Pathology Thread

Acute myelogenous leukemia (AML) is the most common type of acute leukemia in adults, 45% of all leukemias and 80-90% of acute leukemias.

The seven major types of acute nonlymphoid or myeloid leukemia are:

Definition: AML involves the malignant proliferation of immature cells or blasts which are of nonlymphoid or myelogenous type. This proliferation originates in the bone marrow, but involves the peripheral blood and other organs.

Diagnosis of AML:  The presence of > 30% blasts in the marrow as determined by a hematologist on bone marrow aspirate. Frequently see increased peripheral WBC count but it can be increased, normal or decreased.

Diagnosis of MDS:  Marrow blasts are increased but are fewer than 30%, is a myelodysplastic syndrome (MDS). (More about MDS later.) Differentiate AML type by cell morphology, cytochemistry, phenotype, and genotype.

Myeloblasts have nuclei with fine, delicate chromatin and most often prominant nucleoli. The cytoplasm of myeloblasts tends to be moderate in volume and lightly basophilic without granules (primary azurophilic granules may be seen in myeloblasts). Auer rods, which are angular, crystalline, and red staining, are unique to myeloblasts but only seen in about 20% of myeloid leukemias.

Note that myeloblasts do not magically mature from myeloblasts with no granules to fully granulated promyelocytes. Three stages in the cytoplasmic maturation of a myeloblast are recognized.

Type I myeloblasts have no azuriphilic primary granules nor Auer rods.

Type II myeloblasts have a few ( ²20) azuriphilic primary granules. Auer rods may be seen.

Type III myeloblasts have ³20 azuriphilic primary granules without a Golgi zone. Promyelocytes are larger, have a lower N/C ratio with denser chromatin, and usually have a pale paranuclear Golgi.

**** 2YMS do not need to know the different subtypes of blasts but should recognize that differentiation occurrs progressively, from no granules to a point when sufficient granules are present we call the cell a promyelocyte.****

Promyelocytes: larger, lower N/C ratio, denser chromatin, pale paranuclear Golgi

Cytochemical studies show at least some of the blasts of most nonlymphoid leukemias to be positive for myeloperoxidase, and/or nonspecific esterase.

Immunophenotypic studies show expression of CD13 and/or CD33 on 95% of all nonlymphoid leukemias.

CD15 and CD14 are other commonly positive markers on nonlymphoid leukemias.

B and T lymphocyte markers should be negative although some myeloid leukemias express CD7.

The immunophenotype of AML does not correlate well with the FAB categories.

Chromosomal abnormalities are important diagnostic and prognostic findings. The most important are the t(8;21) in M2; t(15;17) in M3, and t(9;11) in M5.

Abnormalities of chromosome 16 are associated with eosinophilic differentiation.

Remember, that the definitive diagnosis of leukemia rests on the finding of increased blasts on bone marrow examination, although it most often presents as blasts in the peripheral blood.

The white blood cell (WBC) count although usually high, is often normal or occassionally even low. The percent of blasts in the peripheral blood is highly variable and may range from 0-100%.