Molecular characterization of a rare case of high-grade B-cell lymphoma with MYC, BCL2, BCL6, and CCND1 rearrangements.
KMT2D
MYC-BCL2 rearrangements
MYC-BCL6 rearrangements
Lymphadenopathy
Quadruple hit lymphoma
Journal
Journal of hematopathology
ISSN: 1865-5785
Titre abrégé: J Hematop
Pays: Germany
ID NLM: 101491976
Informations de publication
Date de publication:
24 Jun 2024
24 Jun 2024
Historique:
received:
04
03
2024
accepted:
12
06
2024
medline:
25
6
2024
pubmed:
25
6
2024
entrez:
24
6
2024
Statut:
aheadofprint
Résumé
Quadruple-hit lymphomas are extremely rare non-Hodgkin lymphomas with a reported dismal prognosis in the few reported cases. A "quadruple hit" has been defined by the presence of concurrent MYC, BCL2, BCL6, and CCND1 chromosomal rearrangements. We report a new case of a quadruple hit lymphoma in a 73-year-old Hispanic man who presented with an enlarging left-sided neck mass. Computed tomography showed a 1.9-cm mass in left the tonsil with bulky cervical lymphadenopathy. The presence of all four chromosomal rearrangements can reportedly occur with disease progression in both diffuse large B-cell lymphomas and mantle cell lymphomas. Further characterization of the tumor by next-generation sequencing may be of benefit to delineate between these two possibilities. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing were used to confirm and classify the diagnosis. Histologic sections of the cervical lymph node demonstrated an atypical lymphoid infiltrate with large and pleomorphic cells, which were positive for CD20, CD10, BCL1 (Cyclin D1), BCL2, BCL6, and cMYC and negative for CD5 and SOX11 on immunohistochemistry with a Ki-67 proliferative index of 70%. FISH demonstrated MYC, BCL2, BCL6, and CCND1 rearrangements and the diagnosis of high-grade B-cell lymphoma with MYC, BCL2, BCL6, and CCND1 was rendered. Our patient was treated with dose adjusted etoposide, doxorubicin, cyclophosphamide, prednisone, and rituximab chemotherapy and has been in remission for 20 months.
Identifiants
pubmed: 38914869
doi: 10.1007/s12308-024-00593-8
pii: 10.1007/s12308-024-00593-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
Références
Alaggio R et al (2022) The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms. Leukemia 36(7):1720–1748. https://doi.org/10.1038/s41375-022-01620-2
doi: 10.1038/s41375-022-01620-2
pubmed: 35732829
pmcid: 9214472
Falini B, Martino G, Lazzi S (2023) A comparison of the International Consensus and 5th World Health Organization classifications of mature B-cell lymphomas. Leukemia 37(1):18–34. https://doi.org/10.1038/s41375-022-01764-1
doi: 10.1038/s41375-022-01764-1
pubmed: 36460764
Kawakami K et al (2004) Case of B-cell lymphoma with rearrangement of the BCL1, BCL2, BCL6, and c-MYC genes. Int J Hematol 79(5):474–479. https://doi.org/10.1532/IJH97.03105
doi: 10.1532/IJH97.03105
pubmed: 15239399
Bacher U, Haferlach T, Alpermann T, Kern W, Schnittger S, Haferlach C (2011) Several lymphoma-specific genetic events in parallel can be found in mature B-cell neoplasms. Genes Chromosomes Cancer 50(1):43–50. https://doi.org/10.1002/gcc.20831
doi: 10.1002/gcc.20831
pubmed: 20960563
Yoshida M et al (2015) Clinicopathological features of double-hit <scp>B</scp> -cell lymphomas with <scp>MYC</scp> and <scp>BCL</scp> 2, <scp>BCL</scp> 6 or <scp>CCND</scp> 1 rearrangements. Pathol Int 65(10):519–527. https://doi.org/10.1111/pin.12335
doi: 10.1111/pin.12335
pubmed: 26224092
Ittel A et al (2015) Four genetic lymphoma-specific events (MYC, BCL2, BCL6 and CCND1) identified in a high grade B lymphoma case. Blood Cancer J 5(12):e374–e374. https://doi.org/10.1038/bcj.2015.99
doi: 10.1038/bcj.2015.99
pubmed: 26657198
pmcid: 4735075
Proulx J et al (2018) Quadruple hit lymphoma: a rare entity with dismal prognosis. Blood 132(Supplement 1):5305–5305. https://doi.org/10.1182/blood-2018-99-120147
doi: 10.1182/blood-2018-99-120147
Meloni-Ehrig A et al (2020) 36. Quadruple-hit B-cell lymphoma with simultaneous BCL2, BCL6, CCND1, and MYC rearrangements: two new cases. Cancer Genet 244:14. https://doi.org/10.1016/j.cancergen.2020.04.040
doi: 10.1016/j.cancergen.2020.04.040
Cheng J et al (2021) CCND1 genomic rearrangement as a secondary event in high grade B-cell lymphoma. Hemasphere 5(1):e505. https://doi.org/10.1097/HS9.0000000000000505
doi: 10.1097/HS9.0000000000000505
pubmed: 33324951
Liu W et al (2021) Quadruple-hit pleomorphic mantle cell lymphoma with MYC, BCL2, BCL6, and CCND1 gene rearrangements. Br J Haematol 195(4):634–637. https://doi.org/10.1111/bjh.17729
doi: 10.1111/bjh.17729
pubmed: 34528238
Vela-ChÁvez T et al (2011) Cyclin D1 positive diffuse large B-cell lymphoma is a post-germinal center-type lymphoma without alterations in the CCND1 gene locus. Leuk Lymphoma 52(3):458–466. https://doi.org/10.3109/10428194.2010.540361
doi: 10.3109/10428194.2010.540361
pubmed: 21281227
pmcid: 6324544
Juskevicius D, Ruiz C, Dirnhofer S, Tzankov A (2014) Clinical, morphologic, phenotypic, and genetic evidence of cyclin D1-positive diffuse large B-cell lymphomas with CYCLIN D1 gene rearrangements. Am J Surg Pathol 38(5):719–727. https://doi.org/10.1097/PAS.0000000000000120
doi: 10.1097/PAS.0000000000000120
pubmed: 24722063
Morin RD, Arthur SE, Hodson DJ (2022) Molecular profiling in diffuse large B-cell lymphoma: why so many types of subtypes? Br J Haematol 196(4):814–829. https://doi.org/10.1111/bjh.17811
doi: 10.1111/bjh.17811
pubmed: 34467527
Zhuang Y et al (2022) Altered pathways and targeted therapy in double hit lymphoma. J Hematol Oncol 15(1):26. https://doi.org/10.1186/s13045-022-01249-9
doi: 10.1186/s13045-022-01249-9
pubmed: 35303910
pmcid: 8932183
Zhang H et al (2022) PIM1 genetic alterations associated with distinct molecular profiles, phenotypes and drug responses in diffuse large B‐cell lymphoma. Clin Transl Med 12(4). https://doi.org/10.1002/ctm2.808
COSMIC (n.d.) Catalogue Of Somatic Mutations In Cancer, COSV65165568 PIM1 gene. Wellcome Sanger Institute. https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=119825033 . Accessed 22 Apr 2024
COSMIC (n.d.) Catalogue Of Somatic Mutations In Cancer, COSV65165412 PIM1 gene. Wellcome Sanger Institute. https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=119827076 . Accessed 22 Apr 2024
COSMIC (n.d.) Catalogue Of Somatic Mutations In Cancer, COSV65165396 PIM1 gene. Wellcome Sanger Institute. https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=119824464 . Accessed 22 Apr 2024
Xu-Monette ZY et al (2016) Clinical and biologic significance of MYC genetic mutations in de novo diffuse large B-cell lymphoma. Clin Cancer Res 22(14):3593–3605. https://doi.org/10.1158/1078-0432.CCR-15-2296
doi: 10.1158/1078-0432.CCR-15-2296
pubmed: 26927665
pmcid: 4947447
Lenz G et al (2007) Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell–like diffuse large B cell lymphoma. J Exp Med 204(3):633–643. https://doi.org/10.1084/jem.20062041
doi: 10.1084/jem.20062041
pubmed: 17353367
pmcid: 2137913
King RL et al (2019) False-negative rates for MYC fluorescence in situ hybridization probes in B-cell neoplasms. Haematologica 104(6):e248–e251. https://doi.org/10.3324/haematol.2018.207290
doi: 10.3324/haematol.2018.207290
pubmed: 30523057
pmcid: 6545835
Krull JE et al (2020) Somatic copy number gains in MYC, BCL2, and BCL6 identifies a subset of aggressive alternative-DH/TH DLBCL patients. Blood Cancer J 10(11):117. https://doi.org/10.1038/s41408-020-00382-3
doi: 10.1038/s41408-020-00382-3
pubmed: 33168821
pmcid: 7652824
Zhang J et al (2015) Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis. Nat Med 21(10):1190–1198. https://doi.org/10.1038/nm.3940
doi: 10.1038/nm.3940
pubmed: 26366712
pmcid: 5145002
Okosun J et al (2014) Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Nat Genet 46(2):176–181. https://doi.org/10.1038/ng.2856
doi: 10.1038/ng.2856
pubmed: 24362818
Schmitz R et al (2018) Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med 378(15):1396–1407. https://doi.org/10.1056/NEJMoa1801445
doi: 10.1056/NEJMoa1801445
pubmed: 29641966
pmcid: 6010183
COSMIC (n.d.) Catalogue Of Somatic Mutations In Cancer, COSV63185584 TNFRSF14 gene. Wellcome Sanger Institute. https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=111831892 . Accessed 22 Apr 2024
COSMIC (n.d.) Catalogue Of Somatic Mutations In Cancer, COSV61374190 BCL2 gene. Wellcome Sanger Institute. https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=122082405 . Accessed 22 Apr 2024