論文

査読有り
2018年2月1日

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

Modern Pathology
  • 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

31
2
開始ページ
313
終了ページ
326
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/modpathol.2017.134
出版者・発行元
Nature Publishing Group

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 (Po0.05). In comparison with highgrade 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.

リンク情報
DOI
https://doi.org/10.1038/modpathol.2017.134
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28984304

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