Cell-of-origin classification using the Hans and Lymph2Cx algorithms in primary cutaneous large B-cell lymphomas

Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin, vol. 480, pp. 667–675

Abstract

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) and primary cutaneous follicle center lymphoma with a diffuse population of large cells (PCFCL-LC) are both primary cutaneous B-cell lymphomas with large-cell morphology (CLBCL) but with different clinical characteristics and behavior. In systemic diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), gene-expression profiling (GEP) revealed two molecular subgroups based on their cell-of-origin (COO) with prognostic significance: the germinal center B-cell-like (GCB) subtype and the activated B-cell-like (ABC) subtype. This study investigated whether COO classification is a useful tool for classification of CLBCL. For this retrospective study, 51 patients with PCDLBCL-LT and 15 patients with PCFCL-LC were analyzed for their COO according to the immunohistochemistry-based Hans algorithm and the NanoString GEP-based Lymph2Cx algorithm. In PCFCL-LC, all cases (100%) classified as GCB by both Hans and Lymph2Cx. In contrast, COO classification in PCDLBCL-LT was heterogeneous. Using Hans, 75% of the PCDLBCL-LT patients classified as non-GCB and 25% as GCB, while Lymph2Cx classified only 18% as ABC, 43% as unclassified/intermediate, and 39% as GCB. These COO subgroups did not differ in the expression of BCL2 and IgM, mutations in MYD88 and/or CD79B, loss of CDKN2A, or survival. In conclusion, PCFCL-LC uniformly classified as GCB, while PCDLBCL-LT classified along the COO spectrum of DLBCL-NOS using the Hans and Lymph2Cx algorithms. In contrast to DLBCL-NOS, the clinical relevance of COO classification in CLBCL using these algorithms has limitations and cannot be used as an alternative for the current multiparameter approach in differentiation of PCDLBCL-LT and PCFCL-LC.

Authors 16

1. Anne M.R. Schrader corresponding Aachen Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. a.m.r.schrader@lumc.nl

   Department of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands

2. Ruben A. L. de Groen Aachen Department of Hematology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

3. Rein Willemze Aachen Department of Dermatology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands

4. Patty M. Jansen Aachen Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands

5. Koen D. Quint Aachen Department of Dermatology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands

6. Tom van Wezel Aachen Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands

7. Ronald van Eijk Aachen Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands

8. Dina Ruano Aachen Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands

9. Cornelis P. Tensen Aachen Department of Dermatology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands

10. Esther I. Hauben

    Universitair Ziekenhuis Leuven

    Affiliation as printed

    Department of Pathology, University Hospitals Leuven, Leuven, Belgium

11. Feng Jung Sherida H. Woei-A-Jin

    Universitair Ziekenhuis Leuven

    Affiliation as printed

    Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium

12. Anne Marie Busschots

    Universitair Ziekenhuis Leuven

    Affiliation as printed

    Department of Dermatology, University Hospitals Leuven, Leuven, Belgium

13. Anke van den Berg

    University Medical Center Groningen

    Affiliation as printed

    Department of Pathology, University Medical Center Groningen, Groningen, The Netherlands

14. Arjan Diepstra

    University Medical Center Groningen

    Affiliation as printed

    Department of Pathology, University Medical Center Groningen, Groningen, The Netherlands

15. Maarten H. Vermeer Aachen Department of Dermatology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands

16. Joost S.P. Vermaat Aachen Department of Hematology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands