Cyclin D1-positive mediastinal large B-cell lymphoma with copy number gains of CCND1 gene: A study of 3 cases with nonmediastinal disease

Bo Jung Chen, Philippe Ruminy, Christine G. Roth, Bettina Bisig, Barbara Mankel, Julia Steinhilber, Elodie Bohers, Fabrice Jardin, Falko Fend, Steven H. Swerdlow, Christiane Copie-Bergman, Laurence De Leval, Leticia Quintanilla-Martinez

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Primary mediastinal large B-cell lymphoma (PMBL) is a mature large B-cell lymphoma of putative thymic B-cell origin involving the mediastinum with younger age distribution and better prognosis than diffuse large B-cell lymphoma (DLBCL), not otherwise specified. Recently, based on gene expression profile analysis and morphologic findings, cases of PMBL without mediastinal involvement have been reported. In this study, we analyzed 3 cases of nodal DLBCL with morphologic features of PMBL presenting in submandibular or supraclavicular lymph nodes, in middle-aged to elderly patients, 2 of them without clinical or radiologic evidence of mediastinal involvement. The 3 patients presented with stage I/II disease and had excellent response to R-CHOP/R-EPOCH therapy. The 3 cases showed MAL expression and were positive for CD23 and/or CD30. All 3 cases expressed cyclin D1 with copy number gains of CCND1 gene but without rearrangement. There was no rearrangement of CIITA or PDL1/PDL2. Reverse transcriptase-multiplex ligation-dependent probe amplification, a mRNA-based gene expression profile analysis revealed high probability of PMBL (87.6%, 98.7%, and 99%) in these 3 cases. Targeted next-generation sequencing analysis showed SOCS1 mutations in the 3 cases, and TNFAIP3 and XPO1 mutations in one, further supporting the diagnosis of PMBL. In conclusion, we report 3 cases of nodal PMBL, 2 of them without mediastinal mass, and expression of cyclin D1 due to copy number gains of CCND1 gene, a diagnostic pitfall with mantle cell lymphoma and DLBCL, not otherwise specified.

Original languageEnglish
Pages (from-to)110-120
Number of pages11
JournalAmerican Journal of Surgical Pathology
Volume43
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • cyclin D1
  • mutational analysis
  • nonmediastinal
  • primary mediastinal large B-cell lymphoma
  • reverse transcriptase-multiplex ligation-dependent probe amplification (RT-MLPA)

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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