Differentiation between Myeloid and Lymphoid Lines

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The page below is a sample from the LabCE course Acute Leukemia with a Focus on WHO Classification. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

Learn more about Acute Leukemia with a Focus on WHO Classification (online CE course)
Differentiation between Myeloid and Lymphoid Lines

The major WHO categories of acute leukemias are:
  • Acute Myeloid Leukemia (AML)
  • Acute Lymphoblastic Leukemia (ALL) - comprised of Acute B Lymphoblastic and Acute T Lymphoblastic
  • Acute Leukemia of Ambiguous Lineage
  • Blastic Plasmacytoid Dendritic Cell Neoplasm
The first two - AML and ALL are by far the most common; the second two are rare. Therefore, this course will cover AML and ALL thoroughly, with only mention of the other two.
Typically, when a white blood cell differential indicates a substantial percentage of blasts, the first thing necessary is to determine whether they are myeloblasts or lymphoblasts. Although it might seem at first like distinguishing between myeloid or lymphocytic cells is quite obvious, that is not always the case when it comes to neoplastic disorders. The first step is to look for obvious clues. Acute leukemias are characterized by a ''leukemic gap', which refers to the presence of both blasts and mature cells, while representative cells in the intermediate stages are absent. So one way to obtain a clue is to look at the mature cells. If most of the mature cells seen are lymphocytes, then it could possibly be ALL. If neutrophils or other cells in the myeloid line are seen, then it is more likely to be an AML.
One clue that is almost foolproof is the presence of Auer Rods. Auer Rods are red staining, elongated needle-like inclusions that can be seen in the cytoplasm of AML myeloblasts. They result from the fusion of azurophilic (red staining) granules. If Auer Rods are seen, you can be certain that the leukemia is of myeloid origin. However, if they are not seen, you can not strictly rule out myeloid leukemias as they aren't seen in everyone or all the time. (Note: the presence of Auer Rods indicates that the cell is of myeloid lineage. but doesn't define it as acute. Most likely it is AML, but Auer Rods can occasionally be seen in other neoplastic disorders of myeloid lineage.) The image to the right shows Auer Rods in myeloblasts. Table 2 can be useful in morphological differentiation.
Table 2. Comparing AML and ALL.
AMLALL
Blast SizeMedium to large Small to medium
CytoplasmFine granules may be present
Usually no granules or few coarse
Presence of Auer RodsYes No
NucleusNuclear chromatin finely dispersed; 2-4 prominent nucleoli 1-3 indistinct nucleoli
Image of Blast
(1)

(2)
If Auer Rods are not seen, then cytochemical stains can be used to distinguish the lineages, or one can go directly to other diagnostic tests. Though not used as often anymore, the following page will give a synopsis of the various cytochemical tests. When not used, the next step for diagnosing the leukemia may be genetic testing or immunophenotyping.
1. Najmaldin Saki, PhD; Ahmad Ahmadzadeh, MD; Marziye Bagheri, MSc. "We present a picture from bone marrow aspiration sample of acute myeloblastic leukemia (AML-M2) patient." American Society of Hematology, 19 Jan 2019, http://imagebank.hematology.org/image/62152/acute-myeloblastic-leukemia-amlm2-3?type=upload
2. VashiDonsk. "A Wright's stained bone marrow aspirate smear of patient with precursor B-cell acute lymphoblastic leukemia. Picture taken by me." Wikimedia Commons, 15 Jan 2007, https://commons.wikimedia.org/wiki/File:Acute_leukemia-ALL.jpg