Abstract
Background: CD160 is a functional receptor on NK cells, T -cells and neoangiogenic blood vessels. CD160 is not expressed on normal B-lymphocytes or myeloid cells. We have previously reported that CD160 is aberrantly expressed on CLL (
Aims: To provide further data on CD160 expression in CLL, assess the pattern of CD23 expression using the CD5+23+ / CD5+19+ ratio and the utility of these markers in differentiating B-LPDs, particularly, atypical CLL and MCL.
Methods: Samples from more than 500 consecutive patients were examined for CD160 expression. Flow cytometry was performed using fresh whole blood and red cell lysis (Pharmalyse solution, BD), with anti-CD160 monoclonal antibody (BY55, Coulter Immunotech, Marseille, France) added to the routine panels. The ‘CLL score’ (Moreau EJ et al. [1997]. Am J of Clin Pathol; 108: 378–382) is based on the markers CD5, CD23, CD79b, FMC7 and IgM. Atypical cases of CLL were confirmed by bone marrow, lymph node and cytogenetic studies. The CD5+23+ / CD5+19+ ratios were calculated for 271 patients with CLL and 7 patients with documented typical CD23+ MCL.
Results: 423/425 (>99%) CLL cases were positive for CD160, including 41/42 (98%) cases with a low CLL score (3 or less).Using CD5, CD23 and CD160 - which are almost universally expressed in CLL - a new ‘mini CLL score’ has been developed with each marker scoring one point. The mini CLL scores for 564 cases of B-LPD including CLL, MCL, Hairy Cell Leukemia (HCL), Splenic Marginal Zone Lymphoma (SMZL), Lymphoplasmacytic Lymphoma(LPC) and Waldenstrom’s Macroglobulinaemia (WM), are shown below:
Mini CLL Scores for 564 cases of B-LPD
| Mini CLL Score . | 0 . | 1 . | 2 . | 3 . |
|---|---|---|---|---|
| CLL | 0 | 0 | 5 | 420 |
| MCL | 0 | 11 | 7 | 4 |
| HCL | 0 | 9 | 19 | 1 |
| SMZL/LPC/WM | 3 | 18 | 9 | 0 |
| Other B-LPD | 22 | 22 | 14 | 0 |
| Mini CLL Score . | 0 . | 1 . | 2 . | 3 . |
|---|---|---|---|---|
| CLL | 0 | 0 | 5 | 420 |
| MCL | 0 | 11 | 7 | 4 |
| HCL | 0 | 9 | 19 | 1 |
| SMZL/LPC/WM | 3 | 18 | 9 | 0 |
| Other B-LPD | 22 | 22 | 14 | 0 |
The CD5+23+ / CD5+19+ ratio proved useful in further differentiating between CLL and MCL. Only 3 out of 271 (1.1%) patients with CLL had a ratio of 0.75 or less, whereas 255 patients (94%) had a ratio of 0.95 or higher. Out of the 7 patients with CD23+ MCL, 6 patients (86%) had a ratio of 0.75 or less. All 4 MCL patients with a mini CLL score of 3 had ratios below 0.75.
CD5+23+ / CD5+19 Ratio (CD23r) for CLL and CD23+ MCL
| CD23r . | >.94 . | .94–76 . | .75–51 . | <.51 . |
|---|---|---|---|---|
| CLL | 255 | 13 | 3 | |
| MCL | 1 | 3 | 3 |
| CD23r . | >.94 . | .94–76 . | .75–51 . | <.51 . |
|---|---|---|---|---|
| CLL | 255 | 13 | 3 | |
| MCL | 1 | 3 | 3 |
Discussion: By using the 3 most robust markers expressed in CLL, the mini CLL score reduces diagnostic doubt and is particularly useful for difficult cases with atypical morphology and immunophenotyping. A mini CLL score of 3 has a positive predictive value for CLL of 99%; the negative predictive value of a score of <3 is 96%. The specificity of the mini score can be further improved by calculating the CD5+23+ / CD5+19+ ratio which in CLL is significantly higher then in CD23+ cases of MCL. Incorporating this tool into diagnostic practice could allow for simpler and cheaper diagnostic antibody panels. In addition to its diagnostic utility, CD160 is a functional molecule in CLL (separate abstract) and has a role in CLL biology.
Author notes
Disclosure: No relevant conflicts of interest to declare.
