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PCPRO<br />

61654<br />

therefore, is an adverse prognostic indicator. Flow cytometric immunophenotyping (FCIP) is a recognized<br />

method for detecting plasma cell Ig light chain restriction. However, shortcomings of this technique, as<br />

traditionally performed, include its relative insensitivity and its consistent underestimation of the number<br />

of clonal plasma cells present. Both of these short-comings are likely attributable to limitations of the<br />

instruments and antibodies used, as well as the presence of intraclonal phenotypic heterogeneity, which<br />

created difficulties in accurately detecting and enumerating all of the clonal plasma cells. For this reason,<br />

the FCIP plasma cell clonality assessment previously performed in our laboratory was supplemented with<br />

a slide-based immunofluorescence technique. However, recent advances in flow cytometry have led to the<br />

development of more powerful instruments and antibody reagents that allow for the use of greater<br />

antibody combinations and increased resolution of the data. With these tools, the ability of FCIP to detect<br />

and enumerate plasma cell clones has been greatly enhanced, allowing us to discontinue the supplemental,<br />

labor-intensive, slide-based plasma cell evaluation in peripheral blood specimens. See Laboratory<br />

Screening <strong>Test</strong>s for Suspected Multiple Myeloma in Special Instructions and the Laboratory Approach to<br />

the Diagnosis of Amyloidosis algorithm in Special Instructions. Also see Diagnosis and Monitoring of<br />

Multiple Myeloma in Publications.<br />

Useful For: Detecting peripheral blood involvement by plasma cell proliferative disorders Establishing<br />

the diagnosis of and determining prognosis for plasma cell proliferative disorders<br />

Interpretation: In normal peripheral blood specimens, no clonal plasma cells are present (polytypic or<br />

too few to detect). Plasma cells are CD38 and CD138 positive. Normal (polyclonal, nonneoplastic)<br />

plasma cells are typically CD19-positive, whereas neoplastic (clonal) plasma cells typically are<br />

CD19-negative. CD19 expression is especially helpful in distinguishing clonal from nonclonal plasma<br />

cells when few analyzable cells are present. CD45 may be expressed by both normal and neoplastic<br />

plasma cells. In some plasma cell proliferative disorders there are both CD45-positive and CD45-negative<br />

subsets within the clonal cell population. The evaluation of these antigens aids in the identification of<br />

abnormal plasma cells, however, they will not be reported independently.<br />

Reference Values:<br />

CD38+/CD138+ plasma cells=0.0<br />

Clinical References: Nowakowski GS, Witzig TE, Dingli D, et al: Circulating plasma cells detected<br />

by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma.<br />

Blood 2006;106(7):2276-2279<br />

Plasma Cell DNA Content and Proliferation, Bone Marrow<br />

Clinical Information: Plasma cell proliferative disorders are a group of plasma cell derived clonal<br />

hematologic neoplasms which exhibit a wide range of biologic activity ranging from monoclonal<br />

gammopathy of uncertain significance (MGUS), a usually indolent disorder with a low rate of disease<br />

progression, to multiple myeloma (MM), a disease that is often aggressive with poor long-term survival.<br />

Detecting plasma cell clonality through demonstrating immunoglobulin (Ig) light chain restriction (ie, the<br />

presence of either predominately kappa or predominately lambda light chains), supplemented by the<br />

plasma cell immunophenotype and DNA index, is an important element in establishing the diagnosis. It is<br />

important to correctly classify patients with plasma cell proliferative disorders as the various disease<br />

entities are treated differently. A number of factors are used for this classification including the proportion<br />

clonal bone marrow plasma cells, the DNA index of the clonal plasma cells, and their proliferative<br />

activity. The plasma cell DNA index and proliferation assessment by flow cytometry are rapid and<br />

reliable. This information can be used to distinguish patients with overt, active MM from less aggressive<br />

diseases such as MGUS and smoldering MM. Furthermore, in combination with other laboratory data, the<br />

results of these studies can be used to as a measure of disease aggressiveness in newly diagnosed MM and<br />

also to determine therapeutic efficacy and detect disease relapse in treated MM patients. See Laboratory<br />

Screening <strong>Test</strong>s for Suspected Multiple Myeloma in Special Instructions. Also see Diagnosis and<br />

Monitoring of Multiple Myeloma in Publications.<br />

Useful For: Establishing a diagnosis of a plasma cell proliferative disorder Providing prognostic<br />

information for newly diagnosed multiple myeloma and other plasma cell proliferative disorders<br />

Assessing response to therapy and detecting disease relapse and progression in treated plasma cell<br />

Current as of January 4, 2013 7:15 pm CST 800-533-1710 or 507-266-5700 or <strong>Mayo</strong><strong>Medical</strong><strong>Laboratories</strong>.com Page 1426

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