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

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

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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 (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.

Original languageEnglish
Pages (from-to)313-326
Number of pages14
JournalModern Pathology
Volume31
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Miyaoka, M., Kikuti, Y. Y., Carreras, J., Ikoma, H., Hiraiwa, S., Ichiki, A., Kojima, M., Ando, K., Yokose, T., Sakai, R., Hoshikawa, M., Tomita, N., Miura, I., Takata, K., Yoshino, T., Takizawa, J., Bea, S., Campo, E., & Nakamura, N. (2018). 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, 31(2), 313-326. https://doi.org/10.1038/modpathol.2017.134