{"title":"血管免疫母细胞型滤泡辅助 T 细胞淋巴瘤患者的克隆性造血和骨髓浸润。","authors":"Lennart Harland , Vanessa Borgmann , Franziska Otto , Mathis Overkamp , Irina Bonzheim , Falko Fend , Leticia Quintanilla-Martinez , Dominik Nann","doi":"10.1016/j.modpat.2024.100519","DOIUrl":null,"url":null,"abstract":"<div><p>Follicular helper T-cell (TFH) lymphoma harbors recurrent mutations of <em>RHOA</em><sup>G17V</sup>, <em>IDH2</em><sup>R172</sup>, <em>TET2</em>, and <em>DNMT3A</em>. <em>TET2</em> and <em>DNMT3A</em> mutations are the most frequently affected genes in clonal hematopoiesis (CH). The aim of our study was to investigate the frequency of CH in bone marrow biopsies (BMB) of TFH/angioimmunoblastic T-cell lymphoma (TFH-AITL) patients and its association with myeloid neoplasms. A total of 29 BMB from 22 patients with a diagnosis of TFH–AITL were analyzed by next-generation sequencing (NGS) with a custom panel. Morphologically, 5 BMB revealed that TFH–AITL infiltrates of >5% of bone marrow (BM) cellularity confirmed in 4 cases by NGS-based T-cell clonality. <em>IDH2</em><sup>R172</sup> was demonstrated only in 1 (3%) of 29, and <em>RHOA</em><sup>G17V</sup> in 2 (7%) of 29 samples. <em>TET2</em> and <em>DNMT3A</em> were identified in 24 (83%) of 29 and 17 (59%) of 29 BMB, respectively. In the parallel lymph node the frequencies of mutations were 27% (<em>IDH2</em><sup>R172</sup>), 64% (<em>RHOA</em><sup>G17V</sup>), 86% (<em>TET2</em>), and 50% (<em>DNMT3A</em>). <em>TET2</em> and/or <em>DNMT3A</em> mutations identical in lymph node and BMB were present in 18 (82%) of 22 patients, regardless of BM infiltration. In 3 cases the CH mutations were detected 13, 41, and 145 months before TFH–AITL diagnosis. Cases with <em>TET2/DNMT3A</em> mutations and BM variant allele frequencies >40% (7/18, 39%) showed lower blood counts. However, only low platelet count was statistically significant (<em>P</em> = .024). Myeloid neoplasms and/or myelodysplastic syndrome-related mutations were identified in 4 cases (4/22; 18%); all with high <em>TET2</em> variant allele frequencies (>40%; <em>P</em> = .0114). In conclusion, CH is present in 82% of TFH–AITL and can be demonstrated up to 145 months before TFH–AITL diagnosis. NGS T-cell clonality analysis is an excellent tool to confirm TFH–AITL BM infiltration. Concurrent myeloid neoplasms were identified in 18% of the cases and were associated with <em>TET2</em> mutations with high allelic burden (>40%). We demonstrated that myeloid neoplasms might occur simultaneously or precede the diagnosis of TFH lymphoma.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1000,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0893395224000991/pdfft?md5=8e7e9df4bc35b4e1648ad9940e77c56a&pid=1-s2.0-S0893395224000991-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Clonal Hematopoiesis and Bone Marrow Infiltration in Patients With Follicular Helper T-Cell Lymphoma of Angioimmunoblastic Type\",\"authors\":\"Lennart Harland , Vanessa Borgmann , Franziska Otto , Mathis Overkamp , Irina Bonzheim , Falko Fend , Leticia Quintanilla-Martinez , Dominik Nann\",\"doi\":\"10.1016/j.modpat.2024.100519\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Follicular helper T-cell (TFH) lymphoma harbors recurrent mutations of <em>RHOA</em><sup>G17V</sup>, <em>IDH2</em><sup>R172</sup>, <em>TET2</em>, and <em>DNMT3A</em>. <em>TET2</em> and <em>DNMT3A</em> mutations are the most frequently affected genes in clonal hematopoiesis (CH). The aim of our study was to investigate the frequency of CH in bone marrow biopsies (BMB) of TFH/angioimmunoblastic T-cell lymphoma (TFH-AITL) patients and its association with myeloid neoplasms. A total of 29 BMB from 22 patients with a diagnosis of TFH–AITL were analyzed by next-generation sequencing (NGS) with a custom panel. Morphologically, 5 BMB revealed that TFH–AITL infiltrates of >5% of bone marrow (BM) cellularity confirmed in 4 cases by NGS-based T-cell clonality. <em>IDH2</em><sup>R172</sup> was demonstrated only in 1 (3%) of 29, and <em>RHOA</em><sup>G17V</sup> in 2 (7%) of 29 samples. <em>TET2</em> and <em>DNMT3A</em> were identified in 24 (83%) of 29 and 17 (59%) of 29 BMB, respectively. In the parallel lymph node the frequencies of mutations were 27% (<em>IDH2</em><sup>R172</sup>), 64% (<em>RHOA</em><sup>G17V</sup>), 86% (<em>TET2</em>), and 50% (<em>DNMT3A</em>). <em>TET2</em> and/or <em>DNMT3A</em> mutations identical in lymph node and BMB were present in 18 (82%) of 22 patients, regardless of BM infiltration. In 3 cases the CH mutations were detected 13, 41, and 145 months before TFH–AITL diagnosis. Cases with <em>TET2/DNMT3A</em> mutations and BM variant allele frequencies >40% (7/18, 39%) showed lower blood counts. However, only low platelet count was statistically significant (<em>P</em> = .024). Myeloid neoplasms and/or myelodysplastic syndrome-related mutations were identified in 4 cases (4/22; 18%); all with high <em>TET2</em> variant allele frequencies (>40%; <em>P</em> = .0114). In conclusion, CH is present in 82% of TFH–AITL and can be demonstrated up to 145 months before TFH–AITL diagnosis. NGS T-cell clonality analysis is an excellent tool to confirm TFH–AITL BM infiltration. Concurrent myeloid neoplasms were identified in 18% of the cases and were associated with <em>TET2</em> mutations with high allelic burden (>40%). We demonstrated that myeloid neoplasms might occur simultaneously or precede the diagnosis of TFH lymphoma.</p></div>\",\"PeriodicalId\":18706,\"journal\":{\"name\":\"Modern Pathology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.1000,\"publicationDate\":\"2024-05-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0893395224000991/pdfft?md5=8e7e9df4bc35b4e1648ad9940e77c56a&pid=1-s2.0-S0893395224000991-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Modern Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0893395224000991\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Modern Pathology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0893395224000991","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
Clonal Hematopoiesis and Bone Marrow Infiltration in Patients With Follicular Helper T-Cell Lymphoma of Angioimmunoblastic Type
Follicular helper T-cell (TFH) lymphoma harbors recurrent mutations of RHOAG17V, IDH2R172, TET2, and DNMT3A. TET2 and DNMT3A mutations are the most frequently affected genes in clonal hematopoiesis (CH). The aim of our study was to investigate the frequency of CH in bone marrow biopsies (BMB) of TFH/angioimmunoblastic T-cell lymphoma (TFH-AITL) patients and its association with myeloid neoplasms. A total of 29 BMB from 22 patients with a diagnosis of TFH–AITL were analyzed by next-generation sequencing (NGS) with a custom panel. Morphologically, 5 BMB revealed that TFH–AITL infiltrates of >5% of bone marrow (BM) cellularity confirmed in 4 cases by NGS-based T-cell clonality. IDH2R172 was demonstrated only in 1 (3%) of 29, and RHOAG17V in 2 (7%) of 29 samples. TET2 and DNMT3A were identified in 24 (83%) of 29 and 17 (59%) of 29 BMB, respectively. In the parallel lymph node the frequencies of mutations were 27% (IDH2R172), 64% (RHOAG17V), 86% (TET2), and 50% (DNMT3A). TET2 and/or DNMT3A mutations identical in lymph node and BMB were present in 18 (82%) of 22 patients, regardless of BM infiltration. In 3 cases the CH mutations were detected 13, 41, and 145 months before TFH–AITL diagnosis. Cases with TET2/DNMT3A mutations and BM variant allele frequencies >40% (7/18, 39%) showed lower blood counts. However, only low platelet count was statistically significant (P = .024). Myeloid neoplasms and/or myelodysplastic syndrome-related mutations were identified in 4 cases (4/22; 18%); all with high TET2 variant allele frequencies (>40%; P = .0114). In conclusion, CH is present in 82% of TFH–AITL and can be demonstrated up to 145 months before TFH–AITL diagnosis. NGS T-cell clonality analysis is an excellent tool to confirm TFH–AITL BM infiltration. Concurrent myeloid neoplasms were identified in 18% of the cases and were associated with TET2 mutations with high allelic burden (>40%). We demonstrated that myeloid neoplasms might occur simultaneously or precede the diagnosis of TFH lymphoma.
期刊介绍:
Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology.
Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.