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Question:

A 24-year-old, previously healthy woman comes to the hospital due to a 3-day history of fever, dyspnea, and cough productive of yellow sputum.  Temperature is 38.8 C (101.8 F), blood pressure is 110/66 mm Hg, and pulse is 110/min.  The patient has bronchial breath sounds and crackles over the right lower lung.  Laboratory results are as follows:

Hemoglobin13 g/dL
Platelets350,000/mm3
Leukocytes54,000/mm3
    Neutrophils65%
    Band forms10%
    Myelocytes3%
    Metamyelocytes1%
    Lymphocytes15%

The leukocyte alkaline phosphatase test score is elevated.  Which of the following is the most likely finding on this patient's peripheral blood smear?

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Explanation:

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This patient most likely has pneumonia with sepsis and an associated leukemoid reaction, a significant leukocytosis (may exceed 50,000/mm3) that occurs in response to an underlying inflammatory condition (eg, severe infection, hemorrhage, solid tumors).  Release of colony-stimulating factors and inflammatory mediators into the circulation causes the bone marrow to increase the production of leukocytes, resulting in leukocytosis.

Blood smear typically shows numerous mature neutrophils, which may have reactive morphologic features, such as Döhle bodies (blue cytoplasmic inclusions of rough endoplasmic reticulum), toxic granulation, and cytoplasmic vacuoles.  Increased neutrophil precursors (eg, bands, metamyelocytes, myelocytes) are also typically present (referred to as "left shift") due to early release from the marrow in response to the increased demand of the inflammatory condition.

Assessment of leukocyte alkaline phosphatase (an enzyme found in maturing neutrophils) can be used to distinguish marked leukocytosis due to leukemoid reaction from chronic myeloid leukemia (CML).  Values are typically normal or increased in leukemoid reaction; in contrast, they are usually low in CML because the abnormal maturing neutrophils have decreased levels of this enzyme.

(Choice B)  Basophilic stippling refers to small, blue granules (ribosomal precipitates) in the cytoplasm of red blood cells.  It is most often seen in thalassemia, alcohol use disorder, and lead/heavy metal poisoning.  This patient's acute presentation and laboratory results are more consistent with leukemoid reaction.

(Choice C)  Hypersegmented neutrophils show ≥6 nuclear lobes and are a feature of megaloblastic anemia, often due to vitamin B12 or folate deficiency.  This patient's normal hemoglobin makes this unlikely.

(Choice D)  The presence of numerous blasts with cytoplasmic Auer rods (fused azurophilic granules) in the blood smear would be concerning for acute myeloid leukemia.  This patient's laboratory results show mainly mature neutrophils with increased neutrophil precursors (eg, bands, metamyelocytes, myelocytes) but not blasts.

(Choice E)  Small lymphoid cells with cleaved nuclei are seen in certain types of lymphoma, particularly follicular lymphoma, a mature B-cell neoplasm.  This patient's clinical symptoms and neutrophilia with left shift are more consistent with leukemoid reaction.

Educational objective:
Leukemoid reaction is a significant leukocytosis (may exceed 50,000/mm3) that occurs in response to an underlying condition, commonly severe infection.  Blood smear often shows neutrophilia with reactive features (eg, Döhle bodies), as well as increased neutrophil precursors (eg, bands, metamyelocytes, myelocytes).  The leukocyte alkaline phosphatase score is normal or increased.