KSHV- and EBV-associated germinotropic lymphoproliferative disorder: A rare lymphoproliferative disease of HIV patient with plasmablastic morphology, indolent course and favourable response to therapy

D’Antonio, Antonio; Boscaino, Amedeo; Addesso, Maria; Piris, Miguel Á.; Nappi, Oscar

doi:10.1080/10428190701387039

Cited by 24 publications

(16 citation statements)

References 10 publications

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“…Previously, six cases of this rare entity have been described in the literature; Du et al [2] described 3 cases, followed by three case reports with one in a 60-year-old male [3], the other in a 49-year-old African American male [4], and the last being successful management in a 75-year-old male [5] (Table 1). We report two additional cases of KSHV-and EBV- associated lymphoproliferative disorder characterized by KSHV and EBV co-infected plasmablasts preferentially involving the germinal centers.…”

Section: Introductionmentioning

confidence: 99%

KSHV-associated and EBV-associated Germinotropic Lymphoproliferative Disorder

Bhavsar

Lee

Perner

et al. 2017

American Journal of Surgical Pathology

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We report two cases of Kaposi sarcoma associated herpesvirus (KSHV) - and Epstein Barr Virus (EBV)-associated germinotropic lymphoproliferative disorder (GLPD). Both cases arose in patients from regions endemic for KSHV, Cape Verde and the Democratic Republic of the Congo, presenting as localized lymphadenopathy. The affected lymph nodes showed colonization of the follicles by clusters of large atypical plasmablasts, but also showed regressive changes with vascular proliferation and interfollicular plasmacytosis, both reminiscent of HHV8-positive multicentric Castleman disease (MCD). The atypical plasmablasts showed dual positivity for HHV-8 and EBV, being positive for LANA and viral IL-6, as well as EBER by in-situ hybridization. They showed a Latency I phenotype, being negative for LMP1, EBNA2 and BZLF-1. The plasmablasts were negative for immunoglobulin light chains, and in one case with successful DNA amplification had a polyclonal immunoglobulin rearrangement pattern. GLPD is a rare disorder, with only 6 cases reported in the literature. We demonstrate for the first time the expression of HHV-8 viral IL-6 and provide evidence for Latency I phenotype for EBV. Additionally, one case progressed to an EBV-positive diffuse large B-cell lymphoma, but interestingly was negative for KSHV/HHV-8, likely indicative of tumor derived from an independent clone.

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Section: Introductionmentioning

confidence: 99%

KSHV-associated and EBV-associated Germinotropic Lymphoproliferative Disorder

Bhavsar

Lee

Perner

et al. 2017

American Journal of Surgical Pathology

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“…Epstein-Barr virus (EBV) is tightly associated with the development of several human malignancies, including nasopharyngeal carcinoma, Hodgkin's lymphoma, Burkitt's lymphoma, and posttransplant lymphoproliferative disease (1). Though both KSHV-and EBV-associated malignancies are rare, their prevalence is elevated in people who are immunocompromised via either immunosuppressive therapies or HIV infection (2)(3)(4).…”

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confidence: 99%

Identification of Alternative Transcripts Encoding the Essential Murine Gammaherpesvirus Lytic Transactivator RTA

Wakeman¹,

Johnson²,

Paden³

et al. 2014

J Virol

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The essential immediate early transcriptional activator RTA, encoded by gene 50, is conserved among all characterized gammaherpesviruses. Analyses of a recombinant murine gammaherpesvirus 68 (MHV68) lacking both of the known gene 50 promoters (G50DblKo) revealed that this mutant retained the ability to replicate in the simian kidney epithelial cell line Vero but not in permissive murine fibroblasts following low-multiplicity infection. However, G50DblKo replication in permissive fibroblasts was partially rescued by high-multiplicity infection. In addition, replication of the G50DblKo virus was rescued by growth on mouse embryonic fibroblasts (MEFs) isolated from IFN-␣/␤R ؊/؊ mice, while growth on Vero cells was suppressed by the addition of alpha interferon (IFN-␣). 5= rapid amplification of cDNA ends (RACE) analyses of RNAs prepared from G50DblKo and wild-type MHV68-infected murine macrophages identified three novel gene 50 transcripts initiating from 2 transcription initiation sites located upstream of the currently defined proximal and distal gene 50 promoters. In transient promoter assays, neither of the newly identified gene 50 promoters exhibited sensitivity to IFN-␣ treatment. Furthermore, in a single-step growth analysis RTA levels were higher at early times postinfection with the G50DblKo mutant than with wild-type virus but ultimately fell below the levels of RTA expressed by wild-type virus at later times in infection. Infection of mice with the MHV68 G50DblKo virus demonstrated that this mutant virus was able to establish latency in the spleen and peritoneal exudate cells (PECs) of C57BL/6 mice with about 1/10 the efficiency of wild-type virus or marker rescue virus. However, despite the ability to establish latency, the G50DblKo virus mutant was severely impaired in its ability to reactivate from either latently infected splenocytes or PECs. Consistent with the ability to rescue replication of the G50DblKo mutant by growth on type I interferon receptor null MEFs, infection of IFN-␣/␤R

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“…Extracavitary PEL has a better median survival of 11 months . Both of our patients are still alive 32 and 50 months after initial diagnosis and probably belong to the sub‐set of PEL patients with relatively favourable outcome . From the clinical point of view case 1 could be regarded as a more conventional manifestation.…”

Section: Discussionmentioning

confidence: 77%