Multiple viral infections in primary effusion lymphoma: a model of viral cooperation in lymphomagenesis

ABSTRACT

Introduction: Primary effusion lymphoma (PEL) is a rare B-cell lymphoid neoplasm mainly associated with HIV infection, presenting as pleural, peritoneal, and pericardial effusions. A defining property of PEL is its consistent association with Kaposi sarcoma associated herpesvirus (KSHV) infection, and, in most cases, Epstein Barr virus (EBV) co-infection. On these grounds, a review of the literature related to viral cooperation and lymphomagenesis can help to understand the complex interplay between KSHV and EBV in PEL pathogenesis.

Areas covered: In this review, the authors highlight clinical, pathologic, genetic and proteomic features of PEL, in the context of viral cooperation in PEL lymphomagenesis.

Expert commentary: Tumour cells are characterized by the overexpression of genes that are involved in inflammation and invasion. Coherently, PEL secretomes are enriched in proteins probably responsible for the particular tropism (cell adhesion and migration) of PEL cells. The development of PEL in HIV+ patients is multifactorial and involves a complex interplay among co-infection with oncogenic viruses (EBV and KSHV), inflammatory factors, and environmental conditions.

KEYWORDS:

• Primary effusion lymphoma
• HIV-associated lymphomas
• large cell lymphomas
• KSHV
• EBV
• viral cooperation
• lymphomagenesis

Acknowledgments

This manuscript is dedicated in memory of Anna Maria Cilia. She contributed as a distinguished researcher to the study of PEL by establishing KSHV infected CRO-AP cell lines at the Department of Pathology of CRO Aviano under the Direction of prof. Antonino Carbone.

The authors thank Professor Gianluca Gaidano for his help with the molecular pathogenesis of AIDS-related PEL and for expert advice on KSHV in human neoplasia and the genotypic characterization of AIDS-related lymphomas.

The Authors also thank Umberto Tirelli, MD and Emanuela Vaccher, MD for their expert advice on treatment of PEL patients.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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Funding

This manuscript is funded by an Institutional grant from Centro di Riferimento Oncologico Aviano for an intramural project ‘Infectious agents and cancer’ (A.C).