Harris N L, Jaffe E S, Diebold J, Flandrin G, Muller-Hermelink H K, Vardiman J
Department of Pathology, Massachusetts General Hospital, Boston, USA.
Ann Oncol. 2000;11 Suppl 1:3-10.
Controversy in lymphoma classification dates back to the first attempts to formulate such classifications. Over the years, much of this controversy arose from the assumption that there had to be a single guiding principle--a 'gold standard'--for classification, and from the existence of multiple different classifications.
The International Lymphoma Study Group (I.L.S.G.) developed a consensus list of lymphoid neoplasms, which was published in 1994 as the 'Revised European-American Classification of Lymphoid Neoplasms' (R.E.A.L.). The classification is based on the principle that a classification is a list of 'real' disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one 'gold standard'. In some tumors morphology is paramount, in others it is immunophenotype, a specific genetic abnormality, or clinical features. An international study of 1300 patients, supported by the San Salvatore Foundation, was conducted to determine whether the R.E.A.L. Classification could be used by expert pathologists and had clinical relevance. Since 1995, the European Association of Pathologists (EAHP) and the Society for Hematopathology (SH) have been developing a new World Health Organization (WHO) Classification of hematologic malignancies, using an updated R.E.A.L. Classification for lymphomas and applying the principles of the R.E.A.L. Classification to myeloid and histiocytic neoplasms. A Clinical Advisory Committee (CAC) was formed to ensure that the WHO Classification will be useful to clinicians.
The International Lymphoma Study showed that the R.E.A.L. Classification could be used by pathologists, with inter-observer reproducibility better than for other classifications (> 85%). Immunophenotyping was helpful in some diagnoses, but not required for many others. New entities not specifically recognized in the Working Formulation accounted for 27% of the cases. Diseases that would have been lumped together as 'low grade' or 'intermediate/high grade' in the Working Formulation showed marked differences in survival, confirming that they need to be treated as distinct entities. Clinical features such as the International Prognostic Index were also important in determining patient outcome. The WHO Clinical Advisory Committee concluded that clinical groupings of lymphoid neoplasms was neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors such as the International Prognostic Index (IPI).
The experience of developing the WHO Classification has produced a new and existing degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies.
淋巴瘤分类的争议可追溯到最初制定此类分类的尝试。多年来，这种争议很大程度上源于这样一种假设，即分类必须有一个单一的指导原则——“金标准”，以及多种不同分类的存在。
国际淋巴瘤研究组（I.L.S.G.）制定了一份淋巴样肿瘤的共识清单，于1994年作为《修订的欧美淋巴样肿瘤分类》（R.E.A.L.）发表。该分类基于这样一个原则，即分类是一份“真实”疾病实体的清单，这些实体由形态学、免疫表型、遗传特征和临床特征的组合来定义。这些特征中每一个的相对重要性在不同疾病中各不相同，不存在一个“金标准”。在某些肿瘤中，形态学至关重要，在其他肿瘤中则是免疫表型、特定的基因异常或临床特征。在圣萨尔瓦托基金会的支持下，对1300名患者进行了一项国际研究，以确定R.E.A.L.分类是否能被专家病理学家使用以及是否具有临床相关性。自1995年以来，欧洲病理学家协会（EAHP）和血液病理学协会（SH）一直在制定新的世界卫生组织（WHO）血液系统恶性肿瘤分类，对淋巴瘤使用更新后的R.E.A.L.分类，并将R.E.A.L.分类的原则应用于髓系和组织细胞肿瘤。成立了一个临床咨询委员会（CAC）以确保WHO分类对临床医生有用。
国际淋巴瘤研究表明，病理学家可以使用R.E.A.L.分类，观察者间的可重复性优于其他分类（>85%）。免疫表型分析在某些诊断中有所帮助，但对许多其他诊断并非必需。工作方案中未明确认可的新实体占病例的27%。在工作方案中会被归为“低级别”或“中/高级别”的疾病在生存率上显示出显著差异，证实它们需要被视为不同的实体。国际预后指数等临床特征在确定患者预后方面也很重要。WHO临床咨询委员会得出结论，淋巴样肿瘤的临床分组既无必要也不可取。患者的治疗取决于淋巴瘤的具体类型，如果适用，还需加上肿瘤类型内的分级以及国际预后指数（IPI）等临床预后因素。
制定WHO分类的经验在全球肿瘤学家和病理学家之间产生了新的且现有的合作与交流程度，这应有助于在血液系统恶性肿瘤的理解和治疗方面取得进展。
