Careful examination of the peripheral blood smear is of
key importance to the diagnosis of leukemia. Most cases of acute
leukemia have blasts or immature cells in the peripheral blood.
Occasionally, patients present with no peripheral blasts (aleukemic
leukemia). Peripheral smears of chronic leukemias usually show
increased numbers of mature cells of a particular lineage (i.e.
myeloid or lymphoid).
You should look for other peripheral blood smear abnormalities
pertinent to a diagnosis of leukemia. Such abnormalities include
dimorphic RBCs and other evidence of dyserythropoiesis, hypogranular
neutrophils, acquired Pelger-Huet abnormality, increased nuclear
excresences, and abnormal platelets. These abnormalities are evidence
of myelodysplasia, a finding frequently associated with acute
Bone Marrow: Both bone marrow aspirate and biopsy are key parts of evaluating
a suspected leukemia patient. Because leukemia arises in the marrow,
the leukemic cells are generally most numerous and thus most easily
examined in marrow samples. In addition, one can evaluate any
remaining normal marrow elements.
Wright's stained marrow aspirate smears provide the best
cytologic view of the leukemic cells and provides material for
cytochemical staining. Using this method, cells are most clearly
identified and any cytoplasmic or nuclear abnormalities are recognized.
Leukemic cells for immunologic and genetic evaluation can be obtained
from either aspirate or biopsy specimens.
The biopsy provides the best evaluation of marrow celluarity
and of the pattern of marrow involvement by the proliferative
cells. In some leukemias marrow reticulin is increased, forming
a fine fibrous network enmeshing the cells. Sometimes this leads
to a dry "tap," or aspirate in which few if any cells are extracted
from the marrow. In such instances the biopsy is invaluable.
In most cases of leukemia the biopsy shows a diffuse infiltration
of the bone marrow by leukemic cells. The presence of > 30%
immature cells (blasts, promyelocytes) in the marrow is generally
regarded as the minimum required for a diagnosis of acute non-lymphoblastic
leukemia, (aka. AML). Normal bone marrow
contains 0-5% blasts.
While most leukemias result in a hypercellular marrow, cellularity
may be either hypo- or normal. Crucial to the diagnosis is the
abnormal increase in the number of blasts.
Once a diagnosis of acute leukemia is made based on the
morphologic findings, we need to determine the blast type to guide
us to an appropriate therapy. Determination of the blast type
is done by morphologic, cytochemical, immunologic, and chromosomal
& molecular genetic analyses.
Normal Bone Marrow
Marrow hematopoietic cellularity ranges from 30-70%. Fat cells
make up the remainder of the readily visible cells, though fibroblasts
and endothelial or sinus lining cells are also present.
Immature myeloid cells are located along the bone trabeculae,
with maturing neutrophils, eosinophils, etc., located more centrally,
or away from bone.
Erythroid and megakaryocytic elements are found in the central
areas, often near marrow sinuses. Erythroid precursors tend to
cluster in red cell islands.
Megakaryocytes are relatively few in number.
Lymphocytes, plasma cells, mast cells, and macrophages are scattered
about in small numbers.
Bone trabeculae are moderately thick and have only thin rims
of osteoid. Occasional osteoblasts and rare osteoclasts are seen
(osteoclasts & osteoblasts are common in children).
Normal bone marrow
Marrow examination generally entails a 500 cell differential
of all nucleated cells.
At left is a table of the approximate ranges for normal marrow
Morphological Evaluation of the Leukemias
The first and most important determination when deciding on chemotherapy
and prognosis, is to determine whether the blasts are myeloid
The morphology of the blasts yields strong evidence of the blast
lineage. Most of the time (probably >80%) one can accurately
predict the blast type from morphology alone. The key features
are the chromatin pattern and the character of the cytoplasm.
coarse chromatin which tends to aggregate into masses
fine delicate chromatin
more basophilic no azurophilic
granules no Auer rods may have non-specific cytoplasmic
less basophilic has primary azurophilic
granules may have Auer rods
Practice Question #1
A 57 year old woman complains of unexplained fatigue and small
bruises over her ankles and lower legs. The peripheral blood WBC
was normal. Platelets were severely decreased in number.
Her marrow aspirate results are shown at left.
What is the most important observation made from the aspirate?
Why is this important?
A. Decreased megakaryocytes
B. Normal numbers of myelocytes
C. Too little iron
D. Too many blasts
E. Decreased red cells
In cases where morphology
alone does not allow you to predict the blast type, other studies
can be used to help make this distinction. See the following sections
for a discussion of these various methods.
Under no circumstances should you share any material downloaded from Student Source course websites with individuals outside the class. Under no circumstances should you repost material downloaded from Student Source to other websites. Some of our pages are restricted to UVa School of Medicine users and require an Oasis account for access.