Cyclin D1-positive Mediastinal Large B-Cell Lymphoma With Copy Number Gains of CCND1 Gene: A Study of 3 Cases With Nonmediastinal Disease. (January 2019)

• Record Type: Journal Article
• Authors: Chen, Bo-Jung; Ruminy, Philippe; Roth, Christine G.; Bisig, Bettina; Mankel, Barbara; Steinhilber, Julia; Bohers, Elodie; Jardin, Fabrice; Fend, Falko; Swerdlow, Steven H.; Copie-Bergman, Christiane; de Leval, Laurence; Quintanilla-Martinez, Leticia
• Is Part Of: American journal of surgical pathology. Volume 43:Number 1(2019)
• Publication Date: 2019-01
• Subjects: primary mediastinal large B-cell lymphoma -- nonmediastinal -- cyclin D1 -- reverse transcriptase-multiplex ligation-dependent probe amplification (RT-MLPA) -- mutational analysis; Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000001154
• Languages: English
• ISSNs: 0147-5185

Abstract

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. Abstract : Supplemental Digital Content is available in the text.