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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
Main Authors: Volaric, Ashley K., Kumar, Jyoti, Nicholas, Veronica, Saleem, Atif, Fernandez-Pol, Sebastian, Suarez, Carlos J., Natkunam, Yasodha
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Suarez, Carlos J.
Natkunam, Yasodha
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.
doi_str_mv 10.1016/j.anndiagpath.2024.152344
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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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