Kaposi sarcoma-associated herpesvirus infects monotypic (IgMlambda) but polyclonal naive B cells in Castleman disease and associated lymphoproliferative disorders

Du, Ming‐Qing; Liu, Hongxiang; Diss, Tim C.; Ye, Hongtao; Hamoudi, Rifat; Dupin, Nicolas; Meignin, Véronique; Oksenhendler, Éric; Boshoff, Chris; Isaacson, Peter G.

doi:10.1182/blood.v97.7.2130

Cited by 340 publications

(294 citation statements)

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“…5 Except for germinotropic lymphoproliferative disorder the majority of these disorders arise in HIV-positive patients. 2,3,6 We report two cases of HHV8-positive lymphoproliferative disorders with pathologic features not previously described. One case occurred in an immunocompetent adult male and had histologic, but not immunophenotypic, features reminiscent of classical Hodgkin's lymphoma, and concurrent infection of neoplastic cells by HHV8 and Epstein-Barr virus (EBV).…”

mentioning

confidence: 72%

“…4,6 Primary effusion lymphoma is a distinctive type of diffuse large B cell initially recognized in HIVpositive patients, characterized by occurrence in a body cavity unassociated with a contiguous solid mass, immunophenotypic and genetic features corresponding to a late postgerminal center B cell in most cases, 2,7-12 a distinctive gene expression profile 13,14 and a poor prognosis. 2,7,8,12,15 Tumor cells are usually coinfected by EBV, a g herpesvirus closely related to HHV8 (Tables 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

“…4 In some cases, plasmablasts proliferate to replace whole follicles (plasmablastic microlymphoma) or grow diffusely (frank plasmablastic lymphoma). 4,6 In the WHO classification, those plasmablastic proliferations that are monoclonal, including the frank plasmablastic lymphomas and a subset of the microlymphomas, are called large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease (Tables 1 and 2). 16 Almost as soon as these associations were established, additional cases of HHV8-associated lymphoproliferative disorders were identified that deviated from the patterns already recognized.…”

Section: Discussionmentioning

confidence: 99%

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HHV8-positive, EBV-positive Hodgkin lymphoma-like large B-cell lymphoma and HHV8-positive intravascular large B-cell lymphoma

et al. 2009

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confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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HHV8-positive, EBV-positive Hodgkin lymphoma-like large B-cell lymphoma and HHV8-positive intravascular large B-cell lymphoma

et al. 2009

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“…Monotypic (IgM/k) LANA-positive lymphoid cells (found in Cases 1, 4 and 5) evoke the plasmablasts of uncertain malignant capacity of MCD in lymphoid organs, 6 and therefore, these pseudo-PEL cases might represent the liquid-phase counterpart of MCD. On the other hand, the effusion with rare non-B/non-T, LANA/CD68R-positive mononuclear cells and a prevalent inflammatory-type reaction (Case 3) is reminiscent of tissue-based early KS lesions, 19 and therefore, it might represent the effusional form of KS.…”

Section: Dear Sirmentioning

confidence: 99%

“…The hyperplastic/poly-oligoclonal vs. neoplastic/monoclonal nature of KS and MCD has been extensively discussed, but monoclonality has been clearly demonstrated in at least a fraction of individual lesions. [4][5][6] On the other hand, while the true neoplastic nature of PEL and its monoclonal origin are wellrecognized, the question whether PEL begins as a polyclonal proliferation of HHV-8-infected lymphoid cells with a subsequent evolution to a monoclonal proliferation remains to be clarified. This point is of interest for diagnostic purposes and for PEL pathogenesis implications, including the role of HHV-8 as lymphomagenic agent.…”

Section: Dear Sirmentioning

confidence: 99%

Kaposi's sarcoma‐associated herpesvirus/human herpesvirus 8‐associated polyclonal body cavity effusions that mimic primary effusion lymphomas

Ascoli

Calabrò

Giannakakis

et al. 2006

Intl Journal of Cancer

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Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) is involved in the pathogenesis of Kaposi's sarcoma (KS) and 2 lymphoproliferative diseases, primary effusion lymphoma (PEL) and the plasmablastic variant of multicentric Castleman's disease (MCD). PEL is defined as a liquid-phase lymphoma harboring monoclonal rearrangements of immunoglobulin (Ig) variable genes or, more rarely, of T-cell receptor (TCR) genes. As a rule, these elements are used for PEL diagnosis together with the demonstration of HHV-8 infection of the tumor clone. We report here a group of five patients with MCD and KS (n = 2) or MCD only (n = 2) or KS only (n = 1); subjects with KS showed cutaneous and visceral involvement. All 5 patients developed recurrent and massive HHV-8-positive body cavity effusions, often in multiple sites, and died shortly after diagnosis. Cytological examination of effusion specimens disclosed the absence of lymphoma cells in all cases. In the context of MCD or MCD and KS, the effusion cell population was found to include 5–30% of atypical lymphoid cells with plasmacytic features and reminiscent of PEL. Our observations suggest that patients with MCD and/or KS (not exclusively in association with HIV infection) may develop recurrent HHV-8-positive body cavity effusions other than PEL, although with a similar poor outcome. Their common morphologic and molecular features appear to identify a nonlymphomatous entity. The identification of HHV-8 in polyclonal effusions that mimic PEL is notable in light of the association between HHV-8 and PEL, and suggests a putative model of PEL lymphomagenesis

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An Abnormal Neck Mass in a Pediatric Patient

Boochoon

Barbieri

Mohyuddin

2020

JAMA Otolaryngol Head Neck Surg

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A 17-year-old white male patient was referred to the otolaryngology clinic with a 6-month history of a left-sided neck mass. His primary care physician initially obtained an ultrasonographic image, which demonstrated a left, level 2 lymph node measuring 4.0 × 1.5 × 2.8 cm. The patient then underwent several courses of antibiotic treatment, but the mass persisted. After a period of conservative management, he developed a sore throat and fever. He subsequently underwent a computed tomographic scan of the neck and chest with contrast, which demonstrated an isolated, enlarged, homogenously enhancing left-neck level 2B lymph node measuring 3.4 × 2.8 × 2.1 cm (Figure 1A). When he presented to our facility, he was found to have an asymptomatically enlarged left level 2/5A neck mass that was nontender and fixed. The patient had an unremarkable medical, surgical, and social history and no known infectious exposures. A white blood cell count and C-reactive protein level were both elevated, at 11 310 cells/μL (to convert to cells × 10 9 per liter, multiply by 0.001) and 56.2 mg/L (to convert to nanomoles per liter, multiply by 9.524), respectively. Studies for influenza A and B, HIV, cytomegalovirus, American foulbrood, Bartonella henselae, infectious mononucleosis, and Epstein-Barr virus had negative results. An ultrasonographyguided needle biopsy was performed. Fine-needle aspiration and flow cytometry had negative results for lymphoproliferative disorders or a malignant condition. A tissue culture had negative results. Given the inconclusive diagnosis, the patient underwent a left neck dissection of levels 2A, 2B, and 5A. Intraoperative frozen sections did not show a malignant process. On final analysis, a pathologic examination of the largest lymph node was performed (Figure 1B). Diagnosis D. Castleman disease DiscussionCastleman disease (CD) is an uncommon, lymphoproliferative dis-

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Kaposi sarcoma-associated herpesvirus infects monotypic (IgMlambda) but polyclonal naive B cells in Castleman disease and associated lymphoproliferative disorders

Abstract: In a previous study, it was shown that the Kaposi sarcoma-associated herpesvirus (KSHV) was specifically associated with monotypic (IgM) plasmablasts in multicentric Castleman disease (

Cited by 340 publications

References 45 publications

HHV8-positive, EBV-positive Hodgkin lymphoma-like large B-cell lymphoma and HHV8-positive intravascular large B-cell lymphoma

HHV8-positive, EBV-positive Hodgkin lymphoma-like large B-cell lymphoma and HHV8-positive intravascular large B-cell lymphoma

Kaposi's sarcoma‐associated herpesvirus/human herpesvirus 8‐associated polyclonal body cavity effusions that mimic primary effusion lymphomas

An Abnormal Neck Mass in a Pediatric Patient

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