MYD88 (L265P) Somatic Mutation: Utility in the Differential Diagnosis of Bone Marrow Involvement by B-Cell Lymphoproliferative Disorders
Sarah L Ondrejka, Jeff Lin, Doug W Warden, Lisa Durkin, James R Cook, Eric D Hsi. Cleveland Clinic, Cleveland, OH
Background: Separation of lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM) from other small B-cell lymphomas (BCL) and plasma cell myeloma (PCM) in bone marrow (BM) biopsies can be difficult. Recently, whole-genome sequencing identified MYD88 L265P as a commonly occurring mutation in WM and non-IgM-secreting LPL, which was absent or rarely present in PCM, marginal zone lymphoma (MZL), and IgM MGUS. We investigated sensitivity/specificity of this mutation in various BCLs in BM and applied it to a diagnostically problematic subset involved by B-cell LPDs originally diagnosed as BCL, not otherwise specified (NOS), with and without plasmacytic differentiation.
Design: Pathology archives were searched for BM biopsies involved by various mature BCLs. Biopsies with successful DNA extraction were analyzed for the MYD88 L265P mutation by allele-specific PCR. Selected positive results, including all those with ambiguous submitted diagnoses, were confirmed by Sanger sequencing. Re-review of cases within the BCL, NOS group was done with all available clinical, histopathologic and immunophenotypic data by 2 hematopathologists who were blinded to the MYD88 status.
|Submitted Diagnosis||Positive/Total; %|
|CyclinD1+ PCN||0/8; 0|
|Mantle Cell Lymphoma||0/7; 0|
|Hairy Cell Leukemia||1/13**; 8|
|Hairy Cell Leukemia Variant||0/2; 0|
|Follicular Lymphoma||0/6; 0|
|Revised diagnosis||Positive/Total; %|
|PCM, small lymphocyte like morphology, cyclinD1 negative||0/2; 0|
|BCL, LPL vs MZL||1/1; 100|
|BCL, other*||1/3; 33|