Despite apparent morphologic and immunophenotypic heterogeneity, Waldenstrom's macroglobulinemia is consistently composed of cells along a morphologic continuum of small lymphocytes, plasmacytoid lymphocytes, and plasma cells

Abstract

We studied the clinical, morphologic, and immunophenotypic features of 26 Waldenstrom's macroglobulinemia (WM) cases, each with an IgM spike of >or=3.0 g/dL. The neoplastic cells were consistently composed of a spectrum of small lymphocytes, plasmacytoid lymphocytes, and plasma cells. Bone marrow (BM) involvement ranged from 10% to 90%, showed four histologic patterns (nodular [75%], interstitial [75%], paratrabecular [42%], and diffuse [4%]), two histologic subtypes (lymphoplasmacytic [87%] and lymphoplasmacytoid [13%]), and several cytologic variants (monocytoid [n = 2], signet-ring cell [n = 2], and hairy cell leukemia-like [n = 1]). By flow cytometry (FC), all cases expressed monoclonal surface immunoglobulin, CD19, and CD20. Most cases (58%) lacked expression of CD5, CD10, and CD23. However, variants such as CD5(+)CD10(-)CD23(-) (n = 3), CD5(+)CD10(-)CD23(+) (n = 1), and CD5(-)CD10(+)CD23(+/-) (n = 2) were seen. At last follow-up, 18 of 26 patients were alive (median survival, 94 months). Causes of death included WM (n = 1), large cell lymphoma (n = 1), acute myeloid leukemia (likely therapy-related [n =2]), and nonhematologic/unknown. When individual WM cases are compared, apparent morphologic diversity is suggested. However, every WM case is comprised of cells along a morphologic continuum from small lymphocytes to plasma cells, delineating a uniform, consistent pathology. As WM shows immunophenotypic heterogeneity, morphology must be the cornerstone of the diagnosis.