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HelpTest ID: LPLFX 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 aspirate
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Yellow top (ACD), green top (sodium heparin)
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) 10 days/Refrigerated 10 days
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Yellow top (ACD), green top (sodium heparin)
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) 10 days /Refrigerated 10 days
Specimen Type: Paraffin-embedded tissue
Container/ Tube: Paraffin block
Collection Instructions:
1. Decalcified specimens (eg, bone marrow core biopsies) are not acceptable.
2. Indicate specimen source.
Specimen Stability Information: Ambient
Additional Information: If the quality of the biopsy specimen is poor, testing should not be ordered. Testing may be canceled if DNA requirements are inadequate.
Acceptable:
Specimen Type: Tissue slide
Slides: 20 unstained slides
Container/ Tube: Transport in plastic slide holders.
Collection Instructions:
1. Send 20 unstained, nonbaked slides with 5-micron thick sections of tissue.
2. Decalcified specimens (eg, bone marrow core biopsies) are not acceptable.
3. Indicate specimen source.
Specimen Stability Information: Ambient
Additional Information: Testing may be canceled if resultant extracted DNA does not meet concentration requirements.
Specimen Type: Frozen tissue
Container/Tube: Plastic container
Specimen Volume: 100 mg
Collection Instructions:
1. Freeze tissue within 1 hour of collection
2. Indicate specimen source.
Specimen Stability Information: Frozen
Specimen Type: Extracted DNA
Container/Tube: 1.5- to 2-mL tube
Specimen Volume: Entire specimen
Collection Instructions:
1. DNA must be extracted within 7 days of collection.
2. Label specimen as extracted DNA and source of specimen.
3. Provide volume and concentration of DNA on label.
Specimen Stability Information: Frozen (preferred)/Refrigerated/Ambient
Additional Information: DNA must be extracted in a CLIA-certified laboratory or equivalent and must be extracted from a specimen type listed as acceptable for this test (including applicable anticoagulants). We cannot guarantee that all extraction methods are compatible with this test. If testing fails, one repeat will be attempted, and if unsuccessful, the test will be reported as failed and a charge will be applied.
Forms
1. Hematopathology Patient Information (T676)
2. If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.
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, CXCR4 testing will be performed at an additional charge. If a MYD88 L265P variant is not detected, the algorithm ends, and no further testing is necessary.
Special Instructions
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 CXCR4Specimen Type
VariesSpecimen Minimum Volume
Whole blood, bone marrow aspirate: 0.5 mL; Frozen tissue: 50 mg; Extracted DNA: 50 mcL at 20 ng/mcL; Tissue slides: 10 unstained slides
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Varies | 10 days |
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.
Clinical Reference
1. Treon SP, Xu L, Yang G, et al. MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia. N Engl J Med. 2012;367(9):826-833. doi:10.1056/NEJMoa1200710
2. Varettoni M, Arcaini L, Zibellini S, et al. Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstrom's macroglobulinemia and related lymphoid neoplasms. Blood. 2013;121(13):2522-2528. doi:10.1182/blood-2012-09-457101
3. Xu L, Hunter ZR, Yang G, et al. MYD88 L265P in Waldenstrom macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction. Blood. 2013;121(11):2051-2058. doi:10.1182/blood-2012-09-454355
4. Poulain S, Roumier C, Decambron A, et al. MYD88 L265P mutation in Waldenstrom macroglobulinemia. Blood. 2013;121(22):4504-4511. doi:10.1182/blood-2012-06-436329
5. Gachard N, Parrens M, Soubeyran I, et al. IGHV gene features and MYD88 L265P mutation separate the three marginal zone lymphoma entities and Waldenstrom macroglobulinemia/lymphoplasmacytic lymphomas. Leukemia. 2013;27(1):183-189. doi:10.1038/leu.2012.257
6. Ondrejka SL, Lin JJ, Warden DW, et al. MYD88 L265P somatic mutation: its usefulness in the differential diagnosis of bone marrow involvement by B-cell lymphoproliferative disorders. Am J Clin Pathol. 2013;140(3):387-394. doi: 10.1309/AJCP10ZCLFZGYZIP
7. Hunter Z, Xu L, Yang G, et al. The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood. 2014;123(11):1637-1646. doi:10.1182/blood-2013-09-525808
9. Poulain S, Roumier C, Venet-Caillault A, et al. Genomic landscape of CXCR4 mutations in Waldenstrom macroglobulinemia. Clin Cancer Res. 2016;22(6):1480-1488. doi:10.1158/1078-0432.CCR-15-0646
10. Roccaro A, Sacco A, Jimenez C, et al. C1013G/CXCR4 acts as a driver mutation of tumor progression and modulator of drug resistance in lymphoplasmacytic lymphoma. Blood. 2014;123(26):4120-4131. doi:10.1182/blood-2014-03-564583
11. Schmidt J, Federmann B, Schindler N, et al. MYD88 L265P and CXCR4 mutations in lymphoplasmacytic lymphoma identify cases with high disease activity. Br J Haematol. 2015;169(6):795-803. doi:10.1111/bjh.13361
12. Treon SP, Cao Y, Xu L, et al. Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstrom macroglobulinemia. Blood. 2014;123(18):2791-2796. doi:10.1182/blood-2014-01-550905
13. Treon SP, Tripsas CK, Meid K, et al. Ibrutinib in previously treated Waldenstrom's macroglobulinemia. N Engl J Med. 2015;372(15):1430-1440. doi:10.1056/NEJMoa1501548
14. Gertz MA. Waldenstrom macroglobulinemia: 2025 Update on diagnosis, risk stratification, and management. Am J Hematol. 2025;100(6):1061-1073. doi:10.1002/ajh.27666
Day(s) Performed
Monday through Friday
Report Available
7 to 10 daysTest 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 |
mml-lymphoma