Acute Myeloid Leukaemia with Eosinophilia (Inversion 16)

This slide has a lot going on!. Everybody should clearly see that the white cell morphology is abnormal, but there are a lot of subtle features which contribute to the final diagnosis. 

The most striking features are the abnormal eosinophils and the population of blasts. This should be enough for most morphologists to come to the conclusion that this is a leukaemia. There is in addition a striking thrombocytopenia (the platelet count for this film was 34) and  reduction in normal neutrophils. Those neutrophils seen are hypogranular and dysplastic. The red cells have very non-specific changes with significant anisocytosis and acanthocytosis. These features support an underlying dysplstic process in the bone marrow and keen observers will note the presence of pappenheimer bodies in the smear. These red cell inclusions are aggregates of ferritin which are seen in cells where the normal production of the red cells is disrupted. They are frequently seen in patients with MDS and sickle cell disease and are a significant finding on this film. 

The eosinophils are particularly abnormal with clumped and coarse granulation. This finding is common in eosinophilia directly associated with malignncy (both eosinophilic leukaemias and AML with eosinophilia). Reactive eosinophilia seen in some haematological malignancies such as Hodgkins tend to have a more normal granulation pattern. These are also distinct from the eosinophilia associated with ALL which tend to have a predominantly tri-lobed appearance. Eosinophilia in acute myeloid leukaemia is strongly associated with the presence of abnormalities in chromosome 16 (particularly inv:16) and in this case is associated with a favourable prognosis (see case series reported in NEJM).

There are also a population of abnormal basophils in the blood here, but this is not to be confused with the basophilia associated with CML. We are taught to hunt for basophilia in patients with AML as a sign that this may have evolved from underlying CML, but in those cases the basophils tend to be more normal in morphology and lack the other features of dysplasia seen in this film (see slide MH002 for an example of this).

The blasts here are heterogenous with varied size, shape, NC ratio and granulation. This is a feature of AML over ALL. Although some of the blasts are hypogranular, some have fine granulation and auer rods are visible in occasional cells. Auer rods can in some leukaemias jump out at you and in others be viisble in only a few blasts - it's worth looking hard because even a single cell with auer rods is a firm clue that this is a myeloid process. The blasts all have open chromatin and prominent nucleolus which point clearly to them being primitive cells. This is a good example of AML because the white cell series shows some degree of maturation - there are neutrophils (albeit abnormal), myelocytes (in this case an eosinophil myelocyte), monocytes and blasts. In ALL there is generally a monomorphic population of blasts with a few normal neutrophils but we do not see other myeloid abnormalities.

To round everything off there are a few other significant findings - there are nucleated red cells in the peripheral blood consistent with an infiltrative bone marrow process, and the platelet morphology is abnormal with hypogranular forms and anisocytosis. 

Well done to anybody that got most of this, or even the correct diagnosis!