ACUTE LEUKAEMIA

Dr Afshan Sumera

Dr Afshan Sumera
 LEARNING OUTCOMES
At the end of this learning session, the
student must be able to
List out common WBC neoplasms
Describe etio-pathogeneis, classification,
morphology, diagnosis & clinical features
of AML & ALL
Discuss the importance of
immunophenotyping, cytogenetics in
the diagnosis of WBC neoplasms

Dr Afshan Sumera
 WHAT IS LEUKEMIA?

Cancer of the white blood cells

Acute or Chronic
Affects ability to produce normal
blood cells
Bone marrow makes abnormally large
number of immature white blood cells
called blasts

Dr Afshan Sumera
 LEUKEMIA

A group of malignant disorders

affecting the blood and blood-
forming tissues of
Bone marrow
Lymph system
Spleen
Occurs in all age groups

Dr Afshan Sumera
 LEUKEMIA

Results in an accumulation of
dysfunctional cells because of a
loss of regulation in cell division
Fatal if untreated
Progressive

Dr Afshan Sumera
 nave

B-lymphocytes

Plasma
Lymphoid cells
progenitor T-lymphocytes

Hematopoietic Myeloid Neutrophils

stem cell progenitor

Eosinophils

Basophils

Monocytes

Platelets

Red cells
Dr Afshan Sumera
 PICTURES OF BLOOD
Platelet Platelet
White Cell Red Cell Red Cell Blasts
White Cell

Normal human blood Blood with leukemia

Sources from beyond2000.com
Sources fromDr Afshan Sumera
Arginine.umdnj.edu
 COMMON WBC
NEOPLASMS
Lymphoid neoplasms
B-cell, T-cell, and NK-cell origin
Myeloid neoplasms
1. Acute myeloid leukemias (AML)
immature progenitor cells accumulate in the bone marrow
2. Myelodysplastic syndromes
ineffective hematopoiesis and resultant peripheral blood
cytopenias
3. Chronic myeloproliferative disorders
increased production of one or more terminally
differentiated myeloid elements (e.g., granulocytes)
The histiocytoses
uncommon proliferative lesions of macrophages and
dendritic cells
Dr Afshan Sumera
 ETIO-PATHOGENESIS
Chromosomal Translocations and Other Acquired
Mutations
Nonrandom chromosomal abnormalities, most
commonly translocations, are present in the majority of
white cell neoplasms

Dr Afshan Sumera
 ETIO-PATHOGENESIS
Inherited Genetic Factors
Bloom syndrome, Fanconi anemia, and
ataxia telangiectasia
promote genomic instability
increased risk of acute leukemia
Down syndrome (trisomy 21) and type I
neurofibromatosis
associated with an increased incidence of
childhood leukemia

Dr Afshan Sumera
 ETIO-PATHOGENESIS

Viruses
have been implicated as causative
agents in particular lymphomas
human T-cell leukemia virus-1 (HTLV-1)
Epstein-Barr virus (EBV)
Kaposi sarcoma herpesvirus/human
herpesvirus-8 (KSHV/HHV-8)

Dr Afshan Sumera
 ETIO-PATHOGENESIS
Chronic Immune Stimulation
localized chronic immune stimulation
predispose to lymphoid neoplasia
almost always arises within the inflamed
tissue
Examples
include the associations between H.
pylori infection and gastric B-cell
lymphomas

Dr Afshan Sumera
 ETIO-PATHOGENESIS

Iatrogenic Factors
radiation therapy
chemotherapy
Smoking
incidence of acute myeloid
leukemia is increased 1.3- to 2-fold
in smokers
exposure to carcinogens
benzene
Dr Afshan Sumera
 WHO CLASSIFICATION OF
AML
1. AML WITH GENETIC ABERRATIONS
important because they correlate with prognosis and
guide therapy
AML with t(15;17) acute promyelocytic leukemia
2. AML WITH MDS-LIKE FEATURES
have distinct genetic features and respond poorly to
therapy
3. AML, THERAPY-RELATED
respond poorly to therapy
4. AML, NOT OTHERWISE SPECIFIED
wastebasket category includes AMLs lacking any of
above features
For detailed classification (WHO & FAB) please refer to Robbins
Dr Afshan Sumera
& Cotran Pathologic Basis of Disease, 8th Edition
 CLASSIFICATION OF
LYMPHOID NEOPLASMS
I. Precursor B-cell neoplasms (neoplasms of immature B
cells)
B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)
II. Peripheral B-cell neoplasms (neoplasms of mature B cells)
III. Precursor T-cell neoplasms (neoplasms of immature T cells)
T-cell acute lymphoblastic leukemia/lymphoma (T-ALL)
IV. Peripheral T-cell and NK-cell neoplasms (neoplasms of
mature T cells and NK cells)
V. Hodgkin lymphoma (neoplasms of Reed-Sternberg cells
and variants)

For detailed classification, please refer to Robbins & Cotran Pathologic

Basis
Dr Afshanof Disease, 8th Edition
Sumera
 SUMMARY OF MAJOR TYPES OF
LYMPHOID LEUKEMIAS AND
NON-HODGKIN LYMPHOMAS
Salient Clinical
Diagnosis Cell of Origin Genotype Features

NEOPLASMS OF IMMATURE B AND T CELLS

B-cell acute Bone marrow precursor Diverse chromosomal Predominantly children;
lymphoblastic B cell translocations; t(12;21) symptoms relating to
leukemia/lymphoma involving CBF and marrow replacement
ETV6 present in 25% and pancytopenia;
aggressive

T-cell acute Precursor T cell (often of Diverse chromosomal Predominantly

lymphoblastic thymic origin) translocations, NOTCH1 adolescent males;
leukemia/lymphoma mutations (50% to 70%) thymic masses and
variable bone marrow
involvement; aggressive

Dr Afshan Sumera
 AML
tumor of hematopoietic progenitors
acquired oncogenic mutations
that impede differentiation
leading to the accumulation of immature myeloid blasts in
the marrow
arrest in myeloid development leads to marrow failure
anemia,
thrombocytopenia
neutropenia.
AML occurs at all ages
incidence rises throughout life
peaking after 60 years of age

Dr Afshan Sumera
 AML-MORPHOLOGY
Diagnosis
presence of at least 20% myeloid blasts in the bone
marrow
Myeloblasts
delicate nuclear chromatin
two to four nucleoli
more voluminous cytoplasm than lymphoblasts
Auer rods
needle-like azurophilic granules
particularly numerous in AML with the t(15;17) (acute
promyelocytic leukemia)

Dr Afshan Sumera
Acute myeloid leukemia without maturation. Myeloblasts have delicate
nuclear chromatin, prominent nucleoli, and fine azurophilic granules in the
Dr Afshan Sumera
cytoplasm
 Acute myeloid leukemia
subtypes.

A, Acute promyelocytic leukemia

with the t(15;17) (FAB M3 subtype).
Bone marrow aspirate shows
neoplastic promyelocytes with
abnormally coarse and numerous
azurophilic granules. Other
characteristic findings include the
presence of several cells with
bilobed nuclei and a cell in the
center of the field that contains
multiple needle-like Auer rods.

B, Acute myeloid leukemia with

monocytic differentiation (FAB
M5b subtype). Peripheral smear
shows one monoblast and five
promonocytes with folded nuclear
Dr Afshan Sumera membranes
 AML-DIAGNOSIS

High index of clinical suspicion

Family history, past history.
Simple PBS examination.
PS, Bone marrow, Cytochemistry,
Immunophenotyping, Cytogenetics
Other lab tests: Serum uric acid, LDH,
RFT, Sr.Ca, electrolytes

Dr Afshan Sumera
 IMPORTANCE OF
IMMUNOPHENOTYPING IN THE
DIAGNOSIS

Immunophenotype
Because it can be difficult to
distinguish myeloblasts and
lymphoblasts morphologically, the
diagnosis of AML is confirmed by
performing stains for
myeloidspecific antigens

Dr Afshan Sumera
 IMPORTANCE OF CYTOGENETICS IN
THE DIAGNOSIS

Cytogenetics
Cytogenetic analysis has a central role in the
classification of AML
Karyotypic aberrations
detected in 50% to 70% of cases with standard
techniques
90% of cases using special high-resolution banding
chromosomal abnormalities correlate with certain
clinical features.
AMLs arising de novo in younger adults are commonly
associated with balanced chromosomal translocations,
particularly t(8;21), inv(16), and t(15;17)

Dr Afshan Sumera
 AML-CLINICAL FEATURES
Most patients present within weeks or a few
months of the onset of symptoms with
anaemia, neutropenia, and
thrombocytopenia
fatigue, fever, and spontaneous mucosal
and cutaneous bleeding
involvement of tissues other than the
marrow are usually less striking in AML than
in ALL

Dr Afshan Sumera
 PLATELET
COAGULATION

Petechiae, Purpura Hematoma, Joint bl.

Dr Afshan Sumera
Dr Afshan Sumera
 AML-GUM HYPERTROPHY

Dr Afshan Sumera
 ORGANOMEGALY

Dr Afshan Sumera
 AML-PROGNOSIS
AML is a difficult disease to treat
Complete remission - 60% with chemotherapy
but only 15% to 30% remain free of disease for 5
years.
AMLs with t(8;21) or inv(16) have a relatively good
prognosis with conventional chemotherapy
Bad prognosis -AMLs that follow MDS or genotoxic
therapy, or that occur in the elderly
Treatment - bone marrow transplantation when
possible
Dr Afshan Sumera
 ALL
Immature B (pre-B) or T (pre-T) cells (lymphoblasts)
childhood acute leukemias- 85% are B-ALLs
less common T-ALLs tend to present in adolescent males as
thymic lymphomas
ALL is the most common cancer of children (under 15 years
of age)
three times as common in whites as in blacks
slightly more frequent in boys than in girls
Hispanics have the highest incidence of any ethnic group
Approximately 90% of ALLs have numerical or structural
chromosomal changes
Dr Afshan Sumera
 ALL-MORPHOLOGY

Marrow is hypercellular and packed with

lymphoblasts, which replace the normal
marrow elements

Mediastinal thymic masses occur in 50% to

70% of T-ALLs
associated with lymphadenopathy and
splenomegaly
Dr Afshan Sumera
Acute lymphoblastic leukemia/lymphoma. Lymphoblasts with condensed
Dr Afshan Sumera
nuclear chromatin, small nucleoli, and scant agranular cytoplasm.
 ALL-CLINICAL FEATURES
Neoplastic blasts in the bone marrow
suppresses normal hematopoiesis by physical crowding,
competition for growth factors, and other poorly
understood mechanisms
Abrupt stormy onset within days to a few weeks of the
first symptoms
Depression of marrow function
fatigue due to anemia; fever, reflecting infections
secondary to neutropenia; and bleeding due to
thrombocytopenia

Dr Afshan Sumera
 ALL-CLINICAL FEATURES
Neoplastic infiltration
bone pain resulting from marrow expansion and
infiltration of the subperiosteum
generalized lymphadenopathy, splenomegaly, and
hepatomegaly; testicular enlargement
T-ALL, complications related to compression of large
vessels and airways in the mediastinum
Central nervous system manifestations
headache, vomiting, and nerve palsies resulting from
meningeal spread

Dr Afshan Sumera
 ALL-PROGNOSIS
95% of children with ALL obtain a complete remission
Worse prognosis
age under 2
presentation in adolescence or adulthood
peripheral blood blast counts greater than 100,000
presence of t(9;22) (the Philadelphia chromosome)
Favorable prognostic markers
age of 2 to 10 years
a low white cell count
Hyperploidy
trisomy of chromosomes 4, 7, and 10
presence of a t(12;21)

Dr Afshan Sumera
 DIAGNOSIS OF ALL

High clinical suspicion

PBS & BM study (aspiration/ biopsy)
Morphological diagnosis
Lymphnode aspiration & biopsy
Immunophenotyping, cytogenetics
Imaging (USG scan, CT)

Dr Afshan Sumera
 THANKS
Dr Afshan Sumera