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Published on: February 16, 2017
Immunophenotyping of subtypes of B-chronic (mature) lymphoid leukemia. A study of 242 cases
1Department of Pathology, Cox Institute, Wright State University School of Medicine, Dayton, Ohio 45429.
Insights
Immunophenotyping using four immune markers accurately differentiates chronic lymphoid leukemia subtypes. This analysis reveals a continuous B-cell differentiation spectrum from early to late mature stages in these leukemias.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- The French-American-British (FAB) classification for chronic lymphoid leukemias (CLL) requires further characterization.
- Immunophenotyping offers a method to expand and refine the understanding of these hematologic malignancies.
Purpose of the Study:
- To evaluate the utility of immunophenotyping in differentiating subtypes of chronic lymphoid leukemias.
- To establish a minimum set of immune markers for accurate diagnosis of CLL subtypes.
Main Methods:
- Peripheral blood samples from 242 patients with various chronic lymphoid leukemia subtypes were analyzed.
- Immunologic evaluation included surface immunoglobulin (SIg) intensity, mouse rosettes (MR), CD5, and CD22 expression.
Main Results:
- Distinct immunophenotypes were identified: CLL and CLL-pleomorphic lymphocytes (CLL-pleo) showed weak SIg, MR+, CD5+, CD22-. Prolymphocytic leukemia (PLL) and hairy cell leukemia (HCL) exhibited strong SIg, MR-, CD5-, CD22+.
- A combination of these four markers achieved 100% diagnostic accuracy for CLL, CLL-pleo, PLL, and HCL.
- CLL/PL cases displayed mixed phenotypes, with 66.67% resembling CLL and 33.33% resembling PLL.
Conclusions:
- Surface immunoglobulin intensity, mouse rosette assay, CD5, and CD22 are essential for the differential diagnosis of chronic lymphoid leukemia subtypes.
- CLL and CLL-pleo share identical phenotypes, suggesting a close relationship.
- The immunophenotypic data support a model of continuous B-cell differentiation across CLL subtypes, from early mature (CLL, CLL-pleo) to late mature stages (PLL, HCL).
Background:
The French-American-British group's proposal for the classification of chronic lymphoid leukemias is unique at this time. Testing, expanding, and adding to the theory by immunophenotyping will help to additionally characterize this group of diseases.
Methods:
Peripheral blood samples from 242 patients with chronic lymphoid leukemias were analyzed for immunologic evaluation of the following subtypes: typical chronic lymphocytic leukemia (CLL), 189; CLL with pleomorphic lymphocytes (CLL-pleo), 19; CLL of mixed cell type (CLL/PL), 20; prolymphocytic leukemia (PLL), 22; hairy cell leukemia (HCL), 10; HCL-variant, 1; and splenic lymphoma with villous lymphocytes, 1.
Results:
The phenotype of CLL and CLL-pleo was weak surface immunoglobulin (SIg) with positive results of mouse rosettes (MR+), CD5+, and CD22-. Of PLL and HCL, it was strong SIg, MR-, CD5-, and CD22+. By analyzing the four markers and accepting the relevant results of two or more as sufficient for diagnosis, all cases (100%) of CLL, CLL-pleo, PLL, and HCL were diagnosed. CLL/PL showed the phenotype of CLL in 66.67% and of PLL in 33.33% of patients. The frequency of cases with weak fluorescence in decreasing order was CLL, CLL-pleo, CLL/PL, and PLL and HCL. The same sequence applied to the mean percentage of mouse rosette-forming cells and CD5 cells, but the sequence was reversed for CD22 cells.
Conclusions:
SIg intensity, MR, CD5, and CD22 constitute the minimum number of immune markers for the differential diagnosis of the subtypes of chronic lymphoid leukemia. The frequency of the four markers among the subtypes suggested that CLL and CLL-pleo have identical phenotypes and that the five subtypes follow a continuous range of B-cell differentiation from early mature (CLL and CLL-pleo) to late mature pre-plasma cell stages (PLL followed by HCL), with CLL/PL of intermediate maturity.
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