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Last reviewed: 14 Mar 2025
Last updated: 16 Dec 2024

Summary

Definition

History and exam

Key diagnostic factors

  • B symptoms (fever, night sweats, weight loss)
  • fatigue/malaise

Other diagnostic factors

  • lymphadenopathy
  • splenomegaly
  • hepatomegaly
  • shortness of breath
  • cough
  • abdominal discomfort
  • headache
  • change in mental status
  • focal neurological deficits
  • chest pain
  • bone pain, back pain
  • jaundice
  • pallor
  • purpura
  • skin lesions
  • neurological abnormalities on examination
  • breast pain
  • swelling or mass in the breast

Risk factors

  • age >50 years
  • male sex
  • Epstein-Barr virus (EBV)
  • human T-lymphocytotrophic virus-1 (HTLV-1)
  • human herpesvirus-8 (Kaposi's sarcoma-associated herpesvirus)
  • Helicobacter pylori
  • coeliac disease
  • HIV
  • hepatitis C virus (HCV)
  • Sjogren syndrome
  • Wiskott-Aldrich syndrome
  • ataxia-telangiectasia
  • use of immunomodulatory drugs
  • organ transplant
  • Borrelia burgdorferi
  • Coxiella burnetii
  • Chlamydia psittaci
  • Campylobacter jejuni
  • rheumatoid arthritis
  • systemic lupus erythematosus (SLE)
  • common variable immunodeficiency
  • Chediak-Higashi syndrome
  • Klinefelter syndrome
  • pesticides
  • phenoxyherbicides
  • breast implants

Diagnostic investigations

1st investigations to order

  • FBC with differential
  • peripheral blood smear
  • comprehensive metabolic panel (including liver function tests [LFTs])
  • serum lactate dehydrogenase (LDH)
  • uric acid
  • lymph node biopsy
  • biopsy (extranodal sites e.g., brain, skin)
  • bone marrow biopsy and aspirate
  • immunohistochemistry
  • flow cytometry
  • fluorodeoxyglucose (FDG)-PET/CT scan

Investigations to consider

  • core needle biopsy
  • fine-needle aspiration (FNA) biopsy
  • genetic testing
  • hepatitis B and C serology
  • HIV testing
  • Epstein-Barr virus (EBV) testing
  • human T-cell lymphotropic virus (HTLV) testing
  • MRI (brain, spine)
  • ultrasound (breast, axilla)
  • lumbar puncture
  • endoscopy and colonoscopy
  • serum protein electrophoresis with immunofixation
  • quantitative immunoglobulins
  • serum beta-2 microglobulin
  • Helicobacter pylori testing
  • multigated acquisition (MUGA) scan
  • echocardiography

Treatment algorithm

Contributors

Authors

Julie E. Chang, MD

Associate Professor

Department of Medicine, Section of Hematology & Oncology

University of Wisconsin School of Medicine and Public Health

Madison

WI

Disclosures

JEC has been paid for time served on advisory boards for MorphoSys, BeiGene, and Genentech. JEC has research funding from Genentech and Celgene.

Acknowledgements

Dr Julie Chang would like to gratefully acknowledge Dr Esther Chan, Dr Chin Hin Ng, Dr Melissa Ooi, Dr Michelle Poon, Dr Boris Kobrinsky, and Dr Kenneth B. Hymes, previous contributors to this topic.

Disclosures

EC, CHN, MO, BK, and KBH declare that they have no competing interests. MP has received sponsorship from Sanofi and Janssen to attend conferences.

Peer reviewers

Leonidas G. Koniaris, MD

Associate Professor Surgery

Department of Cell Biology and Anatomy

University of Miami School of Medicine

Coral Gables

FL

Disclosures

LGK declares that he has no competing interests.

Shankaranarayana Paneesha, MD, MRCP, FRCPath

Consultant Haematologist

Department of Haematology and Stem Cell Transplantation

Heartlands Hospital

Birmingham

UK

Disclosures

SP declares that he has no competing interests.

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