Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma Concomitant With Non-IgM Plasma Cell Neoplasm: Report of 5 Cases With Laboratory Evidence of Biclonal B-Cell Neoplasms in Single Individuals

Abstract

Abstract Introduction Plasma cell neoplasm (PCN) is rarely associated with Waldenstrom macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL), and its clonal relationship to WM/LPL is unclear. Methods We retrospectively analyzed five cases of PCN concomitant with WM/LPL for clinicopathologic features. Results Of five patients, three were female and two were male with a median age of 75 years at diagnosis of concurrent PCN-WM/LPL. Three cases presented with serum paraprotein of IgM type and had a diagnosis of WM/LPL before identifying concurrent PCN, with an interval of 1 to 10 years. In the remaining two cases, PCN and WM/LPL were concurrently diagnosed. All patients demonstrated biclonal M-spikes with distinct heavy chain isotypes but concordant light chain isotype (kappa or lambda) by immunofixation electrophoresis. In all four cases, two neoplastic populations were highlighted with immunohistochemistry, including expression of CD56/cyclin D1 (1), cyclin D1 (2), and IgA (1) in neoplastic plasma cells and negativity of CD56/cyclin D1 in LPL. Of three patients with clinical information available, two were treated with chemotherapy, and the other was treated with autologous stem cell transplant. At follow-up, one patient died of PCN progression at 24 months, one had recurrent WM/LPL at 144 months, and the other was alive with disease 5 months after the diagnosis of concurrent neoplasms. Conclusion Discordant heavy chain isotype restrictions between PCN and WM/LPL suggest biclonal B-cell neoplasms, which is supported by PCN’s phenotypic distinction, such as expression of cyclin D1 and/or CD56, from coexisting WM/LPL. However, our cases had WM/LPL either preceding or concurring with PCN, and all exhibited concordant light chain restrictions, raising a possibility that PCN may be evolved from WM/LPL with class switching. This issue of clonal relationship between the two B-cell neoplasm and underlying pathogenesis remains to be investigated with sequencing analysis on sorted PCN or WM/LPL and comparison of mutation profiles between them.