Non-Hodgkin lymphoma

Last reviewed: 22 Feb 2023
Last updated: 12 Jan 2023



History and exam

Key diagnostic factors

  • night sweats
  • weight loss
  • fatigue/malaise
  • fever
More key diagnostic factors

Other diagnostic factors

  • lymphadenopathy
  • massive splenomegaly in marginal zone lymphoma
  • hepatomegaly
  • shortness of breath
  • cough
  • abdominal discomfort
  • headache
  • change in mental status
  • focal neurologic deficits
  • chest pain
  • bone pain, back pain (bone involvement)
  • jaundice
  • pallor
  • purpura
  • skin lesions
  • neurologic abnormalities on exam
Other diagnostic factors

Risk factors

  • age >50 years
  • male sex
  • Epstein-Barr virus (EBV)
  • human T-lymphocytotrophic virus-1 (HTLV-1)
  • human herpesvirus-8
  • Helicobacter pylori
  • celiac 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
  • rheumatoid arthritis
  • systemic lupus erythematosus (SLE)
  • common variable immunodeficiency
  • Chediak-Higashi syndrome
  • Klinefelter syndrome
  • pesticides
  • phenoxyherbicides
  • breast implants
More risk factors

Diagnostic investigations

1st investigations to order

  • lymph node biopsy
  • PET/CT scan
  • PET scan
  • CBC with differential
  • blood smear
  • skin biopsy
  • bone marrow biopsy
  • basic metabolic panel
  • liver function tests
  • lactate dehydrogenase (LDH)
More 1st investigations to order

Investigations to consider

  • flow cytometry
  • immunohistochemistry
  • polymerase chain reaction for tumor markers
  • immunoglobulin gene rearrangement studies
  • cytogenetics studies with or without fluorescence in situ hybridization (FISH)
  • hepatitis B and C serology
  • HIV antibody
  • lumbar puncture
  • colonoscopy
  • serum protein electrophoresis with immunofixation
  • multiple-gated acquisition scan
  • echocardiography
More investigations to consider

Emerging tests

  • gene expression profiling

Treatment algorithm


aggressive B-cell lymphomas

aggressive T-cell lymphomas

indolent B-cell lymphomas

indolent T-cell lymphomas



Julie E. Chang, MD

Associate Professor

Department of Medicine, Section of Hematology & Oncology

University of Wisconsin School of Medicine and Public Health




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


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.


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



LGK declares that he has no competing interests.

Shankaranarayana Paneesha, MD, MRCP, FRCPath

Consultant Haematologist

Department of Haematology and Stem Cell Transplantation

Heartlands Hospital




SP declares that he has no competing interests.

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