间变性淋巴瘤激酶阳性大 B 细胞淋巴瘤 (ALK LBCL) 是一种罕见且高度侵袭性的淋巴瘤，具有特征性 ALK 重排。涉及 ALK 的多种融合基因已被证实，但 ALK 融合伴侣对 ALK 蛋白表达的影响以及 ALK LBCL 的遗传特征仍然相对未知。在本研究中，我们对7例ALK LBCL进行了广泛的临床病理学和分子分析，探讨ALK融合基因与ALK蛋白表达之间的相关性，从而丰富了该肿瘤的遗传特征。我们整合了临床、组织病理学/免疫表型和分子研究的结果，包括对 3 个样本进行了新一代测序，并对 6 个病例进行了基于 RNA 的 ALK 融合基因检测。我们鉴定了五种不同类型的 ALK 融合基因，包括 CLTC、NPM1、PABPC1、SEC31A 和 TFG。值得注意的是，只有 NPM1::ALK 融合基因显示细胞核和细胞质 ALK 染色，其余四个融合基因导致细胞质 ALK 染色。我们的分析表明，CLTC::ALK 融合导致 ALK 独特的细胞质核周高尔基区局灶颗粒异质染色模式。此外，我们还发现了六种潜在的具有临床意义的基因突变，包括 TET2、CHD2、DTX1、KMT2D、LRP1B 和 XPO1。此外，在所有情况下，均未观察到 5-羟甲基胞嘧啶 (5hmC)。我们介绍了 7 例 ALK LBCL 病例，讨论融合基因与 ALK 蛋白表达之间的相关性，并增强我们对该肿瘤遗传属性的理解。这项研究还显示，几乎所有 7 例 ALK LBCL 病例中都存在 5hmC 缺失，与 TET2 突变无关。版权所有 © 2024 澳大利亚皇家病理学家学院。由 Elsevier B.V. 出版。保留所有权利。

Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+ LBCL) is a rare and highly aggressive lymphoma with characteristic ALK rearrangements. Various fusion genes involving ALK have been demonstrated, but the influence of the ALK fusion partners on ALK protein expression and the genetic characteristics of ALK+ LBCL remain relatively unknown. In this study, we conducted an extensive clinicopathological and molecular analysis on seven cases of ALK+ LBCL to explore the correlation between ALK fusion genes and ALK protein expression, thereby enriching the genetic characteristics of this tumour. We integrated the findings from clinical, histopathological/immunophenotypic, and molecular studies, including three samples subjected to next-generation sequencing, and six cases underwent RNA-based ALK fusion gene detection. We identified five distinct types of ALK fusion genes, including CLTC, NPM1, PABPC1, SEC31A, and TFG. Notably, only the NPM1::ALK fusion showed nuclear and cytoplasmic ALK staining, and the remaining four fusion genes resulted in cytoplasmic ALK staining. Our analysis revealed that the CLTC::ALK fusion resulted in a unique cytoplasmic perinuclear Golgi zone focal granular heterogeneous staining pattern of ALK. Additionally, we identified six potentially clinically significant gene mutations, including TET2, CHD2, DTX1, KMT2D, LRP1B, and XPO1. Furthermore, in all cases, the absence of 5-hydroxymethylcytosine (5hmC) was observed. We present seven cases of ALK+ LBCL, discussing the correlation between fusion genes and ALK protein expression, and enhancing our understanding of the genetic attributes of this tumour. This study also shows the loss of 5hmC in nearly all seven ALK+ LBCL cases, independently of TET2 mutations.Copyright © 2024 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.