What tests are used to diagnose Hodgkin lymphoma?

Diagnostic Tests for Hodgkin Lymphoma

Excisional lymph node biopsy is the gold standard for diagnosing Hodgkin lymphoma, providing sufficient tissue for WHO classification and immunohistochemistry, with core needle biopsy acceptable only when excisional biopsy is not feasible. 1, 2

Tissue Diagnosis

Biopsy Requirements

• Excisional lymph node biopsy is mandatory to obtain adequate tissue for fresh frozen and formalin-fixed samples 1
• Core needle biopsy may be adequate but excisional biopsy is generally preferred 1
• Fine-needle aspiration (FNA) alone is insufficient except in unusual circumstances when combined with immunohistochemistry and reviewed by an expert hematopathologist 1
• The biopsy must provide enough material to distinguish classical Hodgkin lymphoma (95% of cases) from nodular lymphocyte predominant Hodgkin lymphoma (5% of cases) 1, 2

Immunohistochemistry Panel

• Required immunostaining markers include: CD3, CD15, CD20, CD30, CD45, CD79a, and PAX5 1
• Classical Hodgkin lymphoma shows Hodgkin and Reed-Sternberg cells positive for CD30 and CD15, occasionally CD20+, and CD45- 2

Staging and Imaging Studies

Mandatory Imaging

• PET/CT scan from skull base to mid-thigh is essential for accurate staging and response assessment 1, 2
• Contrast-enhanced CT scan of neck, chest, and abdomen is mandatory 1, 2
• Chest X-ray is encouraged for patients with large mediastinal mass 1
• Diagnostic neck CT with contrast is useful when the neck is positive on PET/CT or if neck radiotherapy is planned 1

Bone Marrow Assessment

• Bone marrow biopsy is NOT routinely required if PET scan is negative or shows homogeneous bone marrow uptake 1
• Bone marrow may be assumed involved if PET scan displays multifocal (≥3) skeletal lesions 1
• Bone marrow biopsy should be performed if cytopenias are present 1
• Older guidelines required routine bone marrow aspiration and histology, but this has been superseded by PET/CT in modern practice 1

Laboratory Testing

Mandatory Blood Tests

• Complete blood count with differential 1, 2
• Erythrocyte sedimentation rate (ESR) - critical for risk stratification 1, 2
• Comprehensive metabolic panel including:
  • Alkaline phosphatase (AP) 1
  • Lactate dehydrogenase (LDH) 1
  • Liver enzymes 1
  • Albumin 1
  • Glucose 1
• C-reactive protein (CRP) 1, 2

Infectious Disease Screening

• Hepatitis B and C screening is compulsory 1
• HIV testing should be encouraged for patients with risk factors or unusual disease presentations 1, 2

Pre-Treatment Functional Assessment

Cardiac Evaluation

• Ejection fraction assessment (echocardiography) is recommended for most patients undergoing doxorubicin-based chemotherapy 1, 2
• Cardiac function tests are mandatory before treatment to identify patients at increased risk for acute and long-term complications 1

Pulmonary Evaluation

• Pulmonary function tests including diffusing capacity of lungs for carbon monoxide (DLCO) are recommended for patients receiving bleomycin-based chemotherapy 1
• Pulmonary function tests are mandatory before treatment 1

Additional Pre-Treatment Considerations

• Pregnancy test should be performed before women of childbearing age undergo treatment 1
• Fertility preservation counseling (semen cryopreservation in males, ovarian tissue or oocyte cryopreservation in females) before chemotherapy with alkylating agents or pelvic radiotherapy 1, 2
• Thyroid-stimulating hormone (TSH) baseline measurement 1
• Ear, nose, and throat consultation should be considered, particularly with head and neck involvement 1

Staging System and Documentation

Ann Arbor Staging

• Staging according to Ann Arbor system is mandatory with documentation of: 1, 2
  • B symptoms (fever >38°C, drenching night sweats, unexplained weight loss >10% within 6 months)
  • Bulky disease (mediastinal mass >1/3 thoracic width on chest X-ray or >7.5 cm on CT)
  • Involvement of spleen
  • Extranodal sites
  • Number of involved lymph node areas

Risk Stratification

• Patients are allocated to three categories: limited stage, intermediate stage, or advanced stage based on clinical risk factors 1, 2
• Risk factors include: large mediastinal mass, extranodal involvement, elevated ESR (>30 mm/h for B-stages or >50 mm/h for A-stages), and ≥3 lymph node areas involved 1, 2

Common Pitfalls to Avoid

• Do not rely on FNA alone - it provides insufficient tissue architecture for accurate subtyping 1
• Do not perform staging laparotomy - this is no longer recommended 1
• Do not routinely perform bone marrow biopsy if PET/CT is available and negative 1
• Do not omit PET-CT when available - it has largely replaced invasive procedures and provides superior staging information 2, 3
• Do not forget fertility counseling before initiating treatment in patients of reproductive age 1, 2
• Do not overlook hepatitis and HIV screening - these have significant treatment implications 1, 2