Lymphoma Staging System
Lymphoma is staged using the Ann Arbor classification system (modified by Cotswolds and updated by the Lugano classification), which divides disease into four anatomic stages (I-IV) based on lymph node distribution relative to the diaphragm, with PET-CT as the standard imaging modality for FDG-avid lymphomas. 1
The Four Anatomic Stages
The staging framework defines disease extent as follows:
- Stage I: Single lymph node region or single extralymphatic organ/site involvement 2
- Stage II: Two or more lymph node regions on the same side of the diaphragm 2
- Stage III: Lymph node regions on both sides of the diaphragm 2
- Stage IV: Diffuse or disseminated involvement of one or more extralymphatic organs (such as liver, bone marrow, lung) with or without associated lymph node involvement 2
Symptom Designation (A vs B)
Each stage receives a suffix based on systemic symptoms 1:
- "A" designation: Absence of systemic B symptoms 2
- "B" designation: Presence of at least one of the following: unexplained fever >38.3°C (101°F), drenching night sweats, or unexplained weight loss >10% of body weight within 6 months 1, 2
Important caveat: The Lugano classification recommends that A/B suffixes should only be routinely applied to Hodgkin lymphoma, not non-Hodgkin lymphoma, as these symptoms are not consistently prognostic in most NHL subtypes 1, 2.
Additional Modifiers
Bulky Disease ("X" designation)
Bulky disease is defined by 2:
- Mediastinal mass ratio (MMR) >0.33 (mass width exceeds one-third of the chest diameter on chest radiograph) 1
- Mediastinal thoracic ratio (MTR) >0.35 2
Extranodal Disease ("E" designation)
The "E" designation indicates localized extranodal extension from an adjacent lymph node region 1.
Clinical Risk Stratification
Beyond anatomic staging, patients are classified into treatment-relevant prognostic groups 1:
- Early-stage favorable: Stage I-II without adverse risk factors 1
- Early-stage unfavorable: Stage I-II with risk factors (bulky mediastinal mass, extranodal disease, elevated ESR >50 with B symptoms or >30 without B symptoms, ≥3 involved lymph node areas) 1
- Advanced-stage: Stage III-IV, or stage IIB with bulky disease or extranodal involvement 1
Modern Staging Approach
PET-CT has replaced CT alone as the standard staging modality for FDG-avid lymphomas (including most Hodgkin lymphoma and diffuse large B-cell lymphoma), eliminating the need for invasive procedures like staging laparotomy 1, 2. For non-FDG-avid histologies, contrast-enhanced CT remains the primary staging tool 1.
Required Staging Investigations
- PET-CT scan (for FDG-avid disease) 1, 2
- Contrast-enhanced CT of chest, abdomen, and pelvis 1
- Complete blood count with differential 2
- Erythrocyte sedimentation rate (ESR) 1, 2
- Comprehensive metabolic panel (including liver function tests, LDH, albumin) 2
- Bone marrow biopsy is no longer routinely required for Hodgkin lymphoma or most diffuse large B-cell lymphomas when PET-CT is used, as PET can adequately assess bone marrow involvement 1
Practical Treatment Implications
In clinical practice, treatment decisions are based on limited versus advanced disease rather than strict Ann Arbor stages 1: