Diffuse large B‐cell lymphoma after transformation from low‐grade follicular lymphoma: morphological, immunohistochemical, and FISH analyses

Abstract

(1) FL occurs over a broad range of ages, and most cases are manifested initially in lymph nodes.The risk of FL transformation has been reported as being approximately 20% at 8 years.(2,3) Transformation to DLBCL is observed frequently, with cells most commonly resembling centroblasts, (4) but occasionally resembling anaplastic large cells with CD30 expression.(5) Rare cases have transformed to Burkitt or Burkitt-like lymphoma, (6) or precursor B-lymphoblastic lymphoma/acute lymphoid leukemia.(7) Moreover, composite FL and Hodgkin lymphoma have been suggested to represent two morphologic manifestations of the same tumor clones. (8,9) In recent years, several analyses of genetic alterations that appear to affect the risk for FL transformation have been reported, including c-MYC translocation, (6) p53 mutation, (10,11) deletions of the tumor suppressor genes p15 and p16, (12,13) and chromosomal 6q23-26 and 17q aberrations.(14) However, there have been few immunohistochemical analyses of transformed FL. FL is positive for the pan-B-cell marker CD20, and frequently positive for CD10, Bcl-2 and Bcl-6, but is usually negative for the postgerminal center B-cell or plasma cell markers CD30, MUM1 and CD138, and CD5. Because only one study has demonstrated gain of CD30 expression through FL transformation, (5) we considered that more analyses were needed to clarify the immunophenotypic changes occurring during the transformation of FL to DLBCL.Since 2000 DLBCL has been subdivided into GCB and non-GCB (including the activated B-cell phenotype [ABC] and type 3 phenotype) using the cDNA microarray technique. (15,16) The GCB group shows better outcomes and includes cases with translocation (14;18)(q32;q21). For clinical practice, Hans et al.showed that a panel of immunohistochemical markers comprising CD10, Bcl-6, and MUM1 could be used on paraffin-embedded tissues to separate DLBCL into tumors with a GCB or non-GCB phenotype.(17) Davies et al. examined 35 cases of transformed FL, and found that 89% of them had a GCB phenotype and 9% had a non-GCB phenotype. (18) The translocation (14;18)(q32;q21) is present in 80-100% of FLs in Western countries, (19,20) whereas in South-East Asia, including Japan, the incidence of translocation is considerably lower: about 60%.(21) It is unclear whether FL with t(14;18) frequently transforms to DLBCL.The aim of this study was to clarify the natural history of FL, mainly in view of immunophenotypic changes through transformations. We evaluated low-grade FLs and their transformant DLBCLs using morphological, immunhistochemical, and FISH analyses to delineate the heterogeneity of DLBCL after transformation from low-grade FL. Materials and MethodsPatients. The criteria used for identification of transformed FL were those reported for aggressive B-cell lymphomas in a review based on the workshop of the XIth Meeting of the European Association for Haematopathology.(22) Briefly, it was considered that the term 'transformation' should be used only when there was morphological evidence of simultaneo...

Clinicopathological prognostic indicators in 107 patients with diffuse large B‐cell lymphoma transformed from follicular lymphoma

“…(14,15) However, few histopathological and immunohistochemical analyses of transformed FL have been performed. (12,16,17) Hans et al (16) reported that FL grade 3 cases with a predominant diffuse component (>50% diffuse) had a significantly worse overall survival and event-free survival than the remaining FL grade 3 cases.Since 2000, DLBCL has been subdivided into germinal center B-cell (GCB) and non-GCB subgroups (including the activated B-cell phenotype [ABC] and type 3 phenotype) by using the cDNA microarray technique. (18,19) The GCB subgroup shows a better outcome and includes cases with a translocation (14;18)(q32;q21).…”

“…(23) The outcome of the patients with DLBCL transformed from FL with t(14;18) is unclear, although we recently reported that this fusion does not affect clinical outcome. (17) The aim of this study is to clarify the histopathological prognostic parameters of DLBCL transformed from FL. Eleven histopathological parameters influencing progression-free survival (PFS) and ⁄ or OS were evaluated using univariate and multivariate analyses, including the presence of synchronous ⁄ asynchronous FL and DLBCL, the proportion of DLBCL, the highest grade of FL, expressions of CD10, Bcl-2, Bcl-6, MUM1, cMyc, and Ki-67, classification as GCB ⁄ non-GCB subgroups, and detection of IGH/BCL2 fusion using fluorescence in situ hybridization (FISH) analysis.…”

“…(14,15) However, few histopathological and immunohistochemical analyses of transformed FL have been performed. (12,16,17) Hans et al (16) reported that FL grade 3 cases with a predominant diffuse component (>50% diffuse) had a significantly worse overall survival and event-free survival than the remaining FL grade 3 cases.…”

“…We previously reported that 84% of transformed FL cases had a GCB phenotype and 16% had a non-GCB phenotype. (17) However, the prognostic implications were not determined.…”

Role of activation‐induced cytidine deaminase in the progression of follicular lymphoma

“…(10,11) This transformation is usually associated with acceleration of the clinical course. (12) Transformed FLs generally retain the t(14;18) translocation, (13) and it is believed that other genetic abnormalities are necessary in order for this transformation to occur. These secondary genetic events associated with histological transformation include c-myc amplification and translocation, (14,15) bcl-6 translocation, (16) TP53 mutation, (17) P16 gene inactivation, (18) and c-REL amplification.…”