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Case Report: Sequential Development of Three Mature Lymphoid Neoplasms in a Single Patient: Clonal Relationship and Molecular Insights

Two main variants of Richter syndrome (RS) are recognized, namely, the diffuse large B-cell lymphoma (DLBCL) and the Hodgkin’s lymphoma (HL) variant. Clonal relationship, defined as an identity of the immunoglobulin heavy chain variable (IGHV) region sequence between chronic lymphocytic leukemia (CL...

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Autores principales: Salvetti, Chiara, Vitale, Candida, Griggio, Valentina, Drandi, Daniela, Jones, Rebecca, Bonello, Lisa, Bomben, Riccardo, Bragoni, Alberto, Bagnara, Davide, Fais, Franco, Gattei, Valter, Cavallo, Federica, Zamò, Alberto, Coscia, Marta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207196/
https://www.ncbi.nlm.nih.gov/pubmed/35734588
http://dx.doi.org/10.3389/fonc.2022.917115
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author Salvetti, Chiara
Vitale, Candida
Griggio, Valentina
Drandi, Daniela
Jones, Rebecca
Bonello, Lisa
Bomben, Riccardo
Bragoni, Alberto
Bagnara, Davide
Fais, Franco
Gattei, Valter
Cavallo, Federica
Zamò, Alberto
Coscia, Marta
author_facet Salvetti, Chiara
Vitale, Candida
Griggio, Valentina
Drandi, Daniela
Jones, Rebecca
Bonello, Lisa
Bomben, Riccardo
Bragoni, Alberto
Bagnara, Davide
Fais, Franco
Gattei, Valter
Cavallo, Federica
Zamò, Alberto
Coscia, Marta
author_sort Salvetti, Chiara
collection PubMed
description Two main variants of Richter syndrome (RS) are recognized, namely, the diffuse large B-cell lymphoma (DLBCL) and the Hodgkin’s lymphoma (HL) variant. Clonal relationship, defined as an identity of the immunoglobulin heavy chain variable (IGHV) region sequence between chronic lymphocytic leukemia (CLL) and RS clones, characterizes patients with a poor prognosis. Due to method sensitivity, this categorization is performed without considering the possibility of small-size ancillary clones, sharing the same phenotype with the preexisting predominant CLL clone, but with different IGHV rearrangements. Here we describe and molecularly profile the peculiar case of a patient with a CLL-like monoclonal B-cell lymphocytosis (MBL), who sequentially developed a DLBCL, which occurred concomitantly to progression of MBL to CLL, and a subsequent HL. Based on standard IGHV clonality analysis, DLBCL was considered clonally unrelated to the concomitantly expanded CLL clone and treated as a de novo lymphoma, achieving a persistent response. Three years later, the patient further developed a clonally unrelated HL, refractory to bendamustine, which was successfully treated with brentuximab vedotin and radiotherapy, and later with pembrolizumab. We retrospectively performed additional molecular testing, by applying next-generation sequencing (NGS) of immunoglobulin repertoire (Ig-rep) techniques and a more sensitive allele-specific oligonucleotide-droplet digital PCR (ASO-ddPCR) strategy, in order to quantitatively investigate the presence of the rearranged IGHV genes in tumor specimens collected during the disease course. In this highly complex case, the application of modern and sensitive molecular technologies uncovered that DLBCL, initially considered as a de novo lymphoma, was instead the result of the transformation of a preexisting ancillary B-cell clone, which was already present at the time of first MBL diagnosis. A similar approach was also applied on the HL sample, showing its clonal unrelatedness to the previous MBL and DLBCL.
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spelling pubmed-92071962022-06-21 Case Report: Sequential Development of Three Mature Lymphoid Neoplasms in a Single Patient: Clonal Relationship and Molecular Insights Salvetti, Chiara Vitale, Candida Griggio, Valentina Drandi, Daniela Jones, Rebecca Bonello, Lisa Bomben, Riccardo Bragoni, Alberto Bagnara, Davide Fais, Franco Gattei, Valter Cavallo, Federica Zamò, Alberto Coscia, Marta Front Oncol Oncology Two main variants of Richter syndrome (RS) are recognized, namely, the diffuse large B-cell lymphoma (DLBCL) and the Hodgkin’s lymphoma (HL) variant. Clonal relationship, defined as an identity of the immunoglobulin heavy chain variable (IGHV) region sequence between chronic lymphocytic leukemia (CLL) and RS clones, characterizes patients with a poor prognosis. Due to method sensitivity, this categorization is performed without considering the possibility of small-size ancillary clones, sharing the same phenotype with the preexisting predominant CLL clone, but with different IGHV rearrangements. Here we describe and molecularly profile the peculiar case of a patient with a CLL-like monoclonal B-cell lymphocytosis (MBL), who sequentially developed a DLBCL, which occurred concomitantly to progression of MBL to CLL, and a subsequent HL. Based on standard IGHV clonality analysis, DLBCL was considered clonally unrelated to the concomitantly expanded CLL clone and treated as a de novo lymphoma, achieving a persistent response. Three years later, the patient further developed a clonally unrelated HL, refractory to bendamustine, which was successfully treated with brentuximab vedotin and radiotherapy, and later with pembrolizumab. We retrospectively performed additional molecular testing, by applying next-generation sequencing (NGS) of immunoglobulin repertoire (Ig-rep) techniques and a more sensitive allele-specific oligonucleotide-droplet digital PCR (ASO-ddPCR) strategy, in order to quantitatively investigate the presence of the rearranged IGHV genes in tumor specimens collected during the disease course. In this highly complex case, the application of modern and sensitive molecular technologies uncovered that DLBCL, initially considered as a de novo lymphoma, was instead the result of the transformation of a preexisting ancillary B-cell clone, which was already present at the time of first MBL diagnosis. A similar approach was also applied on the HL sample, showing its clonal unrelatedness to the previous MBL and DLBCL. Frontiers Media S.A. 2022-06-06 /pmc/articles/PMC9207196/ /pubmed/35734588 http://dx.doi.org/10.3389/fonc.2022.917115 Text en Copyright © 2022 Salvetti, Vitale, Griggio, Drandi, Jones, Bonello, Bomben, Bragoni, Bagnara, Fais, Gattei, Cavallo, Zamò and Coscia https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Salvetti, Chiara
Vitale, Candida
Griggio, Valentina
Drandi, Daniela
Jones, Rebecca
Bonello, Lisa
Bomben, Riccardo
Bragoni, Alberto
Bagnara, Davide
Fais, Franco
Gattei, Valter
Cavallo, Federica
Zamò, Alberto
Coscia, Marta
Case Report: Sequential Development of Three Mature Lymphoid Neoplasms in a Single Patient: Clonal Relationship and Molecular Insights
title Case Report: Sequential Development of Three Mature Lymphoid Neoplasms in a Single Patient: Clonal Relationship and Molecular Insights
title_full Case Report: Sequential Development of Three Mature Lymphoid Neoplasms in a Single Patient: Clonal Relationship and Molecular Insights
title_fullStr Case Report: Sequential Development of Three Mature Lymphoid Neoplasms in a Single Patient: Clonal Relationship and Molecular Insights
title_full_unstemmed Case Report: Sequential Development of Three Mature Lymphoid Neoplasms in a Single Patient: Clonal Relationship and Molecular Insights
title_short Case Report: Sequential Development of Three Mature Lymphoid Neoplasms in a Single Patient: Clonal Relationship and Molecular Insights
title_sort case report: sequential development of three mature lymphoid neoplasms in a single patient: clonal relationship and molecular insights
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207196/
https://www.ncbi.nlm.nih.gov/pubmed/35734588
http://dx.doi.org/10.3389/fonc.2022.917115
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