Diffuse large B-cell lymphomas (DLBCL) are a biologically and clinically heterogeneous entity. Although some DLBCL represent transformation of follicular lymphomas (FL), the proportion that is of follicular center cell (FCC) origin remains uncertain. Immunophenotypic and genotypic markers used to suggest a FCC origin for a lymphoma (bcl-6 and CD10 expression, lack of CD138 expression, bcl-2 rearrangements [R]) or to subdivide DLBCL (bcl-2 expresssion, bcl-6 R) were therefore investigated in 22 FL and 44 DLBCL using paraffin section immunostains and Southern blot/polymerase chain reaction analysis. All FL tested were bcl-6؉ (19) and CD138؊ (22) with 16/19 also bcl-2 and CD10؉ (classic phenotype), one bcl2؉, CD10؊ (grade III) and two bcl2؊, CD10؉ (grade II or III). Bcl-2R was identified in 4/5 FL-GrI, 3/6 FL-GrII, and 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 these 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 three with a classic FL phenotype. The vast majority of DLBCL in this study have an immunophenotype that supports a FCC origin. Although the proportion of 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 molecular pathogenesis than most low-grade FL. Bcl-6R did not exclude a FCC origin.
KEY WORDS: BCL-2; BCL-6; CD10; CD138; diffuse large B-cell lymphoma; follicular lymphoma; germinal center Mod Pathol 2000;13(11):1219 -1231Diffuse large B-cell lymphomas (DLBCL), as defined in the REAL and upcoming WHO lymphoma classifications, represent a heterogeneous entity that includes not only transformed (noncleaved or centroblastic) follicular center cell (FCC) lymphomas but also all other lymphomas composed of large and transformed B cells (1-3). The proposed WHO classification recognizes three relatively uncommon subtypes of DLBCL [mediastinal (thymic), intravascular, and primary effusion lymphoma] but the immunoblastic lymphomas, transformed/"high grade" marginal zone lymphomas of mucosaassociated lymphoid tissue (MALT) and presumably nodal types and all other types of transformed B-cell lymphomas are not distinguished from one another. The DLBCL were grouped together for two main reasons. First, it was difficult to reproduce some of the previously described morphologic distinctions (such as those between transformed FCC lymphomas and immunoblastic lymphomas). Second, it was unclear how, for example, large noncleaved (LNC) FCC/centroblastic lymphomas should ...