Hindawi Publishing Corporation Case Reports in Oncological Medicine Volume 2013, Article ID 292301, 12 pages http://dx.doi.org/10.1155/2013/292301 Case Report HHV8-Negative Primary Effusion Lymphoma of B-Cell Lineage: Two Cases and a Comprehensive Review of the Literature Neeraj Saini, 1 Ephraim P. Hochberg, 2, 3 Erica A. Linden, 1, 3 Smita Jha, 1 Heinz K. Grohs, 4 and Aliyah R. Sohani 5 1 Department of Internal Medicine, North Shore Medical Center, Salem, MA 01970, USA 2 Center for Lymphoma, MGH Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA 3 Department of Medicine, Harvard Medical School, Boston, MA 02115, USA 4 Department of Pathology, North Shore Medical Center, Salem, MA 01970, USA 5 Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA Correspondence should be addressed to Neeraj Saini; nsaini@partners.org Received 18 November 2012; Accepted 11 December 2012 Academic Editors: K. Aogi and Y. Niibe Copyright © 2013 Neeraj Saini et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Primary effusion lymphoma (PEL) is a rare extranodal lymphoma that typically presents in a body cavity in the absence of a detectable tumor mass and that occurs predominantly in immunosuppressed individuals. e neoplastic lymphoid cells are frequently infected with human herpes virus 8 (HHV8), also known as Kaposi sarcoma herpes virus (KSHV). We describe two HIV-negative patients who presented with primary effusion lymphoma of B-cell lineage involving the pleural cavity, but whose tumor cells lacked infection by HHV8. We review the English language literature of HHV8-negative PEL of B-cell lineage and compare these lymphomas to HHV8-associated PEL with regard to clinical and pathological characteristics, therapy, and outcome. 1. Introduction Primary effusion lymphoma (PEL) is a rare extranodal lymphoma of large B cells with characteristic clinicopatho- logic features including: initial presentation as a body cavity lymphomatous effusion in the absence of a detectable tumor mass; occurrence mostly in human immunode�ciency virus (HIV)-positive individuals; and expression of antigens asso- ciated with a late stage of B-cell differentiation, such as CD138 and MUM1/IRF4, without pan-B-cell antigen expression [1]. Human herpes virus-8 (HHV8), also known as Kaposi’s sarcoma herpes virus (KSHV), is strongly causally related to PEL and its presence has been incorporated as a diagnostic criterion for PEL [2]. Diffuse large B-cell lymphoma (DLBCL) constitutes approximately 30–40% of all non-Hodgkin’s lymphoma (NHL) and typically presents with a rapidly enlarging symp- tomatic mass, usually due to nodal enlargement. Extranodal disease with involvement of tissue other than lymph node, spleen, Waldeyer’s ring or thymus is quite common in DLBCL, as is secondary involvement of a body cavity by DLBCL [3]. However, primary presentation of DLBCL as a body cavity lymphomatous effusion without any detectable solid mass, similar to HHV8-associated PEL, is extremely rare. Reports of such cases of HHV8-negative PEL of B- cell lineage are limited to isolated case reports and small series. We report two additional cases of this aggressive extranodal lymphoma that presented as a solitary pleural effusion without other sites of disease at the time of diagnosis. In addition, we perform a comprehensive literature review of similar cases with the aim of further characterizing this unusual lymphoma subtype. Case 1. An 87-year-old HIV-negative Portuguese female with a past medical history of heart failure with preserved ejection fraction (EF = 60%), hypertension, atrial �brillation, dyslipidemia, and degenerative joint disease was admitted with progressive shortness of breath of two weeks’ duration. Complete blood count on admission revealed WBC count of 9600/L, hemoglobin of 13.7 g/dL, hematocrit of 42.0%,