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Ferrata Storti Foundation
Haematologica 2021 Volume 106(10):2654-2666
Evolutionary clonal trajectories in nodular lymphocyte-predominant Hodgkin lymphoma with high risk of transformation
Lisa Paschold,1 Edith Willscher,1 Julia Bein,2 Martine Vornanen,3 Dennis A. Eichenauer,4 Donjete Simnica,1 Benjamin Thiele,5 Claudia Wickenhauser,6 Andreas Rosenwald,7 Heinz-Wolfram Bernd,8 Wolfram Klapper,9 Alfred C. Feller,8 German Ott,10 Falko Fend,11 Sylvia Hartmann2,12 and Mascha Binder1
1Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany: 2Dr. Senckenberg Institute of Pathology, Goethe University Hospital of Frankfurt am Main, Frankfurt am Main, Germany; 3Department of Pathology, Tampere University Hospital and University of Tampere, Tampere, Finland; 4University of Cologne, First Department of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf, Cologne, and German Hodgkin Study Group, University Hospital Cologne, Cologne, Germany; 5Department of Hematology and Oncology, University Medical Center Hamburg- Eppendorf, Hamburg, Germany; 6Institute of Pathology, Martin-Luther-University Halle- Wittenberg, Halle (Saale), Germany; 7Institute of Pathology, University of Würzburg and Comprehensive Cancer Center (CCC) Mainfranken, Würzburg, Germany; 8Hematopathology Lübeck, Lübeck, Germany; 9Department of Pathology, Division of Hematopathology and Lymph Node Registry, Schleswig-Holstein Medical Center, Campus Kiel, Kiel, Germany; 10Department of Clinical Pathology, Robert-Bosch- Krankenhaus and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; 11Institute of Pathology, Eberhard Karls University Tübingen, Tübingen, Germany and 12Reference and Consultation Center for Lymph Node and Lymphoma Pathology, Goethe University, Frankfurt am Main, Germany
ABSTRACT
The B-cell architecture of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is complex since it is composed of malignant lymphocyte-predominant cells along with a rich B-cell bystander environment. To gain insight into molecular determinants of disease transformation, we studied B-cell evolutionary trajectories in lymphoma tissue from diagnosis to relapse or transformation to non- Hodgkin lymphoma by next-generation sequencing of immunoglobulin heavy chains. Patients with NLPHL that later transformed were older and showed IgD negativity, absence of the characteristic IGHV3/IGHD3/IGHJ6 lymphocyte-predominant rearrangement and high repertoire clonality. We constructed phylogenetic trees within the compartment of the malignant clone to investigate clonal evolution. In all relapsing cases, the lymphocyte-predominant rearrangement was identical at diagnosis and relapse. NLPHL cases with transformation showed more complex trajectories with strong intraclonal diversifica- tion. The dominant founder clone in transformations showed clonal evolution if derived from the same cell of origin, or arose from a differ- ent cell of origin. Together, our data point to a significant role of anti- genic drive in the transformation of NLHPL and identify high B-cell repertoire clonality with dominant intraclonal lymphocyte-predomi- nant cell diversification as a hallmark of transformation. Sequencing of initial paraffin-embedded tissue may therefore be applied diagnostically to identify NLPHL cases with high risk of transformation.
Introduction
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) accounts for approximately 5-16% of all cases of Hodgkin lymphoma and has a male predilec- tion. The monoclonal tumor cells, termed lymphocyte-predominant (LP)1-3 cells,
Hodgkin Lymphoma
Correspondence:
MASCHA BINDER
Mascha.Binder@uk-halle.de
Received: January 22, 2021. Accepted: March 24, 2021. Pre-published: April 22, 2021.
https://doi.org/10.3324/haematol.2021.278427 ©2021 Ferrata Storti Foundation
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