AML

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INTRODUCTIONThe term acute myeloid leukemia (AML, also known as acute myelogenous
leukemia and less commonly as acute non-lymphocytic leukemia) refers to a group of relatively
well-defined hematopoietic neoplasms involving precursor cells committed to the myeloid line of
cellular development (ie, those giving rise to granulocytic, monocytic, erythroid, or
megakaryocytic elements) (show figure 1).
AML is characterized by a clonal proliferation of myeloid precursors with a reduced capacity to
differentiate into more mature cellular elements. As a result, there is an accumulation of leukemic
blasts or immature forms in the bone marrow, peripheral blood, and other tissues, with a marked
reduction in the production of normal red blood cells, platelets, and mature granulocytes. The
increased production of malignant cells, along with reduction in these mature elements, result in a
variety of systemic consequences including anemia, bleeding, and an increased risk of infection.
(See "Pathobiology of acute myeloid leukemia").
The presenting signs and symptoms and diagnosis of AML will be reviewed in this topic. The
prognosis, cytogenetics, treatment, and complications of AML and issues related to one of the AML
variants, acute promyelocytic leukemia (AML-M3), are discussed separately. (See "Prognosis of
acute myeloid leukemia" and see "Cytogenetics in acute myeloid leukemia" and see "Induction
therapy for acute myeloid leukemia in younger adults" and see "Treatment of acute myeloid
leukemia in older adults" and see "Complications of acute myeloid leukemia" and see "Clinical
manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults").
EPIDEMIOLOGYAML is the most common acute leukemia in adults and accounts for
approximately 80 percent of cases in this group [1]. In the United States, the incidence has been
stable at 3 to 5 cases per 100,000 population. In contrast, AML accounts for less than 10 percent
of acute leukemias in children less than 10 years of age. In adults, the median age at diagnosis is
60 to 65 years. The incidence increases with age with approximately 1.3 and 12.2 cases per
100,000 population for those under or over 65 years, respectively. The male:female ratio is
approximately 5:3.
AML has been associated with environmental factors (eg, exposure to chemicals, radiation, or
chemotherapy drugs) and genetic abnormalities (eg, trisomy 21, trisomy 8, Fanconi's anemia,
Bloom's syndrome). Details regarding these associations and the pathogenesis of AML are
presented separately. (See "Pathobiology of acute myeloid leukemia" section on Multistep and

Last literature review for version 17.2: Maio 1, 2009 | This topic last updated: Junho
16, 2009
Clinical manifestations, pathologic features, and
diagnosis of acute myeloid leukemia
Author
Charles A Schiffer, MD
John Anastasi, MD
Section Editor
Richard A Larson, MD
Deputy Editor
Rebecca F Connor, MD
Page 1 of 34 Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia
08/11/2009 http://www.uptodate.com/online/content/topic.do?topicKey=leukemia/15783&view=print
multicausal pathogenesis of AML)
CLINICAL PRESENTATIONPatients with AML generally present with symptoms related to
complications of pancytopenia (eg, anemia, neutropenia, and thrombocytopenia), including
weakness and easy fatigability [2], infections of variable severity, and/or hemorrhagic findings
such as gingival bleeding, ecchymoses, epistaxis, or menorrhagia. Combinations of these
symptoms are common.
General fatigue is present in the majority of patients and often precedes the diagnosis for a
number of months.
Pallor and weakness are common and attributed to the anemia.
Bone pain is infrequent in adults with AML, although some individuals describe sternal
discomfort or tenderness, occasionally with aching in the long bones. This may be especially
severe in the lower extremities, due to expansion of the medullary cavity by the leukemic
process.
It is generally difficult to date the onset of AML precisely, at least in part because individuals have
different symptomatic thresholds for choosing to seek medical attention. It is likely that most
patients have had more subtle evidence of bone marrow involvement for weeks, or perhaps
months, before diagnosis. This can sometimes make the distinction between de novo leukemia
and leukemia associated with a prior hematologic disorder such as a myelodysplastic syndrome
(MDS) somewhat arbitrary. As an example, it is not uncommon for a patient to present with AML
and to find evidence of a possible undiagnosed and asymptomatic MDS from blood counts
obtained months to years earlier.
FeverIf fever is present, it is almost always related to infection; as such, fever should always
prompt a thorough investigation of potential infectious site and trigger an immediate empiric
administration of broad spectrum antibiotics. A small minority of patients has fever related solely
to the underlying leukemia, which abates with appropriate chemotherapy; this phenomenon may
be more common in patients with acute promyelocytic leukemia [3]. (See "Clinical manifestations,
pathologic features, and diagnosis of acute promyelocytic leukemia in adults").
SkinExamination of the skin can reveal pallor secondary to anemia, petechiae or ecchymoses
secondary to thrombocytopenia or disseminated intravascular coagulation, or infiltrative lesions
suggestive of leukemic involvement (leukemia cutis or myeloid sarcoma). Leukemic involvement
of the skin occurs in up to 13 percent of patients and is most often found in patients with AML with
a prominent monocytic or myelomonocytic component (show figure 3) [4]. The lesions are often
nodular and violaceous/gray-blue in color. Cutaneous sites of infection may be either primary or
embolic.
The presence of erythematous to violaceous tender nodules and plaques suggests the presence of
acute neutrophilic dermatosis (eg, Sweets syndrome). (See "Neutrophilic dermatoses", section on
Sweet's syndrome and see "Cutaneous manifestations of internal malignancy", section on
Vasculitis).
EyesExamination of the ocular fundus reveals hemorrhages and/or whitish plaques in the
majority of patients. The conjunctivae may be pale, according to the magnitude of the anemia,
although the sensitivity and clinical value of this finding are highly variable. (See "Complications of
acute myeloid leukemia", section on Ocular involvement and see "Approach to the adult patient
with anemia", section on Physical examination).
Central nervous systemThe incidence of central nervous system (CNS) involvement at the
time of diagnosis is unknown since routine evaluation in patients without symptoms is not
recommended. Clinically overt CNS involvement developing throughout the entire course of
treatment is uncommon, perhaps related to the administration of high dose cytarabine as post-
remission therapy [5]. CNS involvement may be more common in patients with AML with a
prominent monocytic component (eg, acute monocytic leukemia or acute myelomonocytic
leukemia), hyperleukocytosis, and patients under two years [6,7]. Patients with CNS involvement
may be asymptomatic or complain of headache, cranial nerve palsies, or visual changes.
OropharynxCareful examination of the oropharynx and teeth may reveal leukemic
involvement (eg, gingival hypertrophy, especially in the monocytic subtypes (show photograph 1)
[8]), oral candidiasis, or herpetic lesions. A dental examination should be included in the
pretreatment evaluation so that effective dental prophylaxis (eg, extractions) can be performed, if
time permits, prior to beginning chemotherapy [9].
OrganomegalyPalpable adenopathy is uncommon in patients with AML and significant lymph
node enlargement is rare. Similarly, marked degrees of hepatomegaly and splenomegaly are
uncommon and, if found, may suggest the possibility of acute lymphoblastic leukemia or evolution
of AML from a prior myeloproliferative disorder (eg, blast crisis of chronic myelogenous leukemia).
JointsApproximately 4 percent of patients with AML can present with symmetric or migratory
polyarthritis/arthralgia as well as bone pain and tenderness. However, multiple causes of joint
disease might be present in an AML patient, particularly when one or more joints are involved.
These might include gout, pseudogout, infection, and/or direct synovial infiltration with leukemic
cells. Joint disease in AML is discussed separately. (See "Malignancy and rheumatic disorders",
section on Leukemia, and see "Complications of acute myeloid leukemia", section on Joint
involvement and see "Evaluation of the adult with monoarticular pain").
Myeloid sarcomaOccasional patients will present with prominent extramedullary disease (ie,
myeloid sarcoma, also called granulocytic sarcoma, myeloblastoma, or chloroma). Extramedullary
disease may present simultaneously with or precede bone marrow disease. When found in
association with blood or bone marrow involvement, it occurs most commonly as either cutaneous
or gingival infiltration by leukemic cells, and is most often seen when there is a prominent
monocytoic component to the leukemia (eg, in acute monocytic or monoblastic leukemia or in
acute myelomonocytic leukemia). Sites of isolated myeloid sarcome include bone, periosteum, soft
tissues, lymph nodes, and lymph nodes, and less commonly the intestine, mediastinum, epidural
region, uterus, and ovary [10-14]. Myeloid sarcoma should always be considered in the differential
diagnosis of a "small round blue cell tumor," and should be more seriously suspected if
eosinophilic myelocytes are seen on hematoxylin and eosin-stained biopsies. The definitive
diagnosis rests on identifying the tumor cells as myeloid with the use of myeloperoxidase or
lysozyme staining, flow cytometry, or immunophenotyping from tissue sections [10,13]. (See
"Diagnosis" belowSee "Diagnosis" below).
It is important to note that the approach to treatment of patients with myeloid sarcoma without
evidence of AML on bone marrow biopsy is similar to that for patients with overt AML [15]. (See
"Induction therapy for acute myeloid leukemia in younger adults").
Differential diagnostic considerations for myeloid sarcoma include extramedullary blast crisis of
chronic myelogenous leukemia (CML), or the acute leukemic transformations of other chronic
disorders such as other myeloproliferative neoplasms, particularly primary myelofibrosis. Careful
review of the patient's history and correlation with other findings in the blood and bone marrow
will make these apparent.
PATHOLOGIC FEATURESAlthough a presumptive diagnosis of AML can be made via
examination of the peripheral blood smear when there are circulating leukemic blasts, a definitive
diagnosis usually requires an adequate bone marrow aspiration and biopsy. Occasional patients
may have a "dry tap" on aspiration, due to the presence of a hypercellular marrow packed with
blasts, or extensive fibrosis. An adequate bone marrow biopsy with touch preparations should
provide sufficient material for diagnostic purposes in situations when the marrow cannot be
aspirated. Bone marrow necrosis may be seen in highly aggressive AML variants. If excessive
necrosis is present, the diagnosis must be made from the findings in the peripheral blood or if
inadequate for diagnosis, another bone marrow biopsy site must be considered. (See "Evaluation
of bone marrow aspirate smears", section on Sample preparation).
Despite the presence of neutropenia, thrombocytopenia, and/or coagulopathy, it is unusual to
have bleeding or infection develop at the site of marrow aspiration/biopsy as a complication of the
procedure. The preferred biopsy location in adults is the posterior superior iliac crest and spine,
although a different site should be used if the patient has received prior irradiation to this area.
The sternum is a reasonable alternative site for bone marrow aspiration, although bone marrow
biopsy cannot be performed at this site. (See "Bone marrow aspiration and biopsy: Indications
and technique", section on Choice of aspiration or biopsy site).
It is important that the laboratory be notified at the time of the procedure, as multiple studies
need to be performed on the freshly-obtained specimen. Appropriate handling of the specimen
includes:
Preparation of multiple marrow aspirate smears for Wright or Wright-Giemsa staining (used
for subsequent differential count), and for additional cytochemical reactions (eg, myeloperoxidase
reaction and non-specific esterase reactions). Iron staining is also performed on a marrow
aspirate smear and could be useful for the identification of ring sideroblasts in AML with
myelodysplastic features.
Submission of the biopsy for appropriate fixation, decalcification, and tissue sectioning, and
for subsequent staining with hematoxylin and eosin, reticulin, and for additional
immunohistochemical or cytochemical stains, if required.
Submission of marrow aspirate for cytogenetic and molecular genetic analysis.
Submission of the aspirate for cultures which should be done only if there is suspicion of
infection caused by mycobacteria, yeast, or fungi.
Morphologic, cytochemical or immunophenotypic, and cytogenetic and molecular studies must be
performed in every case. Information derived from these studies is important for the diagnosis,
and also for the subclassification of the process. The selection of treatment modality and an
accurate prognosis are strongly dependent upon information derived from these studies.
Peripheral bloodAnalysis of the peripheral blood at presentation usually reveals a normocytic,
normochromic anemia that can vary in severity. The reticulocyte count is normal or decreased.
Approximately 75 percent of patients have platelet counts below 100x10(9)/L (100,000/microL) at
diagnosis, and about 25 percent will have counts below 25x10(9)/L (25,000/microL). Both
morphologic and functional platelet abnormalities may be seen.
The median leukocyte count at diagnosis is approximately 15x10(9)/L (15,000 cells/microL); 20
percent of patients have a leukocyte count above 100x10(9)/L (100,000 cells/microL) and 25 to
40 percent of patients have a leukocyte count less than 5x10(9)/L (5,000 cells/microL). The vast
majority of patients (95 percent) will have circulating myeloblasts that can be detected on the
peripheral smear. There may or may not be evidence of myelodysplasia.
Myeloblasts are immature cells with large nuclei, prominent nucleoli, and a variable amount of
dark blue cytoplasm after staining with Wright Giemsa. The nuclear to cytoplasmic ratio is high
and the morphology varies depending upon the maturity of the cell. Auer rods, which are
pathognomonic of myeloblasts, vary in frequency depending upon the AML subtype (show table
1A-1B). They can be identified as pink/red rod-like granular structures in the cytoplasm (show
blood smear 1).
A myeloperoxidase reaction is easy to perform, can be done in less than a few minutes, and is a
simple means of determining if the blasts are myeloid. Absence of a reaction product does not rule
out AML as some cases are negative (see "AML not otherwise specified" below).
Flow cytometry of the peripheral blood can identify circulating myeloblasts in the majority of
patients by characteristic patterns of surface antigen expression (show table 3) [16]. The specific
pattern seen differs among the AML subtypes, but the majority of cases express CD34, HLA-DR,
CD117, CD13, and CD33. Generally myeloblasts do not express T or B cell antigens, but in some
cases they do. Care must be taken in interpreting the antigen profile, and in distinguishing AML
from ALL or from acute leukemias with ambiguous lineage (ie, biphenotypic leukemias) [16].
Bone marrow biopsy and aspirate
Blast countBone marrow aspiration and biopsy (usually unilateral) is a key component to
the diagnosis of AML. The bone marrow is usually hypercellular due to a partial or almost total
replacement of the normal cellular components of the marrow by immature or undifferentiated
cells.
The bone marrow biopsy gives a general overview of the degree of involvement and specific
histologic features associated with the process (eg, fibrosis, necrosis). The aspirate provides
material for a 500 cell differential count to determine the percentage of blasts in the marrow; it
also provides for detailed cytologic evaluation of the blasts and other cells which may be residual
normal hematopoietic elements or abnormal cells maturing from the blasts.
Cell originThe blasts in AML must be identified as cells of the myeloid, monocytic,
erythroid, or megakaryocytic lineage and are distinguished from blasts of the lymphoid lineage
seen in acute lymphoblastic leukemia (ALL). The non-lymphoid lineage of the AML blasts can be
identified by any of the following:
The presence of an Auer rod on microscopy (show blood smear 1).
Cytochemical studies demonstrating positivity for sudan black B, myeloperoxidase,
chloroacetate esterase, or nonspecific esterase (show table 1A-1B and show table 3) [17].
Flow cytometry identifying the expression of myeloid antigens. It is notable that up to 20
percent of acute leukemias will demonstrate biphenotypic or mixed lineage with expression of
both myeloid and lymphoid markers.
Specific cytogenetic abnormalities that are seen only in myeloid leukemias.
Evolving techniques include proteomics and gene expression profiling (GEP) (show figure 2). GEP
in particular has shown great value for the diagnosis and classification, as well as prognosis in
AML. This is discussed in more detail separately. (See "Overview of gene expression profiling and
proteomics in clinical oncology", section on Acute leukemia).
Bone marrow infiltrationThe bone marrow biopsy of patients with AML is infiltrated with a
monotonous leukemic (blast) population. In the current WHO classification system, blast forms
must account for at least 20 percent of the total cellularity [18]. Exceptions to this include
leukemias with the following genetic abnormalities which are considered diagnostic of AML without
regard to the blast count:
AML with t(8;21)(q22;q22); RUNX1-RUNX1T1
AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CEFB-MYH11
APL with t(15;17)(q22;q12); PML-RARA
The presence of a myeloid sarcoma is also diagnostic of AML independent of the blast count. Of
note, the previous French, American, and British (FAB) classification system used a blast percent
cutoff value of 30 percent to define AML. Patients with blast counts between 20 and 30 percent
had previously been classified as refractory anemia with excess blasts in transformation. (See
"Evaluation of bone marrow aspirate smears", section on Estimation of cellularity and myeloid to
erythroid ratio).
Cytogenetic featuresAll patients with suspected AML should undergo cytogenetic analysis
of their bone marrow biopsy specimen. Approximately 35 to 50 percent of patients with newly
diagnosed AML will demonstrate cytogenetic abnormalities.
A combination of conventional karyotypic analysis plus reverse transcriptase polymerase chain
reaction (RT-PCR) or fluorescent in situ hybridization (FISH) for specific abnormalities can aid in
the diagnosis, treatment, and post-treatment monitoring of patients with AML:
Certain AML subtypes are defined by recurrent cytogenetic abnormalities (show table 4). (See
"AML with recurrent cytogenetic translocations" below and see "Clinical manifestations, pathologic
features, and diagnosis of acute promyelocytic leukemia in adults").
Karyotype is one of the main determinants of prognosis in AML and is often used to choose
the appropriate post-remission therapy. (See "Post-remission therapy for acute myeloid leukemia
in younger adults" and see "Prognosis of acute myeloid leukemia" and see "Treatment of acute
myeloid leukemia in older adults", section on Unfavorable cytogenetics).
Identified cytogenetic abnormalities can also be used to monitor for minimal residual disease
after treatment if a RT-PCR or FISH probe is available for the abnormality. (See "Cytogenetic and
molecular genetic diagnostic tools" and see "Remission criteria in acute myeloid leukemia and
monitoring for residual disease", section on Significance of residual disease).
Molecular studiesAbnormalities in certain genes (eg, mutations in FLT3, nucleophosmin-
NMP, KIT,CEBPA) as well as gene expression profiles confer prognostic significance in adult
patients with AML and are now considered as provisional entities in the WHO classification.
DIAGNOSISThe diagnosis of AML requires both of the following:
Documentation of bone marrow infiltration Blast forms must account for at least 20 percent
of the total cells of the bone marrow aspirate (from a 500 cell differential count). Exceptions to
this include leukemias with certain genetic abnormalities such as those with t(8;21), inv(16), or t
(16;16) and myeloid sarcoma which are considered diagnostic of AML without regard to the blast
count. In addition, acute promyelocytic leukemia and acute erythroleukemia have different
diagnostic criteria (see "Bone marrow infiltration" above and see "WHO classification" below).
The leukemic cells must be of myeloid origin as demonstrated by either the presence of Auer
rods, cytochemical positivity for myeloperoxidase, or presence of sufficient myeloid markers
recognized by immunophenotyping (see "Cell origin" above).
DIFFERENTIAL DIAGNOSISEntities in the differential diagnosis of AML include those where:
The blast count is borderline at approximately 20 percent (eg, in myelodysplastic or
myelodysplastic/myeloproliferative syndromes); blasts can be elevated in regenerating bone
marrow after chemotherapy or those altered by growth factor effect.
The blasts are difficult to demonstrate as being myeloid (eg, ALL with co-expression of
myeloid markers, in biphenotypic leukemias, and in non-hematopoietic tumors (perhaps most
commonly small cell carcinomas of the lung) where cells infiltrating the marrow are not available
for full immunophenotyping.
Erythroid elements are prominent and mimic erythroleukemia (eg, vitamin B12 and folate
deficiency).
There are 20 percent or more blasts that are clearly myeloblasts but which actually represent
transformations of other chronic myeloid disorders (eg, chronic myelogeneous leukemia in blast
crisis, or myeloproliferative or myelodysplastic neoplasms transforming to AML).
It is critical to distinguish AML from chronic myelogeneous leukemia (CML) in blast crisis due to
the importance of tyrosine kinase inhibitors in the treatment of the latter. AML transforming from
myelodysplastic syndrome (MDS) is still considered AML, but in those transforming from other
myeloproliferative or myelodysplastic/myeloproliferative neoplasms, it may be useful to know that
the acute disease arose from an underlying chronic entity.
WHO CLASSIFICATIONAML is classified using the WHO classification system based upon a
combination of morphology, immunophenotype, genetic features, and clinical features. The
classification attempts to identify biologic entities in the hopes that future work will elucidate
molecular pathways which might be amenable to targeted therapies.
There are four main groups of AML recognized in this classification system:
AML with recurrent cytogenetic translocations
AML with myelodysplasia-related features
Therapy-related AML and MDS
AML, not otherwise specified
AML with recurrent cytogenetic translocationsThis WHO category contains AML variants
that contain genetic abnormalities of prognostic significance:
AML with t(8;21)(q22;q22); RUNX1-RUNX1T1 This leukemia may not have 20 percent
blasts, but can be identified if the cytogenetic abnormality is present. It typically has associated
morphologic features that can suggest its diagnosis. These include blasts with long thin Auer rods,
and maturation of the blasts to abnormal mature granulocytic elements with salmon colored
cytoplasm with blue rims, and cytoplasmic globules, or Chediak-Higashi-like granules. This
leukemia frequently has myeloid markers, but can also express CD19 and CD56. The leukemia is
associated with a good prognosis but surprisingly can have transcripts of the RUNX1-RUNX1T1
detected by RT-PCR even in patients who have been in remission for many years.
AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CEFB-MYH11 (previously acute
myelomonocytic leukemia, AMML, FAB M4Eo) (show bone marrow 6 and show bone marrow 7)
This leukemia occurs in younger patients and can present as an extramedullary myeloid sarcoma.
It is associated with a good prognosis although some cases with an additional c-KIT mutation may
do more poorly.
APL with t(15;17)(q22;q12); PML-RARA This subtype is discussed in more detail in a
separate section. It is notable that the malignant cells in APL are promyelocytes, making this
another AML where the presence of 20 percent blasts is not required. (See "Clinical
manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults").
AML with t(9;11)(p22;q23); MLLT3-MLL This type of leukemia is usually monocytic and
more common in children. It can present with disseminated intravascular coagulation (DIC), and
high white cell counts with gingival or skin infiltration. It has an intermediate prognosis.
AML with t(6;9)(p23;q34); DEK-NUP214 This is a rare type of leukemia which is associated
with basophilia, pancytopenia, and dysplasia. It has a generally poor prognosis.
AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1 This leukemia is also rare,
accounting for only 1 or 2 percent of cases. Patients are anemic but may have normal or elevated
platelet counts. It is frequently associated with dysplasia and is associated with aggressive
disease and a short survival time.
AML (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1 This type of leukemia is also
rare, but is typically a megakaryoblastic process occurring in infants, although it is not seen in
patients with Down Syndrome. Sometimes it can present as a mass and mimic sarcoma.
Two provisional entities identified at the molecular level are:
AML with mutated NPM1 Leukemias with mutations of NPM1 are considered as a provisional
entity. The mutation is seen in about one-third of all cases of AML making it overlap other types,
and thus, not a unique group. In 50 percent of cases, the mutation is seen in AML with normal
cytogenetics. The presence of the NPM1 mutation confers a better prognosis, but only if it is seen
alone. When seen in conjunction with mutations in FLT3, it is associated with a poor prognosis.
AML with mutated CEBPA Mutation in CEBPA are seen in about 6 to 15 percent of AML,
commonly in cases with a normal karyotype. Cases with this mutation are associated with a good
prognosis.
AML with MDS-related featuresAML with myelodysplastic related features (previously called
AML with multilineage dysplasia) is defined by cases which fit the criteria for a diagnosis of AML
(20percentblasts),donothaveahistoryofpriorcytotoxictherapyforanunrelateddisease,
and generally have a poor prognosis. Cases must have any of the following three characteristics
that are related to myelodysplasia [19,20]:
AML that evolves from previously documented myelodysplastic syndrome (MDS). (See
"Clinical manifestations and diagnosis of the myelodysplastic syndromes").
AML that demonstrates MDS-related cytogenetic abnormalities (eg, monosomy 5 or del(5q),
monosomy 7 or del(7q), isochromosome 17p, etc).
AMLwithmorphologicallyidentifiedmultilineagedysplasiadefinedasdysplasiapresentin50
percent of cells in two or more hematopoietic lineages.
The following are examples of dysplastic changes that may be seen in AML with MDS-related
features:
Dysplastic neutrophils may have hypogranular cytoplasm, hyposegmented nuclei (eg, pseudo-
Pelger-Huet anomaly), or bizarrely segmented nuclei.
Dysplastic erythrocytes demonstrate megaloblastoid change, karyorrhexis, nuclear
irregularity, nuclear fragmentation, multinucleation, ring sideroblasts, cytoplasmic vacuoles, or
periodic acid-Schiff positivity.
Dysplastic megakaryocytes include those that are small (ie, micromegakaryocytes) or those of
normal to large size with non-lobulated or multiple nuclei.
Therapy-related AMLThe diagnosis of therapy-related myeloid neoplasm (t-MN) is made
when evaluation of the peripheral blood and bone marrow demonstrates morphologic,
immunophenotypic, and cytogenetic changes consistent with the diagnosis of AML, MDS, or
MDS/MPN in a patient with prior exposure to cytotoxic agents. Details on the diagnosis and
treatment of t-AML are presented separately. (See "Therapy-related myeloid neoplasms: Acute
myeloid leukemia and myelodysplastic syndrome").
AML not otherwise specifiedCases of AML that do not meet the criteria for the categories
described above are classified as AML, not otherwise specified (NOS). These cases are further
subclassified by morphology that is similar to that used in the previous French, American, and
British (FAB) classification system (show table 1A-1B and show table 4) [19,21]:
AML with minimal differentiation (FAB M0, <5 percent of cases). These blast cells are
usually medium sized with a round or minimally indented nucleus, dispersed nuclear chromatin,
and one or two nucleoli (show bone marrow 1) [22-24]. There are no cytoplasmic granules or
Auer rods and they cannot be differentiated from ALL (ie, FAB L2 blasts) based upon morphology
alone. The blasts are negative for the myeloperoxidase (MPO) or sudan black B (SBB) reactions,
but are considered myeloid due to the presence of myeloid associated markers. Most cases
express antigens of early hematopoiesis (eg, CD34, CD38, HLA-DR) and the myeloid antigens
CD13, CD117, and CD33. They lack antigens of more mature myeloid differentiation such as
CD14, CD15, CD11b, and CD64.
AML without maturation (equivalent to FAB M1, 5 to 10 percent of cases). These blasts are
large cells with a high nuclear:cytoplasmic ratio with grayish blue cytoplasm and a nucleus
containing one to two distinct nucleoli (show bone marrow 2). Unlike AML with minimal
differentiation, at least 3 percent of the blasts stain for MPO and/or SBB and some cases may
demonstrate azurophilic granules and/or Auer rods. Many cases express antigens of early
hematopoiesis (eg, CD34, CD38, HLA-DR), but also express one or more myeloid-associated
antigens (eg, CD13, CD33, CD117). Markers of granulocytic maturation (eg, CD15, CD65) are not
expressed in most cases.
AML with maturation (equivalent to FAB M2, 10 percent of cases). The bone marrow
contains blasts with and without azurophilic granules (show bone marrow 3). Auer rods are
common. At least 10 percent of the bone marrow cells are promyelocytes, myelocytes, and/or
mature neutrophils. Eosinophil precursors, basophils, and mast cells may be increased. A fraction
of blasts may express antigens of early hematopoiesis (eg, CD34, CD38, HLA-DR), but the
majority of cells express myeloid-associated antigens (eg, CD13, CD33, CD65, CD11b, and
CD15). Monocytic markers (eg, CD14, CD64) are usually negative.
Acute myelomonocytic leukemia (equivalent to FAB M4, 5 to 10 percent of cases). This
leukemia has at least 20 percent blasts but, in addition, has a significant monocytic component,
with monocytes accounting for at least 20 percent of the marrow cells. The monocytes can be
recognized morphologically or with the help of non-specific esterase reactions, or by flow
immunophenotyping.
Acute monoblastic and monocytic leukemia (equivalent to FAB M5, <5 percent of cases
each). The marrow is composed of an admixture of monoblasts, promonocytes, and monocytes
with a minor percentage of neutrophils (show bone marrow 6). Promonocytes are considered blast
equivalents for determining the blast percentage. Auer rods are rare and hemophagocytosis may
be present.
The terms monoblastic and monocytic leukemia are used depending upon the predominant
component:
Monoblasts are large with abundant moderately to intensely basophilic cytoplasm which may
demonstrate pseudopod formation, scattered fine azurophilic granules, and vacuoles. Nuclei are
round with delicate lacy chromatin and one or more large prominent nucleoli (show blood smear
2).
Promonocytes are large with less basophilic and sometimes more obviously granulated
cytoplasm with occasional large azurophilic granules and vacuoles. The nucleus is irregular with a
delicately convoluted configuration (show blood smear 3 and show bone marrow 8) [25].
Almost all cases express the HLA-DR antigen of early hematopoiesis. Myeloid antigens are variably
expressed and there is usually expression of at least two markers of monocytic differentiation (eg,
CD14, CD4, CD11b, CD11c, CD64, CD68, CD36, and lysozyme).
Acute erythroid leukemia (FAB M6, erythroleukemia, or DiGuglielmo's disease, <5 percent).
Two types of this leukemia are recognized, the erythroid/myeloid type and the "pure" type.
- In the erythroid/myeloid type, erythroid precursors account for more than 50 percent of the
marrow elements and blasts account for more than 20 percent of the non erythroid forms. The
bone marrow is composed of erythroid precursors of all stages of maturation, often with a shift
towards immaturity. Dysplastic changes are present with features of nuclear atypia, gigantism and
multinucleation, admixed with myeloblasts (show bone marrow 9).
- In the "pure" form, erythroblasts, primarily at the pronormocyte stage predominate.
Sometimes they have vacuolization in the cytoplasm.
The erythroblasts do not express markers of myeloid lineage and do not stain with MPO. They may
express CD117 and do react with antibodies to hemoglobin A and glycophorin. It is notable that
cases with prominent dysplasia might better be classified into the AML with myelodysplastic-
related features category. They typically have myelodysplastic associated cytogenetic changes as
well.
Acute megakaryoblastic leukemia (FAB M7, <5 percent). The bone marrow is comprised of
at least 20 percent blasts of which at least half are of megakaryocyte lineage [26-28]. Bone
marrow fibrosis and a leuko-erythroblastic blood picture without splenomegaly (previously called
"acute myelofibrosis") may be present. Megakaryoblasts are differentiated from other blasts by
virtue of either maturation to cells resembling normal megakaryocytes, or by special staining for
the megakaryocytic markers CD41 or CD61 or for the products of megakaryocytes, such as von
Willebrand factor or platelet type glycoproteins. Megakaryoblasts are medium to large cells with
basophilic, often agranular cytoplasm which may have distinct blebs or pseudopod formation. The
nucleus is round, slightly irregular or indented with fine reticular chromatin and one to three
nucleoli (show bone marrow 10). The megakaryoblasts are consistently negative for MPO, SBB,
and naphthyl-ASD-chloroacetate esterase.
Acute megakaryoblastic leukemia in infants and children may be associated with the presence of t
(1;22) [29], and Down syndrome (trisomy 21) [30], and in adults with a high incidence of an
antecedent hematologic disorder, myelodysplastic syndrome, and/or prior chemotherapy [28].
(See "Clinical features and diagnosis of Down syndrome" section on Acute megakaryoblastic
leukemia (AKML)).
Those with t(1;22) are classified into the group with recurring genetic abnormalities, and those
associated with Down syndrome are classified separately. Like erythroleukemia, many cases of
megakaryoblastic leukemia in adults have prominent dysplasia and might better be classified into
the AML with myelodysplastic-related features category. They also typically have myelodysplastic
associated cytogenetic changes.
Acute basophilic leukemia (<1 percent). Blasts are of medium size with moderately
basophilic cytoplasm containing a variable number of coarse basophilic granules that have
metachromatic positivity with toluidine blue. The nucleus is oval, round or bilobed with dispersed
chromatin and one to three prominent nucleoli and a high nuclear to cytoplasmic ratio. Dysplastic
features may be present. Blast cells express myeloid markers (eg, CD13, CD33), CD123, CD203c,
and CD11b, but do not express other monocytic markers. They are negative for CD117. Care
should be taken not to mistake a case of acute basophilic leukemia for chronic myelogenous
leukemia (CML) or CML in blast crisis, as CML typically has increased basophils. If the t(6;9) is
identified, the case is best classified in the group with recurrent cytogenetic abnormalities. (See
"AML with recurrent cytogenetic translocations" above).
Acute panmyelosis with myelofibrosis (extremely rare). Bone marrow is hypercellular and
diffusely fibrotic with increased erythroid, granulocytic, and megakaryocytic precursors.
INFORMATION FOR PATIENTSEducational materials on this topic are available for patients.
(See "Patient information: Acute myeloid leukemia (AML) treatment in adults"). We encourage you
to print or e-mail this topic, or to refer patients to our public web site,
www.uptodate.com/patients, which includes this and other topics.
SUMMARY
PresentationAcute leukemia should be suspected in a patient presenting with varying
combinations of the following (see "Clinical presentation" above):
Signs and symptoms suggestive of anemia (eg, shortness of breath, dyspnea on exertion,
pallor), excess bleeding or bruising, and infection
A marked reduction in red cells, platelets, and mature neutrophils on a complete blood count
Accumulation of leukemic forms in the peripheral blood, bone marrow, and/or other tissues
DiagnosisAcute myeloid leukemia (AML) is diagnosed by bone marrow biopsy using
morphogic, cytochemical, immunophenotypic, and cytogenetic/molecular analysis (see "Diagnosis"
abovesee "Diagnosis" above):
Blast forms must account for at least 20 percent of the total cellularity of the bone marrow
biopsy sample. Exceptions to this include leukemias with certain genetic abnormalities or myeloid
sarcoma, which are considered diagnostic of AML without regard to the blast count. (See "Bone
marrow infiltration" above).
The blast forms must be identified as cells of the myeloid, as distinct from the lymphoid
lineage. (See "Cell origin" above).
AML should be classified into the appropriate subtypes, according to the current WHO classification
scheme. The subtype is important to help select appropriate therapy in some instances, to provide
prognostic information, and in the future to help clarify underlying molecular pathogenesis so that
improved therapies might be developed. (See "WHO classification" above).

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REFERENCES

1. Yamamoto, JF, Goodman, MT. Patterns of leukemia incidence in the United States by
subtype and demographic characteristics, 1997-2002. Cancer Causes Control 2008; 19:379.
2. Meyers, CA, Albitar, M, Estey, E. Cognitive impairment, fatigue, and cytokine levels in
patients with acute myelogenous leukemia or myelodysplastic syndrome. Cancer 2005;
104:788.
3. Daly, PA, Schiffer, CA, Wiernik, PH. Acute promyelocytic leukemia--clinical management of
15 patients. Am J Hematol 1980; 8:347.
4. Ratnam, KV, Khor, CJ, Su, WP. Leukemia cutis. Dermatol Clin 1994; 12:419.
5. Castagnola, C, Nozza, A, Corso, A, Bernasconi, C. The value of combination therapy in adult
acute myeloid leukemia with central nervous system involvement. Haematologica 1997;
82:577.
6. Cassileth, PA, Sylvester, LS, Bennett, JM, Begg, CB. High peripheral blast count in adult
acute myelogenous leukemia is a primary risk factor for CNS leukemia.J Clin Oncol 1988;
6:495.
7. Dekker, AW, Elderson, A, Punt, K, Sixma, JJ. Meningeal involvement in patients with acute
nonlymphocytic leukemia. Incidence, management, and predictive factors. Cancer 1985;
56:2078.
8. Blum, W, Mrozek, K, Ruppert, AS, et al. Adult de novo acute myeloid leukemia with t(6;11)
(q27;q23): results from Cancer and Leukemia Group B Study 8461 and review of the
literature. Cancer 2004; 101:1420.
9. Williford, SK, Salisbury, PL 3d, Peacock, JE Jr, et al. The safety of dental extractions in
patients with hematologic malignancies. J Clin Oncol 1989; 7:798.
10. Yamauchi, K, Yasuda, M. Comparison in treatments of nonleukemic granulocytic sarcoma:
report of two cases and a review of 72 cases in the literature. Cancer 2002; 94:1739.
11. Byrd, JC, Edenfield, WJ, Shields, DJ, Dawson, NA. Extramedullary myeloid cell tumors in
acute nonlymphocytic leukemia: a clinical review. J Clin Oncol 1995; 13:1800.
12. Neiman, RS, Barcos, M, Berard, C, et al. Granulocytic sarcoma: a clinicopathologic study of
61 biopsied cases. Cancer 1981; 48:1426.
13. Paydas, S, Zorludemir, S, Ergin, M. Granulocytic sarcoma: 32 cases and review of the
literature. Leuk Lymphoma 2006; 47:2527.
14. Choi, EK, Ha, HK, Park, SH, et al. Granulocytic sarcoma of bowel: CT findings. Radiology
2007; 243:752.
15. Tsimberidou, AM, Kantarjian,HM, Wen, S, et al. Myeloid sarcoma is associated with superior
event-free survival and overall survival compared with acute myeloid leukemia. Cancer
2008; 113:1370.
16. Kaleem, Z, Crawford, E, Pathan, MH, et al. Flow cytometric analysis of acute leukemias.
Diagnostic utility and critical analysis of data. Arch Pathol Lab Med 2003; 127:42.
17. Baer, MR, Stewart, CC, Dodge, RK, et al. High frequency of immunophenotype changes in
acute myeloid leukemia at relapse: implications for residual disease detection (Cancer and
Leukemia Group B Study 8361). Blood 2001; 97:3574.
18. Swerdlow, SH, Campo, E, Harris, NL, et al. (Eds). World Health Organization Classification of
Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.
19. Swerdlow, SH, Campo, E, Harris, NL, et al. (Eds). World Health Organization Classification of
Tumours of Haematopoietic and Lymphoid Tissues. IARC Press: Lyon 2008.
20. Weinberg, OK, Seetharam, M, Ren, L, et al. Clinical characterization of acute myeloid
leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification
system. Blood 2009; 113:1906.
21. Bennett, JM, Catovsky, D, Daniel, MT, et al. Proposed revised criteria for the classification of
acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann
Intern Med 1985; 103:620.
22. Lee, EJ, Pollak, A, Leavitt, RD, et al. Minimally differentiated acute nonlymphocytic
leukemia: a distinct entity. Blood 1987; 70:1400.
23. Bene, MC, Bernier, M, Casasnovas, RO, et al. Acute myeloid leukaemia M0: haematological,
immunophenotypic and cytogenetic characteristics and their prognostic significance: an
analysis in 241 patients. Br J Haematol 2001; 113:737.
24. Roumier, C, Eclache, V, Imbert, M, et al. M0 AML, clinical and biologic features of the
disease, including AML1 gene mutations: a report of 59 cases by the Groupe Francais
d'Hematologie Cellulaire (GFHC) and the Groupe Francais de Cytogenetique Hematologique
(GFCH). Blood 2003; 101:1277.
25. Haferlach, T, Schoch, C, Schnittger, S, et al. Distinct genetic patterns can be identified in
acute monoblastic and acute monocytic leukaemia (FAB AML M5a and M5b): a study of 124
patients. Br J Haematol 2002; 118:426.
26. Tallman, MS, Neuberg, D, Bennett, JM, et al. Acute megakaryocytic leukemia: the eastern
cooperative oncology group experience. Blood 2000; 96:2405.
27. Dastugue, N, Lafage-Pochitaloff, M, Pages, MP, et al. Cytogenetic profile of childhood and
adult megakaryoblastic leukemia (M7): a study of the Groupe Francais de Cytogenetique
Hematologique (GFCH). Blood 2002; 100:618.
28. Oki, Y, Kantarjian, HM, Zhou, X, et al. Adult acute megakaryocytic leukemia: an analysis of
37 patients treated at M.D. Anderson Cancer Center. Blood 2006; 107:880.
29. Ma, Z, Morris, SW, Valentine, V, et al. Fusion of two novel genes, RBM15 and MKL1, in the t
(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet 2001; 28:220.
30. Zipursky, A. Transient leukaemia - a benignform of leukaemia in newborn infants with
trisomy 21. Br J Haematol 2003; 120:930.

GRAPHICS

Conceptual organization of hematologic malignancies
Organization of tumors of the hematopoietic and lymphoid tissues as described by the World Health
Classification 2008. Swerdlow, SH, Campo, E, Harris, NL, et al. (Eds). World Health Organization
Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.

Leukemia cutis forearms
Leukemia cutis: extensor forearms. Reproduced with permission from:
Stedman's Medical Dictionary. Copyright 2008 Lippincott Williams & Wilkins.

Acute myeloid leukemia gingival infiltration
An otherwise healthy 36-year-old man presented with a 6-day history of
bleeding gums and abdominal pain in the left upper quadrant. He
reported having had fevers, fatigue, decreased appetite, and
unintentional weight loss of 10 lb (4.5 kg) during the previous month. On
physical examination, red, swollen gingivae (Panel A), tender
submandibular lymph nodes, and a palpable spleen were noted.
Laboratory evaluation revealed a peripheral-blood white-cell count of
194,100 per cubic millimeter, with 44 percent blasts, and a peripheral-
blood platelet count of 12,000 per cubic millimeter. Examination of a
bone marrow-biopsy specimen showed acute myelomonocytic leukemia
with dysplastic eosinophils with a deletion of chromosome 16q and
trisomy 22, karyotypic abnormalities (variant M4E). Leukemic infiltration
of the gingivae has been associated with monocytic variants of acute
myelogenous leukemia. After emergency treatment with plasmapheresis
and induction chemotherapy with cytarabine and doxorubicin, the gingival
infiltration resolved (Panel B; image obtained 3 weeks after that in Panel
A). The patient subsequently completed three cycles of consolidation
chemotherapy and remains in remission 1 year later. Reproduced with
permission from: Mani, A, Lee, DA. Leukemic Gingival Infiltration. N Engl J
Med 2008; 358(3): 274. Copyright 2008 Massachusetts Medical Society. All
rights reserved.

FAB classification I

FAB classification of acute myeloid leukemia-I
NEC: nonerythroid cells; PXase: peroxidase; SBB: Sudan black; NSA: nonspecific esterase; PAS: periodic acid-Schiff.
* Abnormal progranulocytes and blasts.
FAB
type
Blasts,
percent
Erythroid
progenitors Morphology Cytochemistry
All
cells NEC
M0 >30 >90 <50 Blasts resemble L2 variant of ALL;
Cytoplasmic granules and auer rods are
not seen.
<3 percent PXase+
or SBB+
M1 >30 >90 <50 >30 percent type 1 and type 2 blasts;
<10 percent differentiated myeloid cells;
Auer rods seen in about 50 percent of
cases
>3 percent PXase+
or SBB+
M2 >30 >30-
89
<50 >30 percent type 1 and type 2 blasts;
>10 percent differentiated myeloid cells;
Auer rods seen in about 70 percent of
cases
PXase+ SBB+
NSE+<20 percent
PAS-
M3 >30* >30-
89
<50 >20 percent abnormal hypergranular
progranulocytes; blast count may be <30
percent; Auer rods and faggot cells seen
in virtually all cases
PXase+ SBB+ PAS-
NSE
M3V >30* >30-
89
<50 >20 percent abnormal hypogranular
progranulocytes; blast count may be <30
percent; Auer rods and faggot cells seen
in virtually all cases
PXase+ SBB+ PAS-
NSE
M4 >30 >30-
79
<50 >20 percent promonocytes and
monocytes; >20 percent granulocytic
cells; peripheral monocytosis (>5 x 10
9
)
elevated serum or urine lysozyme; Auer
rods seen in about 65 percent of cases
PXase+ >20
percent NSE+

FAB classification of acute myeloid leukemia-II
NEC: nonerythroid cells; PXase: peroxidase; SBB: Sudan black; NSA: nonspecific esterase; PAS: periodic acid-Schiff.
FAB
type
Blasts,
percent
Erythroid
progenitors Morphology Cytochemistry
All
cells NEC
M4eo >30 >30-
79
<50 >5% eosinophils and cells with mixed
basophilic and eosinophilic granules,
plus M4 features
PXase+ >20%NSE+
M5a >80# <50 >80% of nonerythroid cells are
monoblasts; Auer rods usually not seen
NSE+
M5b >80# <50 >80% of nonerythroid cells are
monocytes, promonocytes, and
monoblasts; Auer rods can be seen in a
minor population of myeloblasts (30
percent of cases)
NSE+
M6 >30 >50 Erythroid predominance and dysplasia;
>30% blasts among nonerythroid
cells; Auer rods present in blasts in 60%
of cases
PAS+ (erythroid
cells); blasts are
PXase+
M7 >30 <50 Blasts with cytoplasmic blebbing
platelet shedding; marrow fibrosis; Auer
rods are not seen
Platelet PXase+ on
EM

Myeloblasts with Auer rod
Peripheral smear from a patient with acute myeloid leukemia. There are
two myeloblasts, which are large cells with high nuclear-to-cytoplasmic
ratio and nucleoli. Each myeloblast has a pink/red rod-like structure (Auer
rod) in the cytoplasm (arrows). From Brunning, RD, McKenna, RW. Tumors
of the bone marrow. Atlas of tumor pathology (electronic fascicle), Third
series, fascicle 9, 1994, Washington, DC. Armed Forces Institute of
Pathology.

Antigen expression in acute myeloid leukemia
This table indicates the frequencies of antigen expression at diagnosis and at relapse in 153 adult patients
with de novo acute myeloid leukemia enrolled in CALGB 8361. Testing was performed by multiparameter
flow cytometry in a single reference laboratory. Those antigens present in the majority of the cases are
shown in bold type. Adapted from Baer, MR, et al. Blood 2001; 97:3574.
Antigen Expressed at diagnosis, percent Expressed at relapse, percent
CD2 11 22
CD3 2 0
CD4dim 72 78
CD7 22 30
CD8 1 5
CD11b 41 37
CD13 98 97
CD14 12 8
CD15 82 78
CD16 2 3
CD19 5 8
CD32 76 74
CD33 75 78
CD34 64 74
CD38 96 94
CD56 17 21
CD64 50 45
HLADr 76 74

Gene expression profiling in acute leukemia
This figure illustrates the use of gene expression arrays (or profiles) for
distinguishing between acute myeloid leukemia (AML) and acute lymphoblastic
leukemia (ALL). Genes most highly expressed in ALL and AML are shown in the left-
hand and right-hand panels, respectively (ie, "ALL genes" and "AML genes",
respectively). Expression levels of each of the individual genes greater than the mean
are shown in red; those genes expressed below the mean are shown in blue. Each
column (ie, top to bottom) corresponds to a specific gene, while each row (ie, left to
right) corresponds to expression levels in a single sample. The top 11 samples were
from patients with AML, while the remainder were from patients with ALL. Note that,
while the genes as a group appear correlated with either AML or ALL, no single gene
is uniformly expressed in either type of leukemia. Reproduced with permission from
Golub, TR, Slonim, DK, Tamayo, P, et al. Molecular classification of cancer: Class
discovery and class prediction by gene expression monitoring. Science 1999; 286:531.
Copyright 1999 American Association for the Advancement of Science.

WHO classification of acute myeloid leukemia (AML)
* The entities included in this group are defined almost identically as the corresponding entity in the French-American-British
(FAB) classification.
MDS: myelodysplastic syndromes; MPD: myeloproliferative diseases.
Adapted from Brunning, RD, et al. Acute myeloid leukaemia: Introduction. In: Jaffe, ES, Harris, NL, Stein, H,
Vardiman, JW, editors. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours
of Haematopoietic and Lymphoid Tissues. IARC Press: Lyon 2001, p. 77. Permission granted from Harris, NL and
Vardiman, JW.
AML with recurrent genetic abnormalities
AML with t(8;21)(q22;q22), (AML1/ETO)
AML with abnormal bone marrow eosinophils and inv(16)(p13q22) or t(16;16)(p13;q22), (CBF
/MYH11)
Acute promyelocytic leukemia with t(15;17)(q22;q12), PML/RAR-alpha and variants
AML with 11q23 (MLL) abnormalities
AML with multilineage dysplasia
Following MDS or MDS/MPD
Without antecedent MDS or MDS/MPD, but with dysplasia in at least 50 percent of cells in two or
more myeloid lineages
AML and myelodysplastic syndromes, therapy related
Alkylating agent/radiation-related type
Topoisomerase II inhibitor-related type
Other
AML, not otherwise categorized*
AML, minimally differentiated
AML without maturation
AML with maturation
Acute myelomonocytic leukemia
Acute monoblastic/acute monocytic leukemia
Acute erythroid leukemia (erythroid/myeloid and pure erythroleukemia variants)
Acute megakaryoblastic leukemia
Acute basophilic leukemia
Acute panmyelosis with myelofibrosis
Myeloid sarcoma

Acute myelomonocytic leukemia (M4)
Bone marrow smear from a patient with acute myelomonocytic leukemia
(FAB classification M4). (Wright-Giemsa stain). The two promyelocytes on
the left (black arrows) with basophilic cytoplasm containing coarse
azurophilic granules contrast with the two promonocytes on the right
(blue arrows) which have abundant pale cytoplasm and delicate nuclear
folds. From Brunning, RD, McKenna, RW. Tumors of the bone marrow. Atlas
of tumor pathology (electronic fascicle), Third series, fascicle 9, 1994,
Washington, DC. Armed Forces Institute of Pathology.

Acute myelomonocytic leukemia (M4EO)
Bone marrow smear from a patient with acute myelomonocytic leukemia
with increased marrow eosinophils (FAB classification M4EO) and an
associated inv(16) chromosome abnormality. (Wright-Giemsa stain). The
two eosinophilic precursors in this field (arrows) show prominent
basophilic-staining granules. From Brunning, RD, McKenna, RW. Tumors of
the bone marrow. Atlas of tumor pathology (electronic fascicle), Third series,
fascicle 9, 1994, Washington, DC. Armed Forces Institute of Pathology.

Acute myeloid leukemia (AML FAB M0)
Bone marrow aspirate from a patient with AML (FAB classification M0).
(Wright-Giemsa stain). The blasts lack differentiating features and were
nonreactive to Sudan Black B and myeloperoxidase staining. More than
20 percent of the blasts expressed myeloid antigens CD13 and CD33. The
blasts were terminal transferase negative and nonreactive with antibodies
to lymphocytes. Auer rods were not found. From Brunning, RD, McKenna,
RW. Tumors of the bone marrow. Atlas of tumor pathology (electronic
fascicle), Third series, fascicle 9, 1994, Washington, DC. Armed Forces
Institute of Pathology.

Acute myeloid leukemia (M1)
(Wright-Giemsa stain). The majority of cells have a rim of pale to slightly
basophilic agranular cytoplasm. The nuclei have finely dispersed
chromatin and prominent nucleoli. (From Brunning, RD, McKenna, RW.
Tumors of the bone marrow. Atlas of tumor pathology (electronic fascicle),
Third series, fascicle 9, 1994, Washington, DC. Armed Forces Institute of
Pathology.)

Acute myeloid leukemia (M2)
(Wright-Giemsa stain). The WBC count was 70,000/ L and was comprised
almost entirely of myeloblasts with numerous azurophilic granules. From
Brunning, RD, McKenna, RW. Tumors of the bone marrow. Atlas of tumor
pathology (electronic fascicle), Third series, fascicle 9, 1994, Washington, DC.
Armed Forces Institute of Pathology.

Acute monoblastic leukemia (M5)
Peripheral blood smear from a patient with acute monoblastic leukemia
(FAB classification M5). (Wright-Giemsa stain). The two monoblasts on
the left have abundant cytoplasm with numerous azurophilic granules.
The nuclear membrane of the promonocyte on the right has delicate folds
and creases. From Brunning, RD, McKenna, RW. Tumors of the bone
marrow. Atlas of tumor pathology (electronic fascicle), Third series, fascicle 9,
1994, Washington, DC. Armed Forces Institute of Pathology.

Acute monocytic leukemia
Blood smear from a patient with acute monocytic leukemia, differentiated
(FAB AML M5B). The predominant promonocytes have abundant
cytoplasm with scattered myeloperoxidase-negative azurophilic granules.
The nuclei have delicate folds and creases. Nucleoli are inconspiruous
(Wright-Giemsa stain). From Brunning, RD, McKenna, RW. Tumors of the
bone marrow. Atlas of tumor pathology (electronic fascicle), Third series,
fascicle 9, 1994, Washington, DC. Armed Forces Institute of Pathology.

Acute monocytic leukemia
Bone marrow smear from a patient with acute monocytic leukemia with
maturation (FAB M5B). This field shows a range of maturation of
monocytic cells. (Wright-Giemsa stain). From Brunning, RD, McKenna, RW.
Pathology.

Erythroleukemia (M6)
Bone marrow smear from a patient with erythroleukemia (FAB
classification M6). (Wright-Giemsa stain). A megaloblastoid erythroblast
(blue arrow) is shown along with three myeloblasts (black arrows). From
Brunning, RD, McKenna, RW. Tumors of the bone marrow. Atlas of tumor
pathology (electronic fascicle), Third series, fascicle 9, 1994, Washington, DC.
Armed Forces Institute of Pathology.

Acute megakaryoblastic leukemia (M7)
Bone marrow smear from a patient with acute megakaryoblastic leukemia
(FAB classification M7). Panel A shows large blasts and
promegakaryocytes; the latter cells are larger than the blasts and have
coarse nuclear chromatin and irregularly shaped nuclei (Wright-Giemsa
stain). Panel B shows staining of these cells with a monoclonal antibody
to platelet glycoprotein IIIa (CD61). From Brunning, RD, McKenna, RW.
Pathology.
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