What if you had a blood smear in which you thought the diagnosis was chronic myeloid leukemia (CML), but you didn’t have access to a cytogenetic or molecular lab (to look for the Philadelphia chromosome or the bcr-abl translocation)?
Well, first you’d look for all the morphologic clues you could. CML usually presents with a marked leukocytosis (the WBC is often over 100,000), with a left shift all the way back to myeloblasts (though there are relatively few myeloblasts around). A benign left shift usually presents with a mild to moderate leukocytosis (the neutrophil count is often just above normal; it’s generally nowhere near the magnitude often seen in CML), and the neutrophils are shifted back to the metamyelocyte or myelocyte stages (you’ll very rarely see promyelocytes, and you’ll virtually never see myeloblasts). Also, CML tends to have a “bulge” at the metamyelocyte stage, whereas a benign left shift does not (the cells are more or less present in decreasing amounts by stage of maturation, i.e., there are more segmented than band neutrophils, more bands than metamyelocytes, more metamyelocytes than myelocytes, more myelocytes than promyelocytes…and blasts are basically nonexistent). Finally, CML has a basophilia, whereas a benign left shift does not.
But if you wanted more proof that your case was CML, you could do a leukocyte (or neutrophil) alkaline phosphatase (LAP). This test is not done as much as it used to be, because now everyone goes right to cytogenetics or molecular testing in order to find the Philadelphia chromosome or the bcr-abl translocation. But it’s still a good test, and it would be a good thing to do if you couldn’t look for the Philadelphia chromosome.
Here’s the principle behind the test. LAP is an enzyme present in normal neutrophils, but absent (or present at very low concentrations) in malignant neutrophils (i.e., the ones in CML). So if you have a whole bunch of neutrophils around, and the LAP is strongly positive in those cells, as in the top image, you can be quite sure that it is a benign bunch of neutrophils. However, if the LAP is negative, or only weakly positive, as in the bottom image, that probably means that those neutrophils are malignant and that you’re dealing with a case of CML.
You’d still want to send off a blood or bone marrow specimen to a cytogenetics and/or molecular diagnostics lab, but in the meantime, the LAP can help you quickly assess and triage your patient.
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