Immunohistochemistry for BRAF V600E in the Differential Diagnosis of Hairy Cell Leukemia vs Other Splenic B-Cell Lymphomas

Am J Clin Pathol. 2015 Jul;144(1):87-93. doi: 10.1309/AJCP5WVXJ2KTLODO.

Abstract

Objectives: Recent reports have used immunohistochemistry (IHC) with a mutation-specific antibody to detect the BRAF V600E mutation, which is found in nearly all cases of hairy cell leukemia (HCL). To date, however, only a small number of non-HCL, splenic B-cell lymphomas have been examined by IHC.

Methods: We analyzed 121 cases, including 26 HCLs, 52 non-HCL splenic lymphomas, 22 chronic lymphocytic leukemias/small lymphocytic lymphomas (CLLs/SLLs), and 21 plasma cell neoplasms (PCNs) for BRAF V600E expression by IHC. Molecular testing for BRAF V600E was performed in a subset of cases, using allele-specific polymerase chain reaction and/or Sanger sequencing.

Results: Twenty-six (100%) of 26 HCL cases were positive by IHC vs one (1%) of 95 non-HCL cases. Positive staining was identified in one (2%) of 44 splenic marginal zone lymphomas (SMZLs), while each of 22 CLLs/SLLs, 21 PCNs, six unclassifiable splenic lymphomas, and two HCL variants were negative. IHC and molecular results were concordant in all cases examined (21 HCLs and 21 non-HCLs, including the BRAF+ SMZLs).

Conclusions: The detection of BRAF V600E by IHC is useful in the distinction of HCLs from other splenic-based lymphomas, although the identification of at least rare SMZLs containing this abnormality illustrates the continuing need for a multiparameter approach to diagnosis.

Keywords: BRAF; Hairy cell leukemia; Immunohistochemistry.

MeSH terms

  • Aged
  • DNA Mutational Analysis
  • Diagnosis, Differential*
  • Female
  • Humans
  • Immunohistochemistry
  • Leukemia, Hairy Cell / diagnosis*
  • Leukemia, Hairy Cell / genetics*
  • Lymphoma, B-Cell / diagnosis*
  • Lymphoma, B-Cell / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins B-raf / genetics*

Substances

  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf