The incidence of aggressive lymphoma in the setting of HIV infection is significantly increased relative to the general population. Combination antiretroviral therapy (cART) for HIV has reduced the incidence of these neoplasms and has significantly improved clinical outcome for those who do develop lymphoma and require chemotherapy. With the possible exception of those individuals with the most severe immunocompromise, patients with HIV-associated lymphoma can be treated with the same standard immuno-chemotherapy regimens used in the immunocompetent population with similar expectations for good clinical outcome. Infusional regimens like dose adjusted EPOCH-R appear to be highly effective first-line therapy and for relapsed patients high-dose chemotherapy with autologous stem cell support is well-tolerated and effective. However, it should be recognized that there are unique risks associated with management of lymphoma in this patient population. While opportunistic infections are no longer a significant cause of death, antiretroviral agents used for management of HIV infection may interact with chemotherapeutic agents and other adjunctive therapies making communication between the treating Oncologist and the patient's primary HIV treatment provider of prime importance.
"This is followed by pathological evaluations, which include flow cytometry or immunohistochemical staining for immunophenotype.75 For aggressive lymphomas, this includes evaluation of proliferative fraction using Ki-67 or MIB-1 staining as a more aggressive regimen may be indicated for high growth fraction tumors.77 The expression of Ki-67 has been associated with poor outcome and survival in DLBCL patients.79,80 "
[Show abstract][Hide abstract] ABSTRACT: Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of cancer, and predict response to chemotherapy. They offer the hope of early detection as well as tracking disease progression and recurrence. Current progress in the characterization of molecular genetics of HIV-associated cancers may form the basis for improved patient stratification and future targeted or individualized therapies. Biomarker use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. This review focuses on the relevance of biomarkers in the most common HIV-associated malignancies, namely, Kaposi sarcoma, non-Hodgkin's lymphoma, and invasive cervical cancer.
"The frequency of EBV detection in these tumors ranges from 60% in BL to 100% in PCNSL (Carbone et al., 2009). Before the introduction of ART, the incidence of NHL in HIV-1 infected subjects was 100 times higher than in the general population (Goedert et al., 1998; International Collaboration on HIV and Cancer, 2000), PCNSL and high grade IBL being the most common NHL subtypes, followed by BL and intermediate grade DLBCL (Kaplan, 2012). High levels of HIV-1 plasmaviremia and low CD4 cell counts are both risk factors for the onset of NHL. "
[Show abstract][Hide abstract] ABSTRACT: Epstein-Barr virus (EBV) is a ubiquitous human γ-herpes virus which establishes a life-long asymptomatic infection in immunocompetent hosts. In human immunodeficiency virus type 1 (HIV-1) infected patients, the impaired immunosurveillance against EBV may favor the development of EBV-related diseases, ranging from lymphoproliferative disorders to B cell non-Hodgkin's lymphomas (NHL). Antiretroviral therapy (ART) has significantly modified the natural course of HIV-1 infection, resulting in decreased HIV-1 plasmaviremia, increased CD4 lymphocytes, and decreased opportunistic infections, indicating a restoration of immune functions. However, the impact of ART appears to be less favorable on EBV-related malignancies than on other AIDS-defining tumors, such as Kaposi's sarcoma, and NHL remains the most common cancer during the ART era. EBV-driven tumors are associated with selective expression of latent oncogenic proteins, but uncontrolled lytic cycle with virus replication and/or reactivation may favor cell transformation, at least in the early phases. Several host's factors may promote EBV reactivation and replication; besides immunodepression, inflammation/chronic immune stimulation may play an important role. Microbial pathogen-associated molecular patterns and endogenous damage-associated molecular patterns, through Toll-like receptors, activate the immune system and may promote EBV reactivation and/or polyclonal expansion of EBV-infected cells. A body of evidence suggests that chronic immune stimulation is a hallmark of HIV-1 pathogenesis and may persist even in ART-treated patients. This review focuses on lymphomagenesis driven by EBV both in the context of the natural history of HIV-1 infection and in ART-treated patients. Understanding the mechanisms involved in the expansion of EBV-infected cells is a premise for the identification of prognostic markers of EBV-associated malignancies.
Frontiers in Microbiology 10/2013; 4:311. DOI:10.3389/fmicb.2013.00311 · 3.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cardiac lymphomas are rare, and the spectrum of pathologic features is not well defined. We encountered an unusual case of cardiac lymphoma residing within a presumed thrombus. To place such cases in context, we reviewed all cardiac lymphomas presenting to a large US cardiovascular medicine referral center during a 30-year period. A total of 14 cardiac lymphomas were identified, and these included 6 primary cardiac lymphomas (PCLs) and 8 lymphomas secondarily involving cardiac structures. Upon review, 3 of the PCLs were confirmed to be diffuse large B-cell lymphoma, not otherwise specified, involving the myocardium. The other 3 cases of PCL lacked myocardial invasion and showed lymphoma cells embedded in fibrin thrombus. Acute inflammation was not evident. These lymphomas presented in immunocompetent male individuals and involved either a prolapsed myxomatous mitral valve, a pseudomyxoma from the left atrium, or a thrombus arising in a synthetic aortic root graft. All 3 consisted of large atypical lymphocytes expressing a nongerminal center B-cell immunophenotype. Two cases were positive for Epstein-Barr virus (latency type III), but none demonstrated human herpes virus-8 latent nuclear antigen. No systemic disease was found at presentation or during follow-up. In our experience, fibrin-associated large B-cell lymphoma arising in the heart represents a substantial proportion of PCL. These lymphomas appear to represent an underrecognized variant of diffuse large B-cell lymphoma with favorable outcome. Further study is needed to understand their natural history.
The American journal of surgical pathology 10/2012; 36(10):1527-37. DOI:10.1097/PAS.0b013e31825d53b5 · 5.15 Impact Factor
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