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El linfoma de Hodgkin (LH) se debe a la transformación clonal de células originadas en los linfocitos B, lo que genera las células binucleadas patognomónicas de Reed-Sternberg. El LH es una enfermedad de células B con una distribución bimodal, con mayor incidencia en la adolescencia y la tercera década de la vida y un segundo pico en personas mayores de 55 años. Las células del LH clásico habitualmente sufren una reprogramación de la expresión génica, ya que pierden la expresión de la mayoría de los genes típicos de las células B y han adquirido la expresión de múltiples genes que son típicos de otros tipos de células del sistema inmunitario. El algoritmo de tratamiento dependerá si se trata de LH clásico o de predominio linfocítico, si es un estadio temprano con marcadores de pronóstico desfavorables o no, el esquema inicial de manejo y si existe enfermedad voluminosa, entre las variables más relevantes., Hodgkin’s lymphoma (HL) is due to the clonal transformation of cells originating from B lymphocytes, generating the pathognomonic binucleate Reed-Sternberg cells. HL is a B cell disease with a bimodal distribution, with higher incidence in adolescence and the third decade of life, showing a second peak in people over 55 years of age. Classic Hodgkin lymphoma cells routinely undergo gene expression reprogramming, as they lose the expression of most of the typical B-cell genes and acquire the expression of multiple genes that are typical of other types of cells in the immune system. The treatment algorithm will depend on whether it is classic or predominantly lymphocytic HL, if it is early stage with unfavorable prognostic markers or not, the initial management regimen, and whether there is bulky disease, among the most relevant variables., (Copyright: © 2021 Permanyer.)

HIV-positive patients have a 60- to 200-fold increased incidence of Non-Hodgkin Lymphomas (NHL) because of their impaired cellular immunity. Some NHL are considered Acquired Immunodeficiency Syndrome (AIDS) defining conditions. Diffuse large B-cell Lymphoma (DLBC) and Burkitt Lymphoma (BL) are the most commonly observed, whereas Primary Effusion Lymphoma (PEL), Central Nervous System Lymphomas (PCNSL), Plasmablastic Lymphoma (PBL) and classic Hodgkin Lymphoma (HL) are far less frequent. Multicentric Castleman disease (MCD) is an aggressive lymphoproliferative disorder highly prevalent in HIV-positive patients and strongly associated with HHV-8 virus infection. In the pre-Combination Antiretroviral Therapy (CART) era, patients with HIV-associated lymphoma had poor outcomes with median survival of 5 to 6 months. By improving the immunological status, CART extended the therapeutic options for HIV positive patients with lymphomas, allowing them to tolerate standard chemotherapies regimen with similar outcomes to those of the general population. The combination of CART and chemotherapy/ immuno-chemotherapy treatment has resulted in a remarkable prolongation of survival among HIVinfected patients with lymphomas. In this short communication, we briefly review the problems linked with the treatment of lymphoproliferative diseases in HIV patients. Combination Antiretroviral Therapy (CART) not only reduces HIV replication and restores the immunological status improving immune function of the HIV-related lymphomas patients but allows patients to deal with standard doses of chemotherapies. The association of CART and chemotherapy allowed to obtain better results in terms of overall survival and complete responses. In the setting of HIVassociated lymphomas, many issues remain open and their treatment is complicated by the patient's immunocompromised status and the need to treat HIV concurrently., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The pathogenesis of classical Hodgkin lymphoma (cHL) is still enigmatic, largely because its tumor cells, the so-called Hodgkin and Reed-Stenberg (HRS) cells, invariably reside in a prominent reactive microenvironment, are rare and therefore difficult to analyze. On the other hand, the broadly investigated cHL-derived cell lines are not unequivocally considered as suitable and representative models for this puzzling disease. Based on current knowledge, it appears that the cross talk between the tumor cells and the reactive infiltrate of the microenvironment is complex and that multiple mechanisms occur, making cHL a very heterogeneous disease. In 20-40% of cHL cases, HRS cells carry a monoclonal infection by Epstein Barr virus (EBV), which is considered a tumor-initiating factor. In these cases, EBV shows a latency type II infection pattern with the expression of latent membrane protein-1 (LMP-1), a viral oncoprotein that mimics CD40 activation. This scenario is particularly intriguing for the pathogenesis of cHL arising in HIV-infected patients, which, for still obscure reasons, is invariably EBV-associated with LMP-1 expression in HRS cells. Recent evidences are consistent with the occurrence of different pathogenic pathways variably triggered by virus infections (EBV and HIV), genetic alterations, and interactions with critical microenvironmental components. This review focuses on the different microenvironmental niches that characterize cHL of the general population as well as cases of HIV-infected patients. A more comprehensive understanding of the complex interplay existing between HRS and tumor microenvironment is pivotal for the development of more effective treatments, particularly for relapsed or refractory diseases., (© 2016 UICC.)

Pulmonary malignancies are a major source of morbidity and mortality in HIV-infected persons. Non-AIDS-defining lung cancers (mostly non-small cell lung cancers) are now a leading cause of cancer death among HIV-infected persons. HIV-associated factors appear to affect the risk of lung cancer and may adversely impact cancer treatment and outcomes. HIV infection also may modify the potential harms and benefits of lung cancer screening with computed tomography. AIDS-defining lung malignancies include pulmonary Kaposi sarcoma and pulmonary lymphoma, both of which are less prevalent with widespread adoption of antiretroviral therapy., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Despite the immune reconstitution promoted by combined antiretroviral therapy (cART), lymphomas still represent the most common type of cancer in HIV-infected individuals. Cofactors related to immunodeficiency such as oncogenic viruses, chronic antigenic stimulation, and cytokine overproduction are thought to be the main drivers of HIV lymphomagenesis, although the current scenario does not convincingly explain the still-high incidence of lymphomas and the occurrence of peculiar lymphoma histotypes in HIV-infected patients under cART. Recent findings are challenging the current view of a mainly indirect role of HIV in lymphoma development and support the possibility that HIV may directly contribute to lymphomagenesis. In fact, mechanisms other than immune suppression involve biologic effects mediated by HIV products that are secreted and accumulate in lymphoid tissues, mainly within lymph node germinal centers. Notably, HIV-infected patients with lymphomas, but not those not affected by these tumors, were recently shown to carry HIV p17 protein variants with enhanced B-cell clonogenic activity. HIV p17 protein variants were characterized by the presence of distinct insertions at the C-terminal region of the protein responsible for a structural destabilization and the acquisition of novel biologic properties. These data are changing the current paradigm assuming that HIV is only indirectly related to lymphomagenesis. Furthermore, these recent findings are consistent with a role of HIV as a critical microenvironmental factor promoting lymphoma development and pave the way for further studies that may lead to the design of more effective strategies for an early identification and improved control of lymphomas in the HIV setting., (© 2016 by The American Society of Hematology.)

Despite treatment with potent and effective combination antiretroviral medications, the incidence of non-Hodgkin lymphoma (NHL) in the population living with HIV/AIDS remains significantly higher than that in noninfected individuals. The majority of the HIV-infected patients with NHL present with advanced stage extranodal disease of the B-cell phenotype. Lymphomas are the second most common tumors involving the heart in HIV-infected patients. Although the heart may serve as the primary focus of the lymphoma, in most HIV-related cases, cardiac lymphomatous involvement is part of a metastatic process that originated elsewhere., (© The Author(s) 2014.)

Patients with HIV infection are at increased risk of developing non-Hodgkin lymphoma and Hodgkin lymphoma. While the pathogenesis of these lymphomas is incompletely understood, evidence indicates that immune deregulation, genetic alterations and cytokine production play an important role in HIV lymphomagenesis. The lymphoma microenvironment in this heterogeneous group of lymphomas plays an equally critical role in their development, growth and progression. Important components of the microenvironment in HIV-related lymphomas include EBV and/or HHV-8 coinfection, reactive inflammatory cells, tumor microvasculature, and soluble factors. This paper provides a brief overview of HIV-related lymphomas and focuses on their lymphomagenesis and microenvironment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Immunodeficiency dramatically increases susceptibility to cancer as a result of reduced immune surveillance and enhanced opportunities for virus-mediated oncogenesis. Although AIDS-related lymphomas (ARLs) are frequently associated with known oncogenic viruses, many cases contain no known transforming virus. To discover novel transforming viruses, we profiled a set of ARL samples using whole transcriptome sequencing. We determined that Epstein-Barr virus (EBV) was the only virus detected in the tumor samples of this cohort, suggesting that if unidentified pathogens exist in this disease, they are present in <10% of cases or undetectable by our methods. To evaluate the role of EBV in ARL pathogenesis, we analyzed viral gene expression and found highly heterogeneous patterns of viral transcription across samples. We also found significant heterogeneity of viral antigen expression across a large cohort, with many patient samples presenting with restricted type I viral latency, indicating that EBV latency proteins are under increased immunosurveillance in the post-combined antiretroviral therapies era. Furthermore, EBV infection of lymphoma cells in HIV-positive individuals was associated with a distinct host gene expression program. These findings provide insight into the joint host-virus regulatory network of primary ARL tumor samples and expand our understanding of virus-associated oncogenesis. Our findings may also have therapeutic implications, as treatment may be personalized to target specific viral and virus-associated host processes that are only present in a subset of patients., (© 2015 by The American Society of Hematology.)

The incidence of HIV-related lymphomas (HRLs) is increased by 60-100 times in patients with HIV. When compared to the general population, patients with HRLs often present with extranodal lymphoid proliferation, most frequently of the gastrointestinal tract, central nervous system, liver and bone marrow. MicroRNAs (miRs) are non-coding double-stranded RNA molecules of 18-25 nucleotides that regulate post-translational gene expression by inhibiting translation or promoting degradation of messenger RNA complementary sequences. Before their discovery, tumorigenesis was thought to have been caused by the alteration of protein-coding oncogenes and tumor-suppressor genes, but once identified in B-cell chronic lymphocytic leukemia, miRs function as either oncogenes or tumor-suppressor genes was confirmed in different types of malignancies. Since miRs are clearly involved in tumorigenesis in many cancers, their role in HRLs is now receiving attention. A few studies have been conducted thus far in some HRLs on the involvement of miR in the pathogenesis of lymphoid malignancies. Since B-cell lymphomas arise from various stages of B-cell development in both HIV-infected and HIV-naïve patients, investigators have tried to determine the different miR signatures in B-cell development. As classic immunohistochemistry staining is sometimes not enough for the differential diagnosis of HRLs, in the present review, we have described the potential use of miRs in the prognosis and diagnosis of these diseases.