Tiny screen marker tool6/2/2023 9 – 12 Plasma cells typically secrete an intact immunoglobulin that is made up of two identical light chains and two heavy chains. A subsequent antigen dependent development phase is typically triggered by exposure to an antigen, which results in the formation of memory B cells and long lived plasma cells. The progenitor B cell undergoes an initial development process in the marrow that is antigen independent, gaining the ability to produce an intact IgM immunoglobulin followed by migration to the spleen. The precise etiological events that alter the normal development of B-cells into mature plasma cells, to date, are not well understood and are most likely multifactorial. The development and function of plasma cells is tightly regulated. As a consequence, abnormalities of these cells are responsible for a variety of autoimmune diseases in addition to plasma cell neoplasms. 9 – 12 They are the primary mediators of humoral immunity, secreting antigen specific immunoglobulins. Plasma cells are terminally differentiated, non-dividing, effector cells of the B-cell lineage. 5, 6 Despite these challenges, high-sensitivity flow cytometry is evolving into an integral part of the laboratory evaluation and management of plasma cell disorders and can play an important role in the (i) diagnosis and classification, (ii) prognostic stratification, (iii) monitoring of response to therapy and minimal residual disease, (iv) understanding of the biology of disease progression, (v) studying of the role of tumor microenvironment in plasma cell disorders and (vi) identification of potential therapeutic targets on the surface of malignant plasma cells. Some of the controversies in earlier studies most likely ensued from the wide spectrum of disease stages included in the studies, variability in the reagents used, technical differences both in terms of acquisition and gating strategies and inconsistencies in the appreciation of the high inherent autoflourescence of plasma cells. Much of this stems from the contradictory results seen in early studies and the lack of universally acceptable plasma cell specific markers. While flow cytometric methods have become part of the standard diagnostic approach in other hematological malignancies, such as the acute and chronic leukemias, consensus in regards to their routine use in plasma cell disorders is lacking. ![]() This is a major advantage when compared to conventional methods of morphological assessment and immunohistochemistry. Moreover, the ability of flow cytometry to rapidly analyze a large number of cells provides the level of sensitivity of detection required for assessing disease response to treatment and for demonstrating minimal residual disease. These improvements have led to a better insight into the disease biology and have enhanced our diagnostic and prognostic abilities. Increased use of multi-parameter flow cytometry and a broadening array of available reagents for surface and intracellular staining of specific antigens have enhanced our understanding of various aspects of these diseases. However, in the past decade there has been increasing appreciation of the genetic and phenotypic heterogeneities that underlie the plasma cell dyscrasias and the changes that parallel disease evolution. ![]() 1 – 4 Currently, we still depend primarily on morphological features and limited immunophenotypic studies for identification of the clonal plasma cells as well as the clinical manifestations for diagnosis and classification of plasma cell disorders. This book chapter addresses the approaches taken to evaluate monoclonal plasma cell disorders, and the different markers and techniques that are important for the study of these diseases.Ĭlonal plasma cell disorders make up a wide spectrum of disorders, ranging from incidental findings in asymptomatic individuals to life threatening conditions, and can present with a myriad of clinical manifestations. This, along with a better understanding of the phenotypic heterogeneity of the clonal plasma cells in different disorders, has made immunophenotyping an indispensible tool in the diagnosis, prognostic classification and management of plasma cell disorders. Multiparameter flow cytometry has evolved considerably during the past decade with an increasing ability to screen large numbers of events and to detect multiple antigens at the same time. Immunophenotyping has become an invaluable tool in the management of hematological malignancies and is increasingly finding a role in the diagnosis and monitoring of plasma cell disorders. Plasma cell disorders form a spectrum ranging from the asymptomatic presence of small monoclonal populations of plasma cells to conditions like plasma cell leukemia and multiple myeloma, in which the bone marrow can be replaced by the accumulation of neoplastic plasma cells.
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