How can I determine whether a patient's lymphoma is advanced (stage III or IV)?

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Last updated: February 22, 2026View editorial policy

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Determining Advanced-Stage Lymphoma

Advanced-stage lymphoma (Stage III or IV) is determined by identifying nodal involvement on both sides of the diaphragm (Stage III) or additional noncontiguous extralymphatic organ involvement (Stage IV) using PET-CT for FDG-avid lymphomas or CT for non-avid histologies. 1

Imaging Modality Selection

  • PET-CT is the standard imaging technique for staging all FDG-avid lymphomas (including Hodgkin lymphoma and most aggressive non-Hodgkin lymphomas), while CT alone is used for non-avid histologies 1
  • PET-CT has replaced CT as the gold standard because it provides superior accuracy in detecting both nodal and extranodal disease 2

Defining Advanced Stage: Anatomic Criteria

Stage III disease includes:

  • Lymph nodes on both sides of the diaphragm 1
  • Nodes above the diaphragm with spleen involvement (spleen is considered nodal tissue) 1

Stage IV disease includes:

  • Any additional noncontiguous extralymphatic involvement in organs such as liver, bone marrow, lung parenchyma, or abdominal wall 3
  • The "E" designation for extranodal extension is NOT relevant to advanced-stage disease—it only applies to limited disease (Stage IE or IIE with direct extension from adjacent nodes) 1, 3

Bone Marrow Assessment

  • For Hodgkin lymphoma: bone marrow biopsy is no longer required when PET-CT is performed 1
  • For diffuse large B-cell lymphoma (DLBCL): a positive PET scan showing bone or bone marrow involvement is sufficient to designate advanced-stage disease 1
  • However, if PET is negative in DLBCL and identifying discordant histology would impact management (such as for clinical trial eligibility), bone marrow biopsy should be considered 1
  • For other lymphoma histologies: a 2.5-cm unilateral bone marrow biopsy remains recommended, along with immunohistochemistry and flow cytometry 1

Stage II Bulky Disease Consideration

  • Stage II bulky disease occupies a gray zone and may be treated as either limited or advanced disease depending on histology and prognostic factors 1
  • Record the largest tumor diameter rather than using the "X" designation for bulky disease 1

B Symptoms: When They Matter

  • Constitutional B symptoms (fever >38°C, night sweats, weight loss >10% over 6 months) only need to be documented for Hodgkin lymphoma, as they direct treatment decisions in that disease 1, 4
  • For non-Hodgkin lymphomas, B symptoms are not included in major prognostic indices and do not need formal A/B designation 1

Common Pitfalls to Avoid

  • Do not perform routine bone marrow biopsies in Hodgkin lymphoma patients undergoing PET-CT staging—this is outdated practice and adds unnecessary morbidity 1, 5
  • Do not assign the "E" designation to patients with Stage IV disease—this is a frequent error, as "E" only applies to limited-stage disease with direct nodal extension 1, 3
  • Ensure adequate tissue sampling at initial diagnosis (excisional biopsy preferred) to avoid repeat procedures 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Hodgkin Lymphoma Staging and Treatment

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

B Symptoms in Hodgkin Lymphoma

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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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