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than one separate nucleus, large mononuclear cells.
Hypoplastic AML
Sometimes (mostly in the mild or “aleukemic” leukemias of the FAB or
WHO classifications), the bonemarrow is largely empty and shows only a
few blasts, which usually occur in clusters. In such a case, a very detailed
analysis is essential for a differential diagnosis versus aplastic anemia (see
pp. 148f.).
Abnormalities of theWhite Cell Series
 
 
103
a
c
b
d
New WHO classification: AML with dysplasia and hypoplastic
AML
Fig. 34 AML with dysplasia and hypoplastic AML. a AML with dysplasia: megalo-
blastoid (dysplastic) erythropoiesis (1) and dysplastic granulopoiesis with Pelger-
Huët forms (2) and absence of granulation in a myelocyte (3). Myeloblast (4).
b Multiple separated nuclei in a megakaryocyte (1) in AML with dysplasia. Dys-
erythropoiesis with karyorrhexis (2). c and d Hypoplastic AML. c Cell numbers be-
low normal for age in the bonemarrow. dMagnification of the area indicated in c,
showing predominance of undifferentiated blasts (e.g., 1).
 
 
104
Table 16 Immunological classification of acute bilineage leukemias (adapted from BeneMC
et al. (1995) European Group for the Immunological Characterization of Leukemias (EGIL) 9:
1783–1786)
Score B-lymphoid T-lymphoid Myeloid
2 CytCD79a* CD3(m/cyt) MP0
Cyt IgM anti-TCR
1 CD19 CD2 CD117
CD20 CD5 CD13
CD10 CD8 CD33
CD10 CD65
0.5 TdT TdT CD14
CD24 CD7 CD15
CD1a CD64
* CD79a may also be expressed in some cases of precursor T-lymphoblastic leukemia/lym-
phoma.
Abnormalities of theWhite Cell Series
Acute Lymphoblastic Leukemia (ALL)
ALL are the leukemias in which the cells do not morphologically resemble
myeloblasts, promyelocytes, or monocytes, nor do they show the corre-
sponding cytochemical pattern. Common attributes are a usually slightly
smaller cell nucleus and denser chromatin structure, the grainy con-
sistency ofwhich can bemade out onlywith optimal smear technique (i.e.,
very light). The classification as ALL is based on the (often remote) simi-
larities of the cells to lymphocytes or lymphoblasts from lymphnodes, and
on their immunological cellmarker behavior. Insufficiently closemorpho-
logical analysis can also result in possible confusionwith chronic lympho-
cytic leukemia (CLL), but cell surfacemarker analysis (see below) will cor-
rect thismistake. Advanced diagnostics startwith peroxidase and esterase
tests on fresh smears, performed in a hematology laboratory, together
with (as a minimum) immunological marker studies carried out on fresh
heparinized blood samples in a specialist laboratory. The detailed differ-
entiation provided by this cell surface marker analysis has prognostic im-
plications and some therapeutic relevance especially for the distinction to
bilineage leukemia and AML (Table 16).
 
 
105
a
c
b
d
The cells in acute lymphocytic leukemia vary, and the subtypes
can be reliably identified only by immunological methods
Fig. 35 Acute lymphocytic leukemias. a Screening view: blasts (1) and lympho-
cytes (2) in ALL. Further classification of the blasts requires immunological me-
thods (commonALL).b Same case as a . The blasts show a dense, irregular nuclear
structure and narrow cytoplasm (cf. mononucleosis, p. 69). Lymphocyte (2). c ALL
blasts with indentations must be distinguished from small-cell non-Hodgkin
lymphoma (e.g., mantle cell lymphoma, p. 77) by cell surface marker analysis.
d Bone marrow: large, vacuolated blasts, typical of B-cell ALL. The image shows
residual dysplastic erythropoietic cells (arrow).
 
 
106
Table 17 Forms of myelodysplasia
Form ofmyelodysplasia Blood analysis Bonemarrow
RA = refractory anemia Anemia (normo-
chromic or hyper-
chromic); possibly
pseudo-Pelger granulo-
cytes; blasts' 1%
Dyserythropoiesis
(marginal dysgranulo-
poiesis and dysmega-
karyopoiesis" 10%)
$ 5% blasts
RAS = refractory ane-
miawith ring sidero-
blasts (( aquired
idiopathic sideroblastic
anemia, p. 137)
Hypochromic and
hyperchromic erythro-
cytes side by side,
sometimes discrete
thrombopenia and
leukopenia; pseudo-
Pelger cells
More than 15% of the
red cell precursors are
ring sideroblasts;
blasts$ 5%
RAEB = refractory ane-
miawith excess of
blasts
Often thrombocyto-
penia in addition to
anemia; blasts$ 5%,
monocytes$ 1000/µl,
pseudo-Pelger syn-
drome
Erythropoietic hyper-
plasia (with or without
ring sideroblasts);
5–20% blasts
Cont. p. 108
Abnormalities of theWhite Cell Series
Myelodysplasia (MDS)
Clinical practice has long been familiar with the scenario in which, after
years of bone marrow insufficiencywith a more or less pronounced deficit
in all three cell series (tricytopenia), patients pass into a phase of insid-
iously increasing blast counts and from there into frank leukosis
—although the evolution may come to a halt at any of these stages. The
transitions between the forms of myelodysplastic syndromes are very
fluid, and they have the following features in common:
! Anemia, bicytopenia, or tricytopeniawithout known cause.
! Dyserythropoiesis with sometimes pronounced erythrocyte anisocyto-
sis; in the bone marrow often megaloblastoid cells and/or ring sidero-
blasts.
! Dysgranulopoiesis with pseudo-Pelger-Huët nuclear anomaly (hypo-
segmentation) and hypogranulation (often no peroxidase reactivity) of
segmented and band granulocytes in blood and bone marrow.
! Dysmegakaryopoiesiswith micromegakaryocytes.
The FAB classification is the best-known scheme so far for organizing the
different forms of myelodysplasia (Table 17).
 
 
107
a
c
b
d
e
In unexplained anemia and/or leukocytopenia and/or thrombo-
cytopenia, blood cell abnormalities may indicate myelodysplasia
Fig. 36 Myelodysplasia and CMML. a–d Different degrees of abnormal matu-
ration (pseudo-Pelger type); the nuclear density can reach that of erythroblasts
(d). The cytoplasmic hypogranulation is also observed in normal segmented gra-
nulocytes. These abnormalities are seen inmyelodysplasia or after chemotherapy,
among other conditions. e Blood analysis in CMML: monocytes (1), promyelocyte
(2), and pseudo-Pelger cell (3). Thrombocytopenia.
 
 
108
Table 17 Continued
Form ofmyelodysplasia Blood analysis Bonemarrow
CMML = chronicmyelo-
monocytic leukemia
Blasts$ 5%, mono-
cytes" 1000/µl,
pseudo-Pelger syn-
drome
Hypercellular, blasts
$ 20%, elevated pro-
monocytes
RAEB in transformation
(RAEBt)*
Similar to RAEB but
" 5% blasts
Blasts 20–30% (some
cells contain Auer
bodies)
* In theWHOclassification, the categoryRAEBtwouldbelong to thecategoryof acutemyeloid
leukemia.
Table 18 WHO classification of myelodysplastic syndromes
Disease* Dysplasia** Blasts in
peripheral
blood
Blasts in the
bonemarrow
Ring sidero-
blasts in the
bonemarrow
Cytogenetics
5q- syndrome Usually only E $5% $5% $15% 5q only
RA Usually only DysE $1% $5% $15% Variable
RARS Usually only DysE None $5% &15% Variable
RCMD 2–3 lines Rarely $5% $15% Variable
RCMD-RS 2–3 lines Rarely $5% &15% Variable
RAEB-1 1–3 lines $5% 5–9% $15% Variable
RAEB-2 1–3 lines 5–19% 10–19% $15% Variable
CMML-1 1–3 lines $5% $10% $15% Variable
CMML-2 1–3 lines 5–19% 10–19% $15% Variable
MDS-U 1 cell lineage None $5% $15% Variable
* RA= refractory anemia; RARS = refractory anemia with ring sideroblasts; RCMD= refractory
cytopenia with more than one dysplastic cell line; RCMD-RC= refractory cytopenia with more
thanonedysplastic lineageand ring sideroblasts; RAEB = refractory anemiawithelevatedblast
count; CMML= chronic myelomonocytic leukemia, persistent monocytosis (more than
1#109/l) in peripheral blood; MDS-U =MDS, unclassifiable. ** Dysplasia in granulopoie-
sis =Dys G, in erythropoiesis =DysE, in megakaryopoiesis =DysM, multilineage dys-
plasia = two cell lines