Q. Can you tell me the morphological features of AML M0 and M1 blasts versus ALL blasts to differentiate the two? And are there some hints in the other peripheral WBC cells to tell whether one is dealing with ALL or AML? For example, more lymphocytes possibly pointing to ALL?

A. Those are very good questions. The short answer is that it can be very difficult, and sometimes impossible, to tell the difference between myeloblasts and lymphoblasts without special studies (immunophenotyping or cytochemical stains). However, there are some points that might help:

  1. The myeloblasts in M0 are totally undifferentiated, and therefore impossible to tell apart from other types of blasts (like lymphoblasts). They never have Auer rods, and there are no tiny granules like you sometimes see in myeloblasts in other types of AML. Cytochemical stains (like MPO) won’t work either (that’s how undifferentiated they are!). For these myeloblasts, you really need immunophenotyping to definitively call them myeloblasts.
  2. The myeloblasts in M1 are a bit more differentiated (and the ones in M2 are even more so). There are occasionally Auer rods present, and some of the blasts may have a few fine granules in the cytoplasm. If you see an Auer rod, you know it’s a malignant myeloblast! Check out the blood smear above. It is from a case of AML-M2, and there are three blasts in the photo. The one at the top right has an Auer rod in it. But the other two blasts – if you just saw them alone, you wouldn’t know whether they were myeloblasts or lymphoblasts).
  3. In M0, M1, and M2, you can sometimes see dysplastic changes (hypogranularity and/or hyposegmentation) in the neutrophils that are present, and that can be a useful clue that you’re dealing with an AML as opposed to an ALL (in which the neutrophils look completely normal).
  4. In ALL, we identify and classify the blasts according to their immunophenotype (we don’t use the L1 vs. L2 morphologic classification anymore;). Some clues that you’re dealing with an ALL include a range in size within the blast population (some bigger, more L1-like if you prefer that term, and some smaller with more condensed chromatin, more L2-like). Also, lymphoblasts (and lymphocytes in general) tend to be more fragile than myeloid cells, so you may see some “ghost” or “basket” cells, which are just lymphoblasts or lymphocytes that have been damaged during the smear preparation process. The percentages of the non-blast cells are not useful in making the diagnosis of ALL (i.e., the normal lymphocyte count is not increased in cases of ALL).

The bottom line is: if all you have is a population of plain old undifferentiated blasts (without Auer rods), you really need to do cytochemical stains (and probably immunophenotyping) to tell what lineage they are.