title: Fluorescence immunophenotyping and interphase cytogenetics (FICTION) detects BCL6 abnormalities, including gene amplification, in most cases of nodular lymphocyte-predominant Hodgkin lymphoma.
abstract: BACKGROUND
  BCL6 translocations are a frequent finding in B-cell lymphomas of diverse subtypes, including some cases of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). However, reliable analysis of BCL6 rearrangements using fluorescence in situ hybridization is difficult in NLPHL because of the relative paucity of neoplastic cells. Combined immunofluorescence microscopy and fluorescence in situ hybridization, or fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms (FICTION), permits targeted analysis of neoplastic cells.
  
  
  OBJECTIVE
  To better define the spectrum of BCL6 abnormalities in NLPHL using FICTION analysis.
  
  
  METHODS
  We performed an optimized FICTION analysis of 24 lymph nodes, including 11 NLPHL, 5 follicular hyperplasia with prominent progressive transformation of germinal centers, and 8 follicular hyperplasia without progressive transformation of germinal centers.
  
  
  RESULTS
  BCL6 rearrangement was identified in 5 of 11 cases of NLPHL (46%). In addition, BCL6 gene amplification, with large clusters of BCL6 signals in the absence of chromosome 3 aneuploidy, was detected in 3 of 11 cases of NLPHL (27%). One NLPHL showed extra copies of BCL6 present in conjunction with multiple copies of chromosome 3. Altogether, we detected BCL6 abnormalities in 9 of 11 cases of NLPHL (82%). None of the progressive transformation of germinal centers or follicular hyperplasia cases showed BCL6 abnormalities by FICTION.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report of BCL6 gene amplification in NLPHL. Our optimized protocol for FICTION permits detection of cytogenetic abnormalities in most NLPHL cases and may represent a useful ancillary diagnostic technique.
authors.affiliation: From the Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque. Dr Reichard is now with the Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Alexei G
authors.initials: AG
authors.lastname: Bakhirev
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Vasef
authors.forename: Qian-Yun
authors.initials: QY
authors.lastname: Zhang
authors.forename: Kaaren K
authors.initials: KK
authors.lastname: Reichard
authors.forename: David R
authors.initials: DR
authors.lastname: Czuchlewski
mesh_terms: D000328:Adult; D000368:Aged; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase / Q000235:genetics; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051560:Proto-Oncogene Proteins c-bcl-6; D014178:Translocation, Genetic
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6