Mantle cell lymphomas with concomitant MYC and CCND1 breakpoints are recurrently TdT positive and frequently show high-grade pathological and genetic features.

Chromosomal breakpoints involving the MYC gene locus, frequently referred to as MYC rearrangements (MYC - R+), are a diagnostic hallmark of Burkitt lymphoma and recurrent in many other subtypes of B-cell lymphomas including follicular lymphoma, diffuse large B-cell lymphoma and other high-grade B-cell lymphomas and are associated with an aggressive clinical course. In remarkable contrast, in MCL, only few MYC - R+ cases have yet been described. In the current study, we have retrospectively analysed 16 samples (MYC - R+, n = 15, MYC - R-, n = 1) from 13 patients and describe their morphological, immunophenotypic and (molecular) genetic features and clonal evolution patterns. Thirteen out of fifteen MYC - R+ samples showed a non-classical cytology including pleomorphic (centroblastic, immunoblastic), anaplastic or blastoid. MYC translocation partners were IG-loci in 4/11 and non-IG loci in 7/11 analysed cases. The involved IG-loci included IGH in 3 cases and IGL in one case. PAX5 was the non-IG partner in 2/7 patients. The MYC - R+ MCL reported herein frequently displayed characteristics associated with an aggressive clinical course including high genomic-complexity (6/7 samples), frequent deletions involving the CDKN2A locus (7/10 samples), high Ki-67 proliferation index (12/13 samples) and frequent P53 expression (13/13 samples). Of note, in 4/14 samples, SOX11 was not or only focally expressed and 3/13 samples showed focal or diffuse TdT-positivity presenting a diagnostic challenge as these features could point to a differential diagnosis of diffuse large B-cell lymphoma and/or lymphoblastic lymphoma/leukaemia.

Aukema SM ，Croci GA ，Bens S ，Oehl-Huber K ，Wagener R ，Ott G ，Rosenwald A ，Kluin PM ，van den Berg E ，Bosga-Bouwer AG ，Hoogendoorn M ，Hoster E ，Bittmann I ，Nagel I ，Murga Penas EM ，Kreuz M ，Bausinger J ，Belder W ，Oschlies I ，Dyer MJS ，Jayne S ，Siebert R ，Klapper W ... -  《-》

Mutational Landscape of TdT+ Large B-cell Lymphomas Supports Their Distinction From B-lymphoblastic Neoplasms: A Multiparameter Study of a Rare and Aggressive Entity.

In the current World Health Organization classification, terminal deoxynucleotidyl transferase (TdT) expression in a high grade/large cell B-cell lymphoma (LBCL) indicates a B-lymphoblastic lymphoma/leukemia (B-LBL), although TdT expression in what appear to be mature LBCL or following mature B-cell neoplasms is reported. The frequency of TdT+ LBCL, how to best categorize these cases, and their clinicopathologic features, molecular landscape, and relationship to classic B-LBL remain to be better defined. TdT expression was therefore assessed in 258 LBCL and the results correlated with the cytologic, phenotypic, and cytogenetic findings. Targeted mutational analysis, review of prior biopsies, and assessment of clinical associations was performed in the 6 cases with >10% TdT+ cells. All 6 TdT+ LBCL were blastoid-appearing, CD34-, MYC+, BCL2+, and had MYC rearrangements (R) (5/6 with BCL2 and/or BCL6-R). 5/6 had a prior TdT- LBCL and/or follicular lymphoma and all had an aggressive course. Fifteen nonsynonymous variants in 11 genes were seen in the 4/5 tested cases with mutations. TdT+ and TdT- areas in 1 case showed identical mutations. The mutational profiles were more like those reported in germinal center B-cell type-diffuse LBCL rather than B-LBL. Evolution from preceding TdT- lymphomas was nondivergent in 1/3 tested cases and partially divergent in 2. The clinicopathologic and cytogenetic features of these 6 cases were similar to those found in a meta-analysis that included additional cases of TdT+ LBCL or B-LBL following follicular lymphoma. Thus, TdT+, CD34- large B-cell neoplasms with MYC rearrangements and often a "double hit" are rare, frequently a transformational event and aggressive but are distinct from classic B-LBL.

Bhavsar S ，Liu YC ，Gibson SE ，Moore EM ，Swerdlow SH ... -  《-》

Mantle Cell Lymphoma With MYC Rearrangement: A Report of 17 Patients.

Hu Z ，Medeiros LJ ，Chen Z ，Chen W ，Li S ，Konoplev SN ，Lu X ，Pham LV ，Young KH ，Wang W ，Hu S ... -  《-》

Primary large B-cell lymphoma of the central nervous system with cyclin D1 expression and t(11;14) (IGH-CCND1): Diffuse large B-cell lymphoma with CCND1 rearrangement or mantle cell lymphoma?

Mantle cell lymphomas (MCLs) are the prototypic B-cell non-Hodgkin lymphomas defined by cyclin D1 gene (CCND1; or other cyclin D family gene) rearrangements. However, extremely rare cases of diffuse large B-cell lymphomas (DLBCLs) harboring CCND1 rearrangements, resulting in cyclin D1 protein expression, have also been reported. In this report, we describe an unusual primary large B-cell lymphoma of non-germinal center immunophenotype of the central nervous system (CNS) in an elderly male patient, which was negative for CD5 and SOX11, and exhibited cyclin D1 expression. Fluorescence in situ hybridization analysis detected IGH-CCND1 and BCL6 rearrangements. This case may represent the first report of a primary CNS DLBCL with IGH-CCND1 rearrangement. The clinico-pathologic features that can help differentiate primary CNS MCL from primary DLBCL of the CNS with IGH-CCND1 rearrangement are discussed.

Parrott AM ，Haggiagi AM ，Murty VV ，Bhagat G ，Alobeid B ... -  《-》

Large B-cell lymphomas with CCND1 rearrangement have different immunoglobulin gene breakpoints and genomic profile than mantle cell lymphoma.

Özoğul E ，Montaner A ，Pol M ，Frigola G ，Balagué O ，Syrykh C ，Bousquets-Muñoz P ，Royo R ，Fontaine J ，Traverse-Glehen A ，Bühler MM ，Giudici L ，Roncador M ，Zenz T ，Carras S ，Valmary-Degano S ，de Leval L ，Bosch-Schips J ，Climent F ，Salmeron-Villalobos J ，Bashiri M ，Ruiz-Gaspà S ，Costa D ，Beà S ，Salaverria I ，Giné E ，Quintanilla-Martinez L ，Brousset P ，Raffeld M ，Jaffe ES ，Puente XS ，López C ，Nadeu F ，Campo E ... -  《Blood Cancer Journal》