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Notes: Abstract Background:Controversy in lymphoma classification dates back tothe first attempts to formulate such classifications. Over the years, much ofthis controversy arose from the assumption that there had to be a singleguiding principle – a `gold standard' – for classification, andfrom the existence of multiple different classifications. Design:The International Lymphoma Study Group (I.L.S.G.)developed a consensus list of lymphoid neoplasms, which was published in 1994as the `Revised European–American Classification of Lymphoid Neoplasms'(R.E.A.L.). The classification is based on the principle that a classificationis a list of `real' disease entities, which are defined by a combination ofmorphology, immunophenotype, genetic features, and clinical features. Therelative importance of each of these features varies among diseases, and thereis no one `gold standard'. In some tumors morphology is paramount, in othersit is immunophenotype, a specific genetic abnormality, or clinical features.An international study of 1300 patients, supported by the San SalvatoreFoundation, was conducted to determine whether the R.E.A.L. Classificationcould be used by expert pathologists and had clinical relevance. Since 1995,the European Association of Pathologists (EAHP) and the Society forHematopathology (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 AdvisoryCommittee (CAC) was formed to ensure that the WHO Classification will beuseful to clinicians. Results:The International Lymphoma Study showed that the R.E.A.L.Classification could be used by pathologists, with inter-observerreproducibility better than for other classifications (〉85%).Immunophenotyping was helpful in some diagnoses, but not required for manyothers. New entities not specifically recognized in the Working Formulationaccounted for 27% of the cases. Diseases that would have been lumpedtogether as `low grade' or `intermediate/high grade' in the WorkingFormulation showed marked differences in survival, confirming that they needto be treated as distinct entities. Clinical features such as theInternational Prognostic Index were also important in determining patientoutcome. The WHO Clinical Advisory Committee concluded that clinical groupingsof lymphoid neoplasms was neither necessary nor desirable. Patient treatmentis determined by the specific type of lymphoma, with the addition of gradewithin the tumor type, if applicable, and clinical prognostic factors such asthe International Prognostic Index (IPI). Conclusions:The experience of developing the WHO Classificationhas produced a new and exciting degree of cooperation and communicationbetween oncologists and pathologists from around the world, which shouldfacilitate progress in the understanding and treatment of hematologicmalignancies.