Persistent Monotypic Plasma Cells with Absence of Neoplastic B Cell Component in a Treated Case of Waldenström Macroglobulinemia: A Sign of Residual Disease?

Abstract

A 57-year-old male, known case of chronic inflammatory demyelinating polyneuropathy with POEMS Syndrome (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) presented with generalized weakness. Peripheral blood smear findings were within normal limits. Bone marrow smears showed mild increase in lymphoid cells including many lymphoplasmacytoid cells and increased in plasma cells. Bone marrow biopsy revealed hypercellular marrow spaces with small and large lymphoid aggregates interstitially and in paratrabecular location along with few plasma cell clusters. On immunohistochemistry, these lymphoid aggregates were CD20 positive with lambda restriction, and CD 56, CD5 and CD10 negative [ ABSTRACT Waldenström macroglobulinemia (WM) is a rare indolent variant of non-Hodgkin's lymphoma characterised by lymphoplasmacytic infiltration of bone marrow (BM) associated with a serum IgM paraprotein. The WHO classification states that the neoplastic cells of WM usually are positive for monotypic surface immunoglobulin light chain, IgM, CD19, and CD20 and are negative for CD5, CD10, and CD23. Serum monoclonal protein detection by serum protein electrophoresis and bone marrow aspirate and biopsy are required for WM diagnosis, monitoring and response assessment. Pathologist must dissuade themselves from making a hasty decision on calling a complete response in WM when neoplastic B cell component is absent. Evaluation of clonality of any residual plasma cells must be done in all cases of WM to evaluate the presence and extent of residual or persistent disease. Role of additional therapy targeted at these residual plasma cells in WM can be evaluated as tools for achieving complete remission. Herein, we present a case of WM with residual monotypic plasmacytosis in BM, without B lymphocytes after therapy.

Waldenström′s macroglobulinemia: Two malignant clones in a monoclonal disease? Molecular background and clinical reflection

“…Distinguishing the clonal cells in WM patient and their molecular characterization is important step for treatment and subsequent detection of the residual cell clone after clone′s specific therapy. Studies detecting the residual monotypic plasma cells in WM sample after treatment by anti‐B cell–specific antibodies were published …”

Time to Move to the Single-Cell Level: Applications of Single-Cell Multi-Omics to Hematological Malignancies and Waldenström’s Macroglobulinemia—A Particularly Heterogeneous Lymphoma

“…The heterogeneous composition of the bone marrow infiltration in WM, including variable percentages of small lymphocytes, plasmacytoid lymphocytes, and plasma cells [ 101 ], is also amenable to study at the single-cell level. The pathophysiology of the plasma cell involvement is poorly understood, and it has been observed that residual plasma cells may be present even in the complete response when the neoplastic B-cell component is absent [ 102 , 103 ]. Moreover, according to a recent study, concordance between the mutational landscape of WM B-cells and plasma cells is not 100%, suggesting that not all WM B-cells differentiate into plasma cells [ 69 ].…”