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EDUCATIONAL COMMENTARY – BLOOD CELL ID: MORPHOLOGIC CHANGES INDICATIVE OF
INFECTION
Educational commentary is provided through our affiliation with the American Society for Clinical
Pathology (ASCP). To obtain FREE CME/CMLE credits click on Earn CE Credits under Continuing
Education on the left side of the screen.
LEARNING OUTCOMES
On completion of this exercise, the participant should be able to:

describe characteristic features of reactive lymphocytes.

identify significant morphologic findings in normal peripheral blood erythrocytes and
leukocytes.

discuss peripheral blood and cellular morphologic changes indicative of infection.
Case study
A 20 year old male was seen in the emergency room for dizziness and giddiness. His CBC data was as
follows: WBC=11.7 x 109/L, RBC=4.81 x 1012/L, Hgb=14.6 g/dL, Hct=40.8%, MCV=85 fL, MCH=30.4 pg,
MCHC=35.8 g/dL, Platelet=146 x 109/L.
Educational Commentary
The patient in the case study for this testing event has been diagnosed as having relapsing fever caused
by the bacterium Borrelia hermsii. The images provided for review represent normal and abnormal
peripheral blood cells as well as organisms that may be associated with this type of infection.
Image BCI-08 shows a reactive lymphocyte. Sometimes
these cells are also called atypical or variant. Reactive
lymphocytes are cells that have been activated in
response to an infection. Such lymphocytes are most
often associated with viral illnesses, but it is not unusual
to see some reactive lymphocytes as an overall indication
of a heightened immune condition. Because reactive
lymphocytes are responding to an infection, they can
have a variety of appearances. However, several general
characteristics can be described. The nucleus may be
round, oval, lobular, folded, or indented, as in the current example. Nuclear chromatin may be fine, but is
also sometimes moderately to coarsely clumped. Nucleoli may or may not be visible. In reactive
lymphocytes, the cytoplasmic color may be deep blue, gray, or pale blue and areas of clearing are often
seen. In addition, the cytoplasm is frequently abundant. Although reactive lymphocytes may have
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American Proficiency Institute – 2012 2 Test Event
EDUCATIONAL COMMENTARY – BLOOD CELL ID: MORPHOLOGIC CHANGES INDICATIVE OF
INFECTION (cont.)
vacuoles, azurophilic granules, or both, the extensive vacuolization prominent in this particular cell is
unusual. Also, the cytoplasm is slightly indented by adjacent red blood cells (RBCs) and appears a
darker blue at these margins.
The cell identified in Image BCI-09 is a segmented
neutrophil. The nuclear separations seen in this example
are typical. Segmented neutrophils may have as many as
5 nuclear lobes connected by thin strands of chromatin.
The chromatin is clumped and condensed. Numerous
pink, tan, or violet granules are visible in the cytoplasm. In
this example, the granules appear slightly more intense in
color. It is possible that these are toxic granules, another
cellular indicator of infection.
Image BCI-10 illustrates a normal RBC. Several
morphologic features of RBCs should be evaluated when
they are reviewed on a peripheral blood smear. RBCs
should be uniform in size, evenly shaped, distributed
uniformly on the smear, contain no inclusions, and have
an area of central pallor that is about one-third of the
diameter of the cell. The cell in this image satisfies these
criteria.
Image BCI-11 is a band neutrophil. Bands are the stage
of neutrophilic maturation immediately before the
segmented neutrophil. They represent the earliest
precursor that is usually seen in the peripheral blood. The
cytoplasm of band neutrophils is similar to that of the
segmented neutrophil, containing numerous pink, tan, or
violet granules. However, the nucleus is characteristically
shaped like a sausage or the letters C or U. Compared
with those of the segmented neutrophil, the lobes in a
band are connected by a bridge rather than by a filament.
The band’s nuclear chromatin is dense and clumped.
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American Proficiency Institute – 2012 2 Test Event
EDUCATIONAL COMMENTARY – BLOOD CELL ID: MORPHOLOGIC CHANGES INDICATIVE OF
INFECTION (cont.)
Image BCI-12 shows a monocyte. The large size of this
cell is characteristic. Other typical morphologic features
include the abundant blue-gray vacuolated cytoplasm that
appears rough and uneven. Cytoplasmic extensions are
occasionally present, and the cytoplasmic margins are
often not uniform. The nuclei in monocytes are variably
shaped and may be round, oval, indented, or lobated.
Little clumping can be observed because the nuclear
chromatin tends to appear more open and fine, although
this characteristic is difficult to appreciate in this example.
Nucleoli are generally not visible in monocytes.
The arrow in Image BCI-13 identifies a spirochete.
Disease-causing spirochetes are organisms in the genera
Borrelia, Leptospira, and Treponema. It is rare to see any
of these spirochetes in the peripheral blood. Several
species of Borrelia cause various diseases, including
relapsing fever and Lyme disease. The patient in this
case study was diagnosed as having relapsing fever, as
confirmed by positive results on B. hermsii antibody
testing. Such antibody testing is necessary to verify the
causative agent and type of infection because it is not
possible to morphologically identify the specific species of Borrelia by reviewing a stained peripheral
blood smear. Borrelia organisms are most often seen in the blood during febrile periods. Borrelia
bacteria have an affinity for acid dyes, so are well recognized with Wright stain. They are especially
visible when located between RBCs, as in this photograph. They have 4 to 30 loose, helical coils. They
can be distinguished from contaminants, which are less structured.
Another reactive lymphocyte is shown in Image BCI-14.
As in the reactive lymphocyte identified in Image BCI-08,
this cell has sprawling, unevenly stained blue cytoplasm
with some vacuoles. In contrast to the cell in Image BCI08, this lymphocyte also has several azurophilic granules,
which can also be seen in reactive cells. The nucleus is
oval with moderately clumped chromatin.
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American Proficiency Institute – 2012 2 Test Event
EDUCATIONAL COMMENTARY – BLOOD CELL ID: MORPHOLOGIC CHANGES INDICATIVE OF
INFECTION (cont.)
It is also important to distinguish the reactive lymphocytes in Images BCI-08 and BCI-14 from the
monocyte in Image BCI-12. Although reactive lymphocytes can be large, this monocyte is larger.
Likewise, the cytoplasm in the monocyte does not have areas of clearing, but is a more uniformly stained
blue-gray, although the texture appears somewhat rough and uneven. Because vacuoles are seen in all
these cells, it is not reliable to use vacuolization as a feature for differentiating reactive lymphocytes from
monocytes. The nuclear chromatin in monocytes tends to be folded, lacy, and loose versus the usually
more condensed chromatin of reactive lymphocytes. However, the chromatin in the monocyte in Image
BCI-12 is not characteristically dispersed in appearance. In this example, therefore, the large size of the
cell and the typical monocytoid cytoplasm distinguish this cell from the reactive lymphocytes in the other
images.
An additional feature of the segmented neutrophil is evident in Image BCI-14. Two large, dark granules
are located at approximately 10 o’clock and 2 o’clock in the cytoplasm of this cell. These inclusions
represent Döhle bodies, denatured aggregates of rough endoplasmic reticulum or free ribosomes. They
are associated with many conditions, including bacterial infection. These inclusions appear as a result of
a shortened cell maturation time and persistent production activity in neutrophils. Döhle bodies are
generally single or multiple blue or blue-gray masses located near the cytoplasmic periphery of
neutrophils. They vary in size and shape. Although the Döhle bodies in this cell are not the classic blue
or blue-gray color, they are, nevertheless, distinct inclusions positioned on the outer edge of the
cytoplasm. The lack of a characteristic staining reaction in these granules underscores the importance of
using several morphologic features of cells or inclusions in the identification process.
Summary
Several morphologic changes can be evident in the peripheral blood during various infections. The
patient in this case study had relapsing fever. Therefore, not only spirochetes were evident, but also
cellular variations indicative of an immune response. Reactive lymphocytes, a band neutrophil, toxic
granulation, and Döhle bodies all suggest this heightened activity.
© ASCP 2012
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American Proficiency Institute – 2012 2 Test Event