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Objectives: To demonstrate and confirm the existence of cyclin D1-positive diffuse large B-cell lymphoma (DLBCL) with IGH-CCND1 rearrangement and discuss the rationale of differentiating this entity from blastoid and pleomorphic variants of mantle cell lymphoma (MCL).Methods: Two cyclin D1-positive lymphomas with morphologic features of DLBCL and IGH-CCND1 translocations were characterized with respect to clinical features, as well as morphologic, immunophenotypic, cytogenetic, and molecular findings.Results: The large tumor cells were CD20+, CD5-, CD10-, BCL6+, MUM1+, and cyclin D1+ in both cases. SOX11 was negative. Epstein-Barr virus-encoded RNA in situ hybridization demonstrated diffuse positivity in case 1. BCL6 and IGH-CCND1 rearrangements were identified by fluorescence in situ hybridization in both cases. Specifically, the diagnosis of a relapsed DLBCL with acquisition of IGH-CCND1 was rendered for case 1, molecularly confirmed by the detection of identical monoclonal IGH rearrangements between the initial diagnostic DLBCL and relapse lymphoma.Conclusions: Our study demonstrates convincingly that IGH-CCND1 rearrangement leading to cyclin D1 overexpression can occur in DLBCL and pose a potential diagnostic pitfall, requiring thorough knowledge of the clinicopathologic findings to allow accurate discrimination from a blastoid or pleomorphic MCL. The coexistence of IGH-CCND1 and IGH-BCL6 rearrangements suggest that BCL6 and cyclin D1 may cooperate in the pathogenesis of DLBCL. [ABSTRACT FROM AUTHOR]