HHV8/KSHV-Positive Lymphoproliferative Disorders and the Spectrum of Plasmablastic and Plasma Cell Neoplasms

Chadburn, Amy; Said, Jonathan; Gratzinger, Dita; Chan, John K. C.; Jong, Daphne de; Jaffe, Elaine S.; Natkunam, Yasodha; Goodlad, John R.

doi:10.1093/ajcp/aqw218

Cited by 75 publications

(67 citation statements)

References 93 publications

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“…The relationship of PBL with diffuse large B‐cell lymphoma (DLBCL) showing terminal plasma cell differentiation and extramedullary plasma cell tumours (PCTs) remains a diagnostic challenge. Reports have described similarities in clinical presentation, morphological appearances, and immunophenotypes; however, this distinction is significant, because the different entities vary in clinical course, prognosis, and management requirements . The presence of EBV‐encoded RNA significantly favours a PBL diagnosis (50–75%), although studies have shown that both immunocompetent and immunocompromised individuals may develop EBV‐driven extramedullary PCTs and DLBCLs .…”

Section: Introductionmentioning

confidence: 99%

“…Reports have described similarities in clinical presentation, morphological appearances, and immunophenotypes; however, this distinction is significant, because the different entities vary in clinical course, prognosis, and management requirements. [8][9][10] The presence of EBV-encoded RNA significantly favours a PBL diagnosis (50-75%), although studies have shown that both immunocompetent and immunocompromised individuals may develop EBV-driven extramedullary PCTs and DLBCLs. 11,12 However, these tumours are restricted to single case reports and small series, are usually well differentiated, and are not truly plasmablastic.…”

Section: Introductionmentioning

confidence: 99%

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Extraoral plasmablastic lymphomas in a high human immunodeficiency virus endemic area

et al. 2019

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Aims Plasmablastic lymphoma (PBL) occurs mainly in immunocompromised individuals, usually secondary to human immunodeficiency virus (HIV) infection. It classically occurs intraorally, but has been described in extraoral locations. The aim of this study was to define the immunophenotype and Epstein–Barr virus (EBV) status in a large single‐centre cohort of extraoral PBL (EPBL) in South Africa, a high‐prevalence HIV setting. Methods and results This retrospective study of 45 EPBLs included patients' age, gender, race, HIV status, and site. Cases were reviewed histologically, and classified morphologically as pure plasmablastic or plasmablastic with plasmacytic differentiation, and assessed immunohistochemically with antibodies against CD45, CD20, CD79a, PAX5, CD138, MUM1/IRF4, BLIMP1, VS38c, Ki67, bcl‐6, CD10, cyclin D1, and human herpesvirus‐8, by the use of standard automated procedures. EBV was assessed by the use of chromogenic in‐situ hybridisation. Tumours were assessed with a fluorescence in‐situ hybridisation (FISH) MYC break‐apart probe. Twenty‐seven PBLs showed pure plasmablastic morphology, and 18 showed plasmacytic differentiation. The male/female ratio was 1.5:1. The anus was the favoured extraoral site (31.1%), followed by lymph nodes (15.6%). All 29 patients with known HIV status were HIV‐positive. The immunohistochemical profile recapitulated that reported for oral PBLs and EPBLs in HIV‐positive and HIV‐negative patients. EBV was positive in 92.5% of PBLs. FISH analysis showed MYC rearrangement in 48% of cases. Conclusion This study showed a strong association of EPBLs with HIV and EBV infection, similarly to the previously described oral PBL. The strong EBV association together with other clinicopathological parameters and an immunohistochemical profile that includes CD45, CD20, MUM1/IRF4, CD138 and Ki67 may be used in distinguishing PBL from diffuse large B‐cell lymphoma and plasma cell myeloma.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Extraoral plasmablastic lymphomas in a high human immunodeficiency virus endemic area

et al. 2019

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“…Primary effusion lymphoma and germinotropic LPD are two entities that show concurrent HHV8 and EBV infection. Both are rare, especially germinotropic LPD, as only a few cases were described in the literature . In this study, we report two cases of HHV8 + , EBV + lymphoma that show unique clinicopathological features, expanding the spectrum of HHV8 + /EBV + LPD.…”

Section: Discussionmentioning

confidence: 81%

“…Both are rare, especially germinotropic LPD, as only a few cases were described in the literature. 3,[19][20][21][22][23][24][25][26] In this study, we report two cases of HHV8 + , EBV + lymphoma that show unique clinicopathological features, expanding the spectrum of HHV8 + /EBV + LPD. Of note, although both patients had no history of HIV or other immunosuppression, given the patients' age immunosenescence may have played a role in disease development.…”

Section: A S Ementioning

confidence: 99%

Lymphoproliferative disorders with concurrent HHV8 and EBV infection: beyond primary effusion lymphoma and germinotropic lymphoproliferative disorder

2018

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“…In latently KSHV infected B cells, BCR activation can trigger XBP1s-dependent lytic reactivation [132]. Since PEL cells have a plasmablast-like phenotype [133], further differentiation into PCs may increase XBP1s transactivation of RTA, leading to reactivation from latency and escape of the virus from a terminally-differentiated non-replicating host cell type. Conversely, KSHV may actively repress XBP1s activity to maintain tight control of latency, which may halt the differentiation process at a pre-plasma cell differentiation stage.…”

Section: Gammaherpesviruses and The Uprmentioning

confidence: 99%

Herpesviruses and the Unfolded Protein Response

Johnston

McCormick

2019

Viruses

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Herpesviruses usurp cellular stress responses to promote viral replication and avoid immune surveillance. The unfolded protein response (UPR) is a conserved stress response that is activated when the protein load in the ER exceeds folding capacity and misfolded proteins accumulate. The UPR aims to restore protein homeostasis through translational and transcriptional reprogramming; if homeostasis cannot be restored, the UPR switches from "helper" to "executioner", triggering apoptosis. It is thought that the burst of herpesvirus glycoprotein synthesis during lytic replication causes ER stress, and that these viruses may have evolved mechanisms to manage UPR signaling to create an optimal niche for replication. The past decade has seen considerable progress in understanding how herpesviruses reprogram the UPR. Here we provide an overview of the molecular events of UPR activation, signaling and transcriptional outputs, and highlight key evidence that herpesviruses hijack the UPR to aid infection.

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HHV8/KSHV-Positive Lymphoproliferative Disorders and the Spectrum of Plasmablastic and Plasma Cell Neoplasms

Cited by 75 publications

References 93 publications

Extraoral plasmablastic lymphomas in a high human immunodeficiency virus endemic area

Extraoral plasmablastic lymphomas in a high human immunodeficiency virus endemic area

Lymphoproliferative disorders with concurrent HHV8 and EBV infection: beyond primary effusion lymphoma and germinotropic lymphoproliferative disorder

Herpesviruses and the Unfolded Protein Response

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