Acute Leukemias

acute leukemia definition

malignant neoplasm of hematopoietic cells (blasts) that diffusely replace BM

can infiltrate spleen, liver, skin, gonads, brain

primary manifestation = failure of BM → pancytopenia or bicytopenia w leukocytosis

dx of leukemia

req BM biopsy

• microscopy

  • phenotyping: cytochemistry, flow cyto, immunohistochemistry

classification of leukemia

• lymphoid or myeloid

• acute leukemias char by accumulation of blasts, suppression of hematopoiesis, and fulminant clinical course

• chronic leukemias char by persistent proliferation of 1 or more lineages, inc hematopoiesis, and indolent clinical course

ALL

AML

CLL

CMPN: chronic myeloproliferative neoplasm

chronic vs acute leukemia

acute leukemia: lab findings

anemia is almost always present

variable (or no) inc in white cells count (50% have fewer than 10,000/ul)

ID of blasts in blood or BM (20%)

depressed plt count

differentiating ALL vs AML blasts

ALL: coarse chromatin, inconspicuous nucleoli

AML: finer chromatin, more CP, prominent nucleoli

phenotyping by cytochemistry

enzymatic rxn in CP → ID cell lineage & maturation stages

see lecture on this

→ now use flow cytometry

immunophenotyping (flow cytometry)

fluorescent immune (Ag/Ab) rxn

used to subtype ALL and AML

C34: marker of hematopoietic stem cells

ALL vs AML prognosis

ALL: good

AML: devastating disease

acute lymphoblastic leukemia (ALL) (aka B and T cell lymphoblastic leukemia)

aggressive tumors of immature lymphocytes

predom a dz of children and young adults

BM dz (B cells) or mediastinal dz (T cells)

immunophenotyping: what are the markers for ALL?

B cell: CD19, CD20

T cell: CD2, CD 3

__ is a ss-DNA polymerase present in >95% of ALL and less than 5% of AML.

TdT (terminal deoxynucleotidyl transferase)

karyotypic changes in ALL

90% of ALL w non-random chromosomal abnormalities

m/c in pre-B cell leukemia is hyperdiploidy (>50 chromosomes)

… ???

acute myeloid leukemia (AML) morphology

myeloblasts distinguished from lymphoblasts on routine wright-Giemsa stain

delicate chromatin, fine granules, 3-5 nucleoli

Auer rods sometimes present

acute promyelocytic leukemia (APL)

low wbc count

assoc’d w DIC

abnormally granulated, neoplastic promyelocytes, often many Auer rods per cell (Faggot cells)

acute promyelocytic leukemia

leukosis

many abnormal promyelocytes

assoc’d w DIC

irregular nucleus & granulations sparser and finer

Faggot cells less commonly seen

… retinoic acid receptor…. ???

acute myelomonocytic leukemia

basophilic stipplings??

acute monocytic leukemia

predominance of monoblasts in BM, PB

usually kids

gum infiltration common

acute erythroid leukemia

acute megakaryoblastic leukemia

AML-M0 (stem cell leukemia)

myeloblasts >90%, no Auer rods

stem cell leukemia → can’t tell if myeloid or lymphoid, need immunotyping

AML-M1 (AML w/o maturation)

>90% myeloblasts, disperse chromatin

can see Auer rods, <10% maturing myeloid cells

MPO/SBB +

AML-M2 (AML w maturation)

cells beyond myeloblasts, 20-70% blasts

may see Auer rods

maturing neutrophils, monocytes

MPO/SBB ++

AML-M3 (acute promyelocytic leukemia) APL

hyper granular promyelocytes

Auer rod bundles (Faggot cells)

MPO/SBB +

CAE+

inc incidence of DIC - trigger thrombotic cascade

microgranular variant of AML-M3 (M3m)

agranular, hypo, or micro granular

Auer rods are rare, folded, bi/multilobed or monocytoid nuclei

poorer prognosis

AML-M4 (acute myelomonocytic leukemia)

AMML

dual-lineage leukemia: lots of myleoblasts w fraction of monocytic cells, monoblasts & promonocytes

monoblast: large, kidney shaped

MPO/SBB +

NSE + (mono)

10% present w gingival hyperplasia

AML-M4e

big eosinophil w pink granules in BM

AML-M5 (acute monocytic leukemia)

>80% monoblast

NSE ++

AML-M5B (acute monocytic leukemia)

inc in promonocytes + more maturation

AML M6 (acute erythroid leukemia)

pure erythroid leukemia

• dx based on BM → >80% erythroid precursors (giant, bizarre, megaloblastoid), >30% myeloblasts

PAS + (for pronormoblast)

MPO/SBB +

Di Guglielmo syndrome = rare subtype of AEL

AML-M7 (acute megakaryocytic leukemia)

megakaryoblasts w CP projections, 70% blasts in BM (>50% megblasts)

often see micro-megk in PB/BM

plt peroxidase stain +

assoc’d w Down syndrome