You Make the Diagnosis

A 42-year-old male presents with fever and fatigue. A CBC shows the following:

Hgb 14.2 g/dL (normal = 13.5 – 17.5 g/dL)
WBC 18 x 10⁹/L (normal = 4.5 – 11 x 10⁹/L)
Platelet count 320 x 10⁹/L (normal = 150 – 450 x 10⁹/L)

Differential:

• Neutrophils and precursors: 80%
• Lymphocytes: 16%
• Monocytes: 2.5%
• Eosinophils: 1.4%
• Basophils: 0.1%

A review of the blood smear shows a slight left shift in the neutrophil series, with occasional metamyelocytes and rare myelocytes present. Several cells similar to the one shown below are noted.

Which of the following is the most likely diagnosis?

A.  Acute myeloid leukemia
B. Chronic myeloid leukemia
C. Bacterial infection
D. Viral infection
E. Parasitic infection

The answer in this case is C, bacterial infection. The cell shown in the photo is a slightly immature neutrophil showing toxic granulation (heavy, dark azurophilic cytoplasmic granules), a morphologic sign seen most commonly in severe bacterial infections. The elevated neutrophil count with a left shift supports the diagnosis of bacterial infection.

Toxic granulation is thought to be a result of the bone marrow’s response to the need for neutrophils in the peripheral tissues. Promyelocytes are the last dividing stage of the neutrophil series (once a cell reaches the myelocyte stage, it can no longer divide, but only mature). Normally, as promyelocytes divide, their azurophilic granules are dispersed into daughter cells, the end result being a mature neutrophil with few azurophilic granules.

If there is an urgent need for increased numbers of neutrophils, like there is in a severe bacterial infection, promyelocytes may opt to simply mature, rather than divide. As a result, the azurophilic granules are not diluted among daughter cells, but retained in the maturing neutrophil, the end result being a mature neutrophil with many more azurophilic granules than usual.

The normal red cell and platelet count, as well as the lack of a significant number of very immature myeloid cells, rules out the presence of acute myeloid leukemia (AML). In AML, at least 20% of the nucleated cells in the blood or bone marrow must be composed of blast or blast equivalents.

Chronic myeloid leukemia (CML) is often a consideration in patients with an elevated neutrophil count and a left shift. In CML, however, the neutrophil count is usually quite high, and there is a marked left shift, with a particularly large number of myelocytes. In addition, a basophilia is almost always present.

Viral infection often presents with a lymphocytosis, sometimes with reactive changes in the lymphocytes. Finally, some parasitic infections present with an eosinophilia (but not a neutrophilia).

-Kristine Krafts, MD, is an Assistant Professor of Pathology at the University of Minnesota School of Medicine and School of Dentistry and the founder of the educational website Pathology Student.