Test ID: PCLIP
Plasma Cell Labeling Index (PCLI) Profile

Establishing a diagnosis of a plasma cell proliferative disorder

Distinguishing overt multiple myeloma (MM) from monoclonal gammopathy of uncertain significance (MGUS) and smoldering MM

Providing independent prognostic information for MM as a measure of disease activity

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 (MM), 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.

It is important to correctly classify patients with plasma cell proliferative disorders because the various disease entities are treated differently. A number of factors are used to help determine and subclassify the disorders, including the proportion of plasma cells in the bone marrow and the proliferative activity of these plasma cells. The plasma cell labeling index (LI) is a rapid, reliable method that can be used to assess plasma cell proliferative activity. This information can be used to distinguish patients with overt active MM from those with MGUS or smoldering MM, as well as patients in relapse from those in the plateau phase of MM. The plasma cell LI has also proven to be an independent prognostic indicator and measure of disease activity.

See Plasma Cell Labeling in Special Instructions. Also see Diagnosis and Monitoring of Multiple Myeloma in Publications.

PCLI FLOW

PC light chain: no monotypic plasma cell population

Monotypic kappa plasma cells

Monotypic lambda plasma cells

PCLI

0.0-0.2% (low)

0.3-0.99% (intermediate)

1.0-2.99% (high)

>2.99% (very high)

Kappa to lambda Ig light chain (K/L) ratios >3.9 or <0.5 suggest a clonal excess of plasma cells expressing either kappa or lambda Ig light chains, respectively.

The evaluation of these antigens aids in the identification of abnormal plasma cells, however, they will not be reported independently.  

In plasma cells, CD19 expression appears to be associated with the presence of benign, polytypic cell populations. Therefore, CD19 expression is used as a supplemental tool in determining the nature of the plasma cells 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, therefore, inclusion of antibodies to this antigen allows for more sensitive detection of both subtypes.

Labeling index (only performed on monotypic plasma cell populations):

-High values (> or =1.0%) suggests active disease with >90% certainty

-In newly diagnosed myeloma, high labeling indices have a 3-fold decrease in survival. (LI > or =1%; 13% 5-year survival; LI <1%; 41% 5-year survival)

In order to provide an adequate specimen, it is important that the marrow specimen be from a "redirect" marrow aspirate. The marrow needle should be "redirected" so the marrow can be aspirated from a previously unsampled site.

A total of 124 bone marrow aspirate specimens were analyzed both by the previous 4-color flow and the new 6-color flow cytometry methods and the results compared. The concordance between the methods was 83%. In 84 of the cases the 4-color method detected monotypic plasma cells. Of these 84 cases, 81 were also positive by 6-color flow; in 2 of the 3 cases that were 4-color positive but 6-color negative, mononuclear cell enrichment was not performed prior to the analysis. In addition, 6-color flow cytometry detected 6 positive cases among 40 that were negative by the 4-color method. In 5 of these 6 cases the number of monotypic plasma cells was small. Hence the 6-color flow cytometry, when performed with cells isolated by ficoll-gradient preparation, appears to be moresensitive than the 4-color technique.

Greipp PR, Witzig TE, Gonchoroff NJ, et al: Immunofluorescence labeling indices in myeloma and related monoclonal gammopathies. Mayo Clin Proc 1987;62:969-977