Acute Leukemias: Atu Level 300 Practical Section

ACUTE LEUKEMIAS
ATU LEVEL 300 PRACTICAL SECTION

What Is Acute Leukemia?
• The acute leukaemias are a heterogeneous group of malignant disorders,
which are characterized by the uncontrolled clonal proliferation and
accumulation of poorly differentiated blast cells in the bone marrow and
other tissues.
• Thus replacement of normal bone marrow elements with abnormal
(neoplastic) blood cells.
• These leukaemic cells are frequently (but not always) present in the
peripheral blood stream. Subsequently there is a raised total blood count
and evidence of bone marrow failure (i.e. anaemia, neutoropenia,
thrombocytopenia) are ensues.
• In the acute leukaemias the blasts commonly invade reticuloendothelial
tissues including the spleen, liver and lymph nodes. They may also invade
other tissues, infiltrating any organ of the body.
• If left untreated, leukaemia eventually causes death.
ALL
naïve
B-lymphocytes
Plasma
Lymphoid cells
progenitor T-lymphocytes
AML
Hematopoietic Myeloid Neutrophils
stem cell progenitor
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloid maturation
myeloblast promyelocyte myelocyte metamyelocyte band neutrophil
MATURATION
Adapted and modified from U Va website
Acute Leukemia
• accumulation of blasts in the marrow
Marrow failure
• neutropenia: infections, sepsis
• anemia: fatigue, pallor
• thrombocytopenia: bleeding
Lab evaluation
• The lab diagnosis is based on two things
• Finding a significant increase in the number of immature cells in
the bone marrow including blasts, promyelocytes,
promonocytes (>30% blasts is diagnostic)
• Identification of the cell lineage of the leukemic cells
• Peripheral blood:
• Anemia (normochromic, normocytic)
• Decreased platlets
• Variable WBC count
• The degree of peripheral blood involvement determines
classification:
• Leukemic – increased WBCs due to blasts
• Subleukemic – blasts without increased WBCs
• Aleukemic – decreased WBCs with no blasts
Classification of the immature cells involved may be done by:
1- Morphology – an experienced morphologist can look

at the size of the blast, the amount of cytoplasm, the
nuclear chromatin pattern, the presence of nucleoli and
the presence of auer rods (are a pink staining, splinter
shaped inclusion due to a rod shaped alignment of
primary granules found only in myeloproliferative
processes) to identify the blast type:
• AML – the myeloblast is a large blast with a moderate amount
of cytoplasm, fine lacey chromatin, and prominent nucleoli.
10-40% of myeloblasts contain auer rods.
Myeloblasts with auer rods
Morphology, cont.
• ALL – in contrast to the myeloblast, the lymphoblast is a small blast with scant
cytoplasm, dense chromatin, indistinct nucleoli, and no auer rods
Lymphoblast
FAB
• In an attempt to improve the reproducibility and
comparability of the classification process, a grouped of
expert haematologists from French, America, and Britian
(FAB) collaborated to define a more objective criteria for
the classification of acute leukaemias.
• The initial FAB study was based on the examination of

more than 200 different cases of acute leukaemia by expert
morphologists, in addition, a myeloperoxidase or suddan
black stains should be used to facilitate the recognition of
myeloblasts.
Classification of leukemia
Main classification
Chronic leukemia Acute leukemia
FAB
Lymphoid Myeloid Lymphoid Myeloid
L1 AML
M0
L2 M1
L3 M2
M3
M4
M5
M6
M7
FAB Characterization for ALL
• L1: Homogenous population of small lymphoblasts

with scanty cytoplasm and scanty nucleoli. Nucleus
occasionally cleft.
• L2: Heterogeneous population of large lymphoblasts

with moderately abundant cytoplasm & or more
nucleoli. Nucleus commonly intended or cleft.
• L3-Burkitt’s type: Homogenous population of

large lymphoblasts with prominent nucleoli & deeply
basophilic, vacuolated cytoplasm.
Acute Non-Lymphoblastic Leukaemia
Diagnosis Alternative Bone Marrow Appearance
M0 Identified by ultrastructural myeloperoxidase

activity or immunophenotyping.
M1 AML without maturation Monomorphic with one or more distinct nucleoli,

occasional auer rod and at least 3%
myeloperoxidase positivity.
M2 AML with maturation 50% OR > myeloblasts & promyelocytes and
common single auer rod. Dysplastic myeloid
differentiation may also be present.
M3 APL Dominant cell type is promyelocyte with heavy

azurophilic granulation. Bundles of Auer rods
confirm diagnosis. Microgranular variant exist
(M3v)
M4 AMMoL As M2 but > 20% promonocytes & monocytes.
M5 AMoL > 80% monoblasts is poorly differentiated

(M5a)
> 80% monoblasts, promonocytes or
monocytes is well differentiated (m5b)
M6 AEL >50% bizzar, dysplastic nucleated red cells with
multinucleate forms and cytoplasmic bridging.
Myeloblasts usually > 30%.
M7 AMegL Fibrosis, heterogeneous blasts population with

cytoplasmic blebs. Platelet peroxidase positive.
Acute leukemias
• Acute lymphoblastic leukemia –
• They may be classified on the basis of the cytological features of the
lymphoblasts into;
• L1 - This is the most common form found in children and it has the best prognosis. The
cell size is small with fine or clumped homogenous nuclear chromatin and absent or
indistinct nucleoli. The nuclear shape is regular, occasionally clefting or indented. The
cytoplasm is scant, with slight to moderate basophilia and variable vacuoles.
• L2 – This is the most frequent ALL found in adults. The cell size is large and
heterogenous with variable nuclear chromatin and prominent nucleoli. The nucleus is
irregular, clefting and indented. The cytoplasm is variable and often moderate to
abundant, the basophilia is variable and may be deep, and vacuoles are variable.
ALL-L1 (peripheral Blood)
Acute leukemias
• L3 – This is the rarest form of ALL. The cell size is large, with fine, homogenous nuclear
chromatin containing prominent nucleoli.
• The The nucleus is regular oval to round.
• The cytoplasm is moderately abundant and is deeply basophilic and vacuolated.
Acute leukemias
• Incidence – ALL is primarily a disease of young children (2-5 years), but it can
also occur in adults
• Clinical findings – pancytopenia with resulting fatigue, pallor, fever, weight
loss, irritability, anorexia, infection, bleeding, and bone pain.
• L1 occurs in children, L2 in adults, and L3 is called Burkitts leukemia
Acute leukemias
• Prognosis – age, WBC count, and cell type are the most important prognostic
indicators
• Patients younger then 1 and greater than 13 have a poor prognosis
• If the WBC count is < 10 x 109/L at presentation, the prognosis is good; If the WBC count
is > 20 x 109/L at presentation the prognosis is poor
• T cell ALL (more common in males) has a poorer prognosis than any of the B cell ALLs
which have a cure rate of 70%
AML – M1
• Note the myeloblasts and the auer rod:
AML – M2
• Note myeloblasts and hypogranulated PMNs:
AML – M3
• Note hypergranular promyelocytes:
AML – M3m
• Note hypogranular promyelocytes:
AML – M4
• Note monoblasts and promonocytes:
AML – M5A
• Note monoblasts:
AML-M5B
• Note monoblasts, promonocytes, and monocytes:
AML – M6
• Note M1 type monoblasts
2- The Cytochemistry
______________________ALL____________AML__________
• Myeloperoxidase - +
• Suddan black - +
• Non-specific esterase - + in M4, M5
• Periodic acid Schiff (PAS) + in c-ALL + in M6
• Acid phosphatase + in T-ALL + in M6
Distinguishing AML from ALL
• light microscopy
• AML: Auer rods, cytoplasmic granules
• ALL: no Auer rods or granules.
• flow cytometry
• special stains (cytochemistry)
AML
AML
Auer rods in AML
ALL

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ACUTE LEUKEMIAS

ATU LEVEL 300 PRACTICAL SECTION

1- Morphology – an experienced morphologist can look

• The initial FAB study was based on the examination of

Chronic leukemia Acute leukemia

Lymphoid Myeloid Lymphoid Myeloid

• L1: Homogenous population of small lymphoblasts

• L2: Heterogeneous population of large lymphoblasts

• L3-Burkitt’s type: Homogenous population of

M0 Identified by ultrastructural myeloperoxidase

M1 AML without maturation Monomorphic with one or more distinct nucleoli,

M3 APL Dominant cell type is promyelocyte with heavy

M5 AMoL > 80% monoblasts is poorly differentiated

M7 AMegL Fibrosis, heterogeneous blasts population with

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