What is the staging system for Hodgkin's lymphoma?

Hodgkin Lymphoma Staging

Hodgkin lymphoma is staged using the Ann Arbor classification system with Cotswolds modifications, which divides disease into four stages (I-IV) based on anatomic distribution of lymph node involvement relative to the diaphragm, with PET-CT now the preferred imaging modality for staging FDG-avid disease. 1

Core Staging System: Ann Arbor with Cotswolds Modifications

The staging framework defines four anatomic stages 1:

• Stage I: Single lymph node region OR one extralymphatic site (IE) 1
• Stage II: Two or more lymph node regions on the same side of the diaphragm OR local extralymphatic extension plus lymph node regions on the same side of the diaphragm (IIE) 1
• Stage III: Lymph node regions on both sides of the diaphragm, which may include local extralymphatic extension (IIIE) 1
• Stage IV: Diffuse involvement of one or more extralymphatic organs or sites 1

Symptom Classification (A vs B)

Each stage is subdivided based on systemic symptoms 1:

• "A" designation: No systemic symptoms present 1
• "B" designation: Presence of at least one of the following 1:
  • Unexplained weight loss >10% of baseline body weight during the 6 months prior to staging 1
  • Recurrent unexplained fever >38°C 1
  • Recurrent drenching night sweats 1

Important note: The Lugano classification (2014) recommends that A/B suffixes should only be included for Hodgkin lymphoma, not for non-Hodgkin lymphoma. 1

Bulky Disease Definition

Bulky disease is a critical modifier with prognostic implications 1:

• North American/GHSG definition: Mediastinal mass ratio (MMR) >0.33, calculated as the ratio of maximum width of the mass to the maximum intrathoracic diameter 1
• EORTC/Cotswolds definition: Mediastinal thoracic ratio (MTR) >0.35, measured as the ratio of maximum width of mediastinal mass to internal transverse diameter of thorax at T5-T6 interspace on posteroanterior chest X-ray 1
• Alternative definition: Any single node or nodal mass ≥10 cm in largest diameter 1

Modern Imaging-Based Staging

PET-CT has been formally incorporated as the standard staging modality for FDG-avid Hodgkin lymphoma, replacing older invasive procedures. 1

Required Staging Investigations 1:

• PET-CT scan (skull base to mid-thigh) - now preferred over CT alone 1
• Contrast-enhanced CT of neck, chest, abdomen, and pelvis if PET-CT unavailable 1
• Complete blood count with differential and platelets 1
• Erythrocyte sedimentation rate (ESR) 1
• Comprehensive metabolic panel, lactate dehydrogenase (LDH), and liver function tests 1

Bone Marrow Assessment

A bone marrow biopsy is no longer routinely indicated for staging Hodgkin lymphoma when PET-CT is performed. 1 The bone marrow is considered involved if the PET scan displays multifocal (≥3) skeletal lesions. 1 However, bone marrow biopsy may still be performed if cytopenias are present without explanation. 1

Clinical Risk Stratification

Patients are classified into three prognostic groups that guide treatment intensity 1:

Early-Stage Favorable (Stage I-II, No Unfavorable Factors) 1:

• No bulky disease
• No B symptoms
• ESR <50
• ≤3 nodal regions involved (NCCN/EORTC) or ≤2 regions (GHSG)

Early-Stage Unfavorable (Stage I-II with Any Unfavorable Factor) 1:

• Bulky mediastinal disease (MMR >0.33 or MTR >0.35) OR bulky disease >10 cm 1
• B symptoms present 1
• ESR ≥50 1

• 3 involved nodal regions (NCCN/EORTC) or >2 regions (GHSG) 1

• Extranodal involvement 1

Advanced-Stage Disease (Stage III-IV) 1

For advanced disease, the International Prognostic Score (IPS) identifies seven adverse factors, each reducing survival by 7-8% 1:

• Age ≥45 years 1
• Male gender 1
• Stage IV disease 1
• Albumin <4 g/dL 1
• Hemoglobin <10.5 g/dL 1
• White blood cell count >15,000/mm³ 1
• Lymphocyte count <8% of WBC and/or absolute lymphocyte count <600/mm³ 1

Key Staging Pitfalls to Avoid

Do not perform staging laparotomy - this historical procedure has been completely abandoned with modern imaging. 2

Do not routinely perform liver biopsy - PET-CT showing diffuse uptake, solitary mass, miliary lesions, or nodules is adequate for determining liver involvement without biopsy confirmation. 3 Liver biopsy should be restricted to patients with elevated alkaline phosphatase without other explanation or atypical presentations. 3

Do not use gallium scintigraphy or lymphangiography - these have been replaced by PET-CT. 2

Recognize that treatment decisions are based on limited (stages I-II nonbulky) versus advanced (stage III-IV) disease, with stage II bulky disease considered either limited or advanced based on histology and prognostic factors. 1