Atypical Chronic Lymphocytic Leukemia—The Current Status

SIMPLE SUMMARY: The degree of differentiation of leukemic cells seen in clinical practice is significant. The dissimilarities concern morphology, cytogenetics, and immunophenotype. This leads to a distinction between typical chronic lymphocytic leukemia and the atypical one, which is not taken into consideration in the standard diagnostic process yet. The heterogenic course of the disease encourages the search for prognostic factors that would aid in the selection of the most effective individual therapy for each patient. The atypical CLL constitutes a major difficulty in the diagnostic process and, therefore, in the choice of accurate treatment. 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.