What diagnostic tests are used to differentiate between Hodgkin (HL) and non-Hodgkin lymphoma (NHL)?

Diagnostic Tests to Differentiate Hodgkin and Non-Hodgkin Lymphoma

The definitive diagnostic test to differentiate between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) is an excisional lymph node biopsy with immunohistochemistry analysis, as fine needle aspiration is inadequate for initial diagnosis. 1, 2

Biopsy and Histopathology

• Excisional biopsy: Gold standard for diagnosis

  • Incisional biopsy is acceptable when excisional is not possible
  • Core needle biopsy may be considered when excisional/incisional not feasible, but nondiagnostic samples must be followed by excisional biopsy 1

• Histopathologic examination:

  • Hodgkin lymphoma: Characterized by presence of Hodgkin and Reed-Sternberg (HRS) cells 1
  • Non-Hodgkin lymphoma: Lacks HRS cells, shows various patterns of lymphocyte proliferation

Immunohistochemistry (Critical for Differentiation)

• Hodgkin lymphoma markers:

  • HRS cells consistently positive for CD30 and CD15
  • Occasionally positive for CD20
  • Negative for CD45 1

• Non-Hodgkin lymphoma markers:

  • Varies by subtype, but typically:
  • Positive for CD20 and CD45
  • Negative for CD15 and CD30 1, 2

• NLPHL-specific markers (Nodular lymphocyte-predominant Hodgkin lymphoma):

  • Lymphocyte predominant (LP) cells express CD20 and CD45
  • Lack CD15 and CD30 expression 1

Advanced Diagnostic Testing

• Flow cytometry: Essential for NHL diagnosis and subtyping 1, 2

  • Helps identify specific cell populations and their immunophenotype
  • Particularly useful for distinguishing B-cell vs. T-cell origins

• Molecular studies:

  • Used when appropriate to accurately categorize lymphoma subtypes
  • May include PCR for gene rearrangements or FISH for specific translocations 1

Imaging Studies

• PET-CT scan: Preferred for staging FDG-avid lymphomas (most HL and aggressive NHL) 1, 3

  • Provides metabolic information and anatomic localization
  • More sensitive than CT alone for extranodal involvement 4
  • Can help identify optimal biopsy sites in suspected cases of discordant histology 1

• Contrast-enhanced CT: Used for non-FDG-avid lymphomas and for precise nodal measurements 1

  • Provides detailed anatomic information
  • Less sensitive than PET-CT for bone marrow involvement 5

Bone Marrow Assessment

• PET-CT: Now considered adequate for determination of bone marrow involvement in HL 1

  • Bone marrow biopsy no longer indicated in patients with HL undergoing PET-CT evaluation 1

• Bone marrow biopsy: Still recommended for complete staging in NHL 2

  • Provides information on bone marrow infiltration pattern
  • Helps identify discordant histology in bone marrow

Laboratory Tests

• Complete blood count with differential: Required for all patients 2
• Comprehensive metabolic panel: Including liver and kidney function tests 2
• Lactate dehydrogenase (LDH): Important prognostic marker 2
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP): Particularly important for HL 1

Common Pitfalls to Avoid

1. Relying on fine-needle aspiration: Inadequate for initial diagnosis of lymphoma 1, 2
2. Incomplete immunophenotyping: May lead to misclassification between HL and NHL subtypes
3. Starting treatment without definitive diagnosis: Always confirm diagnosis before initiating therapy
4. Overlooking extranodal disease: PET-CT is superior to CT for detecting extranodal involvement 4
5. Assuming all lymphomas are FDG-avid: Some indolent NHL subtypes may have variable FDG uptake 1

Special Considerations

• For suspected relapse, confirmatory biopsy is strongly recommended 2
• In cases of suspected transformation (indolent to aggressive NHL), PET-CT can help identify the optimal biopsy site 1
• Processing of biopsy specimens should include preservation of fresh-frozen tissue when possible for additional studies 1

The diagnostic approach should be comprehensive, with the pathological diagnosis made according to the World Health Organization (WHO) classification system by an experienced hematopathologist.