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

We studied the clinical, morphologic, and immunophenotypic features of 26 Waldenstrom's macroglobulinemia (WM) cases, each with an IgM spike of ≥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, CD 19, 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.