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Test Code MISC2MAYOLPLFX Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia, MYD88 L265P with Reflex to CXCR4, Varies


Shipping Instructions


Whole blood or bone marrow specimens must arrive within 10 days of collection.



Necessary Information


The following information is required:

1. Pertinent clinical history

2. Clinical or morphologic suspicion

3. Date and time of collection

4. Specimen source



Specimen Required


Submit only 1 of the following specimens:

 

Preferred:

Specimen Type: Bone marrow

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD)

Specimen Volume: 2 mL

Collection Instructions:

1. Invert several times to mix bone marrow

2. Send bone marrow specimen in original tube. Do not aliquot.

3. Label specimen as bone marrow

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Specimen Type: Paraffin-embedded tissue

Container/Tube: Paraffin block

Specimen Stability: Ambient

 

Specimen Type: Paraffin-embedded bone marrow aspirate clot

Container/Tube: Paraffin block

Specimen Stability: Ambient

 

Specimen Type: Tissue

Slides: Unstained slides

Specimen Volume: 10 to20 slides

Additional Information: Tissue must demonstrate involvement by a hematologic neoplasm (eg, acute myelocytic leukemia), not solid tumors.

Specimen Stability Information: Ambient

 

Acceptable:

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood

2. Send whole blood specimen in original tube. Do not aliquot.

3. Label specimen as blood

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Specimen Type: Extracted DNA

Container/Tube: 1.5- to 2-mL tube with indication of volume and concentration of the DNA

Specimen Volume: Entire specimen

Collection Instructions: Label specimen as extracted DNA and list the specimen source. Include indication of volume and concentration of the DNA.

Specimen Stability Information: Frozen (preferred)/Refrigerated/Ambient


Forms

1. Hematopathology Patient Information (T676)

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

Secondary ID

61114

Useful For

Establishing a diagnosis of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM)

 

Helping distinguish LPL/WM low-grade B-cell lymphoma from other subtypes

 

Aiding in the prognosis and clinical management of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CXCFX CXCR4, Gene Mutation, Reflex Yes, (order CXLPL), Bill Only No

Testing Algorithm

The algorithm starts with the sensitive MYD88 L265P testing by allele-specific polymerase chain reaction. If a MYD88 L265P variant is detected, additional CXCR4 testing will be performed. If a MYD88 L265P variant is not detected, the algorithm ends, and no further testing is necessary.

Method Name

Allele-Specific Polymerase Chain Reaction (AS-PCR)/Bridged Nucleic Acids (BNA) Clamp Sanger Sequencing/Routine Sanger Sequencing

(BNAClamp is utilized pursuant to a license agreement with BNA Inc.)

Reporting Name

Reflex Testing of MYD88 and CXCR4

Specimen Type

Varies

Specimen Minimum Volume

Whole blood, Bone marrow: 1 mL
Extracted DNA: 50 mcL with a concentration of at least 20 nanograms per mcL
Other specimen types: See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies 10 days

Reject Due To

Gross hemolysis Reject
B5-fixed tissues
Decalcified bone marrow biopsies
Methanol-acetic acid (MAA)-fixed pellets
Paraffin shavings
Frozen tissue
Moderately to severely clotted		 Reject

Clinical Information

The MYD88 L265P abnormality is highly associated (>90%) with the pathologic diagnosis of lymphoplasmacytic lymphoma and the clinical syndrome of Waldenstrom macroglobulinemia (LPL/WM), particularly in the setting of an elevated IgM serum monoclonal paraprotein.

 

CXCR4 mutations are identified in approximately 30% to 40% of LPL/WM patients and are almost always in association with MYD88 L265P, which is highly prevalent in this neoplasm. The status of CXCR4 mutations in the context of MYD88 L265P is clinically relevant as important determinants of clinical presentation, overall survival and therapeutic response to ibrutinib. A MYD88-L265P/CXCR4-WHIM (C-terminus nonsense/frameshift variants) molecular signature is associated with intermediate to high bone marrow disease burden and serum IgM levels, less adenopathy, and intermediate response to ibrutinib in previously treated patients. A MYD88-L265P/CXCR4-WT (wildtype) molecular signature is associated with intermediated bone marrow disease burden and serum IgM levels, more adenopathy, and highest response to ibrutinib in previously treated patients. A MYD88-WT/CXCR4-WT molecular signature is associated with inferior overall survival, lower response to ibrutinib therapy in previously treated patients, and lower bone marrow disease burden in comparison to those harboring a MYD88-L265 variant.

Reference Values

MYD88 L265P: Mutation present or absent based on expected variant polymerase chain reaction product size for the MYD88 gene (NCBI accession NM_002468.4).

 

CXCR4: Mutation present or absent in the test region c. 898-1059 (amino acids 300-353) of the CXCR4 gene (NCBI NM_003467.2, GRCh37).

Interpretation

Mutation present or not detected; an interpretive report will be issued.

Method Description

Extracted DNA from the clinical specimen is subjected to allele-specific polymerase chain reaction (PCR) using MYD88 exon 5 primers that simultaneously amplify both a wild-type sequence fragment and a fragment containing the specific nucleotide change resulting in L265P if present. PCR products are visualized by capillary electrophoresis and the presence of mutated and wildtype amplicons is determined according to the expected specific PCR product sizes.(Unpublished Mayo method)

 

The C-terminal end of CXCR4 (NM_003467.2, c. 898-1059) is amplified from extracted genomic DNA by PCR, followed by Sanger sequencing and capillary electrophoresis analysis. Review of the sequence data is performed using a combination of automated calls and manual inspection. (Unpublished Mayo method)

 

The hotspot mutations c.1013C>G/A (p.S338X) are examined using bridged nucleic acids clamped Sanger sequencing with an analytic sensitivity of 1%. All other genetic mutations in the test region are examined by routine Sanger sequencing with an analytic sensitivity of 15% to 20%.(Unpublished Mayo method)

Day(s) Performed

Monday through Friday

Report Available

7 to 10 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81305

LOINC Code Information

Test ID Test Order Name Order LOINC Value
LPLFX Reflex Testing of MYD88 and CXCR4 82140-5

 

Result ID Test Result Name Result LOINC Value
MP042 Specimen Type 31208-2
601511 LPLFX Reflex Result 82140-5
601510 Final Diagnosis 50398-7