Interpretation

Plasma Cell Clonality:

Plasma cell populations with a kappa to lambda ratio of either greater than 3.9 or less than 0.5 will be considered either kappa or lambda immunoglobulin light chain restricted (monotypic), respectively. As, in rare instances, immunoglobulin light chain restricted plasma cell populations may be polyclonal at the genetic level, the term monotypic rather than monoclonal plasma cells will be used.

In addition to immunoglobulin light chain expression, other data collected will be used to supplement the detection of abnormal plasma cell populations. In plasma cells, CD19 expression is associated with the presence of benign, polytypic cell populations. Therefore, CD19 expression will be used as a secondary element in detecting clonal plasma cells. While loss of plasma cell CD45 expression is associated with neoplasia, CD45 is expressed by both normal and neoplastic plasma cells. Absence of plasma cell CD45 expression will be used as an aid in detecting abnormal 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. In addition, as DNA content will be simultaneously assessed, the detection of plasma cell aneuploidy will also serve as a tool for identifying abnormal plasma cell populations. These additional immunophenotypic tools for identifying abnormal plasma cells will increase the sensitivity of the method beyond examining light chain expression; particularly in biclonal plasma cell proliferative disorders in which there are both kappa and lambda immunoglobulin light chain expressing subsets.

Plasma Cell Proliferation:

The proportion of plasma cells in S-phase will be determined by measuring the proportion of cells with DNA content between the G0/G1 and G2/M peaks. In some instances, plasma cell proliferation will not be able to be determined by this method, including when there are fewer than 300 abnormal plasma cell events and when there are multiple aneuploid plasma cell populations. In newly diagnosed multiple myeloma, a plasma cell S-phase of greater than 2.0%, is associated with a more aggressive disease course; this value is published standard for identifying plasma cell neoplasms with a high proliferative rate, it will be noted in the report if the estimated S-phase exceeds this value.

DNA Index:

Processed cells are stained with DAPI (4',6-diamidino-2-phenylindole) to determine the DNA index of the abnormal plasma cells. This will be determined by dividing the measured DNA content of the G0/G1 abnormal plasma cells by the DNA content of the normal G0/G1 plasma cells present. For this determination, normal plasma cells are the optimal control cell population due to similarities in nuclear and overall cell size. Plasma cells with a G0/G1 DNA content index of less than 0.95 will be considered hypodiploid (worst prognosis); those with a G0/G1 DNA content index of greater than 1.05 will be considered hyperdiploid (favorable prognosis). Plasma cells with a DNA index of 1.9 to 2.1 will be considered tetraploid (non-favorable prognosis) if a confirmatory G2/M population with a DNA index of 4 is identified. As noted above, since normal plasma cells are neither hyper- nor hypodiploid, DNA index will be used as a supplemental tool in detecting clonal plasma cells.

Percent Polyclonal Plasma Cells in Total Plasma Cells:

It has been shown that higher percent polyclonal plasma cells in total plasma cells can mean longer progression-free survival, higher response rates, and lower frequency of high-risk cytogenetics abnormalities. Studies have also shown a higher incidence of polytypic plasma cells in monoclonal gammopathy of uncertain significance and smoldering myeloma in comparison to multiple myeloma.