Identification of CD5/Cyclin D1 Double-negative Pleomorphic Mantle Cell Lymphoma: A Clinicopathologic, Genetic, and Gene Expression Study

Am J Surg Pathol. 2020 Feb;44(2):232-240. doi: 10.1097/PAS.0000000000001390.

Abstract

Pleomorphic mantle cell lymphoma (PMCL) can closely mimic diffuse large B-cell lymphoma (DLBCL) morphologically, and expression of CD5 and cyclin D1 is helpful for differential diagnosis. To date, no cases of CD5/cyclin D1 double-negative PMCL have been reported. Four cases of B-cell lymphoma with an immunophenotype of CD5(-) cyclin D1(-) SOX11(+) and morphologic features compatible with DLBCL were included. Two were previously identified, and the other 2 were screened from 500 cases of B-cell lymphoma. We analyzed their clinicopathologic, immunophenotypic, genetic, and gene expression features. Cases of cyclin D1-positive PMCL, cyclin D1-negative PMCL, germinal center B-cell (GCB) DLBCL, and activated B cell (ABC) DLBCL were also studied for comparison. Similar to other PMCL cases, these 4 patients were mainly elderly male individuals with an aggressive clinical course. None of these tumors had detectable translocations involving CCND1, CCND2, CCND3, CCNE1, CCNE2, MYC, BCL2, or BCL6. The genome-wide copy number profile of these 4 cases was similar to that of cyclin D1-negative PMCL. None of these tumors had high expression of cyclin D1, cyclin D2, or cyclin D3. Similar to cyclin D1-negative PMCL, these cases had higher expression of cyclin E1 and cyclin E2 compared with cyclin D1-positive PMCL. The gene expression pattern of these tumors was also similar to that of cyclin D1-negative PMCL. Here we report for the first time 4 cases of CD5/cyclin D1 double-negative PMCL. SOX11 positivity is useful to identify these rare tumors, and further genetic and gene expression analysis can be used to confirm the diagnosis.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • CD5 Antigens / genetics
  • CD5 Antigens / metabolism*
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Diagnosis, Differential
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lymphoma, Large B-Cell, Diffuse / diagnosis*
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lymphoma, Mantle-Cell / diagnosis*
  • Lymphoma, Mantle-Cell / genetics
  • Lymphoma, Mantle-Cell / pathology
  • Male
  • Middle Aged
  • Phenotype
  • SOXC Transcription Factors / genetics
  • SOXC Transcription Factors / metabolism*

Substances

  • Biomarkers, Tumor
  • CCND1 protein, human
  • CD5 Antigens
  • SOX11 protein, human
  • SOXC Transcription Factors
  • Cyclin D1