Another look at follicular lymphoma: immunophenotypic and molecular analyses identify distinct follicular lymphoma subgroups

Histopathology. 2013 May;62(6):860-75. doi: 10.1111/his.12076. Epub 2013 Mar 20.

Abstract

Aims: The aim of this study was to analyse the immunophenotypic and molecular features of a large series of follicular lymphomas, focusing in particular on atypical cases that fail to express CD10 and/or bcl-2. Such cases present diagnostic pitfalls, especially with regard to the differential diagnosis from follicular hyperplasia and marginal zone B-cell lymphoma. Therefore, we also included an immunohistochemical evaluation of stathmin, which is strongly expressed by germinal centre B cells, as a putative new marker for follicular lymphomas, particularly those with an atypical phenotype.

Methods and results: Two hundred and five follicular lymphomas were investigated with immunohistochemistry and fluorescence in-situ hybridization (FISH). The use of three distinct anti-bcl-2 antibodies together with CD10 expression data and FISH analysis for bcl-2 and bcl-6 rearrangements allowed subclassification of follicular lymphoma into four distinct subgroups: (i) CD10-positive/bcl-2-positive, (ii) CD10-positive/bcl-2-negative, (iii) CD10-negative/bcl-2-positive, and (iv) CD10-negative/bcl-2-negative. All cases were bcl-6-positive. STMN1 (stathmin) was shown to be helpful in diagnosing bcl-2-negative and/or CD10-negative follicular lymphomas, and in their distinction from marginal zone B-cell lymphoma.

Conclusions: Combined immunohistological and molecular analyses reveal that follicular lymphomas showing an atypical immunophenotypic and molecular profile exist, and we demonstrate that STMN1 represents a novel useful diagnostic marker for these.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • DNA-Binding Proteins / genetics*
  • Diagnosis, Differential
  • Female
  • Gene Rearrangement
  • Genes, bcl-2*
  • Humans
  • Immunophenotyping
  • In Situ Hybridization, Fluorescence
  • Lymphoma, B-Cell, Marginal Zone / diagnosis
  • Lymphoma, B-Cell, Marginal Zone / immunology
  • Lymphoma, Follicular / classification
  • Lymphoma, Follicular / genetics*
  • Lymphoma, Follicular / immunology*
  • Male
  • Middle Aged
  • Neprilysin / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Proto-Oncogene Proteins c-bcl-6
  • Stathmin / metabolism
  • Young Adult

Substances

  • BCL6 protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6
  • STMN1 protein, human
  • Stathmin
  • Neprilysin