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Review
. 2023 Sep 5;15(18):4427.
doi: 10.3390/cancers15184427.

Atypical Chronic Lymphocytic Leukemia-The Current Status

Tadeusz Robak  1   2 , Anna Krawczyńska  1   2 , Barbara Cebula-Obrzut  1   2 , Marta Urbaniak  1   2 , Elżbieta Iskierka-Jażdżewska  1   2 , Paweł Robak  1   3
Affiliations
Review

Atypical Chronic Lymphocytic Leukemia-The Current Status

Tadeusz Robak et al. Cancers (Basel). .

Abstract

A diagnosis of typical chronic lymphocytic leukemia (CLL) requires the presence of ≥5000 clonal B-lymphocytes/μL, the coexistence of CD19, CD20, CD5, and CD23, the restriction of light chain immunoglobulin, and the lack of expression of antigens CD22 and CD79b. Atypical CLL (aCLL) can be distinguished from typical CLL morphologically and immunophenotypically. Morphologically atypical CLL cells have been defined mainly as large, atypical forms, prolymphocytes, or cleaved cells. However, current aCLL diagnostics rely more on immunophenotypic characteristics rather than atypical morphology. Immunophenotypically, atypical CLL differs from classic CLL in the lack of expression of one or fewer surface antigens, most commonly CD5 and CD23, and the patient does not meet the criteria for a diagnosis of any other B-cell lymphoid malignancy. Morphologically atypical CLL has more aggressive clinical behavior and worse prognosis than classic CLL. Patients with aCLL are more likely to display markers associated with poor prognosis, including trisomy 12, unmutated IGVH, and CD38 expression, compared with classic CLL. However, no standard or commonly accepted criteria exist for differentiating aCLL from classic CLL and the clinical significance of aCLL is still under debate. This review summarizes the current state of knowledge on the morphological, immunophenotypic, and genetic abnormalities of aCLL.

Keywords: CD23; CD5; CLL; CLL differential diagnosis; atypical CLL.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study, interpretation of the data, writing of the manuscript, or in the decision to publish the review.

Figures

Figure 1
Figure 1
Morphological features of classic (A,B) and large (C,D) CLL cells. Mature CLL cells are lymphocytes with a narrow border of cytoplasm and partially aggregated chromatin in a dense nucleus ((A)—peripheral blood, (B)—bone marrow). Large atypical CLL cells ((C)—peripheral blood, (D)—bone marrow) (magnification 63×).
Figure 2
Figure 2
Morphologic features of atypical CLL cells. Prolymphocytes in peripheral blood (A,B) and cleaved cells (C)—in peripheral blood, (D)—bone marrow (magnification 63×).
Figure 3
Figure 3
Representative flow cytometry of classic CLL cells showed positive expressions of CD5, CD19, and CD23. The population of CD5+/CD19+ and CD23+/CD19+ cells is marked with red color.
Figure 4
Figure 4
Representative flow cytometry of atypical, CD5-negative CLL cells showed positive expression of CD19, CD23, and no expression of CD5. Red color indicates the CD5−/CD19+ cell population, yellow color indicates the CD23+/CD19+ population.
Figure 5
Figure 5
Representative flow cytometry of CLL patients showed positive expression of CD5 and CD19, and negative expression of CD23. The population of CD5+/CD19+ and CD23−/CD19+ cells is marked with red color.
See this image and copyright information in PMC

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