Acute Myeloblastic Leukemia without maturation -
Minimal maturation ( > 90% type I and II blasts
) of marrow nonerythroid cells is present. Most of the
blasts are agranular. Auer rods are infrequent.
Staining: Relatively few blasts (5-10%) are MPO
(myeloperoxidase) positive. A minimum of 3% MPO positive
blasts are required for diagnosis. NSE and PAS are generally
Immunophenotype: Variably positive for CD13, CD14,
CD11b, CD33, and HLA-DR.
Chromosome Abnormalities: t(9;22) Philadelphia
chromosome, 8+, -5, and -7.
**** 2SMD should be familiar with each of the major
types: M0-M7. The underlined phrases indicate the most
important material for 2SMD.****
Acute Myeloblastic Leukemia with maturation - FAB
M2 is the most common (20-40%) type of AML.
Maturation: Type II blasts are common and Auer
rods are frequent (promyelocytes-myelocytes).
Staining: The blasts are largely MPO positive. NSE
and PAS are generally negative.
Immunophenotype: Variable positivity for CD13,
CD33, and HLA-DR, but are negative for CD14 and CD11b.
Chromosome Abnormalities: t(8;21), 8+, -5, and
Cell Morphology: In some cases the immature cells
have abundant, frequently basophilic cytoplasm, with
variable numbers of often indistinct, sometimes coalescent
granules. If such immature cells are < 10% the diagnosis
is M1, but if > 10% the diagnosis becomes M2.
Acute Promyelocytic Leukemia (APL) - FAB
Maturation: In the classic M3 the majority of
the proliferating cells are abnormal promyelocytes with
numerous primary type granules. Auer rods are frequent and
Staining: The cells are MPO and chloroacetate
esterase (CAE) positive, but generally negative for NSE (NSE
positive in 25%).
Immunophenotype: Positivity for CD13 and CD33,
but are usually negative for HLA-DR.
Chromosome Abnormalities: The t(15;17) is
unique to promyelocytic leukemia.
Treatment Options: Why is it critical to
distinguish M3 from other myeloid leukemias?
Microgranular Variant: In the microgranular
variant, M3v, the leukemic cells have a monocytic appearance
with clefted angel-wing nuclei and abundant cytoplasm having
at best indistinct cytoplasmic granulation.
The cytochemical, immunophenotypic and chromosomal
features are indentical to the classic M3.
Both forms of acute promyelocytic leukemia are
associated with a high incidence of disseminated
intravascular coagulation (DIC) and hemorrhage.
Acute Myelomonocytic Leukemia (AMML) - FAB
Maturation: Differentiation along both myeloid
and monocytic lines. Monocytes and promonocytes
represent > 20%, but < 80% of the marrow
Staining: More than 20% of the blasts should be
MPO + and more than 20% should be NSE + .
High serum lysozyme (3x normal)
A peripheral monocytosis of > 5x10/L in
an otherwise M2 marrow and increased lysozyme
A peripheral monocytosis of >5 x10/L in
M2 marrow and >20% NSE + marrow
Chromosome Abnormalities: t(4;11), t(9;11), 8+ and
Variant: M4e variant in which eosinophils
(> 5%) are increased in number and abnormal associated
with abnormalities of chromosome 16.
Staining of Variant: CAE, usually negative in
eosinophils, is frequently positive in the abnormal
eosinophils of M4e.
Acute Monocytic Leukemia (AMoL) - FAB
M5a is the poorly differentiated
M5b is the well-differentiated
Chromosome Abnormalities: t(9;11), 8+, -5, and -7.
Chromosome abnormalities of 11q are closely associated with
Cell Morphology: Note the nuclear folds and the
relatively large nucleoli typical of monoblasts at
occasionally will see slight nuclear fold
few, large nucleoli
typically round nucleus
Acute Monocytic Leukemia (AMoL) - FAB
This is the M5a or poorly differentiated form of
acute monoblastic leukemia. >80% of cells are
Staining: The blasts in M5a are generally MPO
negative, but strongly positive for the nonspecific esterase
(NSE) and inhibited by Fluoride.
Acute Monocytic Leukemia (AMoL) - FAB
This is the M5b or differentiated form of acute
monoblastic leukemia in which > 80% of the leukemic
cells are monoblasts, promonocytes, and monocytes. Note the
large nucleoli so typical of monoblasts
Staining: The blasts of M5b usually contain some
peroxidase activity and, of course, are positive for
nonspecific esterase (NSE) and inhibited by
Acute Erythroblastic Leukemia - FAB M6
Maturation: M6 or erythroleukemia is rare and
difficult to diagnose. More than 50%* of the nucleated
marrow cells are abnormal nucleated red blood cells.
Morphology: The leukemic red cells are
frequently bizarre with extreme dysplastic features
including: giant forms, multinucleation, cytoplasmic
vacuolization, cytoplasmic buds, and megaloblastoid
* 30% considered adequate by some
(Ann Int Med 103:614,1985)
Staining: The blasts are MPO negative, but often
positive for NSE. The malignant red cells are PAS positive,
(forming PAS positive lakes or containing coarse chunks of
PAS positive material).
Immunophenotype:Positive for glycophorin
Chromosome Abnormalities: 8+, -5, del(5q), and
M7 blasts are often resemble lymphoblasts,
although M7 leukemias may be accompanied by atypical
megakaryocytes. The marrow is often fibrotic.
Staining: M7 blasts are MPO negative
and variably positive for PAS and NSE.
M7 blasts may have granular cytoplasm and shed
M7 blasts often clump together.
Diagnosis: Determination of an M7 subtype is
dependent on immunologic evidence or electron microscopic
ultracytochemical identification of platelet peroxidase
Immunophenotypic studies of M7 are positive for
glycoproteins GP Ib andGP IIb/IIIa.
Factor VIII related protein is usually found in the
Chromosome Abnormalities: t(1;22), have been
associated with M7 in infants.
Immunoperoxidase staining (brown) for Factor
VIII related protein identifies the blasts as being
of megakaryocyte lineage.
Myeloid Leukemia with Minimal Differentiation -
M0 is a recently defined FAB nonlymphoid leukemia
dependent on the immunologici dentification of myeloid
antigens. Morphologic and cytochemical studies show
Staining: M0 blasts are nondescript (no Auer rods)
and are MPO, PAS and NSE negative (<3%).
Electron microscopic ultracytochemical studies for
platelet peroxidase are negative.
Immunophenotype: M0 blasts are negative for B and
T lymphoid antigens, platelet glycoproteins GP Ib and GP
IIb/IIIa, and erythroid glycophorin A. Myeloid antigens such
as CD13, CD33 and CD11b are variably positive. CD34 and
HLA-DR are generally positive.
Chromosome Abnormalities: No particular
ADDITIONAL INFORMATION REGARDING LEUKEMIA:
Eosinophilic leukemia is a rare variant of acute
myeloid leukemia in which blasts and immature eosinophils
proliferate. CNS involvement appears to be common. Should be
distinguished from CML with large numbers of
Basophilic leukemia is a rare subset of AML
associated with t(6;9) and abnormal 12p. Ultrastructural
studies of the immature basophilic granules may be
necessary. Philadelphia chromosome positive cases may be
related to the blast crisis of CML.
Extramedullary myeloid cell tumor (EMCT) or
granulocytic sarcoma or chloroma is an extramedullary
tissue mass of blasts and immature myeloid cells. The
surface of a freshly cut EMCT turns light green (hence the
name chloroma) upon exposure to air as large amounts of
peroxidase are oxidized. EMCT may represent the initial
manifestation of acute leukemia or signal relapse. The blast
crisis of chronic myeloid leukemia may present as EMCT.
Masses of monoblasts as may be seen in M5 leukemias are also
sometimes referred to as EMCT.
The surface of this subcutaneous chloroma turned pale
green after exposure to air. The patient had been in
remission following Rx for AML.
Granulocytic sarcoma may represent the initial
manifestation of acute leukemia or signal relapse.
Acute myeloid leukemia may present as gum infiltrates,
especially in cases of acute myelomonocytic leukemia (FAB
M4) and monoblastic leukemia (FAB M5).
Blast crisis of chronic leukemia refers to a phase
of a chronic leukemia resembling an acute leukemia ( in
which blasts are >30%). In chronic myelogenous leukemia
(CML), blast crisis signals the terminal phase of the
disease for which there is no effective therapy.
Secondary (therapy-induced) acute leukemia is
nearly always myeloid and is usually preceeded by a
myelodysplastic syndrome involving all three hematopoietic
cell lines (panmyeloisis).
Abnormalities of chromosomes 5, 7, and 11 are common in
This is most common after alkylating chemotherapy or
radiation therapy, with an average latent period of 5 years
Hypocellular acute leukemia is a situation in
which the marrow cellularity (< 30%) often resembles
aplastic anemia, but with numerous (>30%) blasts in the
interstitium of the marrow. About 5-10% of acute myeloid
leukemias present in this form.
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