How do we exclude extranodal (outside of lymph nodes) involvement in nodal marginal zone lymphoma (NMZL)?

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Last updated: May 24, 2025View editorial policy

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From the Guidelines

To exclude extranodal involvement in nodal marginal zone lymphoma, a comprehensive diagnostic workup including history and physical examination, laboratory tests, bone marrow biopsy, and imaging studies such as complete chest and abdominal computed tomography (CT) scan or magnetic resonance imaging (MRI) is essential. This approach is supported by the European Society for Medical Oncology (ESMO) clinical practice guidelines for diagnosis, treatment, and follow-up of marginal zone lymphomas, as outlined in the Annals of Oncology 1.

The initial work-up should include:

  • History and physical examination, noting lymph node regions, eyes and ears, nose and throat, liver and spleen
  • Full blood and differential counts, with flow cytometry of peripheral blood mandatory in NMZL and SMZL and optional in EMZL 1
  • Biochemistry, including renal and liver function tests
  • Protein electrophoresis
  • Lactate dehydrogenase (LDH) and b2 microglobulin (B2M)
  • Optional direct antiglobulin (Coombs) test in SMZL
  • Serum and urine immunofixation
  • Serology for hepatitis C virus (HCV) and hepatitis B virus (HBV) markers and human immunodeficiency virus (HIV) serology 1

Bone marrow aspirate (with morphology and flow cytometry) and biopsy are mandatory in NMZL and SMZL and highly recommended in EMZL, particularly in non-gastric lymphoma and when only local treatment is planned 1. Imaging should include complete chest and abdominal computed tomography (CT) scan or magnetic resonance imaging (MRI) and imaging of the orbits and salivary glands 1.

While positron emission tomography (PET) scanning has generally been considered of little clinical utility, its use is being reconsidered due to the increased sensitivity of modern PET-CT equipment, and it may be useful in certain cases 1. By following this comprehensive diagnostic approach, clinicians can effectively exclude extranodal involvement in nodal marginal zone lymphoma and make informed treatment decisions.

From the Research

Excluding Extranodal Involvement in Nodal Marginal Zone Lymphoma

To exclude extranodal involvement in nodal marginal zone lymphoma, the following steps can be taken:

  • A thorough work-up and staging are necessary to exclude occult extranodal involvement 2
  • Patients typically present with nodal disease, usually at advanced stages, and a comprehensive evaluation is required to distinguish NMZL from extranodal MZL with lymph node spread 3
  • Bone marrow involvement can be evaluated through biopsy specimens, and patterns of infiltration can be assessed to determine the extent of involvement 4, 5
  • Imaging techniques such as ¹⁸F-FDG PET/CT can also be used to detect bone marrow involvement and recurrent disease 6
  • A combination of clinical features, diagnosis, and management strategies can help exclude extranodal involvement in NMZL, although prospective studies are required to evaluate the therapeutic efficacy of novel agents 3

Diagnostic Challenges

  • Distinguishing NMZL from other types of marginal zone lymphoma can be challenging, and a comprehensive evaluation is required to determine the extent of involvement 4, 5
  • Bone marrow involvement can be difficult to detect, and correlation with CBC count can further enhance the reliability of diagnosing SMZL 5
  • The use of imaging techniques such as ¹⁸F-FDG PET/CT can help detect recurrent disease and bone marrow involvement, but pathological verification is necessary to confirm malignant involvement 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Nodal marginal zone lymphoma.

Leukemia & lymphoma, 2014

Research

Nodal marginal zone lymphoma: Clinical features, diagnosis, management and treatment.

Best practice & research. Clinical haematology, 2017

Research

Comparative study of marginal zone lymphoma involving bone marrow.

American journal of clinical pathology, 2002

Research

Bone marrow involvement by marginal zone B-cell lymphomas of different types.

American journal of clinical pathology, 2008

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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