Impact of flow cytometry on the diagnosis and characterization of lymphomas, chronic lymphoproliferative disorders and plasma cell neoplasias

Lymphocytes can become neoplastic at any stage of their development. When the neoplastic change occurs early on in their ontogeny, they act aggressively, producing a disease designated as lymphoblastic leukemia, invading the marrow, the blood, and sometimes, solid tissues (the latter are called lymphoblastic lymphomas). The antigen profile of these neoplastic cells recapitulates that of lymphoid precursors. When the oncogenic change takes place after lymphocytes have acquired maturation, the neoplastic progeny exhibit the phenotype of adult elements. If these more differentiated lymphocytes infiltrate lymph nodes or other lymphoid tissues or organs, we use the term lymphoma. When mature neoplastic lymphocytes circulate in the blood, they usually produce indolent ailments, generally designated as chronic lymphoproliferative disorders (CLPD). Differences between lymphomas and CLPD are not always distinct, since malignant lymphocytes may simultaneously involve tissues and blood. The term myeloma applies to systemic neoplasias of the bone marrow that are composed of plasma cells, the latest stage in the life of the B-lymphocyte. The nomenclature of lymphoid neoplasias has evolved over time and this process is certain to continue, as new biological advances are made. Until recently, characterization of the lymphomas and lymphoproliferative disorders was largely descriptive and based exclusively on microscopic observations. While useful, this approach is very limited, since the identity of neoplastic cells cannot always be established, nor can their clonal nature be recognized. Descriptive terms, such as large or small, follicular or diffuse, granular, intravascular, anaplastic, plasmacytic, etc., which were prevalent in earlier classifications, are still being used to characterize malignant lymphoid cells, even in modern taxonomies, like the World Health Organization (WHO) classification (1). However, this classification scheme now incorporates more meaningful biological properties for their category definitions, including extensive descriptions of the immunophenotype of the neoplastic cells. Flow cytometry (FCM) has been used in the analysis of human lymphomas since the late 1970s. The earlier studies focused mainly on the measurement of cell cycle phases and ploidy, exploiting the simplicity of measuring DNA content by this technology. In the 1980s, we witnessed a rapid increase in the use of FCM analysis of lymphoid tumors, as the understanding of the biology of the immune cells became much clearer and the production of specific markers such as monoclonal antibodies expanded rapidly. Today, FCM analysis is an accepted and essential medical practice in the clinical evaluation of lymphoid neoplasia. This technology assists in the diagnosis and characterization of lymphomas and CLPD, and in the detection of low-level disease. In patients with plasma cell dyscrasias, FCM is playing an ever-growing role, providing diagnostic support and prognostic information.