title: Large cleaved and immunoblastic lymphoma may represent two distinct clinicopathologic entities within the group of diffuse large B-cell lymphomas.
abstract: OBJECTIVE
  The reliability of immunohistochemistry for subdividing diffuse large B-cell lymphomas (DLBCL) into germinal center B-cell-like (GCB) and non-GCB prognostic subgroups is debated. In this study we evaluated the prognostic significance of such subgrouping on a series of 153 DLBCL patients. Furthermore, we investigated whether both subgroups could comprise clinicopathologic entities recognized by their morphology and characterized by a distinct phenotype, specific genetic abnormalities, and clinical characteristics.
  
  
  METHODS
  All samples from patients were reviewed and morphologically subdivided into large cleaved, immunoblastic, and not otherwise specified DLBCL. GCB and non-GCB immunohistochemical profiles were established. The presence of chromosomal translocations involving BCL2, BCL6, and MYC and/or rearrangements of these genes was investigated.
  
  
  RESULTS
  Subdividing DLBCL with either a GCB or non-GCB immunophenotypic profile was not of prognostic significance. Nevertheless, CD10 expression was a predictor of favorable outcome, whereas high bcl-2 expression and BCL6 rearrangement were adverse predictors of disease-free survival. Interestingly, large cleaved DLBCL was clearly associated with a GCB immunophenotypic profile, CD10 expression, BCL2 rearrangement, age younger than 60 years, and low to low/intermediate International Prognostic Index risk, but was not of prognostic significance. In contrast, immunoblastic morphology was associated with a non-GCB profile and was a significant predictor of unfavorable DFS.
  
  
  CONCLUSIONS
  Subdividing DLBCL into subgroups based on their immunohistochemical profile was not of prognostic significance. Nevertheless, it allowed the additional characterization of two lymphoma subgroups previously recognized in the Working Formulation. Both correspond to two distinct clinicopathologic entities within the DLBCL.
authors.affiliation: Department of Pathology, Ghent University Hospital, Ghent, Belgium. pascale.depaepe@ugent.be
authors.forename: Pascale
authors.initials: P
authors.lastname: De Paepe
authors.forename: Ruth
authors.initials: R
authors.lastname: Achten
authors.forename: Gregor
authors.initials: G
authors.lastname: Verhoef
authors.forename: Iwona
authors.initials: I
authors.lastname: Wlodarska
authors.forename: Michel
authors.initials: M
authors.lastname: Stul
authors.forename: Vera
authors.initials: V
authors.lastname: Vanhentenrijk
authors.forename: Marleen
authors.initials: M
authors.lastname: Praet
authors.forename: Chris
authors.initials: C
authors.lastname: De Wolf-Peeters
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D016400:Lymphoma, Large-Cell, Immunoblastic / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000096:biosynthesis; D011379:Prognosis; D051560:Proto-Oncogene Proteins c-bcl-6; D015203:Reproducibility of Results; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D015260:Neprilysin