What are the guidelines for diagnosing Hodgkin lymphoma?

Guidelines for Diagnosing Hodgkin Lymphoma

Accurate diagnosis of Hodgkin lymphoma requires an excisional lymph node biopsy or sufficiently large surgical specimen to provide adequate material for both fresh frozen and formalin-fixed samples, followed by comprehensive staging according to the Ann Arbor classification system. 1

Diagnostic Approach

Pathological Diagnosis

• Tissue Sampling:

  • Excisional lymph node biopsy is mandatory (core needle biopsies are often inadequate)
  • Specimen must be large enough to provide material for both fresh frozen and formalin-fixed samples
  • Biopsy from another affected organ may be used if lymph nodes are not accessible

• Histological Classification (WHO classification):

  • Classical Hodgkin Lymphoma (cHL) - 95% of cases
    • Nodular sclerosis
    • Mixed cellularity
    • Lymphocyte depletion
    • Lymphocyte-rich
  • Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) - 5% of cases

• Immunophenotyping:

  • Classical HL: Hodgkin and Reed-Sternberg (HRS) cells positive for CD30 and CD15, occasionally positive for CD20, negative for CD45
  • NLPHL: Lymphocyte predominant (LP) cells positive for CD20 and CD45, negative for CD15 and CD30

Staging and Risk Assessment

• Medical History and Physical Examination:

  • Document presence of B symptoms:
    • Fever
    • Drenching night sweats
    • Unexplained weight loss >10% over 6 months
  • Other disease-related symptoms: fatigue, pruritus, alcohol-induced pain
  • Thorough physical examination with attention to all lymph node regions

• Imaging Studies:

  • Chest X-ray
  • Contrast-enhanced CT scan of neck, chest, and abdomen (mandatory)
  • Baseline whole-body PET scan (strongly recommended if available)
    • PET-CT has become standard for initial staging and response assessment

• Laboratory Tests:

  • Full blood cell count
  • Erythrocyte sedimentation rate (ESR)
  • Blood chemistry including:
    • C-reactive protein (CRP)
    • Alkaline phosphatase (AP)
    • Lactate dehydrogenase (LDH)
    • Liver enzymes
    • Albumin
  • Mandatory screening for:
    • Hepatitis B (HBV)
    • Hepatitis C (HCV)
    • Human immunodeficiency virus (HIV)

• Bone Marrow Assessment:

  • Bone marrow biopsy is no longer indicated in patients undergoing PET-CT evaluation due to high sensitivity of PET-CT for bone marrow involvement 1
  • Bone marrow biopsy must be performed only if PET-CT is not available

• Pre-treatment Evaluations:

  • ECG
  • Echocardiography
  • Pulmonary function tests
  • Reproductive counseling for patients of reproductive age
  • Serum pregnancy test for women of reproductive age
  • ENT specialist consultation with fibreoptic nasolaryngoscopy (if PET-CT is not available)

Staging Classification

After completion of diagnostic workup, patients are allocated to one of three categories based on the Ann Arbor classification and clinical risk factors:

• Limited stage
• Intermediate stage
• Advanced stage

The European Organisation for Research and Treatment of Cancer (EORTC)/Lymphoma Study Association (LYSA) and the German Hodgkin Study Group (GHSG) have specific definitions for these categories.

Common Pitfalls and Caveats

• Inadequate Biopsy: Fine needle aspiration or small core biopsies are often insufficient for definitive diagnosis; always obtain an excisional biopsy when possible

• Misdiagnosis: Hodgkin lymphoma can be confused with other lymphomas or reactive conditions; expert hematopathology review is essential

• Incomplete Staging: Failure to perform comprehensive staging can lead to under-treatment or over-treatment

• Extranodal Presentations: While rare, extranodal presentations including primary bone marrow involvement can occur even in immunocompetent patients and may be missed if not specifically considered 2

• PET-CT Limitations: False positives can occur due to inflammation or infection; correlation with clinical findings is essential

• Overlooking Screening: Failure to screen for HBV, HCV, and HIV can lead to complications during treatment

By following these comprehensive diagnostic guidelines, clinicians can ensure accurate diagnosis and appropriate staging of Hodgkin lymphoma, which is critical for selecting optimal therapy and improving patient outcomes.