Distinguishing CML From Reactive Monocytosis
Distinguishing CML From Reactive Monocytosis
To determine whether immunophenotypic features of monocytes are useful in differentiating chronic myelomonocytic leukemia (CMML) from reactive monocytosis, multiparameter flow cytometry was used to immunophenotype 20 bone marrow samples from patients with CMML, 10 normal marrow samples, and 20 marrow samples with reactive monocytosis. Monocytes in CMML exhibited aberrant antigen expression in all 20 cases. Abnormal antigen expression also was observed in monocytes in 11 of 20 reactive marrow samples. However, aberrant expression of 2 or more antigens was significantly less frequent in reactive monocytosis than in CMML (P = .002). CD56 expression with underexpression of a myeloid marker was unique to CMML monocytes. Subpopulations of monocytes with moderate levels of CD14 were present in all 3 groups. The proportion of CD14(moderate) monocytes was highest in CMML and was 20% or more in 13 of 20 CMML cases vs 3 of 20 reactive marrow samples (P = .003) and 2 of 10 normal marrow samples (P = .007). A combination of monocytosis with 2 or more immunophenotypic aberrancies with 20% or more of marrow monocytes showing moderate CD14 expression was 67% sensitive and 100% specific for CMML.
Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder defined as a myeloproliferative/myelodysplastic disease by the World Health Organization based on the variability of the presenting WBC count, marrow cellularity, degree of dysplasia, and splenomegaly. A diagnosis of CMML requires persistent peripheral monocytosis (monocytes, >1,000/µL [1.0 × 10/L]) and myelodysplasia or, if dysplasia is not evident, cytogenetic abnormalities or exclusion of other causes of persistent monocytosis (≥3 months). Although cytogenetic evidence of clonality is found in only 20% to 40% of CMML cases, dysgranulopoiesis is observed frequently. In cases lacking cytogenetic abnormalities in which morphologic dysplasia is subtle, a distinction between CMML and reactive monocytosis is diagnostically challenging.
Flow cytometric immunophenotyping has been applied widely to the diagnosis of acute leukemia and lymphoid neoplasms, but less is known of its role in diagnosis of chronic myeloproliferative disorders (MPDs) and myelo-dysplastic syndromes (MDSs). Clonal myeloid cells in these disorders display aberrant antigen expression. It is important to note, however, nonneoplastic granulocytes and monocytes in reactive states also might exhibit antigenic abnormalities. Previous studies of MDS and MPD primarily have used normal marrow samples for control samples (rather than pathologically altered but nonneoplastic marrow samples), and, thus, the specificity of the antigenic abnormalities is largely undocumented. In the present flow cytometric study, we compared the immunophenotypic features of monocytes in marrow samples from patients with CMML with marrow samples in reactive monocytosis and from healthy people.
Abstract
To determine whether immunophenotypic features of monocytes are useful in differentiating chronic myelomonocytic leukemia (CMML) from reactive monocytosis, multiparameter flow cytometry was used to immunophenotype 20 bone marrow samples from patients with CMML, 10 normal marrow samples, and 20 marrow samples with reactive monocytosis. Monocytes in CMML exhibited aberrant antigen expression in all 20 cases. Abnormal antigen expression also was observed in monocytes in 11 of 20 reactive marrow samples. However, aberrant expression of 2 or more antigens was significantly less frequent in reactive monocytosis than in CMML (P = .002). CD56 expression with underexpression of a myeloid marker was unique to CMML monocytes. Subpopulations of monocytes with moderate levels of CD14 were present in all 3 groups. The proportion of CD14(moderate) monocytes was highest in CMML and was 20% or more in 13 of 20 CMML cases vs 3 of 20 reactive marrow samples (P = .003) and 2 of 10 normal marrow samples (P = .007). A combination of monocytosis with 2 or more immunophenotypic aberrancies with 20% or more of marrow monocytes showing moderate CD14 expression was 67% sensitive and 100% specific for CMML.
Introduction
Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder defined as a myeloproliferative/myelodysplastic disease by the World Health Organization based on the variability of the presenting WBC count, marrow cellularity, degree of dysplasia, and splenomegaly. A diagnosis of CMML requires persistent peripheral monocytosis (monocytes, >1,000/µL [1.0 × 10/L]) and myelodysplasia or, if dysplasia is not evident, cytogenetic abnormalities or exclusion of other causes of persistent monocytosis (≥3 months). Although cytogenetic evidence of clonality is found in only 20% to 40% of CMML cases, dysgranulopoiesis is observed frequently. In cases lacking cytogenetic abnormalities in which morphologic dysplasia is subtle, a distinction between CMML and reactive monocytosis is diagnostically challenging.
Flow cytometric immunophenotyping has been applied widely to the diagnosis of acute leukemia and lymphoid neoplasms, but less is known of its role in diagnosis of chronic myeloproliferative disorders (MPDs) and myelo-dysplastic syndromes (MDSs). Clonal myeloid cells in these disorders display aberrant antigen expression. It is important to note, however, nonneoplastic granulocytes and monocytes in reactive states also might exhibit antigenic abnormalities. Previous studies of MDS and MPD primarily have used normal marrow samples for control samples (rather than pathologically altered but nonneoplastic marrow samples), and, thus, the specificity of the antigenic abnormalities is largely undocumented. In the present flow cytometric study, we compared the immunophenotypic features of monocytes in marrow samples from patients with CMML with marrow samples in reactive monocytosis and from healthy people.
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