Cyclin D1-positive diffuse large B-cell lymphoma with IGH-CCND1 translocation and BCL6 rearrangement: a report of two cases

Am J Clin Pathol. 2015 Feb;143(2):288-99. doi: 10.1309/AJCPUIDW2CPTA1JA.

Abstract

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.

Keywords: BCL6 rearrangement; CCND1 rearrangement; Cyclin D1; Diffuse large B-cell lymphoma; Mantle cell lymphoma.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Cyclin D1 / metabolism*
  • DNA-Binding Proteins / genetics*
  • Gene Rearrangement
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-bcl-6
  • Tissue Array Analysis
  • Translocation, Genetic

Substances

  • BCL6 protein, human
  • Biomarkers, Tumor
  • CCND1 protein, human
  • DNA-Binding Proteins
  • IGH-CCND1 fusion protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins c-bcl-6
  • Cyclin D1