Sect 6 - FAB/WHO Classification of AML

AMLs

FAB and WHO classify

French-American-British

What does FAB stand for?

World Health Organization

What does WHO stand for?

FAB

Which came first: FAB or WHO classifications?

WHO

Which gets updated more often?

M0-M7

What are the FAB Classifications?

AML with minimal differentiation

M0

cells involved in M0 (AML with minimal differentiation)

undifferentiated blasts with myeloid phenotype

CD Markers in M0 (AML with minimal differentiation)

CD13

CD33

CD34

CD117

cytochemical stains of M0 (AML with minimal differentiation)

MPO and SBB: 0-2% pos

Specific Esterase (Chloroacetate): negative

AML without maturation

M1

cells involved in M1 (AML without maturation)

myeloblasts with no/minimal azurophilic granules

CD Markers in M1 (AML without maturation)

CD13

CD33

CD34

CD117 (strong)

cytochemical stains of M1 (AML without maturation)

MPO and SBB: >3% pos

Specific Esterase (Chloroacetate): positive

chromosomal abnormalities of M1 (AML without maturation)

trisomy 8

t(9, 22)

AML with maturation

M2

cells involved in M2 (AML with maturation)

prominent maturation behind myeloblast stage (all stages present/20% myeloblasts)

CD Markers in M1 (AML with maturation)

CD13

CD33

CD34 +/-

CD117

cytochemical stains of M2 (AML with maturation)

MPO and SBB: 50% pos

Specific Esterase (Chloroacetate): positive

chromosomal abnormalities of M2 (AML with maturation)

t(8, 21)

Acute Promyelocytic Leukemia (APL)

M3

cells involved in M3 (Acute Promyelocytic Leukemia (APL))

Abnormal hypergranular promyelocytes

Auer rods in bundles (****** cells)

CD Markers in M3 (Acute Promyelocytic Leukemia (APL))

CD13

CD33

CD117

cytochemical stains of M3 (Acute Promyelocytic Leukemia (APL))

MPO and SBB: 100% pos

Specific Esterase (Chloroacetate): positive

chromosomal abnormalities of M3 (Acute Promyelocytic Leukemia (APL))

t(15, 17); 15q+ / 17q-

forms the PML/RARa (Retinoic Acid Receptor a) gene mutation -- inhibits maturity

treatment for M3/APL

ATRA (Alpha Trans Retinoic Acid)

APL, Microgranular variant

M3m

cells involved in M3m (APL, Microgranular variant)

Promyelocytes with:

indistinct granules

nucleus that are often reniform/bilobed

CD Markers in M3m (APL, Microgranular variant)

same as M3:

CD13

CD33

CD117

cytochemical stains of M3m (APL, Microgranular variant)

same as M3:

MPO and SBB: pos

Specific Esterase (Chloroacetate): pos

chromosomal abnormalities of M3m (APL, Microgranular variant)

same as M3:

t(15, 17); 15q+ / 17q-

forms the PML/RARa (Retinoic Acid Receptor a) gene mutation -- inhibits maturity

Acute Myelomonocytic Leukemia (AMML)

M4

cells involved in M4 (Acute Myelomonocytic Leukemia (AMML))

myelocytic and monocytic precursors

CD Markers in M4 (Acute Myelomonocytic Leukemia (AMML))

CD11b

CD13

CD33

CD117

CD14 +/-

cytochemical stains of M4 (Acute Myelomonocytic Leukemia (AMML))

MPO and SBB: pos

Specific Esterase (Chloroacetate): pos

Non-Specific Esterase (Butyrate): variable (+/-)

AMML with bone marrow eosinophilia

M4eo

cells involved in M4eo (AMML with bone marrow eosinophilia)

myelocytic and monocytic precursors with marrow eosinophilia

cytochemical stains of M4eo (AMML with bone marrow eosinophilia)

same as M4

MPO and SBB: pos

Specific Esterase (Chloroacetate): pos

Non-Specific Esterase (Butyrate): variable (+/-)

chromosomal abnormalities of M4eo (AMML with bone marrow eosinophilia)

16q inversion or deletion

Acute Monoblastic Leukemia (AMoL)

M5a

cells involved in M5a Acute Monoblastic Leukemia (AMoL)

monoblasts predominant

CD Markers in M5a Acute Monoblastic Leukemia (AMoL)

CD11b

CD14

CD33

CD117

will have increased serum muramidase levels

cytochemical stains of M5a Acute Monoblastic Leukemia (AMoL)

MPO and SBB: neg

Specific Esterase (Chloroacetate): neg

Non-Specific Esterase (Butyrate): variable (+/-)

chromosomal abnormalities of M5a Acute Monoblastic Leukemia (AMoL)

Del (11)

t(9, 11)

Acute Monocytic Leukemia with differentiation (AMoL)

M5b

cells involved in M5b (Acute Monocytic Leukemia with differentiation (AMoL))

predominant promonocytes in marrow and more pronounced maturation in PBS

CD Markers in M5b (Acute Monocytic Leukemia with differentiation (AMoL))

same as M5a

CD11b

CD14

CD33

CD117

will have increased serum and urine muramidase levels due to monocytic proliferation

cytochemical stains of M5b (Acute Monocytic Leukemia with differentiation (AMoL))

same as M5a

MPO and SBB: neg

Specific Esterase (Chloroacetate): neg

Non-Specific Esterase (Butyrate): pos

chromosomal abnormalities of M5b (Acute Monocytic Leukemia with differentiation (AMoL))

same as M5a

Del (11)

t(9, 11)

Pure Erythroid Leukemia (EL)

M6

old name: Erythroleukemia

cells involved in M6 (Pure Erythroid Leukemia (EL))

Dysplastic erythroblasts with multinucleated cytoplasmic budding

Vacuolation and megaloblastoid changes

Increase in myeloblasts and promyelocytes in bone marrow

CD Markers in M6 (Pure Erythroid Leukemia (EL))

CD71 (Glycoprotein A)

cytochemical stains of M6 (Pure Erythroid Leukemia (EL))

MPO and SBB: pos

Non-Specific Esterase (Butyrate): variable (+/-)

PAS: pos (erythroblasts)

Megakaryoblastic Leukemia (AMkL)

M7

cells involved in M7 (Megakaryoblastic Leukemia (AMkL))

megakaryoblasts with cytoplasmic projections

CD Markers in M7 (Megakaryoblastic Leukemia (AMkL))

CD41

CD42

CD61 +/-

cytochemical stains of M7 (Megakaryoblastic Leukemia (AMkL))

MPO and SBB: neg

Specific Esterase (Chloroacetate): neg

Non-Specific Esterase (Butyrate): variable (+/-)

Platelet Peroxidase stain (PPO): pos

electron microscopy (FISH) or immunochemical stains

What two tests are necessary to diagnose M7 (AMkL)?

WHO requires blast percentage for diagnosis of AML that must be at least 20% blasts in peripheral blood and/or bone marrow

What differentiate WHO and FAB classifications?

Auer rods

composed of fused primary azurophilic granules

myeloblasts

Auer rods are commonly seen in what cell?

AML (M1)

What condition are is associated with a singular Auer rod?

APL (M3)

What condition are is associated with bundles of Auer rods?

DIC

What condition is increased in M3/APLs due to the bundles of Auer rods?

**hint: RBCs lyse & release rods; rods are sharp and cause damage