How to tell apart CML and benign neutrophilia

We’ve talked already about how you’d differentiate chronic lymphocytic leukemia from a benign lymphocytosis. So how about the same thing for the myeloid series, namely, how do you tell apart chronic myeloid leukemia from a benign neutrophilia?

Chronic myeloid leukemia (CML), a malignant disorder of myeloid cells, can resemble a benign neutrophilia with a marked left shift.  Here are the differences:

1. In CML, the shift to the left is usually much greater than you would see in a benign process.  In a benign left shift, you’ll usually see lots of band neutrophils, fewer metamyelocytes, and even fewer myelocytes. Rarely, you’ll see a promyelocyte. In CML, you see the entire spread (though you don’t see many blasts at all; if you do, it’s CML in blast crisis or some kind of acute myeloid leukemia), with a marked “bulge” at the myelocyte stage.

2. In CML, there is a basophilia; in a benign neutrophilia, there is not.

3. In CML, there is always evidence of the Philadelphia chromosome; in a benign neutrophilia, there never is. This is one of the few times in pathology you can say “always” and “never” with complete confidence. The Philadelphia chromosome is the mutated chromosome 22 that you get from the balanced translocation between chromosomes 9 and 22 that you always see in CML. You must see this translocation, or it is not CML (if it looks like CML, but doesn’t have the Philadelphia chromosome, it’s probably some other chronic myeloproliferative disorder). You can either look for the Philadelphia chromosome using cytogenetics, or you can look for the bcr-abl transcript using molecular studies (like PCR). This is the only way to definitively prove that something is or is not CML.