What Does Atypical Chronic Lymphocytic Leukemia Really Mean? A Retrospective Morphological and Immunophenotypic Study

Area of Science:

• Hematology
• Oncology
• Immunology

Background:

• Chronic lymphocytic leukemia (CLL) is traditionally diagnosed using morphological criteria.
• Deviations in the typical surface immunoglobulin profile suggest an atypical, immunologically defined CLL.
• Morphological and immunophenotypical classifications may not always align.

Purpose of the Study:

• To assess morphological, immunophenotypical, and clinical-biological features of atypical CLL.
• To compare atypical CLL cases with typical CLL cases.
• To evaluate the prognostic significance of morphological and immunophenotypical features in CLL.

Main Methods:

• Retrospective evaluation of a large cohort of CLL patients.
• Assessment of morphological features (FAB criteria).
• Analysis of immunophenotypical profiles, identifying discordances from the typical CLL profile.

Main Results:

• Morphologically atypical CLL exhibited higher unmutated IgVH, CD38 positivity, and CD20 expression.
• Immunophenotypically atypical CLL showed advanced stages, higher CD20, FMC7, CD79b, CD49d positivity, and intermediate-high surface immunoglobulin expression.
• Morphological features were better prognostic indicators for time-to-first-treatment; concordant atypical cases had a worse prognosis.

Conclusions:

• Morphological and immunophenotypical classifications of atypical CLL reveal distinct characteristics.
• Morphology appears to be a stronger predictor of prognosis than immunophenotype in CLL.
• The clinical utility of morphology and immunophenotype versus molecular markers for CLL prognosis requires further investigation.