Who is WHO and what was REAL?

Abstract

The principles of the new WHO classification of haematopoietic and lymphoid tumours are based on those defined in the Revised European American classification of Lymphoid neoplasms (REAL), published by the International Lymphoma Study Group (ILSG) in 1994. Thus, the new WHO classification may be considered an updated version of the REAL classification rather than of the old WHO classification published in 1976. Disease entities are defined on the basis of morphological, phenotypic, genotypic, and clinical data. The relative impact of these characteristics varies among different diseases and there is "no gold standard". Thus, the strict hierarchy among diagnostic criteria, headed by morphology and followed by immunohistochemistry and genetics, has been discontinued. The WHO classification not only encompasses lymphoid tumours but extends to myeloid, mast cell and histiocytic/dendritic cell malignancies. Neoplasms are primarily stratified according to their tumour cell lineage. For each neoplasm a cell of origin is postulated. The classification of lymphoid malignancies recognises three major categories, B-cell neoplasms, T-/NK-cell neoplasms, and Hodgkin lymphomas. B-cell and T-cell lymphomas are further divided into precursor neoplasms and mature neoplasms, the latter being subdivided according to their clinical manifestation into disseminated/leukaemic, extranodal and nodal malignancies. In contrast to previous classifications, the neoplasms are grouped neither according to their histological grade (Kiel classification) nor according to their clinical aggressiveness (International Working Formulation). However, the histological grade is considered a prognostic factor which enters into the description of each disease entity. Hodgkin's disease, now more appropriately termed Hodgkin lymphoma, comprises nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphomas of nodular sclerosis, mixed cellularity, lymphocyte-depleted and lymphocyte-rich subtype. For practical purposes this minireview disregards the description of myeloid, macrophage/histiocytic, dendritic cell and mast cell disorders. Furthermore, the present paper is restricted to those lymphoid tumours that are not already identically described in the REAL classification, in order to focus on what is really new in the WHO classification.