Clinicopathological and genomic analysis of double-hit follicular lymphoma: comparison with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-10-06

AUTHORS

Masashi Miyaoka, Yara Y Kikuti, Joaquim Carreras, Haruka Ikoma, Shinichiro Hiraiwa, Akifumi Ichiki, Minoru Kojima, Kiyoshi Ando, Tomoyuki Yokose, Rika Sakai, Masahiro Hoshikawa, Naoto Tomita, Ikuo Miura, Katsuyoshi Takata, Tadashi Yoshino, Jun Takizawa, Silvia Bea, Elias Campo, Naoya Nakamura

ABSTRACT

Most high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are aggressive B-cell lymphomas. Occasional double-hit follicular lymphomas have been described but the clinicopathological features of these tumors are not well known. To clarify the characteristics of double-hit follicular lymphomas, we analyzed 10 cases of double-hit follicular lymphomas and 15 cases of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements for clinicopathological and genome-wide copy-number alterations and copy-neutral loss-of-heterozygosity profiles. For double-hit follicular lymphomas, the median age was 67.5 years (range: 48–82 years). The female/male ratio was 2.3. Eight patients presented with advanced clinical stage. The median follow-up time was 20 months (range: 1–132 months). At the end of the follow-up, 8 patients were alive, 2 patients were dead including 1 patient with diffuse large B-cell lymphoma transformation. Rearrangements of MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6 were seen in 8, 1, and 1 cases, respectively. The partner of MYC was IGH in 6 cases. There were no cases of histological grade 1, 4 cases of grade 2, 5 cases of grade 3a, and 1 case of grade 3b. Two cases of grade 3a exhibited immunoblast-like morphology. Immunohistochemistry demonstrated 9 cases with ≥50% MYC-positive cells. There was significant difference in MYC intensity (P=0.00004) and MIB-1 positivity (P=0.001) between double-hit follicular lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. The genome profile of double-hit follicular lymphomas was comparable with conventional follicular lymphomas (GSE67385, n=198) with characteristic gains of 2p25.3-p11.1, 7p22.3-q36.3, 12q11-q24.33, and loss of 18q21.32-q23 (P<0.05). In comparison with high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements, double-hit follicular lymphomas had fewer copy-number alterations and minimal common region of gain at 2p16.1 (70%), locus also significant against conventional follicular lymphomas (P=0.0001). In summary, double-hit follicular lymphomas tended to be high-grade histology, high MYC protein expression, high MYC/IGH fusion, and minimal common region of gain at 2p16.1. Double-hit follicular lymphomas seemed to be a different disease from high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements and have an indolent clinical behavior similar to follicular lymphomas without MYC rearrangement. More... »

PAGES

313-326

Journal

TITLE

Modern Pathology

ISSUE

2

VOLUME

31

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/modpathol.2017.134

DOI

http://dx.doi.org/10.1038/modpathol.2017.134

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1092113980

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28984304


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354 grid-institutes:grid.265061.6 schema:alternateName Department of Hematology/Oncology, Tokai University, School of Medicine, Isehara, Japan
355 Department of Pathology, Tokai University School of Medicine, Isehara, Japan
356 schema:name Department of Hematology/Oncology, Tokai University, School of Medicine, Isehara, Japan
357 Department of Pathology, Tokai University School of Medicine, Isehara, Japan
358 rdf:type schema:Organization
359 grid-institutes:grid.412764.2 schema:alternateName Department of Pathology, St Marianna University School of Medicine, Kawasaki, Japan
360 Division of Hematology and Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
361 schema:name Department of Pathology, St Marianna University School of Medicine, Kawasaki, Japan
362 Division of Hematology and Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
363 rdf:type schema:Organization
364 grid-institutes:grid.414944.8 schema:alternateName Department of Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan
365 Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan
366 schema:name Department of Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan
367 Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan
368 rdf:type schema:Organization
 




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