SOX11 is useful in differentiating cyclin D1-positive diffuse large B-cell lymphoma from mantle cell lymphoma

Histopathology. 2012 Oct;61(4):685-93. doi: 10.1111/j.1365-2559.2012.04260.x.

Abstract

Aims: To characterize the frequency and clinicopathological features of cyclin D1-positive diffuse large B-cell lymphoma (DLBCL) and the usefulness of SOX11 in the differential diagnosis from mantle cell lymphoma (MCL).

Methods and results: We retrospectively stained 206 consecutive DLBCLs for cyclin D1, and identified three (1.5%) positive cases, comprising two in the elderly with necrosis, and a third with a starry-sky pattern. All three cases shared the same non-germinal centre B-cell (non-GCB) phenotype [CD5-/CD10-/bcl-6+/MUM1+/SOX11-], Epstein-Barr virus (EBV) negativity, and absence of CCND1 aberrations by fluorescence in-situ hybridization. The third case showed both BCL6 and MYC rearrangements: a double-hit lymphoma. In the same period there were 22 MCLs, all expressing cyclin D1, with 89% cases expressing SOX11, a frequency that is statistically different from cyclin D1-positive DLBCL. Notably, we identified a pleomorphic MCL initially misdiagnosed as DLBCL. A separate cohort of 98 DLBCL cases was negative for SOX11, with only one case expressing cyclin D1 with a GCB phenotype (CD10+/bcl-6+/MUM1-). The two patients with tumour necrosis rapidly died of disease. The other two were in complete remission after immunochemotherapy.

Conclusion: Cyclin D1-positive DLBCLs are rare, and they are negative for SOX11 or CCND1 aberration. SOX11 is useful in differentiating cyclin D1-positive DLBCL from MCL.

Keywords: CCND1; cyclin D1; diffuse large B-cell lymphoma; double-hit lymphoma; mantle cell lymphoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Cyclin D1 / analysis
  • Cyclin D1 / biosynthesis
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lymphoma, Large B-Cell, Diffuse / diagnosis*
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Mantle-Cell / diagnosis*
  • Lymphoma, Mantle-Cell / metabolism
  • Male
  • Middle Aged
  • Retrospective Studies
  • SOXC Transcription Factors / analysis
  • SOXC Transcription Factors / biosynthesis*
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • CCND1 protein, human
  • SOX11 protein, human
  • SOXC Transcription Factors
  • Cyclin D1