definitive guideline for the treatment of PEL, although CHOP-like regimens (cyclophosphamide, doxorubicin, vincristine, and prednisone) are frequently prescribed and, given the rarity of this disease, therapeutic focus is being redirected to personalized and targeted approaches in the experimental realm. Current clinical trials include the combination of lenalidomide and rituximab into the EPOCH regimen and the treatment of individuals with relapsed/refractory EBV-associated disease with tabelecleucel.