Summary
Definition
History and exam
Key diagnostic factors
- age >70 years
- male sex
- white ancestry
Other diagnostic factors
- history of IgM monoclonal gammopathy of undetermined significance (MGUS)
- family history of B-cell lymphoma or myeloma
- family history of WM with or without monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma
- fatigue
- anorexia
- infections
- peripheral neuropathy
- weight loss
- fever
- Raynaud phenomenon
- splenomegaly
- lymphadenopathy
- hepatomegaly
- purpura
- skin and/or mucosal bleeding
- ophthalmologic symptoms
- headache
- dizziness and/or vertigo
- thrombosis
Risk factors
- IgM component monoclonal gammopathy of undetermined significance (MGUS)
- family history of B-cell lymphoproliferative disease or multiple myeloma
- family history of WM
- hepatitis C virus (HCV)
Diagnostic tests
1st tests to order
- CBC with differential
- hematinic test (iron, vitamin B12, and folate)
- renal function panel
- LFTs
- CRP
- high-resolution serum protein electrophoresis (SPEP) with immunofixation
- serum free light chains
- cold agglutinins and cryoglobulins
- lactate dehydrogenase
- beta-2 microglobulin
- serum albumin
- relative serum viscosity
- bone marrow biopsy
- CT chest, abdomen, and pelvis
Tests to consider
- lymph node biopsy
- 18-F-deoxyglucose PET/CT chest, abdomen, and pelvis
- quantitative immunoglobulins
- antimyelin-associated glycoprotein (MAG) antibodies
- antisulfatide IgM antibodies
- electromyography
- fat pad biopsy
- prothrombin time (PT) and activated partial thromboplastin time (APTT)
- viral serology (hepatitis B and C, and HIV)
- genetic mutation testing
Treatment algorithm
asymptomatic
symptomatic with low tumor burden
symptomatic with high tumor burden
responders to initial rituximab-containing treatment
relapse or refractory disease
Contributors
Authors
Guy Pratt, MD, FRCP, FRCPath
Honorary Consultant Haematologist
University Hospitals Birmingham NHS Foundation Trust
Professor of Haematology
Institute of Cancer and Genomic Sciences
College of Medical and Dental Sciences
University of Birmingham
Birmingham
UK
Disclosures
GP has received honoraria for speaking, advisory board memberships, and travel support from Janssen, BMS-Celgene, Beigene, Takeda, Binding Site Ltd, and Amgen. GP is an author of references cited within this topic.
Acknowledgements
Dr Guy Pratt wishes to gratefully acknowledge Dr Boris Kobrinsky and Dr Kenneth Hymes, the previous contributors to this topic.
Disclosures
BK and KH declare that they have no competing interests.
Peer reviewers
Shaji Kumar, MD
Consultant
Department of Hematology
Mayo Clinic
Rochester
MN
Disclosures
SK declares that he has no competing interests.
Madhav Dhodapkar, MD
Professor of Medicine
Chief, Section of Hematology
Department of Internal Medicine
Yale University School of Medicine
New Haven
CT
Disclosures
MD declares that he has no competing interests.
Xavier Leleu, MD, PhD
Instructor in Hematology
Department of Hematology
Hopital Huriez CHRU
Lille
France
Disclosures
XL has received lecture fees and research funding from Janssen-Cilag, Celgene, Chugai, Amgen, Novartis, Mundipharma, and Roche. XL is an author of a number of references cited in this topic.
Shayna Sarosiek, MD
Assistant Professor
Harvard Medical SchoolBostonUSA
Disclosures
SS has received research and consulting funding from BeiGene and ADC Therapeutics.
Differentials
- Multiple myeloma (MM)
- Low-grade B-cell lymphomas (e.g., follicular lymphoma)
- Chronic lymphocytic leukemia (CLL)
More DifferentialsGuidelines
- Diagnosis and management of Waldenström macroglobulinemia: Mayo stratification of macroglobulinemia and risk-adapted therapy (mSMART) guidelines
- Clinical practice guidelines in oncology: hematopoietic cell transplantation (HCT)
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