Role of Tartrate-Resistant Acid Phosphatase (TRAP) in Diagnosing Hairy Cell Leukemia and Other Pathologies
Tartrate-resistant acid phosphatase (TRAP) is a critical diagnostic marker for hairy cell leukemia (HCL), serving as a highly specific enzymatic test that helps distinguish classical HCL from its variant forms and other lymphoproliferative disorders. 1
Diagnostic Value in Hairy Cell Leukemia
Role in Classical HCL Diagnosis
- TRAP staining is a key component of the immunohistochemical panel used to identify hairy cells in bone marrow biopsies 1
- It is particularly valuable in cases where:
- Bone marrow aspiration results in a "dry tap" (common in classical HCL)
- Peripheral blood involvement is minimal
- Differential diagnosis between HCL and other B-cell lymphoproliferative disorders is challenging
Technical Applications
- TRAP staining can be performed on:
- Peripheral blood smears
- Bone marrow aspirates
- Paraffin-embedded tissue sections (using specialized monoclonal antibodies) 2
Diagnostic Accuracy
- Sensitivity: High but not absolute - rare cases of HCL may be TRAP-negative 3
- Specificity: Very high when properly performed - only 3 false positives reported in 800 non-HCL patients in one large study 3
- When intense TRAP activity is observed in peripheral blood cells, it is highly diagnostic for HCL 3
Distinguishing HCL from HCL Variant
TRAP staining helps differentiate classical HCL from HCL variant (HCL-V), which has important therapeutic implications:
| Feature | Classical HCL | HCL-V |
|---|---|---|
| TRAP staining | Positive | Variable |
| Response to purine analogues | Good | Poor |
This distinction is critical as classical HCL typically responds well to purine analogue therapy, while HCL-V shows poor response 1.
Role in Other Pathologies
TRAP is not exclusive to hairy cells and can be found in:
- Osteoclasts: TRAP is abundantly expressed and serves as a marker for osteoclast activity 4
- Macrophages: Certain tissue macrophages express TRAP 2
- Dendritic cells: TRAP activity varies between donors but is reproducible within samples 5
These non-hematological applications make TRAP potentially useful for:
- Monitoring bone diseases with increased osteoclast activity
- Assessing bone metastasis in certain cancers 2
- Studying macrophage and dendritic cell differentiation 5
Technical Considerations and Advances
Traditional Cytochemical Staining
- Limitations: Cannot be effectively performed on paraffin-embedded tissues 2
- Variable expression of TRAP activity within and between HCL patients can cause diagnostic uncertainty 2
Immunohistochemical Approaches
- Monoclonal antibodies (such as 9C5) allow for:
Flow Cytometry Applications
- Flow cytoenzymology techniques enable:
- Quantification of intracellular TRAP activity
- Simultaneous analysis with surface markers
- Detection of TRAP in specific cell subpopulations 5
Clinical Utility in Challenging Cases
TRAP staining is particularly valuable in:
- Hypocellular bone marrow: Even in markedly hypocellular marrows, TRAP staining can reveal the presence of hairy cells 6
- Minimal residual disease: Helps evaluate response to treatment
- Difficult diagnostic cases: When combined with other markers like CD20, CD72, CD11c, CD25, CD103, and annexin A1 1
Pitfalls and Limitations
- False negatives: Rare cases of HCL may be TRAP-negative 3
- Technical factors: Staining quality depends on proper technique and interpretation
- Not exclusive to HCL: Other cells (osteoclasts, macrophages) can be TRAP-positive 2
- Not suitable as a standalone test: Should be used as part of a comprehensive diagnostic panel including flow cytometry and BRAF mutation testing 1
For optimal diagnostic accuracy, TRAP should be used alongside other markers in the diagnostic workup of HCL, particularly flow cytometry with CD11c, CD25, CD103, CD123, and BRAF V600E mutation testing in difficult cases 1.