Mature B-cell lymphoproliferative disorders that present with a leukemic phase may have overlapping morphological and immunophenotypic features. Accurate diagnosis is essential to determine prognosis and therapy. B-cell chronic lymphocytic leukaemia (B-CLL) and mantle cell lymphoma (MCL) both express CD5 but usually have divergent clinical courses. Conventional markers are able to discriminate in many cases but a significant proportion of cases require more detailed analysis. CD200 is a membrane glycoprotein that has been reported to differentiate between B-CLL and MCL. It is expressed on resting and activated T and B cells, but not on NK cells, monocytes, granulocytes or platelets. We prospectively assessed the utility of this antibody in a single centre, servicing haematology units in North London.
Over a 12 month period we prospectively assessed the expression of CD200 (Clone MRC OX-104, BD Pharmingen) on neoplastic cells of patients with presenting with mature B-cell lymphoproliferative disorders. EDTA anti-coagulated peripheral blood and bone marrow underwent a lyse/wash technique before being acquired on a BD FACS Canto II flow cytometer equipped with DIVA 6.1.2 software. A lymphoid gating strategy was used to analyse the data and expression of more than 20% of nucleated cells referenced to a negative internal control was considered positive. A diagnosis was made using all available data according to the WHO classification of haematopoietic tumours, including the 5 point CLL score. The predictive value of CD200 expression was subsequently assessed.
There were 100 patients (58M: 42F) with a median age of 70 years (range 29–92). CD200 was present on the neoplastic cells of all 78 patients with B-CLL; in all 7 MCL patients CD200 was negative; 15 patients had CD5 negative B-cell lymphoproliferative disorder with variable expression of CD200. The specificity of CD200 negativity in the setting of CD5 positive B-cell clone was 100% for MCL. The positive predictive value of CD200 for CLL was 97.5% with a sensitivity of 100% and a Pearson's correlation coefficient of 1.
Our results confirm CD200 expression in the neoplastic cells of B-CLL patients but not in MCL. This antibody may contribute to the accurate differentiation between B-CLL and MCL in patients presenting with the diagnostic problem of a CD5- positive lymphoproliferative disorder. We propose to add CD200 to our diagnostic B-cell lymphoma panel. Further studies are needed to determine whether CD200 could replace other immunophenotypic strategies currently used in this situation, such as CD23, FMC7 and intensity of CD22/CD79b expression.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.