Research Papers:

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

Hanno Witte, Harald Biersack, Svenja Kopelke, Dirk Rades, Hartmut Merz, Veronica Bernard, Hendrik Lehnert and Niklas Gebauer _

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Oncotarget. 2018; 9:19613-19622. https://doi.org/10.18632/oncotarget.24701

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Hanno Witte1,*, Harald Biersack1,*, Svenja Kopelke1, Dirk Rades2, Hartmut Merz3, Veronica Bernard3, Hendrik Lehnert1 and Niklas Gebauer1

1Department of Hematology and Oncology, University Hospital of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany

2Department of Radiation Oncology, University Hospital of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany

3Hämatopathologie Lübeck, Reference Center for Lymph Node Pathology and Hematopathology, Lübeck, Germany

*These authors have contributed equally to this work

Correspondence to:

Niklas Gebauer, email: [email protected]

Keywords: transformed indolent lymphoma; composite histology; de novo diffuse large B-cell Lymphoma; cell-of-origin; prognosis

Received: December 07, 2017     Accepted: March 02, 2018     Published: April 13, 2018


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.

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