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

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: Anne M R Schrader, Ruben A L de Groen, Rein Willemze, Patty M Jansen, Koen D Quint, Tom van Wezel, Ronald van Eijk, Dina Ruano, Cornelis P Tensen, Esther Hauben, F J S H Woei-A-Jin, Anne M Busschots, Anke van den Berg, Arjan Diepstra, Maarten H Vermeer, Joost S P Vermaat
• Journal: Virchows Archiv : an international journal of pathology (Virchows Arch) Vol. 480 Issue 3 Pg. 667-675 (Mar 2022) ISSN: 1432-2307 [Electronic] Germany
• PMID: 35028710 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Topics

• Algorithms
• Germinal Center (pathology)
• Humans
• Immunohistochemistry
• Lymphoma, Large B-Cell, Diffuse (genetics, pathology)
• Retrospective Studies