ABSTRACT
Lymphoplasmacytic lymphoma (LPL) is a low-grade, B-cell neoplasm composed of small lymphocytes, plasmacytoid lymphocytes, and plasma cells that typically involve the bone marrow, and it is associated with an immunoglobulin M (IgM) gammopathy. The definition of Waldenström macroglobulinemia (WM) and its relationship to LPL has been confusing in the past. In addition, the diagnosis of LPL itself can be challenging because LPL lacks disease-specific morphologic, immunophenotypic, and genetic features to differentiate it from other mature B-cell neoplasms. Accurate diagnosis of LPL/WM rests on recognition of the differential diagnostic features between LPL and other diagnostic possibilities and the use of the recently refined definition of WM and its relationship with LPL: The presence of an IgM monoclonal gammopathy of any level in the setting of bone marrow involvement by LPL. This review summarizes the clinical, laboratory, and histologic features of LPL/WM, with particular emphasis on unique aspects of LPL/WM that may aid in accurate diagnosis.
Subject(s)
Monoclonal Gammopathy of Undetermined Significance/diagnosis , Waldenstrom Macroglobulinemia/diagnosis , Bone Marrow/pathology , Female , Humans , Liver/pathology , Lymph Nodes/pathology , Male , Monoclonal Gammopathy of Undetermined Significance/immunology , Prognosis , Spleen/pathology , Waldenstrom Macroglobulinemia/immunology , Waldenstrom Macroglobulinemia/therapyABSTRACT
BACKGROUND AIMS: Mesenchymal stromal cells (MSC) have now been shown to reside in numerous tissues throughout the body, including the pancreas. Ex vivo culture-expanded MSC derived from many tissues display important interactions with different types of immune cells in vitro and potentially play a significant role in tissue homeostasis in vivo. In this study, we investigated the biologic and immunomodulatory properties of human pancreatic islet-derived MSC. METHODS: We culture-expanded MSC from cadaveric human pancreatic islets and characterized them using flow cytometry, differentiation assays and nuclear magnetic resonance-based metabolomics. We also investigated the immunologic properties of pancreatic islet-derived MSC compared with bone marrow (BM) MSC. RESULTS: Pancreatic islet and BM-derived MSC expressed the same cell-surface markers by flow cytometry, and both could differentiate into bone, fat and cartilage. Metabolomics analysis of MSC from BM and pancreatic islets also showed a similar set of metabolic markers but quantitative polymerase chain reactions showed that pancreatic islet MSC expressed more interleukin(IL)-1b, IL-6, STAT3 and FGF9 compared with BM MSC, and less IL-10. However, similar to BM MSC, pancreatic islet MSC were able to suppress proliferation of allogeneic T lymphocytes stimulated with anti-CD3 and anti-CD28 antibodies. CONCLUSIONS: Our in vitro analysis shows pancreatic islet-derived MSC have phenotypic, biologic and immunomodulatory characteristics similar, but not identical, to BM-derived MSC. We propose that pancreatic islet-derived MSC could potentially play an important role in improving the outcome of pancreatic islet transplantation by promoting engraftment and creating a favorable immune environment for long-term survival of islet allografts.
