Acute and Chronic Leukemias in human

1. Leukemia(s): acute & chronic)
Dr. Dana Ahmed Abdullah
MBChB, MSc, PhD
Hematopathology
dana.abdullah@univsul.edu.iq
2023

2. 2
Bone marrow is a secondary lymphoid tissues and
a specialised tissue contains different types of
cells of different maturation stages.
– Most importantly are hematopoietic cells
that form all blood cells.
– stromal cells: there functions are to provide
support for the hematopoietic cells, provide
a specialised environment needed for
hematopoiesis to occur.
– osteoblasts and osteoclasts are concerned
with producing the bone itself.

3. Bone Marrow Biopsy Specimen.
The extravascular tissue consists of
blood cell precursors and various
tissue cells with scattered fat tissue.
A normal healthy adult marrow (aged
50), will displays 50% hematopoietic
cells and 50% fat.

4. 3
Microscopic examination of the bone marrow biopsy: shows
trabeculae and hematopoietic tissues with multiple fat droplets.
Marrow cells Bone trabecula
Fat droplets

5. 4
Marrow cells as seen in x40 power
Marrow cells as seen in x100 power

6. What are“leukemias”?
Leukemias are a group of disorders characterized by accumulation of malignant white
blood cells inside the bone marrow (with possible spill over into the peripheral blood
and tissue infiltration as well). Thus, there will be increased bone marrow cellularity
(consisted mainly of malignant cells on the expense of normal hematopoiesis.
Finally, there will be suppressed normal hematopoiesis.
These abnormal cells are; primitive (blast cells or immature cells) in cases of AML
and ALL, while they are matured cells (as in case of CLL) or matured and maturing
cells (in case of CML).

7. If there are increased lymphoblasts in the bone marrow (≥20% of all marrow cells), the
result will be acute leukemia of lymphoid origin (Acute Lymphoblastic Leukemia).
If there are increased myeloblasts in the bone marrow (≥20% of all marrow cells), the
result will be acute leukemia of myeloid origin (Acute Myeloblastic Leukemia).
If there are increased promyelocytes cells (malignant and dysplastic) in the bone marrow
(≥20% of all marrow cells), the result will be AML-M3 subtype (Acute Promyelocytic
Leukemia).
If there are increased small mature looking lymphoid cells (marrow lymphocytosis) in
the bone marrow (and those cells conformed to be malignant by flow cytometry), the
result will be CLL (Chronic Lymphocytic Leukemia).

8. 7

9. 8
ALL
CLL
AML
CML
AML
(M5)
AML
(M7)
PRV
ET

10. There are four main subtypes of leukemias
2 acute and 2 chronic
we can also say 2 myeloid and 2 lymphoid
as in the following:
Acute Myeloblastic Leukemia
Acute Lymphoblatic Leukemia
Chronic Myelocytic Leukemia
Chronic Lymphocytic Leukemia
AML
ALL
CML
CLL
9

11. Leukemiaversus Lymphoma?
The term leukemia (‘white blood’) refers to a hemopoietic or lymphoid neoplasm that
involves the bone marrow, and usually also the blood, whereas a lymphoma is a
lymphoid neoplasm that presents as a tumor of extramedullarytissues.
The distinction is, to some extent, artificial.
For example:
1) Burkitt lymphoma can present either as a jaw tumor or as a leukemia with blood and
marrow involvement.
2) Adult T‐cell leukemia/lymphoma presents as leukemia in about 90% of patients but
as lymphoma in 10%.
3) Chronic lymphocytic leukemia has a lymphoma equivalent, known as small
lymphocytic lymphoma (SLL). Thus, WHO classification define this disorder as
CLL/SLLdisorder.

12. In leukemia, the normal hematopoiesis inside the bone marrow is
suppressed and replaced by increasing number of malignant cells
(in acute leukemia called blast cells and in chronic leukemia are increasing intermediate and end
stage cells).
These malignant cells could be blast cells (as in acute leukemia)
or more mature cells (as in chronic leukemia)
11

13. 1
2
Main differences between
acute leukemias and chronic leukemias

14. Acute versuschronicleukemia?
In acute leukemias, the disease characterized by the accumulation of blast cells
in the bone marrow (≥20%) on the expense of other normal marrow cells.
These cells may also infiltrate into peripheral blood or other organs and
tissues (splenomegaly, hepatomegaly and lymphadenopathy)
In chronic leukemias, the disease is characterized by accumulation (increase in
the number) of mature cells (as marrow lymphocytosis in CLL) or mature
and maturing cells (as CML). Later, these cells will infiltrate to peripheral
blood and other organs and tissues (splenomegaly, hepatomegaly and
lymphadenopathy).

15. Adverse effectsofleukemia?
How the symptoms of leukemia arise?
What drive the patient to seek medical attention?.
Accumulation of these malignant cells inside the bone marrow will suppress the
normal hematopoiesis (erythropoiesis, leukopoiesis, thrombopoiesis, etc).
Organs and tissues infiltrations: apart from direct effects on bone marrow function
and normal hematopoiesis; these malignant cells are finally infiltrate organs and tissues
like (spleen, liver, lymph nodes, testis, brain, etc).

16. Blastcellsandacuteleukemia”?
Blast cells are immature cells found in the bone marrow, they are produced from stem
cells and their function are to produce other mature cells (a process called
differentiation).
Blast cells are early cells and are not fully developed, and therefore, do not carry out
any normal function that usually performed by maturecells.
Under normal circumstances, blast cells should not be present in peripheral blood.
- Normally, blast cells constitute up to 5% of the total marrow nucleated cells.
- If this count reached 5-19% inside the bone marrow, it is considered abnormal and
required investigation to search for thecauses.
- If this count reached 20% and more, it is defined as acute leukemia (according to
WHO definition of leukemia)

17. Blast cells with:
High n/c ratio
Prominent nucleoli
Irregular cytoplasm outline
Open nuclear chromatin (light chromatin stain)

18. What are the main differences between myeloblastsand
lymphoblasts?
Lymphoblast cells have minimal differentiation.
Myeloblast cells have some differentiation (granulation and differentiation
to neutrophils and monocytes).
Myeloid cells usually have cytoplasmic granules and may also haveAuer
rods (needle shaped structure inside thecytoplasm).
Myeloid cells stain with cytoplasmic MPO while lymphoid cellsare
negative for MPO.
Lymphoid cells are positive for lymphoid specificmarkers
(CD19 and CD20 in B-cells. CD3, CD4, CD5, CD7, and CD8 inT-cells).

19. Pathophysiology of AcuteLeukemia:
1
) Leukemias typically characterized by infiltration of bone marrow with
abnormal cells and thus displacing normalhematopoiesis.
2) The marrow here is essentially 100% cellular but composed mainly of
malignant cells. Thus, normal hematopoiesis is reduced and replaced
by other useless cells.
3) Thus, leukemic patients are prone to anemia, thrombocytopenia, and
granulocytopenia and all the complications particularly complications
of bleeding and infection.
4) Bone marrow failure secondary to leukemic cells proliferation.

20. Essential diagnostic tools used in leukemia?
1) CBC and blood film: to search for abnormal cells (blast cells) that could infiltrated the
peripheral blood. This avoids unnecessary bon marrow examination in some cases.
2) Bone marrow examination: this includes both bone marrow aspiration and bone
marrow biopsy. This is required if we suspect marrow infiltration by malignant cells
with symptoms of marrow failure.
3) Flow cytometry study (immunophenotyping) using specific CD markers: this test is
required to investigate the nature of the malignant cells that infiltered the marrow.
Whether they are blast cells (myeloid or lymphoid lineage).
4) Genetics testing: Fluorescence In Situ hybridization (FISH) and PCR (polymerase
chain reaction) are required in specific circumstances to investigate the nature of
malignant cells and define any alterations in thecells.

21. RoleofMorphologyinLeukemiaDiagnosis and
Classification

22. Acute Lymphoblastic Leukemia(ALL)
This type of Leukemia is characterized by accumulation of lymphoblasts inside the
bone marrow with possible infiltration into PB, tissues, and organs (LAP and SM).
Based on morphology assessment, blast cells can be categorized into 3 different
morphologic subtypes:
L1: all blast cells and small and homogenous.
L2: blast cells consisted of mixture of small and medium to large cells (heterogenous).
L3: blast cells characterized by presence of many cytoplasmic vacuoles.

23. ALL – L1 with a homogenous population of blast cells

24. ALL – L21 with a heterogenous population of blast cells

25. ALL – L3 (Burkitt's’cells) with characteristic cytoplasmicvacuolation

26. What is Burkitt's Leukemia?
the term Burkitt's Leukemia is used when Burkitt’s cells (lymphoblasts with
prominent cytoplasmic vacuolated cells) are increased in the bone marrow (≥20%).
A non common bust fast-growing type of leukemia that requires early interventionand
treatment regimens.
This type pf leukemia is considered as an oncological emergency due to rapid
proliferation of the blast cells.

27. 1. Pediatrics have a better prognosis and cure rate compared to adultsALL.
2. High WBC count (>50,000 cells per uL) at initial presentationis
associated with poor prognosis.
3. Any WBC count >100,000 cells per uL blood called(hyperleukocytosis)
and is commonly associated with bad prognosis and possibly poor
response to chemotherapy.
4. B-ALL account for 85% ofALL and T-ALLaccount for only 15%. B-ALL
usually is of better prognosis compared toT-ALL.
Prognosisin ALL:

28. Specific AML subtypes andtheir
important clinical associations

29. Morphology assessment of the blast cells
+
supported by special stains in selected cases
+
immunophenotyping diagnosis (use of CD markers to define the
detailed nature of the blast cells).
AML is classified into different subtypes

31. 31
AML
AML
(M5)
AML
(M7)
AML
(M6)

32. Diagrammatic representation of granulopoiesis
Source: Bone Marrow Pathology (2017)
? ?
? ?

33. One type of AML requires a particular attention because it is considered as an
oncologic emergency?
Out ofAML subtypes (AML-M0 toAML-M7); onlyAML-M3 (APL) is
associated with high risk of DIC and bleedingtendencies.
The malignant promyelocytes contains many cytoplasmic granules that harbor
procoagulants and stimulate the coagulation cascade.
This subtype called AML-M3 (also called APL or acute promyelocyticleukemia).
- t(15;17) is present in almost every case of classicAPL (hypergranularAPL)
and not in hypogranularAML-M3.
- If treated promptly and well; AML-M3 is among very goodprognosis.
- If not treated early, there is a high risk and mortality from DIC andbleeding.

34. AML-M3 (also called APL or acute promyelocyticleukemia)
Hypergranular promyelocytes:
the cells contains many granules
inside the cytoplasm. Some blast
cells also contain needle shaped
structure (Auer roads) and also
prominent nucleoli inside the
nucleus.
Prominent nucleoli
Prominent cytoplasmic
granulation
Needle shaped structure (Auer roads)

35. What are Auer rods?
Auer rods are clumps of azurophilic granular material that formelongated
needle-shaped lines seen in the cytoplasm of leukemic blasts of the
myeloid origin only (AML).
What is the usefulness of the Auer rods inside themyeloblasts?
1) Morphologically, if we fine Auer rods inside a blast cells, itindicate
that the lineage of that blast cells is myeloid.
2) Presence of Auer rods usually indicate that this cell is malignant,
because normally there are no Auer rods in non-malignant blastcells.

36. Blast cells with Auer rods (pointedmarks)

37. What areFaggot cell?
Faggot cell is a term used for cells found in (AML-M3 subtype).
This term is applied because of the presence of numerous Auer rods in the
cytoplasm that are usually packedtogether. The accumulation of these Auer
rods gives the appearance of a bundle of sticks, from which the cells are
given their name.

38. Malignant Promyelocytes in (AML-M3) with
many Auer rods (Faggot cells)

39. Malignant Promyelocytes in (AML-M3) with
many Auer rods (Faggot cells)

40. Role of genetic testing in the diagnosis of
acute leukemia?
a) In bothALLandAML: cytogenetics and molecular genetic testing
aid in the diagnosis and/or prognostication.
b) InAML-M3: PML-RARAfusion (testing for t(15;17)” inAPL is diagnostic
c) In B-ALL: BCR-ABL1-like in B-ALL cases will carries a poor prognosis.
d) In ALL: Cytogenetics testing in ALL for ploidy (chromosome content in the nucleus).
More chromosome content in malignant blast cells (hyperploidy) is of good prognosis.

41. Diagnostic criteria in
CLL and CML?

44. 44
CLL
CML

45. Diagrammatic representation of granulopoiesis
Source: Bone Marrow Pathology (2017)
45
What are these cells? What are these cells?
What are these cells? What are these cells?