CD200 included in a 4‐marker modified Matutes score provides optimal sensitivity and specificity for the diagnosis of chronic lymphocytic leukaemia

Abstract

CD200, a transmembrane type Ia glycoprotein belonging to the immunoglobulin superfamily, has been shown to have a differential expression in B-cell neoplasms. Here, we retrospectively assessed the diagnostic relevance of CD200 on 427 patients with B-cell chronic neoplasms in leukemic phase (median age, 69 y; range, 35-97 y). The final diagnosis based on the investigator's assessment was chronic lymphocytic leukaemia (CLL) in 75% of cases and non-CLL in 25% of cases. Sensitivity and specificity for the diagnosis of CLL (vs non-CLL) were calculated for the following markers: CD200, CD5, CD22, CD23, CD79b, FMC7, and SmIg. CD23 was the only marker without a statistically significant difference between the investigator assessment and the flowcytometric analysis. The other markers were unable-when individually evaluated-to discriminate between CLL and non-CLL, requiring the integration into a scoring system. The modified score no. 1 (addition of CD200) showed superimposable sensitivity and specificity compared with the Matutes score. The substitution of CD79b (modified score no. 2), surface membrane immunoglobulins (SmIg) (modified score no. 3), and CD79b and FMC7 (modified score no. 4) with CD200 showed that only the modified score no. 4 had both higher sensitivity and higher specificity compared with standard Matutes score. In conclusion, this work defines a simplified score, compared with the classical Matutes score, for the differential diagnosis of chronic B-cell leukaemia-which only requires 4 markers instead of 5 (CD5, CD23, CD200, and SmIg).

The current role of clinical flow cytometry in the evaluation of mature B‐cell neoplasms

“…Kohnke et al used the CLL flow score with the formula based on the % of B-cells with specific phenotypic characteristics: (%CD200+) + (%CD23/ CD5+) -(%CD79b+) -(%FMC7+), with a score greater than zero consistent with CLL. This formula demonstrated sensitivity and specificity of 97.1% and 87.2%, respectively, compared with 98.6% and 53.8% for the classical Matutes score (21). Perhaps when combined with typical morphologic features, this FC information is sufficient to establish a diagnosis of CLL/SLL without the need for cytogenetic or molecular confirmation.…”

“…However, while these typical immunophenotypic patterns are helpful in the distinction between CD5-positive B-cell neoplasms, particularly when found in association with the expected morphologic findings and clinical setting, exceptions do occur and additional markers are sometimes needed. This formula demonstrated sensitivity and specificity of 97.1% and 87.2%, respectively, compared with 98.6% and 53.8% for the classical Matutes score (21). However, it is important to note that approximately 4% MCL cases express CD200, and this appears to correlate with lack of SOX11, hypermutated IGVH genes, and an indolent clinical course (19).…”

“…While there are no specific immunophenotypic or highly recurrent molecular genetic markers of MZL, exclusion of CLL/SLL or MCL allows one to suggest such a diagnosis (17). Recently, a revision of the CLL scoring system of Matutes et al, incorporating CD200, was reported to increase the specificity for diagnosing of CLL (20,21). CD200 is of diagnostic value in CD5-positive small B-cell neoplasms, being highly expressed in CLL/SLL and having high sensitivity and specificity in the distinction between CLL and MCL (18).…”

“…However, it is important to note that approximately 4% MCL cases express CD200, and this appears to correlate with lack of SOX11, hypermutated IGVH genes, and an indolent clinical course (19). Recently, a revision of the CLL scoring system of Matutes et al, incorporating CD200, was reported to increase the specificity for diagnosing of CLL (20,21). Kohnke et al used the CLL flow score with the formula based on the % of B-cells with specific phenotypic characteristics: (%CD200+) + (%CD23/ CD5+) -(%CD79b+) -(%FMC7+), with a score greater than zero consistent with CLL.…”

Positive predictive value of CD200 positivity in the differential diagnosis of chronic lymphocytic leukemia

“…Forty‐three articles and meeting abstracts (Alapat et al, ; Arlindo, Marcondes, Fernandes, & Faulhaber, ; Aytan et al, ; Brunetti et al, ; Challagundla, Medeiros, Kanagal‐Shamanna, Miranda, & Jorgensen, ; D'Arena et al, ; Debord et al, ; Dorfman & Shahsafaei, ; El Desoukey, Afify, Amin, & Mohammed, ; El Din Fouad, Ibrahim, Abdel Aziz, & Ibrahim, ; Espinet et al, ; Falay et al, ; Fan et al, ; Fanoni et al, ; Favre et al, ; Hu et al, ; Köhnke et al, ; Lesesve et al, ; Mason, Pozdnyakova, Li, Dudley, & Dorfman, ; Miao et al, ; Miguet et al, ; Mongeau‐Marceau et al, ; Montesdeoca et al, ; Mora et al, ; Palumbo et al, ; Pillai et al, ; Poongodi, Varma, Naseem, Parveen, & Varma, ; Rahman et al, ; Rahman, Kumar, Gupta, Singh, & Nityanand, ; Rawstron et al, ; Rawstron et al, ; Rawstron et al, ; Sallam, Elsalakawy, El‐Sewefy, & Khattab, ; Sandes et al, ; Sorigue, Franch‐Sarto, Sarrate, & Junca, ; Sorigue, Juncà, et al, ; Sorigue, Junca, & Granada, ; Sorigue, Raya, et al, ; Spacek et al, ; Starostka et al, ; Ting et al, ; van Dongen et al, ; Ye et al, ) were read in full, of which 16 were excluded (Figure S1). Therefore, 27 studies (5,764 patients) were included.…”