CONTEXT: Beginning with the immunologic classifications of Lukes and Collins and Kiel and culminating in the Revised European-American Lymphoma and World Health Organization classifications, the diagnosis of lymphoid tumors relies heavily on the determination of cell lineage, maturation, and function, based on antigen expression in addition to morphology and clinical features. Technologic advances in immunology, antibody production, genetic analysis, cloning, and the identification of new genes and proteins by microarray and proteomics have provided pathologists with many antibodies to use in routine diagnosis. OBJECTIVE: To provide guidance to the practicing pathologist in the appropriate selection of an antibody panel for the diagnosis of lymphoma based on morphology and relevant clinical data and to avoid pitfalls in the interpretation of immunohistochemical data. Attention is given to some of the newer antibodies, particularly against transcription factors, that are diagnostically and prognostically useful. DATA SOURCES: The information presented in this article is based on review of the literature using the OVID database (Ovid MEDLINE 1950 to present with daily update) and 20 years of experience in diagnostic hematopathology. CONCLUSIONS: Immunophenotyping is required for the diagnosis and classification of lymphoid malignancies. Many paraffin-reactive antibodies are available to the pathologist but most are not specific. To avoid diagnostic pitfalls, interpretation of marker studies must be based on a panel and knowledge of a particular antigen's expression in normal, reactive, and neoplastic conditions.
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