Defining Lymphoplasmacytic Lymphoma: Does MYD88L265P Define a Pathologically Distinct Entity Among Patients With an IgM Paraprotein and Bone Marrow-Based Low-Grade B-Cell Lymphomas With Plasmacytic Differentiation?

OBJECTIVES: Lymphoplasmacytic lymphoma (LPL) remains a poorly defined entity, even with the discovery of MYD88L265P mutations and association with Waldenström macroglobulinemia (WM). Among bone marrow (BM)-based, low-grade B-cell lymphoma with plasmacytic differentiation (LGBLPD) and immunoglobulin M (IgM) paraproteins, we sought to determine whether MYD88L265P defines a distinct entity and can help refine diagnostic criteria for LPL. METHODS: BMs diagnosed with LGBLPD or LPL and serum IgM paraprotein were studied (2007-2013). Clinicopathologic features were reviewed and specimens were tested for MYD88L265P. RESULTS: In total, 138 (87%) of 159 cases had MYD88L265P, and 158 of 159 were clinically considered WM. MYD88L265P cases had higher disease burden than MYD88WT. Features associated with MYD88L265P include increased mast cells and lymphocyte (not plasma cell)-predominant infiltrate. Hemosiderin, Dutcher bodies, and paratrabecular growth were not associated with MYD88L265P. CONCLUSIONS: Our data support a clinicopathologic approach to LPL diagnosis and recognition that it may manifest with varying morphologies, phenotypes, and molecular features.