Test Catalog

Test Id : PCPRO

Plasma Cell DNA Content and Proliferation, Bone Marrow

Useful For
Suggests clinical disorders or settings where the test may be helpful

Establishing a diagnosis of a plasma cell proliferative disorder

 

Providing prognostic information for newly diagnosed multiple myeloma and other plasma cell proliferative disorders

 

Assessing response to therapy and detecting disease relapse and progression in treated plasma cell proliferative disorder patients

 

Determining plasma cell DNA content and proliferation

Additional Tests
Lists tests that are always performed, at an additional charge, with the initial tests.

Test Id Reporting Name Available Separately Always Performed
FCINT Flow Cytometry Interp, 2-8 Markers No, (Bill Only) Yes

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, flow cytometry interpretation will always be performed at an additional charge.

 

The following algorithms are available:

-Amyloidosis: Laboratory Approach to Diagnosis

-Multiple Myeloma: Laboratory Screening

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Flow Cytometry/DNA Content/Cell Cycle Analysis

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Plasma Cell Proliferation, Marrow

Aliases
Lists additional common names for a test, as an aid in searching

PC Proliferation

Myeloma Staging

Plasma Cell Staging

Labeling Index

PCLIP

Plasma Cell Labeling Index (PCLI)

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, flow cytometry interpretation will always be performed at an additional charge.

 

The following algorithms are available:

-Amyloidosis: Laboratory Approach to Diagnosis

-Multiple Myeloma: Laboratory Screening

Specimen Type
Describes the specimen type validated for testing

Bone Marrow

Ordering Guidance

This test can be ordered at diagnosis or follow-up of a plasma cell neoplasm (plasma cell proliferative disorder).

 

If CSMRT / mSMART Plasma Cell Proliferative Disorder, Pre-Analysis Cell Sorting, Bone Marrow or MPCDS / mSMART, Plasma Cell Proliferative Disorder, FISH, Bone Marrow is desired to be performed at Mayo, order MSMRT / Mayo Algorithmic Approach for Stratification of Myeloma and Risk-Adapted Therapy Report, Bone Marrow.

 

The Multiple Myeloma: Laboratory Screening algorithm will allow plasma cell fluorescence in situ hybridization (FISH) testing to be added, based on this test's flow cytometry results.

Necessary Information

1. Include patient's disease state (untreated, treated, monoclonal gammopathy of undetermined significance, stable).

2. Indicate if patient is on anti-CD38 therapy.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Specimen Type: Redirected bone marrow

Preferred: Yellow top (ACD)

Acceptable: Lavender top (EDTA) or green top (heparin)

Specimen Volume: 4 mL

Specimen Stability Information: <72 hours

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

2 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Fully clotted Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Bone Marrow Ambient (preferred)
Refrigerated

Useful For
Suggests clinical disorders or settings where the test may be helpful

Establishing a diagnosis of a plasma cell proliferative disorder

 

Providing prognostic information for newly diagnosed multiple myeloma and other plasma cell proliferative disorders

 

Assessing response to therapy and detecting disease relapse and progression in treated plasma cell proliferative disorder patients

 

Determining plasma cell DNA content and proliferation

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, flow cytometry interpretation will always be performed at an additional charge.

 

The following algorithms are available:

-Amyloidosis: Laboratory Approach to Diagnosis

-Multiple Myeloma: Laboratory Screening

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Plasma cell proliferative disorders are a group of plasma cell derived clonal hematologic neoplasms that 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 is often aggressive with poor long-term survival. Detecting plasma cell clonality through demonstrating immunoglobulin (Ig) light chain restriction (ie, the presence of either predominately kappa or predominately lambda light chains), supplemented by the plasma cell immunophenotype and DNA index, is an important element in establishing the diagnosis.

 

It is important to correctly classify patients with plasma cell proliferative disorders as the various disease entities are treated differently. A number of factors are used for this classification including the proportions of clonal bone marrow plasma cells, the DNA index of the clonal plasma cells, and their proliferative activity. The plasma cell DNA index and proliferation assessment by flow cytometry are rapid and reliable. This information can be used to distinguish patients with overt active MM from less aggressive diseases such as MGUS and smoldering MM.

 

Furthermore, in combination with other laboratory data, the results of these studies can be used as a measure of disease aggressiveness in newly diagnosed MM and also to determine therapeutic efficacy and detect disease relapse in treated MM patients.

 

The following algorithms are available:

-Amyloidosis: Laboratory Approach to Diagnosis

-Multiple Myeloma: Laboratory Screening

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Plasma Cell Clonality:

Normal bone marrow

No monotypic clonal plasma cells detected

 

DNA Index:

Normal polytypic plasma cells

DNA index (G0/G1 cells): Diploid 0.95-1.05

Interpretation
Provides information to assist in interpretation of the test results

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. Therefore, 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.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Aljama MA, Sidiqi MH, Lakshman A, et al: Plasma cell proliferative index is an independent predictor of progression in smoldering multiple myeloma. Blood Adv. 2018;2(22):3149-3154

2. Mellors PW, Binder M, Ketterling RP, et al: Metaphase cytogenetics and plasma cell proliferation index for risk stratification in newly diagnosed multiple myeloma. Blood Adv. 2020 May 26;4(10):2236-2244

3.Palva B, Vidriales MB, Mateo G, et al. The persistence of immunophenotypically normal residual bone marrow plasma cells at diagnosis identifies a good prognostic subgroup of symptomatic multiple myeloma patients. Blood. 2009 Nov 12;114(20):4369-4372

4. Sidana S, Jevremovic D, Ketterling RP, et al: Rapid assessment of hyperdiploidy in plasma cell disorders using a novel multi-parametric flow cytometry method. Am J Hematol. 2019 Apr;94(4):424-430

5. Ghosh T, Gonsalves WI, Jevremovic D, et al: The prognostic significance of polyclonal bone marrow plasma cells in patients with relapsing multiple myeloma. Am J Hematol. 2017 Sep;92(9):E507-E512

6. Gonsalves WI, Buadi FK, Ailawadhi S, et al: Bone marrow transplant. Utilization of hematopoietic stem cell transplantation for the treatment of multiple myeloma: a mayo stratification of myeloma and risk-adapted therapy (msmart) consensus statement. 2019 Mar;54(3):353-367

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Flow cytometric immunophenotyping of bone marrow is performed using the following antibodies; CD19, CD38, CD45, CD138, cytoplasmic kappa and lambda immunoglobulin, and DAPI (4',6-diamidino-2-phenylindole). Plasma cell clonality is detected through demonstrating CD38 and CD138 positivity along with immunoglobulin light chain restriction (ie, the presence of either predominately kappa or predominately lambda light chains) and abnormality of CD19 and/or CD45 expression. DNA index of clonal plasma cells and their proliferation activity is determined through staining of double-stranded DNA using DAPI. Plasma cells (monoclonal/monotypic and polyclonal/polytypic) are detected by immunoglobulin light chain restriction, surface immunophenotype, and DNA content. If present, the light chain expressed by the monotypic plasma cells is indicated. The percentage of clonal plasma cells estimated by flow cytometry is affected by specimen processing and antigen loss with specimen aging. Manual differential counting remains the accepted standard for determining the bone marrow plasma cell percentage. The percentage of monotypic plasma cells in S-phase of the cell cycle is determined by quantitative DNA analysis. The DNA index is a calculated value. The presence of more than 1 value indicates the presence of cell populations with differing DNA contents within the monotypic plasma cells.(Sidana S, Jevremovic D, Ketterling RP, et al: Rapid assessment of hyperdiploidy in plasma cell disorders using a novel multi-parametric flow cytometry method. Am J Hematol. 2019 Apr;94(4):424-430)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

1 to 4 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

88182-Flow cytometry, cell cycle or DNA analysis

88184-Flow cytometry; first cell surface, cytoplasmic or nuclear marker

88185 x 5-Flow cytometry; additional cell surface, cytoplasmic or nuclear marker (each)

88187-Flow cytometry interpretation, 2 to 8 Markers (added as FCINT)

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
PCPRO Plasma Cell Proliferation, Marrow 93363-0
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
CK056 Monotypic Plasma Cells: 93362-2
CK057 Monotypic PC per Total Events 93021-4
CK058 Monotypic Plasma Cells S-phase 93361-4
CK059 Monotypic Plasma Cells DNA Index 93360-6
CK060 Monotypic Plasma Cells DNA Ploidy 93359-8
CK061 Polytypic PC per Total Events 93358-0
CK062 Polytypic PC per All Plasma Cells 93020-6
CK063 Final Diagnosis 50398-7

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Create a PDF

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports