Defining lymphoplasmacytic lymphoma: Does MYD88 _L265P 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 MYD88 L265P 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 MYD88 L265P 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 MYD88 L265P. Results In total, 138 (87%) of 159 cases had MYD88 L265P, and 158 of 159 were clinically considered WM. MYD88 L265P cases had higher disease burden than MYD88 WT. Features associated with MYD88 L265P include increased mast cells and lymphocyte (not plasma cell)-predominant infiltrate. Hemosiderin, Dutcher bodies, and paratrabecular growth were not associated with MYD88 L265P. Conclusions Our data support a clinicopathologic approach to LPL diagnosis and recognition that it may manifest with varying morphologies, phenotypes, and molecular features.