Large cleaved and immunoblastic lymphoma may represent two distinct clinicopathologic entities within the group of diffuse large B-cell lymphomas.
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.
De Paepe
Pascale
P
Department of Pathology, Ghent University Hospital, Ghent, Belgium. pascale.depaepe@ugent.be
Achten
Ruth
R
Verhoef
Gregor
G
Wlodarska
Iwona
I
Stul
Michel
M
Vanhentenrijk
Vera
V
Praet
Marleen
M
De Wolf-Peeters
Chris
C
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
C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D015260:Neprilysin