LEUKAEMIA DIAGNOSIS. Leukaemia is a disease resulting from the neoplastic proliferation of haemopoietic or lymphoid cells. Leukaemias are broadly divided into: Acute leukaemias, which, if untreated, lead to death in weeks or months.
Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.
or lymphoid cells.
Leukaemias are broadly divided into:
Acute leukaemias are characterized by a defect in maturation, leading to an imbalance between proliferation and maturation; since cells of the leukaemic clone continue to proliferate without maturing to end cells.
The diagnosis of leukaemia and categorization
required the following parameters.
5- Molecular study.
Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children, representing nearly one third of all pediatric cancers.
The annual incidence rate for acute lymphoblastic leukemia is 30.9 cases per million population. The peak incidence occurs in children aged 2-5 years.
In acute lymphoblastic leukemia, a lymphoid
progenitor cell becomes genetically altered
and subsequently undergoes dysregulated
proliferation, survival, and clonal expansion.
In most cases, the pathophysiology of transformed
lymphoid cells reflects the altered expression of
genes whose products contribute to the normal
development of B cells and T cells
Children with acute lymphoblastic leukemia (ALL) generally
Present with signs and symptoms that reflect bone marrow
infiltration and extramedullary disease.
Because leukemic blasts replace the bone marrow, patients
Present with signs of bone marrow failure, including anemia,
thrombocytopenia, and neutropenia.
Clinical manifestations include fatigue and pallor, petechiae and
bleeding, and fever.
In addition, leukemic spread may manifest as lymphadenopathy
And hepatosplenomegaly. Other signs and symptoms of leukemia
including weight loss, bone pain, and dyspnea.
L1 ALL L2 ALL L3 ALL
Cell size Mainly small Large, heterogeneous Large, homogeneous
Nuclear chromatin Fairly homogeneous Heterogeneous Finely stippled,
Nuclear shape Mainly regular Irregular; clefting Regular
Nucleolus Not visible Usually visible Usually prominent
Amount of cytoplasm Scanty Variable abundant Moderately abundant
Cytoplasmic basophilia Slight to moderate Variable Strong
Cytoplasmic vacuolation Variable Variable Often prominent
Many cases of L3 ALL represent a distinct entity that
requires specific management. However, the categorization
of a case as L1 or L2 ALL is of little importance.
The FAB L1 category includes more childhood
cases with a relatively good prognosis.
The incidence of ALL L1 falls with increasing age whereas
the incidence of ALL L2 does not vary much with age.
ALL L2 has generally been found to have a worse
prognosis, although the difference is not major.
The recent WHO International panel on ALL recommends that
the FAB classification be abandoned, since the morphological
classification has no clinical or prognostic relevance.
1- Acute lymphoblastic leukemia/lymphoma Synonyms:
Former Fab L1/L2
i. Precursor B acute lymphoblastic leukemia/lymphoma.
ii. Precursor T acute lymphoblastic leukemia/lymphoma
2- Burkett's leukemia/lymphoma Synonyms: Former FAB L3
3- Biphenotypic acute leukemia
In general, the most useful antibodies are monoclonal antibodies (McAb) produced by hybridoma technology but, for some antigens, polyclonal antibodies (PcAb) (antisera) are better.
The technique employed for Immunophenotyping may be immunocytochemistry or, much more often, flow cytometry.
Immunophenotyping is essential for the diagnosis of B- or T-lineage acute lymphoblastic leukaemia (ALL).
B lymphoid CD19, CD22, CD79a, CD10
T lymphoid CD3, CD2, CD7
If B lineage cm, k, l, CD20, CD24
If T lineage CD1a, SmCD3, CD4, CD5, CD8, anti-TCR ab, anti-TCR gd
With techniques now available, 70–90% of cases of ALL
have a demonstrable cytogenetic abnormality.
In ALL, chromosomal abnormalities correlate
with other clinical and hematological factors
of prognostic importance but they also have
a considerable independent prognostic
L1 high/ hyperdiploidy.
L1 or L2/t(9;22)/BCR-ABL fusion
L1 or L2/t(4;11)(q21;q23)
L1 or L2/t(12;21)(p12;q22)/early precursor or common ALL
L1 or L2/t(1;19)(q23;p13)/pre-B ALL
L1 or L2/t(10;14)(q24;q11)
L3/t(8;14)(q24;q32) or t(8;22)(q24;q11) or
Correct assignment of patients to the categorize
AML and ALL is very important for prognosis
and choice of therapy.
The FAB group recommended the use of
MPO,SBB and non-specific esterase (NSE)
If Cytochemical reactions for myeloid cells are
negative, presumptive diagnosis of ALL must
be confirmed Immunophenotyping.
AML is the most common acute leukaemia affecting adults, and its incidence increases with age.
Although AML is a relatively rare disease, accounting for approximately 1.2% of cancer deaths in the United States, its incidence is expected to increase as the population ages.
The malignant cell in AML is the myeloblast.
In normal haematopoiesis, the myeloblast is an immature precursor of myeloid white blood cells; a normal myeloblast will gradually mature into a mature white blood cell.
However, in AML, a single myeloblast accumulates genetic changes which "freeze" the cell in its immature state and prevent differentiation Such a mutation alone does not cause leukemia; however, when such a "different combined with other maturation which disrupt genes controlling proliferation, the result is the uncontrolled growth of an immature clone of cells, leading to the clinical entity of AML.
The symptoms of AML are caused by replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets, and normal white blood cells.
These symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection
M0 Undifferentiated acute myeloblastic leukemia.
M1 Acute myeloblastic leukemia with minimal maturation.
M2 Acute myeloblastic leukemia with maturation.
M3 Acute promyelocytic leukemia.
M4 Acute myelomonocytic leukemia.
M4 eosAcute myelomonocytic leukemia with eosinophilia.
Acute monocytic leukemia.
M6 Acute erythroid leukemia.
M7 Acute megakaryoblastic leukemia.
Blasts .30% of bone marrow nucleated cells
Blasts .30% of bone marrow non-erythroid cells <3%
of blasts positive for Sudan black B or for myeloperoxidase
by light microscopy.
Blasts demonstrated to be myeloblasts by immunological
markers or by ultrastructural cytochemistry.
Blasts 30% of bone marrow cells .Blasts .90% of bone marrow
non-erythroid cells .3% of blasts positive for peroxidase or
Sudan black B
Bone marrow maturing monocytic component (promonocytes to
monocytes) .10% of non-erythroid cells
Bone marrow maturing granulocytic component (promyelocytes to
polymorphonuclear leucocytes) .10% of non-erythroid cells
Blasts 30% of bone marrow cells. Blasts 30–89% of bone marrow
Bone marrow maturing granulocytic component (promyelocytes to
polymorphonuclear leucocytes) >10% of non-erythroid cells
Bone marrow monocytic component (monoblasts to monocytes)
<20% of non-erythroid cells and other criteria for M4 not met
Leukaemia M3 AML
In acute hypergranular promyelocytic
leukaemia the predominant cell is a highly
In the majority of cases, blasts are fewer than
30% of bone marrow nucleated cells. The
distinctive cytological features are sufficient to permit a diagnosis and
multiple Auer rods, which are often present
in sheaves or ‘faggots’. Most cases have a minority of cells that are agranular.
M3 AML has been found to be very sensitive
to the differentiating capacity of all-trans-
retinoic acid (ATRA). Following such therapy
an increasing proportion of cells beyond the
promyelocyte stage are apparent.
Blasts .30% of bone marrow cells
Blasts .30% of bone marrow non-erythroid cells
Bone marrow granulocytic component 20% of non-erythroid cells
Significant monocytic component as shown by one of the following:
Bone marrow monocytic component 20% of non-erythroid cells and peripheral blood monocytic.
Bone marrow resembling M2 but peripheral blood monocytic component .5000/cumm.
Blasts .30% of bone marrow cells
Blasts .30% of bone marrow non-erythroid cells
Bone marrow monocytic component .80% of non-erythroid cells
Acute monoblastic leukaemia (M5a)
Monoblasts .80% of bone marrow monocytic component
Acute monocytic leukaemia (M5b)
Monoblasts <80% bone marrow monocytic component
Erythroblasts .50% of bone marrow
Blasts 30% of bone marrow non-erythroid
Blasts 30% of bone marrow nucleated cells.
Blasts demonstrated to be megakaryoblasts by
immunological markers, ultrastructural examination
or ultrastructural cytochemistry
Therapy-related AML and MDS. Alkylating agent-related Topoisomerase II-inhibitor-related Other types
AML with recurrent cytogenetic abnormalities*
AML with t(8;21)(q22;q22)
AML with abnormal bone marrow eosinophils with
inv(16)(p13q22) or t(16;16)(p13;q22)
Acute promyelocytic leukemia with
AML with 11q23 (MLL) abnormalities.
AML with multilineage dysplasia following MDS.
AML not otherwise categorized. This group is nearly similar to FAB group, but blast cells are 20% in stead of 30%
classification assigns some chronic myeloid
leukaemias to a myeloproliferative category and
others, in which there are also dysplastic
features, to a myeloproliferative/myelodysplastic
Chronic myelogenous leukaemia Chronic neutrophilic
Chronic eosinophilic leukaemia
Mast cell leukaemia
Chronic myelomonocytic leukaemia
Chronic myelomonocytic leukaemia with eosinophilia
Myelodysplastic/myeloproliferative disorder associated with
Atypical chronic myeloid leukaemia
Juvenile myelomonocytic leukaemia
Chronic granulocytic leukaemia (CGL) is a disease
entity with specific haematological, cytogenetic
and molecular genetic features.
Alternative designations are chronic myelogenous
leukaemia, chronic myeloid leukaemia and chronic
bi- or triphasic with a chronic and an acute
phase and, sometimes, an intervening
Clinical and haematological features.
CGL is predominantly a disease of adults. The usual clinical
presentation is with splenomegaly, hepatomegaly, symptoms
of anaemia, and systemic symptoms such as sweating and
Occasionally this is an incidental diagnosis when a blood
count is performed for another reason.
and leucocytosis with a very characteristic
The two predominant cell types are the myelocyte and the mature neutrophil .
basophilia and more than 90% have
The platelet count is most often normal or
somewhat elevated but is low in about 5%
with marked granulocytic hyperplasia and
with the myeloid/erythroid (M:E) ratio
being greater than 10:1.
There is hyperplasia of neutrophil,
eosinophil and basophil lineages.
After a variable period in chronic phase, usually
several years, CGL undergoes further evolution.
There may be an abrupt transformation to an
Acute leukaemia, designated blast transformation,
or there may be an intervening phase of
(i) Myeloblasts constitute 10–19% of peripheral blood
white cells or bone marrow nucleated cells.
(ii) peripheral blood basophiles are 20% or more of
(iii) there is persistent thrombocytopenia or persistent
thrombocytosis that does not respond to treatment.
(iv) there is an increasing white cell count and increasing
spleen size that does not respond to treatment.
(v) cytogenetic evolution .
(vi) there is marked granulocyte dysplasia or prominent
proliferation of small dysplastic megakaryocytes in
large clusters or sheets.
Transformation may be myeloid or lymphoid.
It is important to make the distinction since
there lymphoblastic transformation. Lymphoid
blast crisis is more likely to emerge suddenly
without a preceding accelerated phase
CGL was the first malignant disease for which a
consistent association with an acquired non-
random cytogenetic abnormality was recognized.
In 1960 Nowell and Hungerford reported its
Association with an abnormal chromosome designated the Philadelphia (Ph) chromosome after the city of its discovery.
B-lineage lymphoproliferative disorder defined by characteristic morphology and immunophenotype.
Small lymphocytic lymphoma is an equivalent lymphoma without circulating neoplastic cells
Europe and North America with an incidence in
different surveys varying between 1 and more
than 10/100 000/year.
The incidence is lower in Chinese, Japanese and
South American Indians.
It is typically a disease of the elderly with a
higher incidence in males
In the later stages, CLL is characterized
by lymphadenopathy, hepatomegaly,
splenomegaly and eventually by impairment
of bone marrow function.
In the early stages of the disease there are
no symptoms or abnormal physical findings
and the diagnosis is made incidentally
count have been suggested for the diagnosis of
CLL (for example greater than 10 000/cumm).
But the demonstration of a monoclonal population
of B lymphocytes with a characteristic
immunophenotype permits diagnosis at an earlier
stage when the lymphocyte count is less elevated.
Score 1 for each of the following:
• Weak expression of SmIg
• Expression of CD5
• Expression of CD23
• No expression of FMC7
• No expression of CD22
A score of ≥4 points is confirmatory of CLL
two mature lymphocytes and one smear cell
In the early stages of the disease the Peripheral
blood abnormality is confined to the lymphocytes.
Later in the disease course there is a normocytic,
normochromic anaemia and thrombocytopenia.
Neutropenia is uncommon unless cytotoxic therapy
has been administered
The bone marrow aspirate is hypercellular
as a consequence of infiltration by
lymphocytes with similar features to those
in the peripheral blood.
Lymphocytes percentage in the bone
marrow is 40% of all nucleated marrow cells total.
0 Peripheral blood and bone marrow lymphocytosis only.
I Intermediate Lymphocytosis and lymphadenopathy.
II Intermediate Lymphocytosis plus hepatomegaly,
splenomegaly or both.
III Lymphocytosis and anaemia (haemoglobin
concentration less than 11 g/dl).
IV Lymphocytosis and thrombocytopenia (platelet count
less than 100 000/cmm)
Chronic lymphocytic leukaemia may undergo
two types of transformation.
2-large cell transformation, referred to as