MYD88 L265P mutation analysis helps define nodal lymphoplasmacytic lymphoma.The diagnosis of lymphoplasmacytic lymphoma is often challenging, especially in extramedullary tissues where the differential diagnosis includes nodal marginal zone lymphoma, splenic marginal zone lymphoma, or other small B-cell neoplasms with plasmacytic differentiation.  The MYD88 L265P mutation has been recently identified in >90% of bone-marrow-based lymphoplasmacytic lymphoma, but the incidence of this abnormality and corresponding morphologic correlates in nodal lymphoplasmacytic lymphoma have not been established.  We analyzed 87 cases of extramedullary lymphoplasmacytic lymphoma, splenic marginal zone lymphoma, unclassifiable splenic B-cell lymphomas, nodal marginal zone lymphoma with plasmacytic differentiation, and chronic lymphocytic leukemia/small lymphocytic lymphoma with plasmacytic differentiation for MYD88 L265P.  The presence of MYD88 L265P was associated with IgM paraprotein (P<0.001) and a trend for bone marrow involvement (P=0.09).  Morphologic re-review with knowledge of MYD88 mutation status and all available clinical features suggested all MYD88 mutated cases were consistent with lymphoplasmacytic lymphoma (either classic or variant histology), except for one case which remained most consistent with nodal marginal zone lymphoma with plasmacytic differentiation.  These results demonstrate the importance of MYD88 mutational analysis in better defining lymphoplasmacytic lymphoma as a relatively monomorphic small B-cell lymphoma with plasmacytic differentiation that may show total nodal architectural effacement and follicular colonization.  Clinicopathologic review suggests that although MYD88 mutated non-lymphoplasmacytic lymphoma small B-cell neoplasms exist, they are very uncommon.
MYD88