What is the role of bone marrow examination in diagnosing Pyrexia of Unknown Origin (PUO)?

Role of Bone Marrow Examination in Pyrexia of Unknown Origin (PUO)

Bone marrow examination should be performed selectively in patients with PUO based on specific clinical and laboratory indicators rather than routinely in all cases. 1, 2

Diagnostic Value and Yield

• Bone marrow examination has a diagnostic yield of approximately 8-24% in patients with PUO, with higher yields in selected populations with specific clinical features 1, 3
• Trephine biopsy offers significantly higher diagnostic yield (76%) compared to aspiration alone (16.5%) in PUO cases, making the combination of both techniques optimal 4
• Three main categories of diseases diagnosed through bone marrow examination in PUO include:
  • Hematological malignancies (particularly lymphomas and leukemias)
  • Infectious diseases (including tuberculosis, leishmaniasis, and fungal infections)
  • Systemic disorders (including granulomatous diseases) 4, 3

Specific Indications for Bone Marrow Examination

Bone marrow examination should be considered in PUO patients with:

• Hematological abnormalities, particularly anemia and thrombocytopenia, which are the strongest predictors of positive bone marrow findings 3
• Involvement of reticuloendothelial organs (e.g., splenomegaly) 2
• Immunocompromised status (HIV infection, post-transplant, immunosuppressive therapy) 2, 5
• Advanced age 2
• Suspected hematological malignancy based on clinical features 4, 3

Technical Considerations

• Both aspiration and trephine biopsy should be performed concurrently for optimal diagnostic yield in PUO cases 4
• Trephine biopsy is particularly valuable for detecting:
  • Granulomas (found in 70% of diagnostic cases but only 1.6% of aspirates)
  • Lymphomas
  • Tuberculosis
  • Fungal infections 4
• Bone marrow samples should be sent for:
  • Histopathological examination
  • Microbiological cultures (bacterial, mycobacterial, and fungal)
  • Cytogenetic studies when hematological malignancy is suspected 5

Common Pitfalls and Limitations

• Relying solely on bone marrow aspiration without trephine biopsy significantly reduces diagnostic yield 4
• Performing bone marrow examination without appropriate clinical indicators results in low diagnostic yield 1
• Bone marrow cultures have limited value in immunocompetent patients but may be more useful in immunocompromised hosts 3, 5
• Prior corticosteroid use does not significantly affect the diagnostic yield of bone marrow examination 3

Specific Disease Considerations

• In patients with suspected lymphoma, bone marrow biopsy is an essential component of staging 6
• In multiple myeloma, bone marrow examination is crucial for diagnosis and prognostic assessment 6
• In polycythemia vera, bone marrow histology is a key diagnostic feature when combined with serum erythropoietin levels 6
• In Hodgkin lymphoma, routine bone marrow biopsy may be omitted if PET scan is negative or shows homogenous bone marrow uptake 6