[1481] 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.

Table 1. MYD88 (L265P) test-results of 80 BM samples
Submitted DiagnosisPositive/Total; %
LPL13/13*; 100
MZL0/6; 0
CLL/SLL0/9; 0
CyclinD1+ PCN0/8; 0
Mantle Cell Lymphoma0/7; 0
Hairy Cell Leukemia1/13**; 8
Hairy Cell Leukemia Variant0/2; 0
Follicular Lymphoma0/6; 0
*11/11 with available data had an IgM monoclonal paraprotein, **all positive for BRAF V600E

Table 2. Re-review of the BCL, NOS group
Revised diagnosisPositive/Total; %
LPL4/4; 100
MZL1/6; 17
PCM, small lymphocyte like morphology, cyclinD1 negative0/2; 0
BCL, LPL vs MZL1/1; 100
BCL, other*1/3; 33
*2 cases are consistent with monoclonal B-lymphocytosis and 1 case (positive for MYD88) represents BM involvement by an unclassifiable low-grade B-cell LPD in a patient with a double hit large cell lymphoma with BCL2 and MYC translocations.

Of the 21 MYD88 L265P mutated cases, 16 had immunofixation analysis data. 15 had an IgM monoclonal paraprotein and 1 had kappa light chains only. Two cases of SMZL with IgM monoclonal paraproteinemia were negative for MYD88 L265P.
Conclusions: We confirm that MYD88 L265P is characteristic of LPL and absent or rarely present in PCM and other small BCLs (sensitivity 100%, specificity 95%). In a subset of problematic BCL, NOS cases, mutation testing accurately identified LPL from non-LPL cases in 14/16 cases and may be a useful adjunct in the diagnosis of small BCLs in the BM.
Category: Hematopathology

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 227, Monday Morning


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