Last reviewed: 28 Dec 2021
Last updated: 29 Oct 2021



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
  • hemorrhage

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 investigations

1st investigations 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
  • high-resolution urine protein electrophoresis (UPEP) and 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

Investigations to consider

  • lymph node biopsy
  • 18-F-deoxyglucose (18F-FDG) 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



Guy Pratt, MD, FRCP, FRCPath

Consultant Haematologist

University Hospitals Birmingham NHS Foundation Trust

Honorary Professor

Institute of Immunology and Immunotherapy

College of Medical and Dental Sciences

University of Birmingham




GP has received honoraria for speaking, advisory board memberships, and travel support from Janssen, Celgene, Takeda, Binding Site Ltd, and Amgen.


Dr Guy Pratt wishes to gratefully acknowledge Dr Boris Kobrinsky and Dr Kenneth Hymes, the previous contributors to this topic.


BK and KH declare that they have no competing interests.

Peer reviewers

Shaji Kumar, MD


Department of Hematology

Mayo Clinic




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



MD declares that he has no competing interests.

Xavier Leleu, MD, PhD

Instructor in Hematology

Department of Hematology

Hopital Huriez CHRU




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.

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