Plasmablastic lymphoma (PBL) is an aggressive lymphoma commonly associated with HIV infection. However, PBL can also be seen in patients with other immunodeficiencies as well as in immunocompetent individuals. Because of its distinct clinical and pathological features, such as lack of expression of CD20, plasmablastic morphology, and clinical course characterized by early relapses and subsequent chemotherapy resistance, PBL can represent a diagnostic and therapeutic challenge for pathologists and clinicians alike. Despite the recent advances in the therapy of HIV-associated and aggressive lymphomas, patients with PBL for the most part have poor outcomes. The objectives of this review are to summarize the current knowledge on the epidemiology, biology, clinical and pathological characteristics, differential diagnosis, therapy, prognostic factors, outcomes, and potential novel therapeutic approaches in patients with PBL and also to increase the awareness toward PBL in the medical community.
HIV infection has been recognized as a prothrombotic condition and this association has now been proven by a large number of studies with a reported VTE frequency among HIV-infected patients ranging from 0.19% to 7,63 %/year. HIV infection is associated with a two to tenfold increased risk of venous thrombosis in comparison with a general population of the same age. Some risk factors demonstrated a strongest association with VTE such as, low CD4+ cell count especially in the presence of clinical AIDS, protein S deficiency, and protein C deficiency. Whereas other risk factors are still controversial like protease inhibitor therapy, presence of active opportunistic infections and presence of antiphospholipid antibodies, including anticardiolipin antibodies and lupus anticoagulant. Physicians caring for HIV positive patients should be able to recognize and treat not only the well-known opportunistic infections and malignancies associated with this chronic disease, but also be alert to the less well-known complications such as thromboses. Pulmonary embolism should be included in the differential diagnosis when patients with HIV/AIDS have unexplained dyspnea or hypoxemia. In younger individuals with VTE, especially men, without other identifiable risk factors for VTE, HIV should be considered. Because interactions between warfarin and antiretrovirals is possible, health care providers should also be alert to the potential of dangerously high or low INRs when they are giving anticoagulants to patients with HIV infection who are undergoing antiretroviral therapy.
HIV-associated lymphoproliferative disorders represent a heterogeneous group of diseases, arising in the presence of HIV-associated immunodeficiency. The overall prevalence of HIV-associated lymphoma is significantly higher compared to that of the general population and it continues to be relevant even after the wide availability of highly active antiretroviral therapy (HAART) (1). Moreover, they still represent one of the most frequent cause of death in HIV-infected patients. Epstein–Barr virus (EBV), a γ-Herpesviruses, is involved in human lymphomagenesis, particularly in HIV immunocompromised patients. It has been largely implicated in the development of B-cell lymphoproliferative disorders as Burkitt lymphoma (BL), Hodgkin disease (HD), systemic non Hodgkin lymphoma (NHL), primary central nervous system lymphoma (PCNSL), nasopharyngeal carcinoma (NC). Virus-associated lymphomas are becoming of significant concern for the mortality of long-lived HIV immunocompromised patients, and therefore, research of advanced strategies for AIDS-related lymphomas is an important field in cancer chemotherapy. Detailed understanding of the EBV lifecycle and related cancers at the molecular level is required for novel strategies of molecular-targeted cancer chemotherapy The linkage of HIV-related lymphoma with EBV infection of the tumor clone has several pathogenetic, prognostic and possibly therapeutic implications which are reviewed herein.
HIV infection has been associated with an increased risk of developing several types of malignancies, including aggressive peripheral T‐cell lymphomas (PTCL). However, this is a rare occurrence with no more than a hundred cases reported in the literature. The purpose of this multicenter study is to describe the characteristics and to identify prognostic factors in patients with HIV‐associated PTCL. Data from HIV‐positive patients with a pathological diagnosis of non‐primary cutaneous, non‐leukemic PTCL were gathered retrospectively and are reported using descriptive statistics. Univariate and multivariate survival analyses were also performed. Fifty one patients were included in our analysis. Median age was 38 years with a 5:1 male‐to‐female ratio. Patients presented with a median CD4+ count of 173 cells mm−3, and a median HIV viral load of 334,787 copies ml−1. The median time from HIV diagnosis to PTCL diagnosis was 4.5 years. About 75% of patients presented with advanced clinical stage and 66% with B symptoms. The most common subtypes were PTCLU (61%) and anaplastic large cell lymphoma (ALCL, 22%). None of the ALCL patients tested expressed ALK. The median overall survival (OS) for the group was 12 months. In the multivariate survival analysis, the use of HAART and patients' performance status were independently associated with OS. HIV‐associated PTCL presents predominantly in young men with low CD4+ counts and high HIV viral loads. Both HIV‐related and lymphoma‐related factors were associated with OS. Am. J. Hematol. 2011. © 2011 Wiley‐Liss, Inc.
BACKGROUND: Plasmablastic lymphoma (PBL) is a rare and aggressive B‐cell lymphoma strongly associated with human immunodeficiency virus (HIV) infection. The authors conducted a multi‐institutional, retrospective study to describe characteristics and determine prognostic factors in HIV‐associated PBL. METHODS: For this study, the investigators included consecutive, HIV‐positive patients diagnosed between the years 2000 and 2010 whose tumors had a plasmablastic morphology, were cluster of differentiation 20 (CD20)‐negative, and expressed markers of plasmacytic differentiation. RESULTS: Fifty patients from 13 institutions were evaluated. The median age was 43 years, and there was a male predominance. The median count of cells that were positive for CD4 (a glycoprotein expressed on the surface of T‐helper cells, monocytes, macrophages, and dendritic cells) was 206 cells/mm3. At presentation, 90% of patients had extranodal involvement, 69% presented with advanced stage disease, and 27% had oral involvement. Rearrangements of v‐myc myelocytomatosis viral oncogene homolog (MYC) were detected in 41% of the tested patients. Eighty‐five percent of patients received chemotherapy, with 63% receiving cyclophosphamide, doxorubicin, vincristine, and prednisone and 37% receiving more intensive regimens. The complete response (CR) rate was 66%. The median overall survival (OS) was 11 months regardless of the intensity of chemotherapy. In the survival analysis, an Eastern Cooperative Oncology Group performance status ≥2, advanced stage, and MYC rearrangements were associated significantly with a worse outcome, whereas attaining a CR with chemotherapy was associated with a better outcome. CONCLUSIONS: The prognosis of PBL in HIV‐infected individuals remains poor in the highly active antiretroviral therapy era. Intensive chemotherapy regimens do not seem to increase survival in patients with HIV‐associated PBL. Cancer 2012. © 2012 American Cancer Society.
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