Significance of MYD88 L265P Mutation Status in the Subclassification of Low-Grade B-Cell Lymphoma/Leukemia

Arch Pathol Lab Med. 2015 Aug;139(8):1035-41. doi: 10.5858/arpa.2014-0322-OA.


Context: Lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) are well-defined clinicopathologic entities. However, distinguishing LPL from MZL and from atypical cases of CLL can sometimes be difficult because of overlapping features. Recent studies have identified a recurrent L265P mutation in the MYD88 gene in most cases of LPL. Although this represents a promising diagnostic marker for LPL, the mutation is also reported in rare cases of MZL and CLL (as well as other types of B-cell lymphoma). Detection rates for this mutation have varied depending on the analytic methodology.

Objective: To assess the diagnostic utility of MYD88 L265P mutation in diagnosing low-grade B-cell lymphomas.

Design: We developed a novel pyrosequencing assay for the MYD88 L265P mutation and assessed its diagnostic utility in 317 cases of low-grade B-cell lymphoma (45 LPL [14%], 53 MZL [17%], and 219 CLL [69%]). We incorporated formal clinical and pathologic review of selected cases to ensure the most accurate diagnosis and subclassification.

Results: The MYD88 L265P mutation was identified in 43 cases of LPL (96%), including 3 nonimmunoglobulin-M LPL cases. In contrast, the mutation was present in only 2 cases of MZL (4%), and 5 cases of CLL (2%). Thus, pyrosequencing for the MYD88 L265P mutation demonstrates a high clinical sensitivity and specificity to distinguish LPL from MZL and CLL.

Conclusions: This study confirms the strong association of the MYD88 L265P mutation with LPL, as well as the existence of rare cases of small B-cell lymphoma that complicate this association.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Aged, 80 and over
  • DNA Mutational Analysis
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / classification
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Myeloid Differentiation Factor 88 / genetics*
  • Neoplasm Grading
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity


  • MYD88 protein, human
  • Myeloid Differentiation Factor 88