ACUTE

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

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
 LEUKAEMIA

• A group of malignant disorders affecting the

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

Results in an accumulation of dysfunctional cells

because of a loss of regulation in cell division

Fatal if untreated
• Progressive
 ALL CLL Lymphomas MM
naïve

B-lymphocytes

Plasma
Lymphoid cells
progenitor T-lymphocytes

AML Myeloproliferative neoplasms/disorders

Hematopoietic Myeloid Neutrophils

stem cell progenitor

Eosinophils

Basophils

Monocytes

Platelets

Red cells
 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 from Arginine.umdnj.edu
 COMMON WBC
NEOPLASMS
Lymphoid neoplasms
• B-cell, T-cell, and NK-cell origin

Myeloid neoplasms
• Acute myeloid leukemias (AML)
• immature progenitor cells accumulate in the bone marrow
• Myelodysplastic syndromes
• ineffective hematopoiesis and resultant peripheral blood cytopenias
• Chronic myeloproliferative disorders/neoplasms
• increased production of one or more terminally differentiated myeloid elements
(e.g., granulocytes)

The histiocytoses
• uncommon proliferative lesions of macrophages and dendritic cells
 ETIO-PATHOGENESIS
• Chromosomal Translocations
and Other Acquired Mutations
• Nonrandom chromosomal
abnormalities, most commonly
translocations, are present in the
majority of white cell neoplasms
• 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

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)

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

ETIO-PATHOGENESIS
 ETIO-PATHOGENESIS

Iatrogenic • radiation therapy

Factors • chemotherapy

• incidence of acute myeloid leukemia is increased

1.3- to 2-fold in smokers
Smoking • exposure to carcinogens
• benzene
 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

WHO CLASSIFICATION OF
AML
For detailed classification (WHO & FAB) please refer to Robbins & Cotran Pathologic Basis of Disease, Latest 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 of Disease, Latest Edition
 AML
• acquired oncogenic mutations
tumor of hematopoietic • that impede differentiation
progenitors • leading to the accumulation of immature myeloid blasts in the
marrow

arrest in myeloid • anemia,

development leads to • thrombocytopenia
marrow failure • neutropenia.

• incidence rises throughout life

AML occurs at all ages • peaking after 60 years of age
 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)
Acute myeloid leukemia without maturation. Myeloblasts have delicate nuclear
chromatin, prominent nucleoli, and fine azurophilic granules in the 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 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
• Immunophenotype
• Because it can be difficult to distinguish
myeloblasts and lymphoblasts
morphologically, the diagnosis of AML is
confirmed by performing stains for
myeloidspecific antigens

IMPORTANCE OF
IMMUNOPHENOTYPING IN THE
DIAGNOSIS
 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)
 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
 PLATELET COAGULATION

Petechiae, Purpura Hematoma, Joint bl.

AML-GUM HYPERTROPHY
ORGANOMEGALY
• 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

AML-PROGNOSIS
• 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

ALL
• 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

ALL-MORPHOLOGY
Acute lymphoblastic leukemia/lymphoma. Lymphoblasts with condensed 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
 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
• 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)

ALL-PROGNOSIS
• High clinical suspicion
• PBS & BM study (aspiration/ biopsy)
• Morphological diagnosis
• Lymphnode aspiration & biopsy
• Immunophenotyping, cytogenetics
• Imaging (USG scan, CT)

DIAGNOSIS OF ALL
QUESTION:
List four morphological differences between myeloblast and lymphoblast .

Myeloblast Lymphoblast
1
2
3
4
 REFERENCES
• Robbins and Cotran Pathologic Basis of Disease
• Essential Haematology, A. V. Hoffbrand
THANKS