Immunophenotypic and genotypic markers of follicular center cell neoplasiain diffuse large B-cell lymphomas

Diffuse large B-cell lymphomas (DLBCL) are a biologically and clinically he terogeneous entity. Although some DLBCL represent transformation of follicu lar lymphomas (FL), the proportion that is of follicular center cell (FCC) origin remains uncertain. Immunophenotypic and genotypic markers used to su ggest a FCC origin for a lymphoma (bcl-6 and CD10 expression, lack of CD138 expression, bcl-2 rearrangements [RI) or to subdivide DLBCL (bcl-2 express ion, bcl-6 R) were therefore investigated in 22 FL and 44 DLBCL using paraf fin section immunostains and Southern blot/polymerase chain reaction analys is. All FL tested were bcl-6+ (19) and CD138- (22) with 16/19 also bcl-2 an d CD10+ (classic phenotype), one bcl2+, CD10- (grade III) and two bcl2-, CD 10+ (grade II or III). Bcl-2R was identified in 4/5 FL-GrI, 3/6 FL-GrII, an d 1/3 FL-GrIII. Bcl-6R was found in 0/5, 2/4, and 0/3 FL, respectively. All but 3/41 DLBCL were bcl-6+ with 17/37 also bcl-2+ and CD10+. Three of thes e cases were also CD138+. Twelve bcl-6+ cases were bcl-2+, CD10-, six bcl-2 -, CD10+, and two bcl-2-, CD10-. The three bcl-6- cases were bcl-2+, CD138- and two were CD10+. Bcl-2R was identified in 5/27 DLBCL with 4/5 bcl-2+, 3 /4 tested CD10+ and 4/4 bcl-6+. Bcl-6R was identified in 7/26 including thr ee with a classic FL phenotype. The vast majority of DLBCL in this study ha ve an immunophenotype that supports a FCC origin. Although the proportion o f DLBCL that co-expressed bcl-6, CD10 and bcl-2 was lower than for the FL, absence of bcl-2 or CD10 may be associated with higher grade FL. It is also possible that bcl-6 expression is not completely specific for a FCC origin . Only a minority of cases suggested postfollicular differentiation. Only a minority of DLBCL show bcl-2R, suggesting that many have a different molec ular pathogenesis than most low-grade FL. Bcl-6R did mot exclude a FCC orig in.