Clinical Features and Outcome of Primary Effusion Lymphoma in HIV-Infected Patients: A Single-Institution Study By Cecilia Simonelli, Michele Spina, Roberta Cinelli, Renato Talamini, Rosamaria Tedeschi, Annunziata Gloghini, Emanuela Vaccher, Antonino Carbone, and Umberto Tirelli Purpose: To describe the clinical features and outcome of HIV-associated primary effusion lymphoma (PEL) and to compare them with those of the other HIV-associated non- Hodgkin’s lymphomas (NHLs). Patients and Methods: From April 1987 to June 2002, 277 patients with HIV infection and systemic NHL were diagnosed and treated in our institution. Clinical features and outcome of PEL patients were compared with the fea- tures and outcomes of 162 patients belonging to the follow- ing histologic subtypes: plasmoblastic lymphoma of oral cavity (PBLOC, n  11), immunoblastic lymphoma (IBL, n  76), and centroblastic B-cell lymphoma (CBCL, n  75). Results: Among the 277 NHL patients, PEL was diag- nosed in 11 patients (4%). Eight of 11 patients were treated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)–like regimen. Complete remission was reached in 42% of patients, with a median survival time of 6 months. When the clinical features and outcome of 11 PEL patients were compared with the other three groups of patients affected by NHL, at the onset of the disease, no statistically significant differences were observed in demo- graphic data, CD4 absolute number, HIV viremia plasma levels, and clinical characteristics. When we compared the outcome of PEL patients with the CBCL group, a statistically significant worse outcome was observed; however, the clinical outcome of PEL patients was not significantly differ- ent from the outcome observed in the other two groups (PBLOC and IBL groups). Conclusion: PEL is a rare HIV-associated NHL type occur- ring as a late manifestation of HIV infection with a poor clinical outcome and a shorter overall survival compared with CBCL patients. J Clin Oncol 21:3948-3954. © 2003 by American Society of Clinical Oncology. P RIMARY EFFUSION lymphoma (PEL) is a peculiar clini- copathologic entity characterized by human herpesvirus 8 (HHV-8) infection of tumor clone and by a peculiar tropism of the serous body cavities. 1,2 HHV-8 occurs in 100% of patients and is frequently, although not always, associated with Epstein- Barr virus infection. 3-7 At the clinicopathologic level, PEL is characterized by growth in the liquid phase in the absence of detectable tumor masses spreading along serous membranes without infiltrative growth patterns. Extraserous involvement of PEL has been reported. Some cases of PEL extend into tissues underlying the serous cavities, including the omentum and the lymph nodes, mediastinum, and lung. 1,2,5,6,8 Moreover, some cases of extracavitary nodal presentation with a subsequent development of effusion have been reported. 5 PEL usually displays a non-B or non-T phenotype, but immunogenotypic studies have defined its B-cell origin. Morphologically, PEL bridges immunoblastic anaplastic features and displays a certain degree of plasma-cell differentiation as shown by immunoglob- ulin positivity for CD138/syndecan-1, a plasma cell–specific antigen. 1,6,7,9-12 The differential diagnosis of PEL from other non-Hodgkin’s lymphomas (NHLs) involving body cavities is not feasible on pure clinical and morphologic grounds, but it is enhanced by biologic characteristics, such as positivity for HHV-8 sequences on biopsies. 13,14 PEL is a rare subset of large B-cell lymphoma that mainly occurs in AIDS patients and less frequently occurs in other groups, including elderly patients and organ transplantation recipients. 13,15-19 HIV patients affected by PEL usually have advanced AIDS, and they have been described as poor candi- dates for aggressive chemotherapy (CT). 10 In previous multi- institutional clinical series, the median survival time has been reported to be no longer than 3 months. 5,10 The aim of our study was to describe the clinical features and outcome of HIV-associated PEL diagnosed and treated in our institution from April 1987 to June 2002. Moreover, we com- pared the clinical characteristics and outcome of HIV-associated PEL with those of the other HIV-associated NHLs diagnosed and treated during the same period in our institution. PATIENTS AND METHODS The PEL relative incidence was calculated from the overall number of patients with HIV infection who had systemic NHL that was diagnosed and treated at the Aviano Cancer Center (Aviano, Italy) from April 1987 to June 2002. The clinical features and the outcome of 11 PEL patients were compared with 162 patients affected by the following histologic subtypes: plasmoblastic lymphoma of oral cavity (PBLOC, n = 11), immunoblastic lymphoma (IBL, n = 76), and centroblastic B-cell lymphoma (CBCL, n = 75). Seventy-four cases of Burkitt’s and Burkitt’s-like lymphomas were not included in the analysis. PEL patients are different from patients with From the Divisions of Medical Oncology A and Pathology, and Epidemi- ology and Microbiology Units, National Cancer Institute, Aviano, Italy. Submitted June 3, 2003; accepted August 11, 2003. Supported by grants from the Associazione Italiana per la Ricerca sul Cancro and Istituto Superiore Di Sanita. Authors’ disclosures of potential conflicts of interest are found at the end of this article. Address reprint requests to Umberto Tirelli, MD, Division of Medical Oncology A, National Cancer Institute, Via Pedemontana Occidentale 12, 33081 Aviano (PN), Italy; e-mail: omaoffice@cro.it. © 2003 by American Society of Clinical Oncology. 0732-183X/03/2121-3948/$20.00 3948 Journal of Clinical Oncology, Vol 21, No 21 (November 1), 2003: pp 3948-3954 DOI: 10.1200/JCO.2003.06.013