Aggressive B-cell non-Hodgkin lymphomas: a report of the lymphoma workshop of the 20th meeting of the European Association for Haematopathology

Abstract

Aggressive B-cell non-Hodgkin lymphomas are a heterogeneous group of diseases and our concepts are evolving as we learn more about their clinical, pathologic, molecular genetic features. Session IV of the 2020 EAHP Workshop covered aggressive, predominantly high-grade B-cell lymphomas, many that were difficult to classify. In this manuscript, we summarize the features of the submitted cases and highlight differential diagnostic difficulties. We specifically review issues related to high-grade B-cell lymphomas (HGBCLs) with MYC and BCL2 and/or BCL6 rearrangements including TdT expression in these cases, HGBCL, not otherwise specified, large B-cell lymphomas with IRF4 rearrangement, high-grade/large B-cell lymphomas with 11q aberration, Burkitt lymphoma, and pleomorphic mantle cell lymphoma. Since the workshop, the 5th edition of the WHO Classification for Haematolymphoid Tumours (WHO-HAEM5) and International Consensus Classification (ICC) 2022 were published. We endeavor to use the updated terminology.

Keywords: Burkitt lymphoma; Diffuse large B-cell lymphoma/high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; High-grade B-cell lymphoma; High-grade B-cell lymphoma/large B-cell lymphoma with 11q aberration; Large B-cell lymphoma with IRF4 rearrangement.

Fig. 1

Schematic demonstrating MYC FISH break apart probe design. The black box represents the MYC locus on chromosome 8q14. Probe set 1, with a MYC-centric design narrowly flanks MYC. Probe set 2, with a “wide gap” design flanks MYC with larger region of intervening DNA. The short brown arrow represents a “genic” break point immediately upstream of MYC which typically involved IGH as the partner gene. It would be detected by splits on both probe sets 1 and 2. The long brown arrows represent “non-genic” breakpoints that are enriched for non IGH partner genes and would be detected by probe set 2 but not probe set 1. FISH, fluorescence in situ hybridization

Fig. 2

DHL/THLs with TdT expression. Low-magnification H&E images (A, B, C, 10 ×), high-magnification H&E images (D, E, F, 40 ×), and TdT immunostain (G, H, I, 40 ×) of double or triple hit lymphoma with TdT expression. These cases represent the morphologic spectrum of such cases including blastoid (D), diffuse large B-cell lymphoma (E), or high-grade B-cell lymphoma morphology (F)

Fig. 3

High-grade B-cell lymphoma, nos, case 759: A Peripheral blood with leukemic cells (100 ×). B Pelvic mass with blastoid morphology (H&E 40 ×). This patient was a 55-year-old woman who presented with a pelvic mass and bone marrow involvement. Flow cytometry showed a bright CD45 + B-cell population (CD19 + , CD10 + . CD20-, CD22 + , CD34-, TdT-, BCL2-, surface immunoglobulin negative). IGH::MYC rearrangement was present by FISH and t(8;14) was seen by karyotyping. Case 794: C Peripheral blood involvement (100 ×). D Cervical lymph node biopsy showing high-grade, Burkitt-like morphology (H&E, 40 ×) with a tingible body macrophage (center). This patient was 62-year-old woman who presented with splenomegaly and generalized lymphadenopathy. The cells express CD20, PAX5, BCL2, and MUM1 with near 100% MYC staining. The cells were negative for CD5, CD10, and BCL6. IGH::MYC but no IGH::BCL2 or BCL6-rearrangement was seen

Fig. 4

Large B-cell lymphoma with IRF4-rearrangement. A H&E, 4 × ; B H&E, 60 × , C CD21 immunostain, 4 × ; D CD20 immunostain, 4 × ; E CD5 immunostain, 4 × ; F CD10 immunostain, 4 × ; G MUM1 immunostain, 20 × . This case expressed BCL6 as well (not shown)

Fig. 5

Burkitt lymphoma with granulomatous reaction, case 184. H&E 40 × , typical small centroblastic cells of Burkitt lymphoma with admixed granulomas

Fig. 6

Aggressive B-cell lymphoma with MYC-R and 11q aberration (case 694). This case was problematic in classification. It had high-grade features with starry sky and tingible body macrophages with coarse apoptotic debris (A, H&E, 10 ×) seen in HG/LBCL-11q. However, the cytomorphology on H&E stain (B, 40 ×) and Giemsa stain (C, 50 ×) is closer to diffuse large B-cell lymphoma. The cells lacked BCL2 (D, 40 ×) but highly expressed MYC (E) by immunostaining. This case had both MYC-R and the 11q aberration