Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, University Hospital Tübingen, Liebermeisterstrasse 8, 72076, Tübingen, Germany.
Virchows Arch. 2023 Mar;482(3):551-560. doi: 10.1007/s00428-023-03516-7. Epub 2023 Feb 22.
Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin lymphoma (B-NHL) in adults. These lymphomas are classified according to gene expression profiling (GEP) into germinal center B-cell (GCB) and activated B-cell type (ABC). Recent studies have suggested new subtypes of large B-cell lymphoma, based on genetic and molecular alterations, among them is large B-cell lymphoma with IRF4-rearrangement (LBCL-IRF4). We used fluorescence in situ hybridization (FISH), GEP (using the DLBCL COO assay by HTG Molecular Inc), and next generation sequencing (NGS) to comprehensively characterize 30 cases of LBCLs located in Waldeyer's ring in adult patients and to identify LBCL-IRF4. FISH revealed breaks of IRF4 in 2/30 cases (6.7%), BCL2 breaks in 6/30 cases (20.0%), and IGH breaks in 13/29 cases (44.8%). GEP classified 14 cases each as GCB or ABC subtype, and 2 cases remained unclassified; this was concordant with the immunohistochemistry (IHC) in 25/30 cases (83.3%). A subgrouping, based on GEP, was performed: group 1 included 14 GCB cases with the most frequent mutations in BCL2 and EZH2 in 6/14 cases (42.8%). The two cases with IRF4 rearrangement were assigned to this group by GEP and showed IRF4 mutations, supporting the diagnosis of LBCL-IRF4. Group 2 included 14 ABC cases; the most frequent mutations were CD79B and MYD88 identified in 5/14 patients (35.7%). Group 3 included 2 unclassifiable cases in which no molecular patterns were detected. Overall, LBCLs of Waldeyer's ring in adult patients are a heterogeneous group, including LBCL-IRF4, which shares several features with cases in the pediatric population.
弥漫性大 B 细胞淋巴瘤（DLBCL）是成人中最常见的 B 细胞非霍奇金淋巴瘤（B-NHL）。这些淋巴瘤根据基因表达谱（GEP）分为生发中心 B 细胞（GCB）和活化 B 细胞型（ABC）。最近的研究基于遗传和分子改变，提出了大 B 细胞淋巴瘤的新亚型，其中包括 IRF4 重排的大 B 细胞淋巴瘤（LBCL-IRF4）。我们使用荧光原位杂交（FISH）、GEP（使用 HTG Molecular Inc 的 DLBCL COO 检测）和下一代测序（NGS）全面分析了 30 例位于成人咽淋巴环的 LBCL，并鉴定 LBCL-IRF4。FISH 显示 2/30 例（6.7%）存在 IRF4 断裂，6/30 例（20.0%）存在 BCL2 断裂，13/29 例（44.8%）存在 IGH 断裂。GEP 将 14 例分类为 GCB 或 ABC 亚型，2 例未分类；这与 25/30 例（83.3%）的免疫组化（IHC）一致。基于 GEP 进行了亚组分类：第 1 组包括 14 例 GCB 病例，其中 6/14 例（42.8%）最常见的突变发生在 BCL2 和 EZH2 中。2 例 IRF4 重排的病例通过 GEP 被归类为该组，并显示 IRF4 突变，支持 LBCL-IRF4 的诊断。第 2 组包括 14 例 ABC 病例；最常见的突变是在 5/14 例患者（35.7%）中发现的 CD79B 和 MYD88。第 3 组包括 2 例无法分类的病例，未检测到分子模式。总的来说，成人咽淋巴环的 LBCL 是一组异质性群体，包括与儿科患者的病例具有一些共同特征的 LBCL-IRF4。
