Over the last decade, many AIDS Malignancy Consortium (AMC) investigators have witnessed an increase in the proportion of HIV-associated lymphomas with plasmablastic pathology (PBL), which accounted for 17% of participants treated on the recent prospective frontline trial for B-cell HIV lymphomas (AMC-075). PBL is a relatively uncommon type of non-Hodgkin lymphoma (NHL), typically associated with Epstein Barr virus (EBV) and predominately affecting persons with immunosuppression related to HIV. Historically, PBL has been associated with low rates of remission and long-term survival. Despite recent reports finding improved outcomes, long-term progression-free survival is reported to be as low as 25% at 2 years in a retrospective analysis, and as high as 60% at 3 years in the prospective AMC075 trial. A genomic evaluation of 15 PBL cases found a transcriptional profile distinct from diffuse large B cell lymphoma, with increased expression of targets of the MYC and MYB transcription factors. However, the study did not explore an association between gene expression profiles and clinical outcomes. Optimal therapy has yet to be defined and little is known about prognostic factors in HIV-associated PBL (HIVPBL). We hypothesize that there will be a subset of clinical characteristics and differentially expressed genes in HIV-PBL tumors which will be of prognostic value for this disease, when data from long- and short-term HIV-PBL survivors are compared. The specific aims of this retrospective trial are to identify: (1) baseline clinical characteristics and treatment strategies and (2) differentially expressed genes in HIVPBL associated with survival greater than 2 years. This will be accomplished by collection of clinical data, including patient demographics, lymphoma factors (stage, disease phenotype, EBV and MYC status) treatment type, response and survival data, as well as gene expression profiling of tumor cells by RNA-Seq. In all, we will assess 100 HIV-PBL cases, of which approximately 50% are long-term (>2 years) survivors. In addition to the 17 HIV-PBL cases at UCSD, we have enlisted collaborators from across the U.S. and from the AIDS and Cancer Specimen Resource (ACSR) to provide cases. This will be the largest study of its kind on HIV-PBL and the only one addressing disease characteristics important for prognosis and survival. Knowledge of these prognostic clinical and genomic features of HIV-PBL could lead to improvements in disease stratification and may inform investigators how to better target the disease with novel treatment approaches.