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22 Part I: Clinical Evaluation of the Patient Chapter 2: Examination of Blood Cells 23

is not segmented but is sausage-shaped or U-shaped (see Fig. 2–4). granules of basophils. In mucopolysaccharidoses, coarse, dark granules
Nuclear chromatin is slightly less condensed than the mature neutrophil may be found in the neutrophils, and large azurophilic granules in some
(Chap. 60). lymphocytes and monocytes (see Fig. 2–6). Huge misshapen granules
Eosinophils are on the average slightly larger than neutrophils are found in the neutrophils, and giant azurophilic granules are present
(Chap. 62). The nucleus usually has two lobes (see Fig. 2–4). The chro- in the lymphocytes of patients exhibiting the Chédiak-Higashi anomaly
matin pattern is the same as that of the neutrophil, but the nucleus (see Fig. 2–6; Chap. 66). Auer rods are sharply outlined, red-staining
tends to be more lightly stained. The differentiating characteristic of rods found in the cytoplasm in blast cells, and occasionally in more
these cells is the presence of many refractile, orange-red granules that mature leukemic cells, in the blood of some patients with acute myelog-
are distributed evenly throughout the cell and may be visible overlying enous leukemia or myelodysplastic syndromes (Chap. 88).
the nucleus. These granules are larger than those in the neutrophil and
are more uniform in size. Occasionally, some of the granules in eosino- Abnormal Neutrophil Inclusions
phils stain light blue rather than orange-red. Light blue round or oval Döhle bodies, approximately 1 to 2 μm in
Basophils are similar to the other polymorphonuclear cells and diameter, may be seen in the cytoplasm of neutrophils of patients with
are slightly smaller than neutrophils (Chap. 63). The nucleus may stain infections, burns, and other inflammatory states (see Fig. 2–6). The blue
more faintly and usually is less segmented and has less distinct chro- staining is caused by RNA of the rough-surfaced endoplasmic reticulum
matin condensation than is the case in neutrophils. The large deeply contained in Döhle bodies. These bodies are thought to be a reflection of
basophilic granules of basophils are fewer in number and less regular in accelerated maturation of neutrophils with residual endoplasmic reticu-
size and shape than in the eosinophil. The granules are visible overlying lum from the promyelocyte stage. They usually occur in circumstances
the nucleus and, in some cells, almost completely obscure the lightly in which toxic granulation may be present. May-Hegglin anomaly is one
stained nuclear chromatin. Because the granular constituents are water of several MYH9 disorders, autosomal dominant macrothrombocy-
soluble, some granules may stain only faintly or not at all or may be lost topenias secondary to defective megakaryocyte maturation and frag-
from the cell during preparation (see Fig. 2–4). mentation, with leukocyte inclusion bodies (also Fechtner, Sebastian,
Lymphocytes on blood films are usually smaller than other leu- Epstein, and Alport-like syndromes; Chap. 112). The leukocytic inclu-
kocytes, approximately 10 μm in diameter, but large lymphocytes up sions, pale blue-stained, irregularly shaped inclusions are precipitates
to 20 μm in diameter occasionally are seen (see Fig. 2–4). The small of nonmuscle myosin heavy chains (see Fig. 2–6). Neutrophil function
lymphocyte, the predominant type in normal blood, is round and is normal.
contains a relatively large, round, densely stained nucleus (Chap. 73).
The cytoplasm is scanty and stains pale to dark blue. In the large lym-
phocytes, the nuclear-to-cytoplasmic ratio is lower and the chromatin LEUKOCYTE ARTIFACTS
is slightly less condensed than in the small lymphocytes. The nucleus
is usually round but may be oval or indented. The cytoplasm is abun- Damaged (“Smudge,” “Basket”) and Apoptotic Cells
dant and may contain a few azurophilic granules. Large granular During film preparation, leukocytes may be damaged, resulting in
lymphocytes contain azurophilic granules and relatively abundant cyto- an enlarged nucleus with homogeneous, slightly reddish chromatin
plasm, and generally represent cytotoxic T or natural killer (NK) cells strands with a large blue nucleolus. There is no specific association with
(Chap. 94). Reactive lymphocytes, as seen in viral infections caused by disease other than chronic lymphocytic leukemia (Chap. 92), where
Epstein-Barr virus, cytomegalovirus, adenovirus, or other organisms, increased cell fragility commonly results in variable numbers of smudge
are large with indented nuclei and abundant blue cytoplasm (Chap. 82). cells, which connote a favorable prognosis. Eosinophils and basophils
Nuclear chromatin condensation is variable, and nucleoli may be evi- often are partially or largely degranulated in preparation film with the
dent. A low nuclear-to-cytoplasmic ratio and greater degree of chroma- granules scattered beside the cell. Occasional neutrophils may be seen
tin condensation distinguishes them from neoplastic cells. in stages of apoptosis after standing in anticoagulated blood at room
Monocytes are the largest normal cells in the blood, usually measur- temperature (see Fig. 2–6).
ing from 15 to 22 μm in diameter (see Fig. 2–4). The nucleus is of various
shapes—round, kidney-shape, oval, or lobular—and frequently appears Radial Nuclear Segmentation
to be folded (Chap. 67). The lacy chromatin is arranged in fine strands This refers to abnormal segmentation of the nuclei of leukocytes on the
with sharply defined margins. The cytoplasm is light gray, contains vari- blood film, in which the lobes appear to radiate from a single point,
able numbers of fine lilac or purple granules, and is often vacuolated. giving a cloverleaf or cartwheel picture. This change is common in cyto-
The gray (as opposed to blue) color of monocyte cytoplasm is a result of centrifuged preparations (i.e., from a body fluid), EDTA anticoagulated
fine granules (staining pink) seen on the background of RNA-containing blood after excessive storage, and samples collected in oxalate.
cytoplasm (staining blue), and helps to distinguish between monocytes
and reactive lymphocytes. The monocyte nuclear chromatin contains a Vacuolization
fine, string-like structure as opposed to the smudgy-appearing clumps Vacuoles may develop in the nucleus and cytoplasm of leukocytes,
of the lymphoid chromatin. Nuclear shape and cytoplasmic vacuoliza- especially monocytes and neutrophils, with prolonged storage in EDTA
tion are less reliable for distinguishing features between monocytic and anticoagulated blood. Vacuoles may be associated with swelling of the
lymphoid cells. nuclei and loss of granules from the cytoplasm. In blood films prepared
without anticoagulation, vacuoles in neutrophils suggest sepsis.
LEUKOCYTE INCLUSIONS Endothelial Cells
Abnormal Granules If the blood film is prepared from the first drop of blood issuing from
In a systemic inflammatory reaction, neutrophil granules may appear fingerstick, endothelial cells may be present singly, in clumps, or as
larger than normal and stain more darkly, often assuming a dark strings of attached cells (see Fig. 2–6). These cells en face may simulate
blue-black color. This has been called toxic granulation (see Fig. 2–6). the appearance of abnormal cells and may be misinterpreted as blasts or
These granules if unusually prominent can be confused with the larger metastatic tumor cells.

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