Cyclin D1 rearranged diffuse large B-cell lymphoma-an evolving concept

Rearrangement of Cyclin D1 (CCND1-R) is the hallmark genetic lesion of mantle cell lymphoma (MCL). However, recently diffuse large B-cell lymphomas (DLBCL) have been described carrying a CCND1-R, often with additional rearrangements of BCL2, BCL6 and/or MYC raising the question if these are bona fide DLBCL or pleomorphic MCL. Protein expression and fluorescence in situ hybridisation (FISH) screening of 708 aggressive B-cell lymphomas failed to disclose CCND1-R, demonstrating the rarity of such cases. Fifteen large B-cell tumours, with CCND1-R were collected from different institutions and characterized by immunohistochemistry and for their molecular features. Three of 15 cases were CD5 positive, and all cases were negative for SOX11 but exhibited cyclin D1 staining and CCND1-R by FISH. In 10/15 cases IG could be determined as rearrangement partner by FISH or WGS with occurrence of both aberrant VDJ rearrangement and IGH class-switch recombination (CSR). Eight of 15 tumours had additional translocations involving MYC, BCL2, or BCL6. 8/12 evaluable cases showed significantly mutated IGHV genes and evidence of intraclonal variations in their rearranged IGHV genes. WES disclosed a mutational spectrum typical of DLBCL in 14/14 evaluable cases. We conclude that DLBCL CCND1-R do exist and that CCND1-R in DLBCL can occur without additional translocations.