What tests should be sent on a lymph node biopsy if I suspect tuberculosis (TB) and lymphoma?

Diagnostic Tests for Lymph Node Biopsy When Suspecting TB and Lymphoma

For lymph node biopsy specimens when suspecting both tuberculosis (TB) and lymphoma, comprehensive testing should include histopathology with special stains, microbiological cultures, molecular testing, and immunophenotyping to ensure accurate diagnosis of both conditions.

Essential Tests for TB Diagnosis

When TB is suspected in lymph node specimens, the following tests are crucial:

• Histopathology:

  • Hematoxylin and eosin (H&E) staining to identify granulomas, caseation, and giant cells 1
  • Ziehl-Neelsen (ZN) staining for acid-fast bacilli (AFB) identification 2
  • Note that ZN staining has limited sensitivity (3-61.7%) in lymph node TB 2, 3

• Microbiological testing:

  • Mycobacterial culture of fresh tissue (sensitivity 20-83%) 4
  • Note that culture remains the gold standard for TB confirmation and is required for drug susceptibility testing 1

• Molecular testing:

  • Nucleic Acid Amplification Tests (NAAT) such as GeneXpert MTB/RIF 1
  • NAAT provides rapid results (24-48 hours) with high positive predictive value (>95%) when AFB smear is positive 1, 4

• Immunohistochemistry:

  • Anti-MPT64 immunostaining (sensitivity 92%, specificity 97%) for detecting M. tuberculosis complex specific antigen 5

Essential Tests for Lymphoma Diagnosis

For lymphoma diagnosis, the following tests are necessary:

• Histopathology:

  • H&E staining for morphological assessment of cell size and pattern 1

• Immunophenotyping:

  • Immunohistochemistry panel on paraffin sections: CD3, CD5, CD10, CD20, CD23, cyclin D1 1
  • Flow cytometry when available: kappa/lambda, CD19, CD20, CD5, CD23, CD10 1

• Genetic testing (when indicated):

  • Cytogenetics and/or FISH to detect characteristic translocations 1
  • PCR for immunoglobulin heavy chain and T-cell receptor gene rearrangements 1

Diagnostic Algorithm

1. Obtain adequate tissue sample:

   • Excisional or incisional biopsy is preferred over fine needle aspiration (FNA) 1
   • Core needle biopsy may be acceptable when combined with appropriate ancillary techniques 1

2. Split the specimen appropriately:

   • Fresh unfixed tissue for microbiological culture and flow cytometry
   • Formalin-fixed tissue for histopathology and immunohistochemistry

3. Process for both diagnoses simultaneously:

   • Submit tissue for both TB and lymphoma workup concurrently, as these conditions can coexist 6

Important Considerations

• TB and lymphoma can present with similar clinical and histological features, making concurrent testing essential 7, 6
• A negative AFB smear does not exclude TB, as sensitivity is limited in lymph node specimens 1, 3
• Rapid-access lymph node biopsy clinics have shown to reduce diagnostic delays significantly (13.5 vs 48 days) 7
• Consider empiric anti-TB therapy if clinical suspicion remains high despite negative initial tests 4

Pitfalls to Avoid

• Relying solely on ZN staining for TB diagnosis, as sensitivity is low in lymph node specimens 2, 3
• Assuming TB diagnosis based on granulomatous inflammation alone without microbiological confirmation 6
• Delaying lymphoma diagnosis due to concurrent TB treatment 6
• Using FNA or core needle biopsy alone for initial lymphoma diagnosis 1

By implementing this comprehensive testing approach, clinicians can accurately diagnose both TB and lymphoma, leading to appropriate treatment and improved patient outcomes.