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Plasma cell proliferative disorders are a group of hematologic neoplasms, all of which are derived from clonal plasma cells. These disorders exhibit a wide range of biologic activity ranging from monoclonal gammopathy of uncertain significance (MGUS), a usually indolent disorder with a low rate of disease progression, to multiple myeloma, a disease that most often is aggressive with poor long-term survival. Detecting plasma cell immunoglobulin (Ig) light chain restriction (ie, the presence of either predominately kappa or predominately lambda light chains) is an important element in assessing plasma cell clonality and, hence, establishing the diagnosis. Furthermore, a greater degree of peripheral blood involvement by these disorders is associated with more aggressive disease types and, therefore, is an adverse prognostic indicator.
Flow cytometric immunophenotyping (FCIP) is a recognized method for detecting plasma cell Ig light chain restriction. However, shortcomings of this technique, as traditionally performed, include its relative insensitivity and its consistent underestimation of the number of clonal plasma cells present. Both of these short-comings are likely attributable to limitations of the instruments and antibodies used, as well as the presence of intraclonal phenotypic heterogeneity, which created difficulties in accurately detecting and enumerating all of the clonal plasma cells. For this reason, the FCIP plasma cell clonality assessment previously performed in our laboratory was supplemented with a slide-based immunofluorescence technique.
However, recent advances in flow cytometry have led to the development of more powerful instruments and antibody reagents that allow for the use of greater antibody combinations and increased resolution of the data. With these tools, the ability of FCIP to detect and enumerate plasma cell clones has been greatly enhanced, allowing us to discontinue the supplemental, labor-intensive, slide-based plasma cell evaluation in peripheral blood specimens.
The following algorithms are available in Special Instructions:
-Laboratory Screening Tests for Suspected Multiple Myeloma
-Laboratory Approach to the Diagnosis of Amyloidosis
Also see in Publications:
-Diagnosis and Monitoring of Multiple Myeloma
Detecting peripheral blood involvement by plasma cell proliferative disorders
Establishing the diagnosis of and determining prognosis for plasma cell proliferative disorders
In normal peripheral blood specimens, no clonal plasma cells are present (polytypic or too few to detect).
Plasma cells are CD38 and CD138 positive.
Normal (polyclonal, nonneoplastic) plasma cells are typically CD19-positive, whereas neoplastic (clonal) plasma cells typically are CD19-negative. CD19 expression is especially helpful in distinguishing clonal from nonclonal plasma cells when few analyzable cells are present.
CD45 may be expressed by both normal and neoplastic plasma cells. In some plasma cell proliferative disorders there are both CD45-positive and CD45-negative subsets within the clonal cell population.
The evaluation of these antigens aids in the identification of abnormal plasma cells, however, they will not be reported independently.
No significant cautionary statements
CD38+/CD138+ plasma cells=0.0
Nowakowski GS, Witzig TE, Dingli D, et al: Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. Blood 2006;106(7):2276-2279