title: Bcl-2, Bcl-6 and CD10 expression in cutaneous B-cell lymphoma: further support for a follicle centre cell origin and differential diagnostic significance.
abstract: BACKGROUND
  Primary cutaneous follicle centre cell lymphomas (PCFCCLs) are the most common type of cutaneous B-cell lymphoma. There is ongoing discussion on the origin of the neoplastic B cells in these PCFCCLs, and consequently on their relation to the groups of primary cutaneous marginal zone B-cell lymphomas (PCMZLs) and nodal follicular lymphomas.
  
  
  OBJECTIVE
  To define better the neoplastic B cells in PCFCCLs, and to find out if differences in the expression of the antiapoptopic protein Bcl-2, and Bcl-6 and CD10, molecules which are normally expressed by the neoplastic B cells in nodal follicular lymphomas, might have diagnostic or prognostic significance in cutaneous B-cell lymphoproliferative disorders.
  
  
  METHODS
  Pretreatment biopsies of well-defined groups of PCFCCL (n = 24), PCMZL (n = 14), primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg; n = 19), secondary cutaneous follicular lymphoma (n = 3) and cutaneous pseudo-B-cell lymphoma (n = 6) were investigated by immunohistochemistry for expression of Bcl-2, Bcl-6 and CD10.
  
  
  RESULTS
  The PCFCCLs consistently expressed Bcl-6, whereas CD10 and Bcl-2 were expressed in only one and two of 24 cases, respectively. In contrast, PCMZLs were always negative for Bcl-6 and CD10, but were Bcl-2 positive, whereas skin and lymph node localizations of secondary cutaneous follicular lymphomas consistently expressed all of Bcl-2, Bcl-6 and CD10. Reactive follicle centre cells in pseudo-B-cell lymphomas expressed Bcl-6 (six of six cases) and CD10 (five of six cases), but not Bcl-2. PCLBCL-leg was Bcl-6 positive and CD10 negative in all cases, irrespective of clinical outcome, and strongly expressed Bcl-2 protein in all but two cases.
  
  
  CONCLUSIONS
  The results of the present study provide further support for the follicle centre cell origin of both PCFCCL and PCLBCL-leg, and indicate that staining for Bcl-2, Bcl-6 and CD10 can serve as an important adjunct in the differential diagnosis of cutaneous B-cell lymphoproliferative disorders.
authors.affiliation: Department of Dermatology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Hoefnagel
authors.forename: M H
authors.initials: MH
authors.lastname: Vermeer
authors.forename: P M
authors.initials: PM
authors.lastname: Jansen
authors.forename: G J
authors.initials: GJ
authors.lastname: Fleuren
authors.forename: C J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: R
authors.initials: R
authors.lastname: Willemze
mesh_terms: D004268:DNA-Binding Proteins / Q000032:analysis*; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016130:Immunophenotyping; D007866:Leg; D016393:Lymphoma, B-Cell / Q000737:chemistry* / Q000473:pathology; D008224:Lymphoma, Follicular / Q000737:chemistry* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000473:pathology; D015260:Neprilysin / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D051560:Proto-Oncogene Proteins c-bcl-6; D019310:Pseudolymphoma / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000737:chemistry*; D014157:Transcription Factors / Q000032:analysis*
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D015260:Neprilysin