Does the proliferation fraction help identify mature B cell lymphomas with double- and triple-hit translocations?

Histopathology. 2012 Dec;61(6):1214-8. doi: 10.1111/j.1365-2559.2012.04351.x. Epub 2012 Nov 21.

Abstract

Aims: The entity 'B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL)' refers to B cell neoplasms that share overlapping characteristics of BL and DLBCL. A subset of these 'grey-zone lymphomas' possesses C-MYC and IGH translocations but, in addition, contains additional rearrangements of BCL2 and/or BCL6 genes. The aim of this study was to investigate if the proliferation fraction by Ki67 immunostaining can be used to identify such double-/triple-hit lymphomas.

Methods and results: We studied 492 cases of mature aggressive B cell neoplasms by histology, immunohistochemistry and interphase fluorescence in-situ hybridization (FISH) using break-apart probes against C-MYC, BCL2, BCL6, IGH, MALT1, PAX5 and CCND1. Forty Burkitt lymphomas and 28 cases of MYC(+) double-/triple-hit lymphomas were identified. Of the latter, 77% and 54% displayed proliferation fractions exceeding 75% and 90%, respectively. With a cut-off of >75% by Ki67 immunostaining, the sensitivity and specificity for detection of MYC(+) double/triple translocations was 0.77 and 0.36. Raising the proliferation fraction criterion to >90% improved the specificity to 0.62 at the expense of a low sensitivity of 0.54.

Conclusions: Immunostaining for Ki67 is not a useful approach to prescreen B cell lymphomas for MYC(+) double/triple translocations.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Burkitt Lymphoma / diagnosis
  • Burkitt Lymphoma / genetics*
  • Burkitt Lymphoma / pathology*
  • Cell Proliferation*
  • Diagnosis, Differential
  • Early Detection of Cancer / methods
  • Female
  • Genetic Testing / methods
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Ki-67 Antigen / metabolism
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology*
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • Retrospective Studies
  • Sensitivity and Specificity
  • Translocation, Genetic / genetics*

Substances

  • Immunoglobulin Heavy Chains
  • Ki-67 Antigen
  • MYC protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6
  • Proto-Oncogene Proteins c-myc