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A 63-year-old man comes to the office due to fatigue and easy bruising.  He has no lymphadenopathy on physical examination.  Laboratory results are as follows:

Complete blood count
    Hemoglobin8.0 g/dL
    Platelets40,000/mm3
    Leukocytes20,500/mm3

The patient's peripheral blood smear is shown in the image below:

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Which of the following is the most likely diagnosis?

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This patient's peripheral blood smear shows very large nucleated cells (see red cell size for comparison) with scant cytoplasm.  These are blast cells, the finding of which makes acute leukemia likely.  Closer examination of the smear reveals linear, purple-red inclusions in some of the cells, called Auer rods.  These represent fused granules and may be single or multiple within immature myeloid precursors.  Auer rods are highly suggestive of acute myeloid leukemia (AML) but not of acute lymphoblastic leukemia (ALL) (Choice A).  Although Auer rods are most commonly associated with the M1, M2, and M3 subtypes of AML, they may be found in any type of AML.

The vast majority of AML cases occur in adults, with a median age of 65 and median white blood cell count of about 15,000/mm3 at diagnosis.  Most patients present with complications of pancytopenia (eg, fatigue from anemia, bruising/bleeding from thrombocytopenia, infection from functional neutropenia [despite leukocytosis]).  Diagnostic criteria generally require the presence of >20% myeloblasts in the bone marrow or peripheral blood.

(Choices C and D)  Chronic leukemia causes a prevalence of mature cells in the peripheral blood.  In chronic myeloid leukemia (CML), peripheral smears usually show many mature granulocytes and few blasts (generally <2%).  In chronic lymphocytic leukemia (CLL), smears show many mature lymphocytes.

(Choice E)  Patients with hairy cell leukemia have splenomegaly, cytopenias, and circulating hairy cells.  On peripheral blood smear, hairy cells take the appearance of small- to medium-sized lymphoid cells with circumferential "hairy" projections.

(Choice F)  Patients with Hodgkin lymphoma generally present with a mass (eg, mediastinal mass, enlarged lymph nodes).  The finding of circulating neoplastic cells is extremely rare.  Histologically, Reed-Sternberg cells are characteristic.  These are large cells with abundant basophilic cytoplasm and >2 nuclear lobes or nuclei.

(Choice G)  Patients with infectious mononucleosis have fatigue, lymphadenopathy, and splenomegaly.  Thrombocytopenia can be a complication of this infection.  Peripheral blood smear will show few circulating atypical lymphocytes, not numerous blasts.

Educational objective:
The finding of Auer rods (linear purple-red inclusions within immature myeloid precursors) is helpful in making the diagnosis of acute myeloid leukemia.  Auer rods are not found in acute lymphoblastic leukemia.  In chronic myeloid leukemia, there are more mature cells and fewer blasts.