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...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.917115/full |
| _version_ | 1811244537753894912 |
|---|---|
| author | Chiara Salvetti Chiara Salvetti Candida Vitale Candida Vitale Valentina Griggio Daniela Drandi Rebecca Jones Lisa Bonello Lisa Bonello Riccardo Bomben Alberto Bragoni Davide Bagnara Franco Fais Franco Fais Valter Gattei Federica Cavallo Federica Cavallo Alberto Zamò Marta Coscia Marta Coscia |
| author_facet | Chiara Salvetti Chiara Salvetti Candida Vitale Candida Vitale Valentina Griggio Daniela Drandi Rebecca Jones Lisa Bonello Lisa Bonello Riccardo Bomben Alberto Bragoni Davide Bagnara Franco Fais Franco Fais Valter Gattei Federica Cavallo Federica Cavallo Alberto Zamò Marta Coscia Marta Coscia |
| author_sort | Chiara Salvetti |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T14:27:01Z |
| format | Article |
| id | doaj.art-d6713a2ace5046119295bf31f8366cdd |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T14:27:01Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-d6713a2ace5046119295bf31f8366cdd2022-12-22T03:29:25ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.917115917115Case Report: Sequential Development of Three Mature Lymphoid Neoplasms in a Single Patient: Clonal Relationship and Molecular InsightsChiara Salvetti0Chiara Salvetti1Candida Vitale2Candida Vitale3Valentina Griggio4Daniela Drandi5Rebecca Jones6Lisa Bonello7Lisa Bonello8Riccardo Bomben9Alberto Bragoni10Davide Bagnara11Franco Fais12Franco Fais13Valter Gattei14Federica Cavallo15Federica Cavallo16Alberto Zamò17Marta Coscia18Marta Coscia19Division of Hematology, University of Torino, A.O.U. Città della Salute e della Scienza di Torino, Torino, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Torino, ItalyDivision of Hematology, University of Torino, A.O.U. Città della Salute e della Scienza di Torino, Torino, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Torino, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Torino, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Torino, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Torino, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Torino, ItalyMolecular Pathology Unit, A.O.U. Città della Salute e della Scienza di Torino, Torino, ItalyClinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, IRCCS, Aviano, ItalyPathology Unit, Department of Medical Sciences, University of Torino, Torino, ItalyDepartment of Experimental Medicine, University of Genova, Genova, ItalyDepartment of Experimental Medicine, University of Genova, Genova, ItalyU.O. Molecular Pathology, I.R.C.C.S. Policlinico San Martino, Genova, ItalyClinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, IRCCS, Aviano, ItalyDivision of Hematology, University of Torino, A.O.U. Città della Salute e della Scienza di Torino, Torino, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Torino, ItalyInstitute of Pathology, University of Würzburg, Würzburg, GermanyDivision of Hematology, University of Torino, A.O.U. Città della Salute e della Scienza di Torino, Torino, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Torino, ItalyTwo 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.917115/fullRichter’s syndromechronic lymphocytic leukemiamonoclonal B-cell lymphocytosisIGHV genesHodgkin lymphoma |
| spellingShingle | Chiara Salvetti Chiara Salvetti Candida Vitale Candida Vitale Valentina Griggio Daniela Drandi Rebecca Jones Lisa Bonello Lisa Bonello Riccardo Bomben Alberto Bragoni Davide Bagnara Franco Fais Franco Fais Valter Gattei Federica Cavallo Federica Cavallo Alberto Zamò Marta Coscia Marta Coscia Case Report: Sequential Development of Three Mature Lymphoid Neoplasms in a Single Patient: Clonal Relationship and Molecular Insights Frontiers in Oncology Richter’s syndrome chronic lymphocytic leukemia monoclonal B-cell lymphocytosis IGHV genes Hodgkin lymphoma |
| 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 | Richter’s syndrome chronic lymphocytic leukemia monoclonal B-cell lymphocytosis IGHV genes Hodgkin lymphoma |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.917115/full |
| work_keys_str_mv | AT chiarasalvetti casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT chiarasalvetti casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT candidavitale casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT candidavitale casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT valentinagriggio casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT danieladrandi casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT rebeccajones casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT lisabonello casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT lisabonello casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT riccardobomben casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT albertobragoni casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT davidebagnara casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT francofais casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT francofais casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT valtergattei casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT federicacavallo casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT federicacavallo casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT albertozamo casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT martacoscia casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights AT martacoscia casereportsequentialdevelopmentofthreematurelymphoidneoplasmsinasinglepatientclonalrelationshipandmolecularinsights |