Pediatric diffuse large B-cell lymphoma demonstrates a high proliferation index, frequent c-Myc protein expression, and a high incidence of germinal center subtype: Report of the French-American-British (FAB) international study group

Abstract

Background: Diffuse large B-cell lymphoma (DLBCL) makes up 10-20% of pediatric non-Hodgkin lymphoma, and these patients have a significantly better prognosis than adults with DLBCL. The difference in prognosis may be related to clinical, phenotypic, and/or biological differences between adult and pediatric DLBCL. In adult DLBCL, the germinal center (GC) phenotype is associated with a better prognosis than the activated B-cell (ABC) phenotype. However, a high proliferative index and expression of Bcl2 and c-Myc protein have all been associated with worse outcomes. While multiple studies have addressed the phenotype and expression patterns of adult DLBCL, relatively little is known about these biological variables in pediatric DLBCL. The goal of this study was to investigate the proliferative index, the relative frequencies of the GC and non-GC subtypes, and the expression of Bcl2 and c-Myc protein in a cohort of children with DLBCL treated in a uniform manner.

Procedure: We performed immunohistochemistry (IHC) for MIB1, CD10, Bcl6, MUM1, Bcl2, and c-Myc on DLBCL tissue from children treated uniformly in the FAB LMB96 trial (SFOP LMB96/CCG5961/UKCCSG/NHL 9600).

Results: Compared to published adult DLBCL studies, pediatric DLBCL demonstrated moderate to high proliferation rates (83%), increased c-Myc protein expression (84%), decreased Bcl2 protein expression (28%), and an increased frequency of the GC phenotype (75%).

Conclusions: These findings suggest that there are significant biologic differences between pediatric and adult forms of DLBCL, which may contribute to the superior prognosis seen in the pediatric population relative to adult disease.

(c) 2008 Wiley-Liss, Inc.

Figures

Figure 1

IHC of representative examples of phenotypic subtypes. The GC-subtype case (top row) shows strong expression of CD10 (A) and Bcl6 (B) without MUM1 (C). A non-GC subtype case (middle row) lacks CD10 (D) and Bcl6 (E) but expresses MUM1 (F). A representative example of a mediastinal DLBCL case (bottom row) lacks CD10 (G) and expresses Bcl6 (H) and MUM1 (I). Samples were stained for indicated target antigen by IHC and counterstained with hematoxylin; original magnification 400×.

Figure 2

Event-free survival from trial entry. The non-GC group showed a trend toward worse survival that did not reach statistical significance and disappeared after adjustment on risk group.