Smudge Cells Reporting in Chronic Lymphocytic Leukemia: Evaluation of Manual Differential Blood Count and the Impact of Albumin Pre-treatment

Abstract

Background: Smudge cells are damaged leukocytes commonly seen in blood smears of patients with chronic lymphocytic leukemia (CLL). Their number reflects lymphocyte fragility but varies widely among patients. Additionally, reporting practices regarding smudge cell number significantly differ among laboratories, sometimes also including sample pre-treatment with albumin, which can reduce their formation. Although this approach can substantially facilitate morphological differential count in CLL patients, its widespread in routine hematology remains uncertain. Aims: This study aims to compare various manual approaches for smudge cell reporting with analyzer differentials in order to identify the most reliable and practical method for routine CLL diagnostics. Methodology: We conducted a comparative analysis of manual differential blood count (mDIFF)    to a hematological analyzer differential (aDIFF). mDIFF was conducted in three manners: by excluding smudge cells from 100 leukocyte count (mDIFF1); by including smudge cells into lymphocyte count (mDIFF2); differential on an albumenized smear (mDIFF_alb). The Mann-Whitney test was used for smudge cell count comparison in standard and albuminized smears, and Friedman’s test for comparison of differential counts (lymphocytes, neutrophils and their ratio). P-value <0.05 was considered significant. Results: The smudge cell count was significantly lower in albumenized smears (median 7, IQR 4 - 14), compared to standard smears (median 25, IQR 17 - 81), P<0,0001. mDIFF2 results significantly differed in neutrophil and lymphocyte count compared to other methods (P<0.05). The relative lymphocyte count in a manual method mDIFF1 did not significantly differ from the aDIFF. Conclusion: Although albumin pre-treatment effectively reduces smudge cell formation, it is not essential for obtaining clinically reliable differentials in routine practice. Reporting smudge cells as their number per 100 leukocytes provides a suitable alternative to automated differential leukocyte counts.