Institute of Pathology and Neuropathology and Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany.
Pathology-DNA, Location Rijnstate Hospital, Arnhem, the Netherlands.
Virchows Arch. 2024 Feb;484(2):195-214. doi: 10.1007/s00428-023-03644-0. Epub 2023 Sep 25.
With the explosion in knowledge about the molecular landscape of lymphoid malignancies and the increasing availability of high throughput techniques, molecular diagnostics in hematopathology has moved from isolated marker studies to a more comprehensive approach, integrating results of multiple genes analyzed with a variety of techniques on the DNA and RNA level. Although diagnosis of lymphoma still relies on the careful integration of clinical, morphological, phenotypic, and, if necessary molecular features, and only few entities are defined strictly by genetic features, genetic profiling has contributed profoundly to our current understanding of lymphomas and shaped the two current lymphoma classifications, the International Consensus Classification and the fifth edition of the WHO classification of lymphoid malignancies. In this review, the current state of the art of molecular diagnostics in lymphoproliferations is summarized, including clonality analysis, mutational studies, and gene expression profiling, with a focus on practical applications for diagnosis and prognostication. With consideration for differences in accessibility of high throughput techniques and cost limitations, we tried to distinguish between diagnostically relevant and in part disease-defining molecular features and optional, more extensive genetic profiling, which is usually restricted to clinical studies, patients with relapsed or refractory disease or specific therapeutic decisions. Although molecular diagnostics in lymphomas currently is primarily done for diagnosis and subclassification, prognostic stratification and predictive markers will gain importance in the near future.
随着人们对淋巴肿瘤分子特征的认识不断深入，高通量技术的应用也日益广泛，血液病理学中的分子诊断已从单一标志物研究发展为更全面的方法，将 DNA 和 RNA 水平上多种技术分析的多个基因的结果整合在一起。尽管淋巴瘤的诊断仍然依赖于临床、形态学、表型特征的仔细综合，必要时还需要分子特征，只有少数实体严格由遗传特征定义，但基因谱分析极大地促进了我们对淋巴瘤的现有认识，并塑造了当前的两种淋巴瘤分类，即国际共识分类和第五版世界卫生组织淋巴肿瘤分类。在这篇综述中，总结了淋巴增生性疾病分子诊断的最新技术，包括克隆性分析、突变研究和基因表达谱分析，重点介绍了诊断和预后的实际应用。考虑到高通量技术的可及性和成本限制的差异，我们试图区分诊断相关的和部分疾病定义的分子特征以及可选的、更广泛的遗传谱分析，后者通常仅限于临床研究、复发或难治性疾病患者或特定的治疗决策。虽然目前淋巴瘤的分子诊断主要用于诊断和分类，但在不久的将来，预后分层和预测标志物将变得更加重要。
