[Harald Theml, Heinz Diem, Torsten Haferlach] Colo(b ok.org)

which shows the start of azurophilic granulation
(arrow), and a promyelocyte (2) with copious large azurophilic granules, typically
in a perinuclear location. d Large promyelocyte (1), myelocyte (2), metamyelo-
cyte (3), and polychromatic erythroblast (4).
 
 
36
Partly Mature White Cell Precursors: Myelocytes and
Metamyelocytes
Myelocytes are the direct product of promyelocyte mitosis and are always
clearly smaller than their progenitors. The ovoid nuclei have a banded
structure; the cytoplasm is becoming lighterwithmaturation and in some
cases acquiring a pink tinge. A special type of granules, which no longer
stain red like the granules in promyelocytes (“specific granules,” perox-
idase-negative), are evenly distributed in the cytoplasm. Myelocyte mor-
phology is wide-ranging because myelocytes actually cover three differ-
ent varieties of dividing cells.
Metamyelocytes (young granulocytes) are the product of the final myelo-
cyte division and show further maturation of the nucleus with an increas-
ing number of stripes and points of density that give the nuclei a spotted
appearance. The nuclei slowly take on a kidney bean shape and have some
plasticity. Metamyelocytes are unable to divide. From this stage on, only
further maturation of the nucleus occurs by contraction, so that the dis-
tinctions (between metamyelocytes, band neutrophils, and segmented
neutrophils) aremerely conventional, although they do relate to the vary-
ing “maturation” of these cell forms.
Diagnostic Implications. Like their precursors, myelocytes and metamy-
elocytes normally appear in the peripheral blood only during increased
cell production in response to stress or triggers, especially infections (for
an overview of possible triggers, see p. 112). Under these conditions, they
are, however, more abundant than myeloblasts or promyelocytes.
Normal Cells of the Blood and Hematopoietic Organs
 
 
37
a b
c d
Myelocytes and metamyelocytes also occur in the blood stream
in severe reactive disease
Fig 11 Myelocytes and metamyelocytes. a Early myelocyte. The chromatin
structure is denser than that of promyelocytes. The granules do not lie over the
nucleus (as can be seen by turning the fine focus adjustment of themicroscope to
and fro). The blood smear is from a case of sepsis, hence the intensive granulation.
b Slightly activated myelocyte (the cytoplasm is still relatively basophilic). c Typi-
cal myelocyte (1) close to a segmented neutrophil (2). d This metamyelocyte is
distinguished from a myelocyte by incipient lobe formation.
 
 
38
Mature Neutrophils: Band Cells and Segmented
Neutrophils
Band cells (band neutrophils) represent the further development of
metamyelocytes. Distinguishing between the different cell types is often
difficult. The term “band cell” should be usedwhen all nuclear sections of
the nucleus are approximately the same width (the “bands”). The begin-
nings of segmentation may be visible, but the indentations should never
cut more than two-thirds of the way across the nucleus.
Segmented neutrophils represent the final stage in the lineage that started
with myeloblasts, forming gradually, without any clear transition or
further cell divisions, by increasing contraction of their nuclei. Finally, the
nuclear segments are connected only by narrow chromatin bridges, which
should be no thicker than one-third of the average diameter of the nu-
cleus. The chromatin in each segment forms coarse bands, or patches and
is denser than the chromatin in band neutrophils.
The cytoplasm of segmented neutrophilic granulocytes varies after
staining fromnearly colorless to soft pink or violet. The abundant granules
are often barely visible dots.
The number of segments increaseswith the age of the cells. The follow-
ing approximate values are taken to represent a normal distribution:
10–30% have two segments, 40–50% have three segments, 10–20% have
four segments, and 0–5% of the nuclei have five segments. A left shift to
smaller numbers of segments is a discreet symptom of reactive activation
of this cell series. A right shift to higher numbers of segments (over-
segmentation) usually accompanies vitamin B12 and folic acid deficien-
cies.
Diagnostic Implications. Banded neutrophilic granulocytes (band neutro-
phils)may occur in small numbers (up to 2%) in a normal blood count. This
is of no diagnostic significance. A higher proportion than 2%may indicate
a left shift and constitute the first sign of a reactive condition (p. 113). The
diagnostic value of segmented neutrophilic granulocytes (segmented
neutrophils) is that normal values are the most sensitive diagnostic in-
dicator of normally functioning hematopoiesis (and, especially, of normal
cellular defense against bacteria). An increase in segmented neutrophils
without a qualitative left shift is not evidence of an alteration in bonemar-
row function, because under certain conditions stored cells may be re-
leased into the peripheral blood (for causes, see p. 111). In conjunction
with qualitative changes (left shift, toxic granulations), however,
granulocytosis does in fact indicate bonemarrowactivation thatmay have
a variety of triggers (pp. 110f.), and if the absolute number has fallen
below the lower limit of the normal range (Table 2, p. 12), a bone marrow
defect or increased cell death must be considered.
Normal Cells of the Blood and Hematopoietic Organs
 
 
39
a b
c
e
d
f
g
Advancing nuclear contraction and segmentation: continuous
transformation from metamyelocyte to band cell and then seg-
mented neutrophilic granulocyte
Fig. 12 Neutrophils (neutrophilic granulocytes). a Transitional form between a
metamyelocyte and a band cell. b Copious granulation in a band cell (1) (toxic gra-
nulation) next to band cells (2) with Döhle bodies (arrows). c Two band cells.
d Band cells can also occur as aggregates. e Segmented neutrophilic granulo-
cytes. f Segmented neutrophilic granulocyte after the peroxidase reaction.
g Segmented neutrophilic granulocyte after alkaline leukocyte phosphatase (ALP)
staining.
 
 
40
Cell Degradation, Special Granulations, and Nuclear
Appendages in Neutrophilic Granulocytes and Nuclear
Anomalies
Toxic granulation is the term used when the normally faint stippled
granules in segmented neutrophils stain an intense reddish violet, usually
against a background of slightly basophilic cytoplasm; unlike the normal
granules, they stain particularly well in an acidic pH (5.4). This phenome-
non is a consequence of activity against bacteria or proteins and is ob-
served in serious infections, toxic or drug effects, or autoimmune
processes (e.g., chronic polyarthritis). At the same time, cytoplasmic
vacuoles are often found, representing the end stage of phagocytosis (es-
pecially in cases of sepsis), as are Döhle bodies: small round bodies of ba-
sophilic cytoplasm that have been described particularly in scarlet fever,
but may be present in all serious infections and toxic conditions. A defi-
ciency or complete absence of granulation in neutrophils is a sign of
severe disturbance of the maturation process (e.g., in myelodysplasia or
acute leukemia). The Pelger anomaly, named after its first describer, is a
hereditary segmentation anomaly of granulocytes that results in round,
rod-shaped, or bisegmented nuclei. The same appearance as a nonheredi-
tary condition (pseudo-Pelger formation, also called Pel–Ebstein fever, or
[cyclic] Murchison syndrome) indicates a severe infectious or toxic stress
response or incipient myelodysplasia; it also may accompany manifest
leukemia.
Normal Cells of the Blood and Hematopoietic Organs
 
 
41
a b
c d
Note the granulations, inclusions, and appendages in segmen-
ted neutrophilic granulocytes
Fig. 13 Variations of segmented neutrophilic granulocytes. a Reactive state