Last reviewed: 29 Oct 2021
Last updated: 30 Mar 2021



History and exam

Key diagnostic factors

  • history of Helicobacter pylori gastritis
  • history of autoimmune disorder
  • age >60 years
  • dyspepsia
  • epigastric discomfort
  • skin lesions
  • red eye ± photophobia
  • painless proptosis, diplopia, motility disturbances of the eye, ptosis, decreased vision

Other diagnostic factors

  • nausea and/or vomiting
  • GI bleeding
  • fever
  • night sweats
  • weight loss
  • shortness of breath, hemoptysis, cough
  • salivary gland swelling
  • thyroid swelling
  • breast lump
  • focal neurologic deficits
  • lymphadenopathy

Risk factors

  • Helicobacter pylori infection
  • age >60 years
  • autoimmune diseases
  • female sex
  • Chlamydia psittaci infection
  • Campylobacter jejuni infection
  • Borrelia burgdorferi infection
  • hepatitis C virus infection
  • HIV infection

Diagnostic investigations

1st investigations to order

  • CBC
  • blood smear
  • upper GI endoscopy
  • biopsy of affected tissue
  • staging CT scan
  • H pylori serology
  • H pylori stool antigen test
  • LFTs
  • basic metabolic panel

Investigations to consider

  • bone marrow biopsy
  • immunohistochemistry
  • reverse transcriptase polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH)
  • immunoglobulin gene rearrangement studies
  • serum electrophoresis
  • serum LDH
  • serum beta-2 microglobulin
  • 18F-fluorodeoxyglucose (FDG) PET/CT scan
  • endoscopic ultrasound of the stomach
  • double contrast radiograph of the GI tract
  • lower GI endoscopy
  • endoscopic otolaryngology
  • CT scan of salivary glands
  • MRI orbit
  • hepatitis C serology
  • hepatitis B serology
  • HIV serology
  • multiple-gated acquisition scan (MUGA)
  • echocardiography
  • ethylenediamine tetraacetic acid glomerular filtration rate (EDTA GFR)

Treatment algorithm



Christopher McNamara, MBBS (Hons), FRACP, FRCPA, FRCPath

Consultant Haematologist

Royal Free Hospital




CM declares that he has no competing interests.


Dr Christopher McNamara wishes to gratefully acknowledge Dr Rahul Joshi, a previous contributor to this topic. RJ declared that he had no competing interests. Unfortunately, we have since been made aware that Dr Rahul Joshi is deceased.

Peer reviewers

Markus Raderer, MD

Professor of Medicine

Department of Internal Medicine I

Division of Oncology

Medical University Vienna



MR is an author of a number of references cited in this topic.

Alan Lichtin, MD

Staff Hematologist

Cleveland Clinic Taussig Cancer Center




AL declares that he has no competing interests.

Ian Chau, MD

Consultant Medical Oncologist

Royal Marsden Hospital




IC has been reimbursed by Roche Products, the manufacturer of rituximab, for attending several conferences. IC has also served on advisory boards and received honorarium for giving presentations for Roche Products. IC has received research funding from Novartis to conduct academic studies in the treatment of colorectal cancer.

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