title: Are you sure this is Waldenstrom macroglobulinemia?
abstract: Waldenström macroglobulinemia (WM) is a rare lymphoproliferative disorder characterized by the presence of lymphoplasmacytic cells in the BM and IgM monoclonal protein in the serum. The origin of the malignant clone is thought to be a B cell arrested after somatic hypermutation in the germinal center and before terminal differentiation to plasma cells. In this review, recent advances in the genetic and epigenetic regulators of tumor progression are discussed. Risk factors include IgM-monoclonal gammopathy of undermined significance, familial disease, and immunological factors. The clinical manifestations of the disease include those related to clonal infiltration of the BM, lymph nodes, and, rarely, other sites such as pulmonary or CNS infiltration (Bing-Neel syndrome). Other manifestations are related to the IgM monoclonal protein, including hyperviscosity, cryoglobulinemia, protein-protein interactions, Ab-mediated disorders such as neuropathy, hemolytic anemia, and Schnitzler syndrome. IgM deposition in organs can lead to amyloidogenic manifestations in WM. The diagnostic workup for a patient with WM and rare presentations of WM are described herein. Prognosis of WM depends on 5 major factors in the International Staging System, including age, anemia, thrombocytopenia, β-2 microglobulin, and IgM level. The differential diagnosis of WM includes IgM-multiple myeloma, marginal zone lymphoma, mantle cell lymphoma, and follicular lymphoma.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. Irene_ghobrial@dfci.harvard.edu
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
mesh_terms: D000328:Adult; D000368:Aged; D000682:Amyloid / Q000378:metabolism; D003449:Cryoglobulinemia / Q000378:metabolism; D003582:Cytogenetics; D003937:Diagnosis, Differential; D018450:Disease Progression; D044127:Epigenesis, Genetic; D018628:Gene Dosage; D016678:Genome; D006405:Hematology / Q000379:methods*; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D018442:Lymphoma, B-Cell, Marginal Zone / Q000175:diagnosis; D008224:Lymphoma, Follicular / Q000175:diagnosis; D020522:Lymphoma, Mantle-Cell / Q000175:diagnosis; D008875:Middle Aged; D008954:Models, Biological; D011379:Prognosis; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis*
chemical_list: D000682:Amyloid; D007075:Immunoglobulin M