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MYD88 L265P mutation analysis helps define nodal lymphoplasmacytic lymphoma.
Mod Pathol. 2015 Apr; 28(4):564-74.MP

Abstract

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. Eighteen cases (21%) were positive, including 9/9 (100%) lymphoplasmacytic lymphomas with classic histologic features, 5/12 (42%) cases that met 2008 WHO criteria for lymphoplasmacytic lymphoma but with atypical morphologic features, 3/15 (20%) cases initially considered nodal marginal zone lymphoma with plasmacytic differentiation, and 1/6 (17%) unclassifiable splenic B-cell lymphomas. The presence of MYD88 L265P was associated with IgM paraprotein (P<0.001) and a trend for bone marrow involvement (P=0.09). Each of 44 splenectomy-defined splenic marginal zone lymphomas (19 with plasmacytic differentiation) and the chronic lymphocytic leukemia/small lymphocytic lymphoma with plasmacytic differentiation were negative for the mutation. 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. Cases previously considered lymphoplasmacytic lymphoma that are more polymorphous and are often associated with histiocytes should no longer be included in the lymphoplasmacytic lymphoma category. Clinicopathologic review suggests that although MYD88 mutated non-lymphoplasmacytic lymphoma small B-cell neoplasms exist, they are very uncommon.

Authors+Show Affiliations

Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.Department of Pathology, University of Virginia, Charlottesville, VA, USA.Division of Hematopathology, University of Pittsburgh, Pittsburgh, PA, USA.Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25216226

Citation

Hamadeh, Fatima, et al. "MYD88 L265P Mutation Analysis Helps Define Nodal Lymphoplasmacytic Lymphoma." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 28, no. 4, 2015, pp. 564-74.
Hamadeh F, MacNamara SP, Aguilera NS, et al. MYD88 L265P mutation analysis helps define nodal lymphoplasmacytic lymphoma. Mod Pathol. 2015;28(4):564-74.
Hamadeh, F., MacNamara, S. P., Aguilera, N. S., Swerdlow, S. H., & Cook, J. R. (2015). MYD88 L265P mutation analysis helps define nodal lymphoplasmacytic lymphoma. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 28(4), 564-74. https://doi.org/10.1038/modpathol.2014.120
Hamadeh F, et al. MYD88 L265P Mutation Analysis Helps Define Nodal Lymphoplasmacytic Lymphoma. Mod Pathol. 2015;28(4):564-74. PubMed PMID: 25216226.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MYD88 L265P mutation analysis helps define nodal lymphoplasmacytic lymphoma. AU - Hamadeh,Fatima, AU - MacNamara,Stephen P, AU - Aguilera,Nadine S, AU - Swerdlow,Steven H, AU - Cook,James R, Y1 - 2014/09/12/ PY - 2014/06/17/received PY - 2014/07/30/accepted PY - 2014/9/13/entrez PY - 2014/9/13/pubmed PY - 2016/3/25/medline SP - 564 EP - 74 JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JO - Mod. Pathol. VL - 28 IS - 4 N2 - 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. Eighteen cases (21%) were positive, including 9/9 (100%) lymphoplasmacytic lymphomas with classic histologic features, 5/12 (42%) cases that met 2008 WHO criteria for lymphoplasmacytic lymphoma but with atypical morphologic features, 3/15 (20%) cases initially considered nodal marginal zone lymphoma with plasmacytic differentiation, and 1/6 (17%) unclassifiable splenic B-cell lymphomas. The presence of MYD88 L265P was associated with IgM paraprotein (P<0.001) and a trend for bone marrow involvement (P=0.09). Each of 44 splenectomy-defined splenic marginal zone lymphomas (19 with plasmacytic differentiation) and the chronic lymphocytic leukemia/small lymphocytic lymphoma with plasmacytic differentiation were negative for the mutation. 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. Cases previously considered lymphoplasmacytic lymphoma that are more polymorphous and are often associated with histiocytes should no longer be included in the lymphoplasmacytic lymphoma category. Clinicopathologic review suggests that although MYD88 mutated non-lymphoplasmacytic lymphoma small B-cell neoplasms exist, they are very uncommon. SN - 1530-0285 UR - https://www.unboundmedicine.com/medline/citation/25216226/MYD88_L265P_mutation_analysis_helps_define_nodal_lymphoplasmacytic_lymphoma_ L2 - http://dx.doi.org/10.1038/modpathol.2014.120 DB - PRIME DP - Unbound Medicine ER -