Human herpesvirus 8-unrelated primary effusion lymphoma-like lymphoma that developed during myelodysplastic syndrome

Abstract We describe a case of an 87-year-old human immunodeficiency virus (HIV)–negative man who developed a primary pleural lymphoma without any identifiable tumor mass associated with human herpesvirus 8 (HHV-8) infection. A large T-cell lymphoma was diagnosed based on morphologic, immunophenotypic, and molecular findings. The HHV-8 DNA sequences were detected using specific polymerase chain reaction amplification in the lymphomatous effusion. Study of the patient's serum confirmed the HHV-8 infection. This case report displays the characteristic features of HHV-8–related body cavity-based lymphoma/primary effusion lymphoma previously reported in HIV-seronegative patients, except that it is of T-cell origin. Whether this case may be included or not within the primary effusion lymphoma entity, the association of a pleural T-cell non-Hodgkin lymphoma with HHV-8 infection raises the question of the possible occurrence of T cells as the target of malignant transformation associated with HHV-8 infection.

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Human herpesvirus-8-unrelated primary effusion lymphoma of the elderly not associated with an increased serum lactate dehydrogenase level: A benign sub-group of effusion lymphoma without chemotherapy

Leukemia & Lymphoma ◽

10.3109/10428194.2015.1088649 ◽

2016 ◽

Vol 57 (7) ◽

pp. 1625-1632 ◽

Cited By ~ 2

Author(s):

Yoshitaka Zaimoku ◽

Wakana Takahashi ◽

Noriko Iwaki ◽

Chizuru Saito ◽

Akiyo Yoshida ◽

...

Keyword(s):

Lactate Dehydrogenase ◽

Primary Effusion Lymphoma ◽

Human Herpesvirus ◽

Lactate Dehydrogenase Level ◽

The Elderly ◽

Serum Lactate ◽

Human Herpesvirus 8 ◽

Serum Lactate Dehydrogenase ◽

Herpesvirus 8 ◽

Serum Lactate Dehydrogenase Level

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A Systems Biology Approach To Identify the Combination Effects of Human Herpesvirus 8 Genes on NF-κB Activation

Journal of Virology ◽

10.1128/jvi.01512-08 ◽

2009 ◽

Vol 83 (6) ◽

pp. 2563-2574 ◽

Cited By ~ 38

Author(s):

Andreas Konrad ◽

Effi Wies ◽

Mathias Thurau ◽

Gaby Marquardt ◽

Elisabeth Naschberger ◽

...

Keyword(s):

Systems Biology ◽

Primary Effusion Lymphoma ◽

Human Herpesvirus ◽

Etiologic Agent ◽

Lytic Replication ◽

Fine Tuning ◽

Human Herpesvirus 8 ◽

Systematic Analysis ◽

Herpesvirus 8 ◽

Infected Cells

ABSTRACT Human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi's sarcoma and primary effusion lymphoma. Activation of the cellular transcription factor nuclear factor-kappa B (NF-κB) is essential for latent persistence of HHV-8, survival of HHV-8-infected cells, and disease progression. We used reverse-transfected cell microarrays (RTCM) as an unbiased systems biology approach to systematically analyze the effects of HHV-8 genes on the NF-κB signaling pathway. All HHV-8 genes individually (n = 86) and, additionally, all K and latent genes in pairwise combinations (n = 231) were investigated. Statistical analyses of more than 14,000 transfections identified ORF75 as a novel and confirmed K13 as a known HHV-8 activator of NF-κB. K13 and ORF75 showed cooperative NF-κB activation. Small interfering RNA-mediated knockdown of ORF75 expression demonstrated that this gene contributes significantly to NF-κB activation in HHV-8-infected cells. Furthermore, our approach confirmed K10.5 as an NF-κB inhibitor and newly identified K1 as an inhibitor of both K13- and ORF75-mediated NF-κB activation. All results obtained with RTCM were confirmed with classical transfection experiments. Our work describes the first successful application of RTCM for the systematic analysis of pathofunctions of genes of an infectious agent. With this approach, ORF75 and K1 were identified as novel HHV-8 regulatory molecules on the NF-κB signal transduction pathway. The genes identified may be involved in fine-tuning of the balance between latency and lytic replication, since this depends critically on the state of NF-κB activity.

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Prognostic Factors and Outcome of Human Herpesvirus 8–Associated Primary Effusion Lymphoma in Patients With AIDS

Journal of Clinical Oncology ◽

10.1200/jco.2005.07.084 ◽

2005 ◽

Vol 23 (19) ◽

pp. 4372-4380 ◽

Cited By ~ 200

Author(s):

Emmanuelle Boulanger ◽

Laurence Gérard ◽

Jean Gabarre ◽

Jean-Michel Molina ◽

Christophe Rapp ◽

...

Keyword(s):

Prognostic Factors ◽

Survival Rate ◽

Median Survival ◽

Primary Effusion Lymphoma ◽

Performance Status ◽

Human Herpesvirus ◽

Disease Free Survival ◽

Hazard Ratio ◽

Human Herpesvirus 8 ◽

Herpesvirus 8

PurposePrimary 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 MethodsWe 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.ResultsAfter 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.ConclusionBased 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.

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Human herpesvirus 8‐related primary effusion lymphoma in four HIV‐uninfected patients without organ transplantation

Respirology Case Reports ◽

10.1002/rcr2.508 ◽

2019 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

Hung‐I Kuo ◽

Yu‐Ting Yu ◽

Kung‐Chao Chang ◽

Po‐Lan Su ◽

Sin‐Syue Li ◽

...

Keyword(s):

Organ Transplantation ◽

Primary Effusion Lymphoma ◽

Human Herpesvirus ◽

Human Herpesvirus 8 ◽

Herpesvirus 8

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Differential Expression of Viral Bcl-2 Encoded by Kaposi's Sarcoma-Associated Herpesvirus and Human Bcl-2 in Primary Effusion Lymphoma Cells and Kaposi's Sarcoma Lesions

Journal of Virology ◽

10.1128/jvi.76.5.2551-2556.2002 ◽

2002 ◽

Vol 76 (5) ◽

pp. 2551-2556 ◽

Cited By ~ 23

Author(s):

Isabelle Widmer ◽

Marion Wernli ◽

Felix Bachmann ◽

Fred Gudat ◽

Gieri Cathomas ◽

...

Keyword(s):

Kaposi's Sarcoma ◽

Mononuclear Cells ◽

Primary Effusion Lymphoma ◽

Human Herpesvirus ◽

Kaposi’S Sarcoma ◽

Human Herpesvirus 8 ◽

Lymphoma Cells ◽

Herpesvirus 8 ◽

Primary Effusion Lymphoma Cell ◽

Spindle Cells

ABSTRACT Expression of human herpesvirus 8 viral Bcl-2 protein was demonstrated in spindle cells of late-stage Kaposi's sarcoma lesions but not in primary effusion lymphoma cell lines. In contrast, strong expression of human Bcl-2 was found in stimulated primary effusion lymphoma cells, whereas in Kaposi's sarcoma lesions preferential mononuclear cells, and to a lesser extent spindle cells, stained positive.

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Primary Effusion Lymphoma: Cytopathologic Diagnosis Using In Situ Molecular Genetic Analysis for Human Herpesvirus 8

Modern Pathology ◽

10.1038/modpathol.3880635 ◽

2002 ◽

Vol 15 (9) ◽

pp. 944-950 ◽

Cited By ~ 32

Author(s):

Paul E Wakely ◽

Geetha Menezes ◽

Gerard J Nuovo

Keyword(s):

Genetic Analysis ◽

Primary Effusion Lymphoma ◽

Molecular Genetic ◽

Human Herpesvirus ◽

Molecular Genetic Analysis ◽

Human Herpesvirus 8 ◽

Herpesvirus 8

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Clinicopathological characteristics compared between primary effusion lymphoma and human herpesvirus 8 (HHV8)-unrelated primary effusion lymphoma-like lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e19024 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e19024-e19024

Author(s):

Junghoon Shin ◽

Youngil Koh

Keyword(s):

Primary Effusion Lymphoma ◽

Human Herpesvirus ◽

B Cell Lymphoma ◽

Clinicopathological Characteristics ◽

Small Sample ◽

Human Herpesvirus 8 ◽

Vitreous Fluid ◽

Female Ratio ◽

Herpesvirus 8 ◽

Significant Difference

e19024 Background: Primary effusion lymphoma (PEL) and human herpesvirus 8 (HHV8)-unrelated primary effusion lymphoma-like lymphoma (PEL-LL) are among the most rare subtypes of non-Hodgkin B-cell lymphoma. Although a few number of case reports and small case series have suggested a better outcome of PEL-LL compared to PEL, systematic comparison of prognosis between PEL and PEL-LL has never been conducted owing to their rare incidence. Methods: We consecutively collected PEL and PEL-LL patients diagnosed between 2000 and 2016 in 10 institutions in South Korea. All patients were cytogically confirmed and received systemic evaluation to exclude detectable tumor formation. Clinicopathological characteristics and prognosis were compared. Results: A total of 12 PEL and 4 PEL-LL cases were analyzed. Median age at diagnosis was 68.5 (range, 40-88) and 68.5 (range, 59-77) for PEL and PEL-LL, respectively. Male-to-female ratio was 7:5 and 3:1 in each group. Pleural effusion was the most common presentation in both groups. One patient in PEL-LL group presented with vitreous fluid containing lymphoma cells. Seven and two PEL patients were treated with CHOP and CVP-based chemotherapy, respectively and 3 did not receive chemotherapy due to poor performance. Three PEL-LL patients were treated with R-CHOP and the remaining 1 patient with malignant vitreous fluid received high dose methotrexate. One PEL patient received autologous hematopoietic stem cell transplantation after second remission and lived over 14 years thereafter. With estimated median follow-up duration of 99.6 and 20.7 months for PEL and PEL-LL respectively, 3 and 1 death occurred during the entire period in each group. Median overall survival was 119.6 and 66.5 months in PEL and PEL-LL group respectively without statistically significant difference. Conclusions: In our study, long-term prognosis of PEL and PEL-LL showed no difference. This result might be attributed to 2 remarkably long-lived patients in PEL group (longer than 174 and 123 months, respectively) and low statistical power owing to the small sample size.

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