Evidence map›Paper›PMID 32483241›Full record

ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2020

Frequent traces of EBV infection in Hodgkin and non-Hodgkin lymphomas classified as EBV-negative by routine methods: expanding the landscape of EBV-related lymphomas.

Lucia Mundo, Leonardo Del Porro, Massimo Granai, Maria Chiara Siciliano, Virginia Mancini, Raffaella Santi, Lynnette Marcar, Katerina Vrzalikova, Federica Vergoni, Gioia Di Stefano and 11 more

Erratum issuedOpen access · hybridAbstract readMulticenter Study
In one paragraph

Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
3.8field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 71 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 7 institutions in 5 countries.

Lucia MundoSection of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy.
Leonardo Del PorroSection of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy.
Massimo GranaiSection of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy.
Maria Chiara SicilianoSection of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy.
Virginia ManciniSection of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy.
Raffaella SantiSection of Pathology, University of Florence, Florence, Italy.
Lynnette MarcarBioMaterials Cluster, Bernal Institute, University of Limerick, Limerick, Ireland.
Katerina VrzalikovaInstitute of immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
Federica VergoniSection of Pathology, University of Florence, Florence, Italy.
Gioia Di StefanoSection of Pathology, University of Florence, Florence, Italy.
Gianluca SchiavoniSection of Haematology and Clinical Immunology, Department of Medicine, University and Hospital of Perugia, Perugia, Italy.
Giovanna SegretoSection of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy.
Noel OnyangoDepartment of Clinical Medicine and Therapeutics, Unit of Medical Oncology, University of Nairobi, Nairobi, Kenya.
Joshua Akelo NyagolDepartment of Clinical Medicine and Therapeutics, Unit of Medical Oncology, University of Nairobi, Nairobi, Kenya.
Teresa AmatoSection of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy.
Cristiana BellanSection of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy.
Ioannis AnagnostopoulosDepartment of Anatomical Pathology, University of Charité Berlin, Berlin, Germany.
Brunangelo FaliniSection of Haematology and Clinical Immunology, Department of Medicine, University and Hospital of Perugia, Perugia, Italy.
Lorenzo LeonciniSection of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy.
Enrico Tiacci *Section of Haematology and Clinical Immunology, Department of Medicine, University and Hospital of Perugia, Perugia, Italy. enrico.tiacci@unipg.it.
Stefano Lazzi *Section of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy. lazzi2@unisi.it.
University of Siena · ITUniversity of Florence · ITUniversity of Perugia · ITUniversity of Nairobi · KECharité - Universitätsmedizin Berlin · DEUniversity of Birmingham · GBUniversity of Limerick · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Epstein-Barr virus (EBV) is linked to various B-cell lymphomas, including Burkitt lymphoma (BL), classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) at frequencies ranging, by routine techniques, from 5 to 10% of cases in DLBCL to >95% in endemic BL. Using higher-sensitivity methods, we recently detected EBV traces in a few EBV-negative BL cases, possibly suggesting a "hit-and-run" mechanism. Here, we used routine and higher-sensitivity methods (qPCR and ddPCR for conserved EBV genomic regions and miRNAs on microdissected tumor cells; EBNA1 mRNA In situ detection by RNAscope) to assess EBV infection in a larger lymphoma cohort [19 BL, 34 DLBCL, 44 cHL, 50 follicular lymphomas (FL), 10 T-lymphoblastic lymphomas (T-LL), 20 hairy cell leukemias (HCL), 10 mantle cell lymphomas (MCL)], as well as in several lymphoma cell lines (9 cHL and 6 BL). qPCR, ddPCR, and RNAscope consistently documented the presence of multiple EBV nucleic acids in rare tumor cells of several cases EBV-negative by conventional methods that all belonged to lymphoma entities clearly related to EBV (BL, 6/9 cases; cHL, 16/32 cases; DLBCL, 11/30 cases), in contrast to fewer cases (3/47 cases) of FL (where the role of EBV is more elusive) and no cases (0/40) of control lymphomas unrelated to EBV (HCL, T-LL, MCL). Similarly, we revealed traces of EBV infection in 4/5 BL and 6/7 HL cell lines otherwise conventionally classified as EBV negative. Interestingly, additional EBV-positive cases (1 DLBCL, 2 cHL) relapsed as EBV-negative by routine methods while showing EBNA1 expression in rare tumor cells by RNAscope. The relapse specimens were clonally identical to their onset biopsies, indicating that the lymphoma clone can largely loose the EBV genome over time but traces of EBV infection are still detectable by high-sensitivity methods. We suggest EBV may contribute to lymphoma pathogenesis more widely than currently acknowledged.

Indexed as

Epstein-Barr Virus InfectionsEpstein-Barr Virus Nuclear AntigensHerpesvirus 4, HumanHodgkin DiseaseHumansItalyLymphoma, Non-HodgkinMolecular Diagnostic TechniquesRNA, MessengerRNA, ViralU937 CellsViral LoadEBV-encoded nuclear antigen 1Epstein-Barr Virus Nuclear AntigensRNA, MessengerRNA, Viral

Identifiers

PMID32483241
PMCPMC7685982
OpenAlexW3032800433

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.