MYD88 L265P Mutation Detection

Technical Brief

MYD88 L265P Mutation Detection


Test Name

MYD88 L265P Mutation Analysis (MYD88)

CPT Codes

81305
G0452

Methodology

Allele-specific Polymerase Chain Reaction (PCR)

Real-Time PCR

Turnaround Time

7 days

Specimen Requirements

Type:
Blood, whole

Volume:
4 mL

Minimum Volume:
1 mL

Specimen Container:
Lavender BD Hemogard™ K2EDTA Tube

Transport Temperature:
Refrigerated

Type:
Bone marrow

Volume:
2 mL

Minimum Volume:
0.5 mL

Specimen Container:
Lavender BD Hemogard™ K2EDTA Tube

Transport Temperature:
Refrigerated

Type:
Paraffin block, formalin-fixed
Bone marrow clot

Volume:
1 block

Transport Temperature:
Ambient

Stability

Blood, Bone Marrow

Ambient:
24 hours

Refrigerated:
5 days

Frozen:
Unacceptable

Stability

FFPE, Bone Marrow Clot

Ambient:
Indefinitely

Refrigerated:
Indefinitely

Frozen:
Indefinitely

Reference Range

MYD88 L265P mutation not detected.

Background Information

Lymphoplasmacytic lymphoma (LPL) is a small B-cell neoplasm with plasmacytic differentiation that typically involves the bone marrow, but may also involve spleen and lymph nodes. In most cases, LPL is associated with an IgM paraprotein (Waldenstrom’s macroglobulinemia).1,2 Distinguishing LPL from other small B-cell neoplasms that may show plasmacytic differentiation, especially marginal zone lymphomas, is often challenging.

Recently, the MYD88 L265P mutation has been identified in >90% of cases of LPL.3 This mutation may also be found in diffuse large B-cell lymphomas, especially those with a nongerminal center phenotype, but the mutation is only rarely found in other small B-cell neoplasms. The detection of an MYD88 L265P mutation can, therefore, assist in establishing the diagnosis of LPL.3-5

Cleveland Clinic Laboratories has developed, validated and implemented a sensitive PCR assay for the detection of MYD88 L265P in peripheral blood, bone marrow, or formalin-fixed, paraffin-embedded tissues.

Clinical Indications

MYD88 L265P mutation testing is useful in the evaluation of small B-cell neoplasms, especially those with plasmacytic differentiation.

Interpretation

Normal Results:

MYD88 L265P mutation not detected.”

Positive Results:

MYD88 L265P mutation detected.”  An interpretation is also provided.

Methodology

DNA is extracted from the sample. Real-time PCR is performed using primers specific for the L265P mutation and a reference primer set for a non-mutated portion of the MYD88 gene.

Limitations

This assay has a sensitivity of 0.5% mutant alleles.

This assay detects only the L265P point mutation, and a negative result does not exclude a diagnosis of lymphoplasmacytic lymphoma.

References

1. Swerdlow S.H., Berger F., Pileri S.A., et al. Lymphoplasmacytic lymphoma. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC: Lyon 2008. Swerdlow SH, Campo E. Harris EL, et al (Eds). Pp 194-195.

2. Treon SP, Hunter ZR, Castillo JJ, et al. Waldenström macroglobulinemia. Hematol Oncol Clin North Am. 2014 Oct;28(5):945-70.

3. Treon SP, Xu L, Yang G, et al. MYD88 L265P somatic mutation in Waldenström’s macroglobulinemia. N Engl J Med. 2012 Aug 30;367(9):826-33.

4. Hamadeh F, MacNamara SP, Aguilera NS, et al. MYD88 L265P mutation analysis helps define nodal lymphoplasmacytic lymphoma. Mod Pathol. 2014 Sep 12. [Epub ahead of print]

5. 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 Sep;140(3):387-94.