Hematopathology: integration of morphologic features and biologic markers for diagnosis

The Revised European-American Classification of Lymphoid Neoplasms (REAL) represented a new paradigm for the classification of lymphomas. Although earlier classification schemes relied strictly on morphologic features or immunophenotype for the definition of diagnostic categories, the REAL classification emphasized that each disease was a distinct entity, defined by a constellation of clinical and laboratory features, i.e., morphologic and genetic features, immunophenotype, clinical presentation, and course. It also noted that the site(s) of presentation were often a signpost for important underlying biologic distinctions. The inclusion of clinical criteria for the definition of disease entities was one of the more novel aspects of the REAL classification. These principles of classification of lymphomas and leukemias also have an impact on diagnostic hematopathology. The REAL classification stresses that diagnoses are based on a multiparameter approach. Although morphologic features alone might suffice for some diagnoses, diagnostic accuracy and reproducibility are enhanced when immunophenotypic and genetic studies are also used. In addition, adequate clinical information is essential for some diagnoses, in particular the mature T-cell lymphomas and leukemias. The proposed World Health Organization classification of lymphoid and hematopoietic neoplasms incorporates these principles of classification and diagnosis.