title: Cyclin D1-positive diffuse large B-cell lymphoma with IGH-CCND1 translocation and BCL6 rearrangement: a report of two cases.
abstract: OBJECTIVE
  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.
authors.affiliation: From the Division of Hematopathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Al-Kawaaz
authors.affiliation: From the Division of Hematopathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Susan
authors.initials: S
authors.lastname: Mathew
authors.affiliation: From the Division of Hematopathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Yifang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: From the Division of Hematopathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Gomez
authors.affiliation: From the Division of Hematopathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Felicia
authors.initials: F
authors.lastname: Chaviano
authors.affiliation: From the Division of Hematopathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Knowles
authors.affiliation: From the Division of Hematopathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
authors.affiliation: From the Division of Hematopathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY. wtam@med.cornell.edu.
authors.forename: Wayne
authors.initials: W
authors.lastname: Tam
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D019938:Cyclin D1 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D051560:Proto-Oncogene Proteins c-bcl-6; D046888:Tissue Array Analysis; D014178:Translocation, Genetic
chemical_list: C084103:BCL6 protein, human; D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D004268:DNA-Binding Proteins; C529133:IGH-CCND1 fusion protein, human; D015514:Oncogene Proteins, Fusion; D051560:Proto-Oncogene Proteins c-bcl-6; D019938:Cyclin D1
keywords: BCL6 rearrangement; CCND1 rearrangement; Cyclin D1; Diffuse large B-cell lymphoma; Mantle cell lymphoma