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1.
Kaposi's sarcoma (KS) is an angioproliferative disease particularly frequent and aggressive in patients with AIDS but occurring also in post-transplant patients or in immunocompetent individuals of certain geographic areas. At least in its early stages, KS behaves as a reactive hyperplastic process mediated by inflammatory cytokines and angiogenic factors triggered or exacerbated by human herpesvirus-8 (HHV-8) infection. The HIV Tat protein appears to be responsible for the highly aggressive nature of AIDS-KS. Over time, however, KS may evolve into a true sarcoma in association with the expression of oncogenes and/or HHV-8 latency genes endowed with growth and anti-apoptotic properties. HHV-8 infection is also associated with primary effusion lymphoma (PEL), a rare tumor that similarly develops more frequently in the setting of HIV infection. HHV-8 latency genes are likely to contribute to the neoplastic phenotype of PEL cells, whose growth in vivo may require cytokines and factors from the host, or encoded by the virus.  相似文献   

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Oral Kaposi's sarcoma (OKS) from Tanzanian patients (78) at Muhimbili National Hospital/Muhimbili University College of Health Sciences corresponding to approximately 10% of KS registered during 1990-2005, were diagnosed (ELISA) as HIV-infected (OAKS) (74/78) and endemic KS (4/78). Females were 69.2% (54/78) with median age 31 and males 30.8% (24/78) with median age 38. More males (50%) had systemic KS than females (37%) and 4-times more multicentric OKS. All tested (34) oral KS patients sera had HHV-8 antibodies. Available (31/78) blood showed very low CD4+ T-lymphocyte counts. Most OKS (61.5%) had nodular histology. Immunostaining showed adult male nodular OAKS to have a significantly higher frequency of viral LANA+, endothelial CD34+ tumour spindle-cells (SC) and more Ki-67+ (median =24.1%) proliferating cells compared to females (17.2%). Juvenile nodular OAKS had more LANA+ and Ki-67+ cells than corresponding adult cases. Significantly more LANA+ and Ki-67+ cells were found in nodular OAKS compared to cutaneous HIV/AIDS Kaposi's sarcoma (CAKS). A positive correlation (60%) was found between the proliferation index (Ki-67+ cell frequency) and LANA+/CD34+ SC. OKS in Tanzania is since 1990, mostly seen in females, associated with HIV/AIDS and advanced (nodular) histopathology. Males have more systemic tumour burden while more females develop primary OAKS. HHV-8+ cells were more frequent in nodular male than female and in juvenile than adult nodular OAKS than cAKS. Higher tumoral HHV-8 content appeared to be correlated to proliferation index.  相似文献   

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Primary effusion lymphoma (PEL) is a unique clinicopathological entity usually associated with human herpesvirus-8 (HHV-8) infection. It occurs almost exclusively in human immunodeficiency virus (HIV) -infected individuals. We presented a rare case of HIV-negative PEL in an elderly HHV-8-negative patient who developed cardiac tamponade due to pericardial effusion. The patient was treated with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). This disease generally has a poor prognosis; however, this patient achieved complete remission and remains without signs of disease 30 months after the last treatment. Because most HIV-negative and HHV-8- negative PEL cases show pan-B-cell markers, there is considerable usage of rituximab, though its optimal usage for PEL is unclear. To the best of our knowledge, there have been five reported cases where rituximab treatment has been used against HIV-negative and HHV-8-negative PEL. The clinical courses of these cases were relatively good without specific adverse effects. HIV-negative and HHV-8-negative PEL appears to be a reasonably new clinicopathological entity. While further investigation will of course be needed, the use of rituximab is worth considering for treatment of such patients.  相似文献   

5.
Deep immunosuppression and Epstein-Barr virus (EBV) infection promote the emergence of lymphoproliferative disorders in patients undergoing solid organ transplantation. In the last few years a new herpesvirus, named human herpesvirus-8 (HHV-8), has been identified in Kaposi's sarcoma and primary effusion lymphoma (PEL) developing in AIDS patients. Subsequently, the same viral DNA sequences have been identified in almost all cases of Kaposi's sarcoma emerged outside HIV infection, thus suggesting their possible pathogenetic role in this tumor. Similarly, the association between HHV-8 and PEL also emerged in cases without HIV infection, even though the total number of these patients is still limited. Here, we focus on the emergence of this unusual lymphoma in patients undergoing solid organ transplant and underline once again its association with the HHV-8. Moreover, despite the characteristic local growth of this peculiar type of lymphoma, we demonstrate at the molecular level, an early neoplastic spread to the bone marrow suggesting the need to investigate in more detail the origin of the disease, as well as the molecular mechanisms controlling its systemic dissemination.  相似文献   

6.
Primary effusion lymphoma (PEL) is a newly described high-grade B cell lymphoma which develops in association with Kaposi's sarcoma-associated herpesvirus (KSV) in human immunodeficiency virus (HIV)-infected individuals. We hereby describe a very unusual presentation of PEL that developed in the abdominal cavity of an HIV negative, KSV negative patient with a 1-year history of refractory ascites due to alcohol-related liver cirrhosis. Possible factors aiding lymphomagenesis in the cirrhotic state are discussed.  相似文献   

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Human herpesvirus 8 (HHV8) is the etiologic agent for primary effusion lymphoma (PEL). The aim of this study is to investigate the effects of cisplatin on the PEL cells. Cisplatin treatment induced apoptosis and inhibited the growth of PEL cells, and the effect was more profound in the HHV8-positive lymphoma cells compared with the EBV-positive lymphoma cells. Cisplatin treatment decreased the expression of HHV8 latent genes and activated p53 at serine 15 in PEL cells. Our results indicate that cisplatin can disrupt HHV8 latency and induce reactivation of p53 and highly selective treatment modality for this virally induced lymphoma.  相似文献   

10.
Primary effusion lymphoma (PEL) is an unusual class of non-Hodgkin's lymphoma, which is characterised by lymphomatous effusions in body cavities, but no associated mass lesions. It is usually associated with an immunodeficient state most often with the human immunodeficiency virus (HIV). We describe a case of a man with HIV-negative, human-herpes-virus-8 (HHV8)-negative PEL, with a history of heavy alcohol intake. The abdominal cavity was the only area involved; no solid tumour masses were observed on scanning, and the bone-marrow investigations were normal. The ascites contained numerous pleomorphic lymphoid, lymphoplasmacytoid cells of B-cell origin. The immunophenotyping was moderately positive for CD 38 and 138, and strongly positive for Ki 67. It is postulated that the immunosuppressed state in this patient may have been caused by the long history of heavy alcohol intake.  相似文献   

11.
Human herpesvirus 8 (HHV-8 or Kaposi's sarcoma herpesvirus) is a gamma herpesvirus that is most likely the etiologic agent of both Kaposi's sarcoma and primary effusion lymphoma (PEL), a rare HIV-associated lymphoma. The role of HHV-8 in post-transplant lymphoma is less well characterized. We demonstrate that HHV-8 is constitutively present in LH5-21 cells, an atypical patient derived posttransplant PEL cell line. LH5-21 cells lack detectable Epstein-Barr virus, express T cell-associated surface markers and have undergone immunoglobulin heavy chain gene rearrangement. Incubation with 12-O-tetradecanoyl-phorbol- 13-acetate or butyrate induces high levels of several HHV-8 encoded genes that are associated with lytic replication. The patient from whom this cell line was derived demonstrated a dramatic clinical response to withdrawal of immunosuppressive therapy. While HHV-8 associated PELs in the post-transplant setting are rare, this study suggests that improvement in the host immunologic function might help in the management of some PELs.  相似文献   

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In order to establish if immunologic alterations seen in acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma are also present in the primary form of this malignancy, peripheral blood T-lymphocyte characterization and HLA A, B, C, and DR phenotyping have been carried out in 18 patients with the primary form of the disease. HLA antigen distribution was not significantly different from that of the normal population and, in particular, DR5 was only marginally increased. The T4/T8 ratio was significantly higher in the patients than in the control group, and this was due to a marked decrease in suppressor cells. The possible pathogenetic relevance of these findings is discussed.  相似文献   

14.
PURPOSE: Primary effusion lymphoma (PEL) is a rare high-grade B-cell non-Hodgkin's lymphoma associated with Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) infection, and is mostly observed in the course of HIV infection. The prognosis is poor, with reported median survival time shorter than 6 months. To date, no prognostic factor has been identified in this subset of lymphoma. PATIENTS AND METHODS: We describe here a large series of HIV-infected patients with PEL, including 28 cases diagnosed in six centers during an 11-year time period. Prognosis analysis was performed using a Cox proportional hazard regression model. Statistically significant covariates were further analyzed in a forward, stepwise multivariate model. RESULTS: After a median follow-up of 3.8 years (range, 10 months to 10.8 years), nine patients (32%) were still alive, and eight of them remained progression free. The median survival was 6.2 months, and the 1-year overall survival rate was 39.3%. Fourteen patients (50%) achieved complete remission, with a 1-year disease-free survival rate at 78.6%. In a multivariate analysis, only a performance status more than 2 (hazard ratio, 5.84; 95% CI, 1.76 to 19.33) and the absence of highly active antiretroviral therapy (HAART) before PEL diagnosis (hazard ratio, 3.26; 95% CI, 1.14 to 9.34) were found to be independent predictors for shorter survival. CONCLUSION: Based on a retrospective series of 28 patients, two prognostic factors were identified as being independently associated with impaired clinical outcome in HIV-related PEL--(1) a poor performance status and (2) the absence of HAART before PEL diagnosis.  相似文献   

15.
Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, has been implicated in the pathogenesis of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease, and recently multiple myeloma (MM). DNA sequence analyses of HHV-8 suggest that multiple HHV-8 strains exist. We extracted DNA from 24 patients with MM and 3 patients with monoclonal gammopathy of undetermined significance and compared HHV-8 open reading frames (ORFs) 26 and 65 sequences with those derived from patients with KS, PEL, and two HHV-8-positive PEL cell lines KS-1 and BC-1. ORF26 sequence data suggest that MM patients are consistently carriers of HHV-8 strain subtype C3. All MM patients also consistently revealed either a single bp deletion or substitution at position 112197 in ORF65. This unique alteration is not present in patients with KS or PEL or in PEL cell lines. It occurs in the portion of ORF65 that is known to be responsible for a serological response to HHV-8.  相似文献   

16.
The presence and distribution of Epstein-Barr virus (EBV), as well as human herpesvirus-6 and-8 (HHV-6 and HHV-8) was investigated by polymerase chain reaction in 191 samples from a variety of lymphoproliferative disorders. HHV-6 DNA was detected in 18% (30 of 169) of non-HHV-8 related lymphoproliferative disorders, with the highest frequency in AIDS-related lymphomas (8 of 25, 32%). In contrast, HHV-6 DNA was present in less than 5% (1 of 22) of HHV-8 related lymphoproliferative disorders [21 primary effusion lymphomas (PEL), and 1 cases of Castleman disease]. As compared to HHV-6, EBV DNA was frequently detected in PEL (11 of 19 samples, 58%). This study suggests that transformation to PEL is not enhanced by HHV-6, furthermore HHV-6 and -8 may interfere with each other.  相似文献   

17.
We linked records of 83,434 AIDS cases reported to AIDS registries through 1990 to cancer registry records during times when overlap in registration existed. Of 8,496 Kaposi's-sarcoma (KS) cases meeting enrollment criteria, 1,045 occurred semesters 2 through 4 (6 through 23 months) after another AIDS-defining illness. KS risk in this period after AIDS declined steadily over the 1980s. Adjusting for age, gender, ethnic origin and calendar time period, we found the relative risk (RR) of KS to be 106,000 for homo/bisexual men with AIDS and 13,000 for other men with AIDS. Risk was highest for homo/bisexual men between 30 and 39 years old and among 20- to 29-year-old non-homo/bisexual men. The RR in black men was approximately half that reported in white men among homo-bisexual men and others. Between the second and fourth semester after AIDS, the ratio of RR of KS to that of non-AIDS-related cancers increased 1.5-fold. In a similar analysis, there were 335 non-Hodgkin's lymphoma (NHL) cases in semesters 2 through 4 after AIDS. The overall risk was elevated 283-fold in homo/bisexual men and the RR ratio increased 1.8-fold between semester 2 and 4 after AIDS. In summary, the risk of KS following another AlDS-defining illness is strikingly high, more in white men than in black men, and the risks of KS and, especially, NHL appear to increase with time from AIDS. (This article is a US Government work and, as such, is in the public domain in the United States of America.) © 1996 Wiley-Liss, Inc.  相似文献   

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Primary effusion lymphoma (PEL) is a novel lymphoma entity consistently infected by HHV-8 that occurs predominantly in immunodeficient patients and is characterized by liquid growth in the serous body cavities. In order to facilitate the understanding of PEL pathogenesis and histogenesis, we have established three PEL cell lines termed CRO-AP/2, CRO-AP/3 and CRO-AP/5. All cell lines have been derived from HIV positive homosexual men affected by PEL with (in the case of CRO-AP/2 and CRO-AP/5) or without (in the case of CRO-AP/3) a previous history of Kaposi's sarcoma. The cell lines are representative of both virologic variants of PEL, i.e. HHV-8+ EBV+ PEL (CRO-AP/2 and CRO-AP/5) and HHV-8+ EBV- PEL (CRO-AP/3). Morphologic and phenotypic features of CRO-AP/2, CRO-AP/3 and CRO-AP/5 are typical of PEL, and include morphology bridging immunoblastic and anaplastic features as well as an indeterminate (non B- non T-cell) phenotype. The B-cell nature of the cell lines is documented by the presence of rearranged immunoglobulin genes. The detailed analysis of the molecular and phenotypic features of CRO-AP/2, CRO-AP/3 and CRO-AP/5 has allowed the identification of recurrent chromosomal abnormalities of PEL and has contributed to the definition of PEL as a lymphoma of post-germinal center, pre-terminally differentiated B-cells.  相似文献   

20.
Prior to the AIDS epidemic, Kaposi's sarcoma (non-AIDS-KS) in Europe was mainly a disease of elderly Mediterranean men. In 1989 AIDS data from 15 European countries were collected to study proportional trends in AIDS-related Kaposi's sarcoma (AIDS-KS) in order to determine whether specific factors in Southern Europe might be important in the development of KS among AIDS patients. Another AIDS-related cancer, non-Hodgkin's lymphoma (NHL) was included as a malignancy control. Of 22,367 AIDS cases reported, 3,779 (16.9%) were KS and 741 (3.3%) were NHL. A significant, continuous fall in the percentage of AIDS-KS was seen for both homosexual men and other members of exposure groups during the period 1981-89 (p-trend less than 0.0001). The proportion with AIDS-KS decreased from 40.5% in 1983 to 26.5% in 1988 in homosexual men and from 12.2 to 3.6% in other exposure groups, respectively. No significant change was observed in the proportion of NHL cases among any of the risk groups over time, although a tendency towards a slight increase was noted for homosexual men. Comparing proportional trends of KS and NHL geographically, no significant difference was found overall, by time or by exposure group. In conclusion, a specific decline is observed over time for AIDS-KS. However, if geographically-restricted factors are important in the development of non-AIDS-KS in Europe, the same factors do not appear to affect the risk of AIDS-KS.  相似文献   

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