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Targeted mutational profiling of Epstein Barr virus-positive mucocutaneous ulcer: Implications for differential diagnosis with EBV-positive diffuse large B-cell lymphoma
Epstein Barr Virus-positive mucocutaneous ulcer (EBVMCU) can be difficult to distinguish from EBV-positive diffuse large B cell lymphoma (DLBCL). We used targeted next-generation sequencing (NGS) to explore genetic alterations in EBVMCU to aid in this diagnostic challenge. Ten cases of EBVMCU were e...
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Published in: | Annals of diagnostic pathology 2024-12, Vol.73, p.152344, Article 152344 |
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description | Epstein Barr Virus-positive mucocutaneous ulcer (EBVMCU) can be difficult to distinguish from EBV-positive diffuse large B cell lymphoma (DLBCL). We used targeted next-generation sequencing (NGS) to explore genetic alterations in EBVMCU to aid in this diagnostic challenge. Ten cases of EBVMCU were evaluated by a targeted NGS panel of 164 genes. Targeted NGS identified 18 variants in 15 genes in eight cases of EBVMCU. Loss of function TET2 variants were most frequently identified (3 of 10 cases, 30 %). One TET2 variant occurred at low variant allele frequency (VAF) of 3 %, which may be suggestive of clonal hematopoiesis of indeterminate potential. One case harbored a loss of function DNMT3A variant at low VAF. Two cases demonstrated missense variants in the IRF8 gene. Both variants occurred at a VAF close to 50 % and with an estimated high burden of disease (75 %). Two cases of mucosal gastrointestinal involvement had no reportable variants. Mutational profiling of EBVMCU identified TET2 loss of function variants at an elevated frequency in our cohort; however, the findings are not specific and its clinical significance cannot be completely elucidated. Further studies are needed to confirm the findings in an independent and larger cohort of EBVMCU, to determine the cell of origin of the variants, and to further assess their significance in the pathogenesis of this disorder.
•EBVMCU shares histologic and immunophenotypic features with aggressive lymphomas.•Mutational profiling of EBVMCU showed TET2 and DNMT3A loss of function in a subset.•The significance of the variants identified in EBVMCU requires further study. |
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•EBVMCU shares histologic and immunophenotypic features with aggressive lymphomas.•Mutational profiling of EBVMCU showed TET2 and DNMT3A loss of function in a subset.•The significance of the variants identified in EBVMCU requires further study.</description><identifier>ISSN: 1092-9134</identifier><identifier>ISSN: 1532-8198</identifier><identifier>EISSN: 1532-8198</identifier><identifier>DOI: 10.1016/j.anndiagpath.2024.152344</identifier><identifier>PMID: 38820910</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Diagnosis, Differential ; Diffuse large B-cell lymphoma ; Dioxygenases ; DNA Mutational Analysis - methods ; DNA-Binding Proteins ; Epstein-Barr Virus ; Epstein-Barr Virus Infections - complications ; Epstein-Barr Virus Infections - diagnosis ; Epstein-Barr Virus Infections - genetics ; Epstein-Barr Virus Infections - virology ; Female ; Herpesvirus 4, Human - genetics ; Herpesvirus 4, Human - isolation & purification ; High-Throughput Nucleotide Sequencing - methods ; Humans ; Immune deficiency ; Lymphoma, Large B-Cell, Diffuse - diagnosis ; Lymphoma, Large B-Cell, Diffuse - genetics ; Lymphoma, Large B-Cell, Diffuse - pathology ; Lymphoma, Large B-Cell, Diffuse - virology ; Male ; Middle Aged ; Mucocutaneous ulcer ; Mutation ; Mutation profiling ; Next-generation sequencing ; Ulcer - diagnosis ; Ulcer - genetics ; Ulcer - pathology ; Ulcer - virology</subject><ispartof>Annals of diagnostic pathology, 2024-12, Vol.73, p.152344, Article 152344</ispartof><rights>2024 Elsevier Inc.</rights><rights>Copyright © 2024 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c251t-fb6f5d78e51a2703753d1b0d09c22d1a0dcdd1a709366a9e9ebaa9f9399e85533</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38820910$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Volaric, Ashley K.</creatorcontrib><creatorcontrib>Kumar, Jyoti</creatorcontrib><creatorcontrib>Nicholas, Veronica</creatorcontrib><creatorcontrib>Saleem, Atif</creatorcontrib><creatorcontrib>Fernandez-Pol, Sebastian</creatorcontrib><creatorcontrib>Suarez, Carlos J.</creatorcontrib><creatorcontrib>Natkunam, Yasodha</creatorcontrib><title>Targeted mutational profiling of Epstein Barr virus-positive mucocutaneous ulcer: Implications for differential diagnosis with EBV-positive diffuse large B-cell lymphoma</title><title>Annals of diagnostic pathology</title><addtitle>Ann Diagn Pathol</addtitle><description>Epstein Barr Virus-positive mucocutaneous ulcer (EBVMCU) can be difficult to distinguish from EBV-positive diffuse large B cell lymphoma (DLBCL). We used targeted next-generation sequencing (NGS) to explore genetic alterations in EBVMCU to aid in this diagnostic challenge. Ten cases of EBVMCU were evaluated by a targeted NGS panel of 164 genes. Targeted NGS identified 18 variants in 15 genes in eight cases of EBVMCU. Loss of function TET2 variants were most frequently identified (3 of 10 cases, 30 %). One TET2 variant occurred at low variant allele frequency (VAF) of 3 %, which may be suggestive of clonal hematopoiesis of indeterminate potential. One case harbored a loss of function DNMT3A variant at low VAF. Two cases demonstrated missense variants in the IRF8 gene. Both variants occurred at a VAF close to 50 % and with an estimated high burden of disease (75 %). Two cases of mucosal gastrointestinal involvement had no reportable variants. Mutational profiling of EBVMCU identified TET2 loss of function variants at an elevated frequency in our cohort; however, the findings are not specific and its clinical significance cannot be completely elucidated. Further studies are needed to confirm the findings in an independent and larger cohort of EBVMCU, to determine the cell of origin of the variants, and to further assess their significance in the pathogenesis of this disorder.
•EBVMCU shares histologic and immunophenotypic features with aggressive lymphomas.•Mutational profiling of EBVMCU showed TET2 and DNMT3A loss of function in a subset.•The significance of the variants identified in EBVMCU requires further study.</description><subject>Adult</subject><subject>Aged</subject><subject>Diagnosis, Differential</subject><subject>Diffuse large B-cell lymphoma</subject><subject>Dioxygenases</subject><subject>DNA Mutational Analysis - methods</subject><subject>DNA-Binding Proteins</subject><subject>Epstein-Barr Virus</subject><subject>Epstein-Barr Virus Infections - complications</subject><subject>Epstein-Barr Virus Infections - diagnosis</subject><subject>Epstein-Barr Virus Infections - genetics</subject><subject>Epstein-Barr Virus Infections - virology</subject><subject>Female</subject><subject>Herpesvirus 4, Human - genetics</subject><subject>Herpesvirus 4, Human - isolation & purification</subject><subject>High-Throughput Nucleotide Sequencing - methods</subject><subject>Humans</subject><subject>Immune deficiency</subject><subject>Lymphoma, Large B-Cell, Diffuse - diagnosis</subject><subject>Lymphoma, Large B-Cell, Diffuse - genetics</subject><subject>Lymphoma, Large B-Cell, Diffuse - pathology</subject><subject>Lymphoma, Large B-Cell, Diffuse - virology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mucocutaneous ulcer</subject><subject>Mutation</subject><subject>Mutation profiling</subject><subject>Next-generation sequencing</subject><subject>Ulcer - diagnosis</subject><subject>Ulcer - genetics</subject><subject>Ulcer - pathology</subject><subject>Ulcer - virology</subject><issn>1092-9134</issn><issn>1532-8198</issn><issn>1532-8198</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqNkUtv1DAUhSMEoi_-AjI7Nhn8yMvsmNFAK1XqpnRreezrGY-cONjOVP1J_EscUh7Lrq4X5zv3XJ-i-EDwimDSfDqu5DBoK_ejTIcVxbRakZqyqnpVnJOa0bIjvHud35jTkhNWnRUXMR4xJqSq27fFGes6ijnB58XPexn2kECjfkoyWT9Ih8bgjXV22CNv0HaMCeyA1jIEdLJhiuXoo032BJlRXmVuAD9FNDkF4TO66Udn1W-viIwPSFtjIMCQbPaeYw-Zj-jRpgParh_-2c3CKQJycya0LhU4h9xTPx58L6-KN0a6CO-e52Xx_ev2fnNd3t59u9l8uS0VrUkqza4xtW47qImkLWZtzTTZYY25olQTibXSebSYs6aRHDjspOSGM86hq2vGLouPi2_-hR8TxCR6G-cky5WC4YZVDesanKV8kargYwxgxBhsL8OTIFjMTYmj-K8pMTcllqYy-_55zbTrQf8l_1STBZtFAPnYk4UgorIwKNA2gEpCe_uCNb8AOf-vbQ</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Volaric, Ashley K.</creator><creator>Kumar, Jyoti</creator><creator>Nicholas, Veronica</creator><creator>Saleem, Atif</creator><creator>Fernandez-Pol, Sebastian</creator><creator>Suarez, Carlos J.</creator><creator>Natkunam, Yasodha</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202412</creationdate><title>Targeted mutational profiling of Epstein Barr virus-positive mucocutaneous ulcer: Implications for differential diagnosis with EBV-positive diffuse large B-cell lymphoma</title><author>Volaric, Ashley K. ; Kumar, Jyoti ; Nicholas, Veronica ; Saleem, Atif ; Fernandez-Pol, Sebastian ; Suarez, Carlos J. ; Natkunam, Yasodha</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c251t-fb6f5d78e51a2703753d1b0d09c22d1a0dcdd1a709366a9e9ebaa9f9399e85533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Diagnosis, Differential</topic><topic>Diffuse large B-cell lymphoma</topic><topic>Dioxygenases</topic><topic>DNA Mutational Analysis - methods</topic><topic>DNA-Binding Proteins</topic><topic>Epstein-Barr Virus</topic><topic>Epstein-Barr Virus Infections - complications</topic><topic>Epstein-Barr Virus Infections - diagnosis</topic><topic>Epstein-Barr Virus Infections - genetics</topic><topic>Epstein-Barr Virus Infections - virology</topic><topic>Female</topic><topic>Herpesvirus 4, Human - genetics</topic><topic>Herpesvirus 4, Human - isolation & purification</topic><topic>High-Throughput Nucleotide Sequencing - methods</topic><topic>Humans</topic><topic>Immune deficiency</topic><topic>Lymphoma, Large B-Cell, Diffuse - diagnosis</topic><topic>Lymphoma, Large B-Cell, Diffuse - genetics</topic><topic>Lymphoma, Large B-Cell, Diffuse - pathology</topic><topic>Lymphoma, Large B-Cell, Diffuse - virology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mucocutaneous ulcer</topic><topic>Mutation</topic><topic>Mutation profiling</topic><topic>Next-generation sequencing</topic><topic>Ulcer - diagnosis</topic><topic>Ulcer - genetics</topic><topic>Ulcer - pathology</topic><topic>Ulcer - virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Volaric, Ashley K.</creatorcontrib><creatorcontrib>Kumar, Jyoti</creatorcontrib><creatorcontrib>Nicholas, Veronica</creatorcontrib><creatorcontrib>Saleem, Atif</creatorcontrib><creatorcontrib>Fernandez-Pol, Sebastian</creatorcontrib><creatorcontrib>Suarez, Carlos J.</creatorcontrib><creatorcontrib>Natkunam, Yasodha</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of diagnostic pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Volaric, Ashley K.</au><au>Kumar, Jyoti</au><au>Nicholas, Veronica</au><au>Saleem, Atif</au><au>Fernandez-Pol, Sebastian</au><au>Suarez, Carlos J.</au><au>Natkunam, Yasodha</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeted mutational profiling of Epstein Barr virus-positive mucocutaneous ulcer: Implications for differential diagnosis with EBV-positive diffuse large B-cell lymphoma</atitle><jtitle>Annals of diagnostic pathology</jtitle><addtitle>Ann Diagn Pathol</addtitle><date>2024-12</date><risdate>2024</risdate><volume>73</volume><spage>152344</spage><pages>152344-</pages><artnum>152344</artnum><issn>1092-9134</issn><issn>1532-8198</issn><eissn>1532-8198</eissn><abstract>Epstein Barr Virus-positive mucocutaneous ulcer (EBVMCU) can be difficult to distinguish from EBV-positive diffuse large B cell lymphoma (DLBCL). We used targeted next-generation sequencing (NGS) to explore genetic alterations in EBVMCU to aid in this diagnostic challenge. Ten cases of EBVMCU were evaluated by a targeted NGS panel of 164 genes. Targeted NGS identified 18 variants in 15 genes in eight cases of EBVMCU. Loss of function TET2 variants were most frequently identified (3 of 10 cases, 30 %). One TET2 variant occurred at low variant allele frequency (VAF) of 3 %, which may be suggestive of clonal hematopoiesis of indeterminate potential. One case harbored a loss of function DNMT3A variant at low VAF. Two cases demonstrated missense variants in the IRF8 gene. Both variants occurred at a VAF close to 50 % and with an estimated high burden of disease (75 %). Two cases of mucosal gastrointestinal involvement had no reportable variants. Mutational profiling of EBVMCU identified TET2 loss of function variants at an elevated frequency in our cohort; however, the findings are not specific and its clinical significance cannot be completely elucidated. Further studies are needed to confirm the findings in an independent and larger cohort of EBVMCU, to determine the cell of origin of the variants, and to further assess their significance in the pathogenesis of this disorder.
•EBVMCU shares histologic and immunophenotypic features with aggressive lymphomas.•Mutational profiling of EBVMCU showed TET2 and DNMT3A loss of function in a subset.•The significance of the variants identified in EBVMCU requires further study.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>38820910</pmid><doi>10.1016/j.anndiagpath.2024.152344</doi></addata></record> |
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subjects | Adult Aged Diagnosis, Differential Diffuse large B-cell lymphoma Dioxygenases DNA Mutational Analysis - methods DNA-Binding Proteins Epstein-Barr Virus Epstein-Barr Virus Infections - complications Epstein-Barr Virus Infections - diagnosis Epstein-Barr Virus Infections - genetics Epstein-Barr Virus Infections - virology Female Herpesvirus 4, Human - genetics Herpesvirus 4, Human - isolation & purification High-Throughput Nucleotide Sequencing - methods Humans Immune deficiency Lymphoma, Large B-Cell, Diffuse - diagnosis Lymphoma, Large B-Cell, Diffuse - genetics Lymphoma, Large B-Cell, Diffuse - pathology Lymphoma, Large B-Cell, Diffuse - virology Male Middle Aged Mucocutaneous ulcer Mutation Mutation profiling Next-generation sequencing Ulcer - diagnosis Ulcer - genetics Ulcer - pathology Ulcer - virology |
title | Targeted mutational profiling of Epstein Barr virus-positive mucocutaneous ulcer: Implications for differential diagnosis with EBV-positive diffuse large B-cell lymphoma |
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