WBC DISORDERS

Neoplastic disorders

Bone marrow haematopoiesis

Releases only mature cells in peripheral

blood

Leukemia

Progressive, neoplastic disease of

hematopoietic system . It is widespread
within the marrow with involvement of
peripheral blood (not always)

Unregulated proliferation of immature

haemopoetic cells in the marrow

Classification
Acute

Chronic

Rapid growth of
immature blood
cells
( blasts )
Rapid onset
Very aggressive
Mostly in children,
young adults

Excessive build up of
relatively mature blood
cells
Insidious in onset
Less aggressive
Mostly in older
patients

Classification
Lymphoid

Myeloid

Affects

Affects eosinophils,
neutrophils,basophils

lymphocytes &
plasma cells
Lymphocytic
leukemia

Myelogenous
leukemia

Myeloid leukemia
Arises from these cells

Lymphoid leukemia
Arises from these cells

Etiopathogenesis

Chromosomal translocation & acquired mutations

Inherited genetic factors

Viruses

Chronic immune stimulation

Iatrogenic factors

Smoking

Symptoms of leukemia

Unregulated proliferation and

invasion of immature blood
cells in bone marrow and
other tissues

BONE TENDERNESS
HEPATOSPLENOMEGALY
LYMPHADENOPATHY

Suppression of normal
haemopoetic cells

- ANAEMIA
- LEUKOPENIA
- THROMBOCYTOPENIA

ACUTE
LEUKEMIA

ALL & AML - proliferation of undifferentiated

cells (BLASTS)

How do we
differentiate myeloblast
from lymphoblast ?

Morphology

Myelobalst

Lymphoblast

Myeloblast Vs
Lymphoblast
Myeloblast
Lymphoblast
Cytoplasm

abundant

scant

Granules

Auer rods

Chromatin

Fine

condensed

Nucleolus

2-3 , prominent

inconspicuous

Nucleus

Cytochemistry
Cytochemistry
Myeloblast

Lymphoblast

Myeloperoxidase

Sudan Black

PAS

-/+

Esterases

Immunophenotyping
Antibody

Myeloblast

Lymphoblast

CD13,CD33,
CD65

CD3

+(T)

CD19

+(B)

tDT

ACUTE MYELOID
LEUKEMIA

Definition

Tumour of hematpoietic progenitors

Acquired oncogenic mutations

Impede differentiation

Accumulation of immature myeloid blasts in

marrow

Definition

Proliferation of immature myeloid cells

WHO classification

WHO classification incorporates

morphological, immunophenotypic,
genetic and clinical features.
Defined by presence of >20% blasts in
blood or bone marrow nucleated cells.
(FAB > 30%)
Diagnosis of AML can be made in blasts
<20% when associated with t(8:21)
(q22;q22) and inv (16)(p13;q22) or
t(16:16)(p13:q22 )

WHO classification

AML NOS is morphology based and

reflect FAB classification with some
modification
AML with recurrent translocations occur in
younger individual and have better
prognosis.
AML with multilineage dysplasia occurs in
older and have unfavorable outcome.

WHO 2008

AML with recurrent genetic

abnormalities

AML with t(8;21)(q22;q22); RUNX1-RUNX1T1

AML with inv(16)(p13.1q22) or t(16;16)
(p13.1;q22); CBFB-MYH11
Acute promyelocytic leukemia with t(15;17)
(q22;q12); PML-RARA
AML with t(9;11)(p22;q23); MLLT3-MLL
AML with t(6;9)(p23;q34); DEK-NUP 214

WHO 2008

AML with recurrent genetic

abnormalities

AML with inv(3)(q21q26.2) or t(3;3)

(q21;q26.2); RPN1-EVI1
AML (megakaryoblastic) with t(1;22)(p13;q13);
RBM15-MKL1
AML with mutated NPM1
AML with mutated CEBPA

AML with myelodysplasia-related

changes

WHO 2008

Therapy-related myeloid neoplasms

Acute myeloid leukaemia, NOS

AML with minimal differentiation

AML without maturation
AML with myelocytic maturation
Acute myelomonocytic leukaemia
Acute monoblastic and monocytic leukaemia
Acute erythroid leukaemia
Acute megakaryoblastic leukaemia
Acute basophilic leukaemia
Acute panmyelosis with myelofibrosis

WHO 2008

Myeloid sarcoma

Myeloid proliferations related to Down

syndrome

Transient abnormal myelopoiesis

Myeloid leukaemia associated with Down
syndrome

Blastic plasmacytoid dendritic cell

neoplasm

FAB classification

AML, minimally differentiated (M0)

AML, without maturation (M1)

AML, with maturation (M2)

Acute promyelocytic leukemia (M3)

FAB classification

Acute myelomonocytic leukemia (M4)

Acute monocytic leukemia (M5)

Acute erythroid leukemia (M6)

Acute megakayoblastic leukemia (M7)

Clinical features

Primarily affects adults.

Peak age: 15- 39 yrs.
Can occur in children and older individuals

Criteria for diagnosis

> 20% Myeloblasts in the marrow

Due to suppression of bone

marrow
Anemia
Thrombocytopenia
leucopenia

Due to infiltration

Bony tenderness

Hepatosplenomegaly
AML-M3: Bleeding due to DIC
AML M4/M5: Gum hyperplasia

Signs &
Symptoms

Organomegaly
Purpura
Organomegaly

Pathogenesis

Genetic alterations inhibit terminal

maturation
Marrow replaced by premature cells
BLOCKED MATURATION & SURVIVAL
Accumulating neoplastic cells - suppress normal
hematopoietic cells anemia &
thrombocytopenia

Cytogenetics

AML M3: t (15;17)

AML M2: t(8;21)

AML M4: inv 16

AML M5: abnormalities of chromosome 11

Hematological findings

CBP

Hb
TLC > 100,000
Presence of myeloblasts
Platelets

Hematological findings

Bone marrow aspiration

Hypercellular marrow

Erythroid, lymphoid & megakaryocytic cells

supressed

>20% blasts seen

Cytochemistry

MPO +

Sudan Black +

PAS negative

Esterases -/+

MPO

SBB

AML M0

AML M1

AML M2

AML M3

Auer rods
Needle like Cytoplasmic inclusions, red purple
with Leishmans stain
Positive staining with MPO &
Sudan black
Faggot cells(M3): formed by the fusion of primary
granules

AML M3 hypogranular variant

AML M4

AML M5

AML M6

AML M7

Characteristic features

M3--Young, better prognosis, retinoic acid, DIC

M4 , M5--lysozyme in urine, NSE+++, gum

hypertrophy

M6--PAS++, Atypical erythroblasts

M7--marrow fibrosis, pancytopenia

ACUTE
LYMPHOBLASTIC
LEUKEMIA(ALL)

Definition

Malignant proliferation of immature lymphoid

stem cells

Definition

Neoplasms Immature B or T cells

85% - B-ALL childhood

T-ALL - adolescents

Clinical features

2-5 yrs
Anemia, infections, bleeding symptoms
Lymphadenopathy, organomegaly
Mediastinal mass
Bone pain-periosteal involvement

WHOClassification

Precursor B-cell Neoplasm

B cell lymphoblastic leukemia/ lymphoma (B-ALL)

Precursor T-cell Neoplasm

T cell lymphoblastic leukemia/ lymphoma (T-ALL)

FAB Classification

L1 - Small, homogenous (uniform )

lymphoblasts

FAB Classification

L2 - Large, heterogenous (pleomorphic)

lymphoblasts

FAB Classification

L3 - Large,homogenous with vacuolated and

deeply basophilic cytoplasm)- Burkitts type

Lab diagnosis

CBC

RBC count : ed
WBC count : ed with presence of >20%
lymphoblasts
Platelet count : ed

Bone marrow aspiration

Hypercellular
>20% blasts seen

Lab diagnosis

Histochemical markers

Myeloperoxidase negative

PAS positive

tdT positive

SIg -ve

Lab diagnosis

CD markers

CD3 - T cell

CD19 - B cell

CD10 Pre B cell (CALLA)

Thank You