Tuesday, November 29, 2011

New Perspective on Smudge Cells


What exactly are smudge cells (also known as basket cells)? In patients with Chronic Lymphocytic Leukemia (CLL), it is a comment used to describe cells that look exactly like that, a cell that has been run over by a steam roller and flattened out. They are formed as a result of the action of the blood being spread out over the glass slide used to make the differential. There are apoptotic lymphocytes , more fragile than regular lymphocytes.
Conventional wisdom was that they were an artefact and only the presence of them was all that was needed to be reported. Some labs went even further by adding a drop of bovine albumin to the blood before making a smear, since this additive preventing the lymphocytes from becoming damaged while the smear was made. Since it is possible for smudge cells to be present in a normal blood smear, the presence of smudge cells by itself do not indicate a pathological condition. Before CLL can be diagnosed, flow cytometry is required.
For patients with diagnosed CLL, the presence of smudge cells was noted, but no measurement of them was done.
Two recent articles may change that:

Johansson P. Et al , ‘Percentage of smudge cells determined on routine blood smears is a novel prognostic factor in Chronic Lymphocytic Leukemia, Leuk Res 2010:34:892-8.

Nowakovski, GS et al, Percentage of smudge cells on routine blood smears predicts survival in chronid lymphocytic leukemia.

Basically a smudge cell is a lymphocyte lacking a protein called vimentin in its cytoskeleton. Vimentin is responsible for the rigidity and integrity of cells, as well as playing a role in activation and transduction. Leukemic cells that are ZAP70/CD38 positive will have vimentin and be resistant to becoming smudge cells and be virulent . Leukemic cells that lack vimentin will become smudge cells and be less virulent.
Therefore a smear from a patient with a high percentage of smudge cells will have less virulent cells and a better outcome than a patient with few smudge cells.
The challenge will be twofold, determining how to consistently identify smudge cells, and how to present the data in a consistent form.

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