Haematologica 2018 03 22() pii 10.3324/haematol.2017.181024
A linear progression model of follicular lymphomas (FL) FL1, FL2 and FL3A has been favored, since FL 3A often coexist with a FL1/2 component. FL3B, in contrast, is thought to be more closely related to diffuse large B-cell lymphoma (DLBCL), and both FL3B and DLBCL are often simultaneously present in one tumor (DLBCL/FL3B). To obtain more detailed insights into FL progression, comprehensive analysis of a well-defined set of FL1/2 (n=22), FL3A (n=16), FL3B (n=6), DLBCL/FL3B (n=9) and germincal center B-cell(GCB)-type DLBCL (n=45) was performed using gene expression profiling, immunohistochemical staining and genetic analysis by fluorescence in situ hybridization (FISH). While immunohistochemical (CD10, IRF4/MUM1, Ki67, BCL2, BCL6) and genetic profiles (translocations of BCL2, BCL6 and MYC) delineate FL1-3A from FL3B and DLBCL/FL3B, significant differences were observed between FL1/2 and FL3A upon gene expression profiling (GEP). Interestingly, FL3B turned out to be closely related to FL3A, not categorizing within a separate GE cluster, and both FL3A and FL3B showed overlapping profiles in between FL1/2 and DLBCL. Finally, basing upon their gene expression pattern, DLBCL/FL3B represents a composite form of FL3B and DLBCL, with the majority of samples more closely resembling DLBCL. The fact that gene expression profiling clearly separated FL1/2 from both FL3A and FL3B suggests a closer biological relationship of the latter. This notion, however, stands in a certain contrast to immunohistochemical and genetic profiles of the different histologic FL subtypes that point to a closer relationship of FL1/2 and FL3A, and separating them from FL3B.