Indolent lymphoma with composite histology and simultaneous transformation at initial diagnosis exhibit clinical features similar to de novo diffuse large B-cell lymphoma

Abstract

While various studies characterized clinical and prognostic properties of de novo diffuse large B-Cell lymphoma (DLBCL) and transformed indolent lymphomas, the clinicopathological features of indolent lymphoma and simultaneous secondary transformation upon initial diagnosis (ssDLBCL) are insufficiently established.Between 2010 and 2017, 247 consecutive patients admitted to our institution and treated for DLBCL were investigated for composite histology of ssDLBCL-type. Upon systematical histopathological evaluation composite histology was identified in 22/247 cases (8.9%).The predominant histology of the underlying indolent lymphoma was follicular lymphoma of variable grading (I-IIIA; 81.8%) whereas marginal zone lymphoma represented a minor sub group (18.2%). Clinicopathological investigation revealed a high degree of concordance between ssDLBCL and de novo DLBCL upon initial diagnosis and clinical courses were shown to be strikingly similar. The predominant fraction of ssDLBCL were germinal center derived lymphomas (GCB-type) with a trend towards a superior outcome compared with non-GCB-type ssDLBCL. Additionally, we demonstrate a significant adverse prognostic impact of an underlying indolent lymphoma component other than follicular-type lymphoma (e.g. marginal zone lymphoma). Moreover, the frequency of double-hit (DHL) or double-expressor lymphomas (DEL) appears to be low.Our findings provide substantial insight into the behavior of ssDLBCL, highlight the ramifications of the concurrent high-grade fraction within indolent lymphomas and underline therapeutic efficacy of R-CHOP type immunochemotherapy in the majority of ssDLBCL patients.

A Clinico-Genotypic Prognostic Index for De Novo Composite Diffuse Large B-Cell Lymphoma Arising from Follicular Lymphoma in Asian patients treated in the Rituximab Era

“…Our study also suggests that patients with composite FL and DLBCL carrying the ABC subtype tended to have a shorter OS as compared to those with the GCB subtype, even though this finding was short of statistical significance and not incorporated into the CGI model. This is similar to the findings reported in Witte et al, 2018 where non-germinal centre derived composite FL and DLBCL had an inferior clinical outcome bordering on statistical significance as compared to cases with GCB subtype 26 . We compared these results to studies analysing the prognostic value of Han's algorithm in de novo DLBCL.…”

Impact of concurrent indolent lymphoma on the clinical outcome of newly diagnosed diffuse large B-cell lymphoma

“…This distribution pattern of COO is consistent with results from prior smaller studies. 9,10 In contrast, for DLBCL concurrent with other indolent NHLs, the GCB and the non-GCB subtypes were equally common in our series (thus enriched for non-GCB relative to DLBCL alone cases). One recent study reported that DLBCL with discordant bone marrow involvement was predominantly the GCB subtype, 14 although some cases may have had FL in the bone marrow.…”

“…[4][5][6] In the rituximab era, several small retrospective series of concurrent DLBCL and FL (,60 cases each) have been described, with contradicting results for PFS and OS in comparison with DLBCL. [7][8][9][10] Likewise, DLBCL with discordant bone marrow involvement of an indolent NHL has been retrospectively studied by several groups, [11][12][13][14] most of which included ,60 cases except for a recent MD Anderson study (n 5 90), 14 again with inconsistent results regarding PFS compared with DLBCL without bone marrow involvement.…”

Transformed diffuse large B-cell lymphoma from marginal zone lymphoma in the anterior mediastinum: A case report and review of the literature

“…21 Conversely, another study revealed that concurrent DLBCL with indolent lymphoma other than follicular lymphoma has a significantly poor prognosis. 22 Indeed, one MZL case in the mediastinum that transformed to DLBCL was refractory to R-CHOP therapy. 23 Therefore, although CMR with chemoradiotherapy was achieved in our case, careful follow-up is necessary in the future.…”