Lymphomas and Leukemias (MedLive by DR Priyanka)

HAEMATOLOGY
Disorders of Leucocytes and Lymphoreticular Tissues
DR. PRIYANKA SACHDEV , MD
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Hematology is the study of the various cells and
components of the blood→
1. RBC
2. WBC
3. Platelets

• Circulating blood normally contains 3 main types of
mature blood cells—
1. The red cells (erythrocytes)

2. The white cells (leucocytes)
3. The platelets (thrombocytes)
WHITE BLOOD CELLS:
1. Granulocytes
2. Agranulocytes

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Granulocytes
• Depending upon the colour and content of granules,

Granulocytes
are of 3 types:
1. Neutrophils
2. Eosinophils
3. Basophils

Agranulocytes
• The Agranulocytes are 2 types of lymphocytes:
1. T, B lymphocytes
2. Monocyte

• GRANULOPOIESIS
• LYMPHOPOIESIS

• The formed elements of blood—red cells, granulocytes,
monocytes, platelets, and lymphocytes—have a common
origin from HSCs, pluripotent cells that sit at the apex of
a hierarchy of bone marrow progenitors

• HSCs have two essential properties that are required
for the maintenance of hematopoiesis:
1. Pluripotency
2. Capacity for self-renewal

• HSC differentiate into two types of progenitors—
1. Lymphoid (immune system) stem cells→ develop into T, B

and NK cells
2. Nonlymphoid or myeloid (trilineage) stem cells →
differentiate into 3 types of cell lines
a. Granulocyte-monocyte progenitors (producing neutrophils,

eosinophils, basophils and monocytes),
b. Erythroid progenitors (producing red cells)
c. Megakaryocytes (producing platelets).
HSC
Lymphoid stem cells Myeloid (trilineage) stem cells
Prolymphocyte
Granulocyte-monocyte p. Erythroid p Megakaryocytes
T, B and NK cells Neutrophils RBC Platelet

Eosinophils
Basophils
Monocytes
ERYTHROID SERIES

• GRANULOPOIESIS
• LYMPHOPOIESIS

WBC Formation
GRANULOPOIESIS LYMPHOPOIESIS
MYELOID SERIES MONOCYTE-MACROPHAGE SERIES
Neutrophil Monocyte Lymphocyte

Eosinophil Macrophage
Basophil
GRANULOPOIESIS
• MYELOID SERIES
• MONOCYTE-MACROPHAGE SERIES

WBC Formation

Basophil
MYELOID SERIES
• Myemonoloblast (most primitive precursor)
• Myeloblast
• Promyelocyte
• Myelocyte
• Metamyelocyte
• Band forms
• Neutrophil
Granulopoisis

During their development
from myeloblas
1. The nuclei of successive stages become
progressively coarser
2. The nuclei lose their nucleoli
3. The cytoplasm loses its blue colour.
4. As the cells become mature lysosomal granules
appear; firstly non-specific primary or azurophilic
granules appear which are followed by specific or
secondary granules that differentiate the
neutrophils, eosinophils and basophils.
Granulopoisis

REMEMBER
• Azurophilic (primary or non- specific) granules appears
at PROMYELOCYTE stage
• Specific or secondary granules appear at MYELOCYTE

stage and accordingly, the cell can be identified at this
stage as belonging to the neutrophilic, eosinophilic or
basophilic myelocyte.

Granulopoisis

WBC Formation

Basophil
MONOCYTE-MACROPHAGE SERIES
• Myemonoloblast (most primitive precursor)

• Monoblast
• Promonocyte
• Monocyte
• Macrophage (in tissue)

Granulopoisis

• GRANULOPOIESIS
• LYMPHOPOIESIS

WBC Formation

Basophil
LYMPHOPOIESIS
• Lymphoblast
• Prolymphocyte
• Lymphocyte

LYMPHOID SERIES

MYELOID SERIES

LYMPHOID SERIES

Antigen Designation
CLUSTER OF DIFFERENTIATION

REMEMBER

POLLS 1
B

D

A

NORMAL COUNTS

POLYMORPHS (NEUTROPHILS)
• 12-15 μm in diameter.
• It consists of a characteristic dense nucleus, having
2-5 lobes
• Pale Cytoplasm containing numerous fine violet
pink granules → 2 types

Primary or azurophilic granules
• Large and coarse
• Appear early at the promyelocyte stage.
• These granules contain hydrolases, elastase,
myeloperoxidase, cathepsin-G, cationic proteins,
permeability increasing protein, and microbicidal protein
called defensins.

Secondary or specific granules
• Smaller and more numerous

• Appear later at myelocyte stage
• These are are MPO negative
• These contain lactoferrin, NADPH oxidase,
histaminase, vitamin B12 binding protein, and
receptors for chemoattractants and for laminin.

MNEMONIC

Neutrophilia
• An increase in circulating neutrophils above 7,500/μl

• 1. Acute infections→ For example: pneumonia, cholecystitis ,salpingitis,
meningitis, diphtheria, plague, peritonitis, appendicitis, actinomycosis,
poliomyelitis, abscesses, furuncles, carbuncles, tonsillitis, otitis media,
osteomyelitis etc.
• 2. Other inflammations e.g. tissue damage resulting from burns,
operations, ischaemic necrosis (such as in MI), gout, collagen-vascular
diseases, hypersensitivity reactions etc.
• 3. Intoxication e.g. uraemia, diabetic ketosis, eclampsia, poisonings by
chemicals and drugs.
• 4. Acute haemorrhage, internal or external.
• 5. Acute haemolysis.
• 6. Disseminated malignancies.
• 7. Myeloproliferative disorders e.g. myeloid leukaemia, polycythaemia
vera, myeloid metaplasia. Dr. PRIYANKA SACHDEV
Neutropenia
• When the absolute neutrophil count falls below 2,500/μl

• 1. Certain infections e.g. typhoid, paratyphoid, brucellosis, influenza,
measles, viral hepatitis, malaria, kala-azar etc.
• 2. Drugs induce aplasia of the bone marrow cause neutropenia, e.g.
antimetabolites, nitrogen mustards, benzene, ionising radiation.
• 3. Certain haematological and other diseases e.g. pernicious anaemia,
aplastic anaemia, cirrhosis of the liver with splenomegaly, SLE, Gaucher’s
disease.
• 4. Cachexia and debility.
• 5. Anaphylactoid shock.
• 6. Certain rare hereditary, congenital or familial disorders e.g. cyclic
neutropenia, primary splenic neutropenia, idiopathic benign neutropenia.

‘Shift-to-left’ is appearance of neutrophils with decreased number of
nuclear lobes in the peripheral blood e.g. presence of band and stab
forms and a few myelocytes in the peripheral blood.
• It is seen in severe infections, leucoerythroblastic reaction or
leukaemia.
‘Shift-to-right’ is appearance of hypersegmented (more than 5

nuclear lobes) neutrophils in the peripheral blood
• such as in megaloblastic anaemia, uraemia

MYELOID SERIES

LYMPHOCYTES
1. Small (9-12 μm in diameter)
2. Large lymphocytes (12-16 μm in diameter)
• Round or slightly indented nucleus with coarsely-clumped

chromatin
• Scanty basophilic cytoplasm.
• Plasma cells are derived from B lymphocytes under the influence of
appropriate stimuli.
• The nucleus of plasma cell is eccentric and has cart-wheel pattern
of clumped nuclear chromatin.

Lymphocytosis
• Above 4,000/μm

• 1. Certain acute infections e.g. pertussis, infectious
mononucleosis, viral hepatitis, infectious lymphocytosis.
• 2. Certain chronic infections e.g. brucellosis, tuberculosis,
secondary syphilis.
• 3. Haematopoietic disorders e.g. lymphocytic leukaemias,
lymphoma, heavy chain disease.
• 4. Relative lymphocytosis is found in viral exanthemas,
convalescence from acute infections, thyrotoxicosis, conditions
causing neutropenia.

Lymphopenia
• Below 1,500/μm

• 1. Severe bone marrow failure.
• 2. Corticosteroid and immunosuppressive therapy.
• 3. Widespread irradiation.

MONOCYTES
• The monocyte is the largest mature leucocyte in the
peripheral blood measuring 12-20 μm in diameter.
• It possesses a large, central, oval, notched or indented
or horseshoe-shaped nucleus which has
characteristically fine reticulated chromatin network.
• The cytoplasm is abundant, pale blue and contains
many fine dust-like vacuoles

Monocytosis
• A rise in the blood monocytes above 800/μl

• 1. Certain bacterial infections e.g. tuberculosis, subacute bacterial
endocarditis, syphilis.
• 2. Viral infections.
• 3. Protozoal and rickettsial infections e.g. malaria, typhus,
trypanosomiasis, kala-azar.
• 4. Convalescence from acute infection.
• 5. Haematopoietic disorders e.g. monocytic leukaemia, lymphomas,
myeloproliferative disorders, multiple myeloma, lipid storage disease.
• 6. Malignancies e.g. cancer of the ovary, stomach, breast.
• 7. Granulomatous diseases e.g. sarcoidosis, inflammatory bowel disease.
• 8. Collagen-vascular diseases

EOSINOPHILS
• Eosinophils are similar to segmented neutrophils in
size (12-15 μm in diameter)
• Coarse, deep red staining granules in the cytoplasm
• Have usually two nuclear lobes.

Eosinophilia
• Above 400/μl

• 1. Allergic disorders e.g. bronchial asthma, urticaria,
angioneurotic oedema, hay fever, drug hypersensitivity.
• 2. Parasitic infestations e.g. trichinosis, echinococcosis, intestinal
parasitism.
• 3. Skin diseases e.g. pemphigus, dermatitis herpetiformis,
erythema multiforme.
• 4. Löeffler’s syndrome.
• 5. Pulmonary infiltration with eosinophilia (PIE) syndrome.
• 6. Tropical eosinophilia.

BASOPHILS
• Coarse, intensely basophilic granules which usually fill the
cytoplasm and often overlie and obscure the nucleus

Basophilia
Above 100/μl

• 1. Chronic myeloid leukaemia
• 2. Polycythaemia vera
• 3. Myelosclerosis
• 4. Myxoedema
• 5. Ulcerative colitis
• 6. Following splenectomy
• 7. Hodgkin’s disease
• 8. Urticaria pigmentosa.

POLLS 2
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D

• 1. Certain infections e.g. typhoid, paratyphoid, brucellosis, influenza,
measles, viral hepatitis, malaria, kala-azar etc.
• 2. Drugs induce aplasia of the bone marrow cause neutropenia, e.g.
antimetabolites, nitrogen mustards, benzene, ionising radiation.
• 3. Certain haematological and other diseases e.g. pernicious anaemia,
aplastic anaemia, cirrhosis of the liver with splenomegaly, SLE, Gaucher’s
disease.
• 4. Cachexia and debility.
• 5. Anaphylactoid shock.
• 6. Certain rare hereditary, congenital or familial disorders e.g. cyclic
neutropenia, primary splenic neutropenia, idiopathic benign neutropenia.

C

LEUKEMIAS AND LYMPHOMAS

• Leukemia is used for lymphoid neoplasms presenting with
widespread involvement of the bone marrow usually
accompanied by the presence of large number of tumour
cells in the peripheral blood.
• Lymphoma is used to describe proliferations arising as

discrete tissue masses.

MYELOID SERIES

Leukemia is a neoplasm of blood cells with primary
involvement of bone marrow.
Lymphoma is a solid tumor with primarily involvement of

solid organ (mostly lymph nodes, but may also be spleen,
liver and other organs).

• Many entities called “lymphoma” occasionally have leukemic
presentations, and evolution to “leukemia” is not unusual
during the progression of incurable “lymphomas.”
• Conversely, tumors identical to “leukemias” sometimes arise

as softtissue masses without detectable bone marrow
disease.
• Hence, when applied to particular neoplasms, the terms
leukemia and lymphoma merely reflect the usual tissue
distribution of each disease at presentation
Normal lymph node

Lymphomas:
• 1) Hodgkins lymphoma/Hodgkins disease (HD)
• (2) Non-Hodgkin’s lymphoma (NHL).

HODGKIN’S DISEASE
• Hodgkin’s disease (HD) primarily arises within the lymph
nodes and involves the extranodal sites secondarily.
• The term “Hodgkin lymphoma” encompasses a group of

lymphoid neoplasm that is characterized by the presence of
distinctive neoplastic giant cells called Reed-Sternberg cells
• This group comprises about 8% of all cases of lymphoid

neoplasms.
• HD is a group of lymphoid neoplasms arising in a single
node and spreads from the nodes to spleen, then liver
and finally bone marrow.

• Bimodal peaks —one in young adults between the age of 15 and
35 years and the other peak after 5th decade of life.
• The HD is more in adult males than females.
• The classical diagnostic feature is the presence of Reed-Sternberg

(RS) cell (or Dorothy-Reed- Sternberg cell)
• RS cells are derived from B-cells of germinal center

PATHOGENESIS

EBV causes infection of epithelial cells of oropharynx and B- cells
because of the presence of CD21 molecule on the surface of
these cells
LMP-1 gene present in the EBV integrate with human DNA
Activation of NF-kB and JAK/STAT signaling pathways
promoting B-cell survival and proliferation (This increases the

chances of B- cell lymphoma)

WHO CLASSIFICATION (modified
REAL classification)

• The classification is based on Immunophenotyping of
RS cells

1. Classical HD → All subtypes into this group have Reed-
sternberg cells with same immunotype ie. positive for CD 15
and CD 30
2. Non-classical /Nodular lymphocytic predominance type →

This subtype is histogenically distinct from other (classical)
subtypes in that the Reed-sternberg cells are positive for CD
20 and BCL-6 but are negative for CD 15 and CD 30.

TYPES OF RS Cells
• A) Classical Reed-Sternberg cells
• B) Lacunar cells
• C) Lympho-histocytic (L&H cells) or popcorn cells
• D) Pleomorphic variant

A) Classical Reed-Sternberg cells
• This is a large cell which has characteristically a bilobed nucleus
appearing as mirror image of each other but occasionally the
nucleus may be multilobed.
• Each lobe of the nucleus contains a prominent, eosinophilic,

inclusion-like nucleolus with a clear halo around it, giving an owl-
eye appearance.
• The cytoplasm of cell is abundant and amphophilic.
• Found in mixed cellularity type HD and lymphocyte rich type
• These are positive for CD 15 and CD 30, and PAX-5 (B-cell

transcription factor).
B) Lacunar cells
• It is smaller
• In addition to above features has a pericellular space or
lacuna in which it lies, which is due to artefactual
shrinkage of the cell cytoplasm.
• Found in nodular sclerosis variety of HD

C) Lympho-histocytic (L&H cells)
or popcorn cells
• This type of RS cell is larger with lobulated nucleus in
the shape of popcorn
• Found in lymphocyte predominance (non classical

type) type of HD.

D) Pleomorphic variant
• These cells have pleomorphic and atypical nuclei.
• Found in lymphocyte depletion type.

TYPES OF RS Cells
• A) Classical Reed-Sternberg cells
• B) Lacunar cells
• C) Lympho-histocytic (L&H cells) or popcorn cells
• D) Pleomorphic variant

REMEMBER
• Most sensitive marker of Reed-Sternberg cells is CD 30
• Most specific marker is PAX 5
• Reed Sternberg cells are not absolutely specific for

Hodgkins disease and have also been noticed in cases of
infectious mononudeosis and other malignancies
including lymphoma, carcinoma and sarcomas.
Therefore, Reed-Sternberg, cells are not sufficient to
establish the diagnosis of Hodgkins disease.
CLASSIFICATION OF HODGKINs
LYMPHOMA

1) Nodular sclerosis
• It is the most common variant of HD.
• It is the only variant which is equally common in females and
males (all other variants are more common in males).
• It occurs in adolescent and young adults.
• It frequently involves mediastinum.
• It has excellent prognosis (2nd best after lymphyocytic

predominance type).
• RS cells are positive for CD 15 and CD 30.
• It has no association with EBV (EBV negative).
Morphology
• Fibrous bands are present which divide cellular areas into
nodules: nodular sclerosis.
• Lacunar RS cells are seen on histology

LYMPHOMA

Mixed cellularity
• It is the 2nd most common type overall, but the most

common type of HD in India.
• It is more common in males
• has biphasic age incidence (Bimodal age distribution),
i.e. seen in young adults and in older age > 55 years.
• It is associated with EBV (EBV positive).

Morphology
• Replacement of entire affected lymph nodes by
heterogeneous mixture of various types of apparently
normal cells.
• These include proliferating lymphocytes, histiocytes,

eosinophils, neutrophils and plasma cells.
• Clasical Reed-Sternberg cells are seen

LYMPHOMA

Lymphocyte depletion
• It is the least common type of HD.
• It is more common in older males

• HIV-infected individuals.
• Cells are positive for CD 15 and CD 30.

• It has the worst prognosis.

Morphology
• There is paucity of lymphocytes.
• Pleomorphic variants RS cells are seen, along with
Hodgkin cells (atypical histiocytes).
• It has maximum area of necrosis

LYMPHOMA

Lymphocytic Rich
• It is more common in males and is seen in older adults
• It has frequent classical RS cells.
• It is associated with EBV (EBVpositive).
• Prognosis is good to excellent.

• Proliferation of small lymphocytes admixed with a
varying number of histiocytes forming diffuse pattern
• Classical variant of RS cells seen

LYMPHOMA

II. NODULAR LYMPHOCYTE-
PREDOMINANT HD
Non classical type
• This is a newly described entity which is distinct from the classic
HD described above.
• It is more common in young males.

• Popcorn cells (Lympho histocytic cells: L&H cells ) are seen
• RS cells are positive for CD 20, but negative for CD 15 and CD
30
• It is not associated with EBV
• It has the best prognosis Dr. PRIYANKA SACHDEV
Morphology
• These cases of HD have a nodular growth pattern (similar to
nodular sclerosis type).
• Like lymphocyte-rich pattern of classic type, there is

predominance of small lymphocytes with sparse number of RS
cells.
• Popcorn cells (Lympho histocytic cells: L&H cells ) are seen

CLINICAL FEATURES
• Hodgkin’s disease is particularly frequent among young
and middle-aged adults.
• All histologic subtypes of HD, except the nodular sclerosis
variety, are more common in males.

• 1. Most commonly, patients present with painless, movable
and firm lymphadenopathy. The cervical and mediastinal
lymph nodes are involved most frequently. Other lymph node
groups like axillary, inguinal and abdominal are involved
sometimes.
• 2. splenomegaly ,Liver enlargement
• 3. Constitutional symptoms (type B symptoms) → low-grade

fever (Pel Ebstein fever) with night sweats and weight loss.
Staging

• Stage I -» Involvement of single lymph node or single
extralymphoid site
• Stage II -> Involvement of 2 or more lymph node on the same
side of diaphragm
• Stage III -» Involvement of both sides of diaphragm which may
also be accompanied by localized involvement of single
extralymphoid site or spleen
• Stage IV -> Diffuse or disseminated involvement of one or more
extra lymphoid organs or tissue with or without associated lymph
node involvement
Each of these stages is divided into A & B category.
• A category —> Without symptoms

• B category —> With symptoms such as unexplained weight
loss, unexplained fever & night sweats

Poor prognostic factors
Beside staging and histological type, following poor prognostic
factors have been described
• 1. Male gender
• 2. Age > 45 years
• 3. Stage IV disease
• 4. Haemoglobin < 10.5g/dl
• 5. Leucocytosis with WBC > 15,000
• 6. Lymphocytopenia
• 7. A Serum albumin level < 4g/dl.
POLLS 3
A

A

D

A

C

C

A

C

C

B

D

D

D

A

A

C

C

Leukamoid reaction
• An elevated WBC count (leukocytosis), that is a
physiological response to stress or infection (in contrast to
a primary blood malignancy, such as leukemia).
• It is a leukocytosis exceeding 50000/Cu.mm not exceeding

100,000/μl.

MYELOID SERIES

TYPES
1. MYELOID LEUKAEMOID REACTION → significant
increase in early neutrophil precursors in
peripheral blood myelocytes, metomyelocytes,
promyelocytes and even myeloblasts.
2. LYMPHOID LEUKAEMOID REACTION

Causes of leukamoid reaction
• 1. Infections e.g. staphylococcal pneumonia,
disseminated tuberculosis, meningitis, diphtheria,
sepsis, endocarditis, plague, infected abortions etc.
• 2. Intoxication e.g. eclampsia, mercury poisoning,
severe burns.
• 3. Severe haemorrhage and severe haemolysis.

LABORATORY FINDINGS
• 1. Leucocytosis, usually moderate, not exceeding 100,000/μl.
• 2. Proportion of immature cells mild to moderate, comprised by

metamyelocytes, myelocytes (5-15%), and blasts fewer than 5% i.e.
the blood picture simulates somewhat with that of CML
• 3. Infective cases may show toxic granulation and Döhle bodies in

the cytoplasm of neutrophils.
• 4. Neutrophil (or Leucocyte) alkaline phosphatase (NAP or LAP)

score in the cytoplasm of mature neutrophils in leukaemoid reaction
is characteristically high
Differentiating features from leukemia
(CML) are
• 1) Increased leukocyte alkaline phosphate (LAP) score (LAP
score is decreased in CML).
• 2) Blasts cells are <5% (in leukemia it is > 20%).
• 3) Presence of toxic granules are Dohle bodies in

neutrophils (Dohle bodies are absent in leukemias).
• 4) There is no basophilia (in CML there is basophilia).

REMEMBER

POLLS 4


B

D

LEUKEMIAS
• Leukemias are lymphoid neoplasms presenting with
widespred involvement of bone marrow usually
accompanied by the presence of large number of tumor
cells in peripheral blood
• In contrast to lymphomas where there is proliferations of

tumor cells to produce discrete tissue masses

TYPES
1) Lymphoid:
• (i) Acute Lymphoid leukemia (ALL)
• (ii) Chronic Lymphoid leukemia (CLL)
2) Myeloid:
• (i) Acute Myeloid leukemia (AML)
• (ii) Chronic myeloid leukemia (CML)
MYELOID SERIES

LYMPHOID SERIES

• Acute leukemias have a high rate of proliferation
without differentiation and their clinical course is
rapid.
• Chronic leukemias have a low rate of proliferation of

tumor cells with good differentiation and their clinical
course is slow.
• CML
• AML
• ALL
• CLL
MYELOID NEOPLASMS

• CML
• AML
• ALL
• CLL
OVERVIEW
• Introduction
• Age
• Pathogenesis
• Classification
• Clinical features
• Lab diagnosis
• Treatment
• Prognosis
CHRONIC MYELOID LEUKAEMIA (CML)
• CML is an acquired disease of haemopoietic stem cell that is
characterized by→
1. Leucocytosis with granulocytic immaturities

2. Basophilia
3. Splenomegaly
4. Distinct chromosomal abnormality - Philadelphia (Ph’)
chromosome.
MYELOID SERIES

AGE
• CML presents in old age (> 50 years )

OVERVIEW
• Introduction
• Age
• Pathogenesis
• Classification
• Lab diagnosis
• Treatment
• Prognosis
Pathophysiology
• Translocations t(9;22) / ABL-BCR Translocation → Ph
chromosome

MYELOID SERIES

ABL-BCR hybrid gene
NORMALLY→
• ABL gene is a protooncogene having tyrosine kinase

activity.
• ABL gene → normal location on chromosome 9

• BCR gene→normal location on chromosome 22
IN TRANSLOCATION

ABL gene → normal location on chromosome 9
It is translocated to chromosome 22
It fuses with BCR (breakpoint cluster region) gene
Forms an ABL-BCR hybrid gene → Philadelphia chromosome
This hybrid do a more potent and abnormal signal transduction even without
growth factors
Uncontrolled mitosis
CML
• BCR ABL gene is hallmark of CML.

Phases of CML
• 3 Phases→

OVERVIEW
• Introduction
• Age
• Pathogenesis
• Classification
• Lab diagnosis
• Treatment
• Prognosis
Clinical Features
• I. DUE TO BONE MARROW FAILURE→
• 1. Anaemia producing pallor, lethargy, dyspnoea.

• 2. Bleeding manifestations due to thrombocytopenia
causing spontaneous bruises, petechiae, bleeding from
gums and other bleeding tendencies.
• 3. Infections are quite common and include those of
mouth, throat, skin, respiratory, perianal and other sites.
• II. Symptoms due to hypermetabolism such as weight
loss, lassitude, anorexia, night sweats.
• III. Splenomegaly is massive. In some patients, it may

be associated with acute pain due to splenic
infarction.

Laboratory Findings
I. BLOOD PICTURE
II. BONE MARROW EXAMINATION
III.Cytogenetics
IV.CYTOCHEMISTRY
V.OTHER INVESTIGATIONS

I. BLOOD PICTURE
• 1. Anaemia→ normocytic normochromic
• 2.Thrombocytopenia

3. White blood cells →
a) Marked leucocytosis (approximately 200,000/μl or

more at the time of presentation).
b) Immature WBCs
c) Basophilia
d) Eosinophilia
• The natural history of CML consists of 3 phases—
chronic, accelerated, and blastic.
Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
IV.CYTOCHEMISTRY

• 1. Cellularity→ There is hypercellularity with total or
partial replacement of fat spaces by proliferating
myeloid cells.

• 2. Myeloid cells The myeloid cells predominate in the
bone marrow with increased myeloid-erythroid ratio.
• 3. Erythropoiesis → reduction in erythropoietic cells.
• 4. Megakaryocytes → Megakaryocytes are normal

but are usually smaller in size than normal.
Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
IV.CYTOCHEMISTRY

III. Cytogenetics
• Cytogenetic studies on blood and bone marrow cells
show the characteristic chromosomal abnormality called
Philadelphia (Ph) chromosome seen in 90-95% cases of
CML.
• Ph chromosome is formed by reciprocal balanced

translocation between part of long arm of chromosome
22 and part of long arm of chromosome 9{(t(9;22)
(q34;11)} forming product of fusion gene, BCR/ ABL
Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
IV.CYTOCHEMISTRY

IV. CYTOCHEMISTRY
• Reduced scores of neutrophil alkaline phosphatase
(NAP) which helps to distinguish CML from myeloid
leukaemoid reaction in which case NAP scores are
elevated
• However, NAP scores in CML return to normal with

successful therapy

Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
IV.CYTOCHEMISTRY

V. OTHER INVESTIGATIONS
• 1. Elevated serum uric acid (hyperuricaemia).

Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
IV.CYTOCHEMISTRY

OVERVIEW
• Introduction
• Age
• Pathogenesis
• Classification
• Lab diagnosis
• Treatment
• Prognosis
Treatment
TREATMENT OF ANAEMIA AND HAEMORRHAGE
a) Anaemia and haemorrhage are managed by fresh blood
transfusions and platelet concentrates.
b) Patients with severe thrombocytopenia (platelet count

below 20,000/μl) require regular platelet transfusions
since haemorrhage is an important cause of death in
these cases.
1. Imatinib oral therapy
• The basic principle underlying imatinib oral treatment is
to competitively inhibit ATP binding site of the ABL
kinase, which in turn, inhibits signal transduction
BCR/ABL fusion protein
• Imatinib induces apoptosis in BCR/ ABL-positive cells

and thus eliminates them
• Complete haematologic remission is achieved for 18

months in 97% cases treated with imatinib.
• 2. Allogenic bone marrow (stem cell) transplantation
• Although this treatment modality offers proven cure, it

is complicated with mortality due to procedure and
development of post-transplant graft-versus-host
disease (GVHD) and, therefore, post-transplant
immunosuppressive treatment has to be continued.

• 3. Interferon-α Prior to imatinib and allogenic
transplantation, chronic phase of CML used to be
treated with interferon-α was the drug of choice.
• 4. Chemotherapy → busulfan, cyclophosphamide

(melphalan) and hydroxyurea.
• 5. Others → splenic irradiation, splenectomy and

leucopheresis.

Index for prognosis of CML

POLLS 5
C

D

D

B

• CML
• AML
• ALL
• CLL
ACUTE MYELOID LEUKAEMIA
• Acute myeloid leukaemia (AML) is a heterogeneous

disease characterised by infiltration of malignant
myeloid cells into the blood, bone marrow and other
tissues.

MYELOID SERIES

OVERVIEW
• Introduction
• Age
• Pathogenesis
• Classification
• Lab diagnosis
• Treatment
• Prognosis
AGE
• AML is mainly a disease of adults (median age 50
years)

Pathophysiology
• AML develops due to inhibition of maturation of
myeloid stem cells due to mutations
• Translocations {t(8;21)(q22q22)}
• Translocations {t(15;17)(q22;q12)}
• inversions {inv(16) (p13;q22)}

MYELOID SERIES

• These mutations may be induced by several etiologic
factors—heredity, radiation, chemical carcinogens
(tobacco smoking, rubber, plastic, paint, insecticides
etc) and long-term use of anti-cancer drugs but
viruses do not appear to have role in the etiology of
AML.

CLASSIFICATION

MYELOID SERIES

OVERVIEW
• Introduction
• Age
• Pathogenesis
• Classification
• Lab diagnosis
• Treatment
• Prognosis
Clinical Features

mouth, throat, skin, respiratory, perianal and other sites.

II. DUE TO ORGAN INFILTRATION
→
• Due to replacement of the marrow and other tissues by
leukaemic cells.
• 1. Pain and tenderness of bones (e.g. sternal tenderness)

• 2. Lymphadenopathy and enlargement of the tonsils may
occur.
• 3. Splenomegaly of moderate grade may occur. Splenic
infarction, subcapsular haemorrhages, and splenic rupture
may occur
• 4. Hepatomegaly
• 5. Leukaemic infiltration of the kidney
• 6. Gum hypertrophy due to leukaemic infiltration of the
gingivae is a frequent finding in myelomonocytic (M4)
and monocytic (M5) leukaemias.
• 7. Chloroma or granulocytic sarcoma is a localised
tumour forming mass occurring in the skin or orbit
• 8. Meningeal involvement

Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
IV.Immunophenotyping
V.CYTOCHEMISTRY
VI.OTHER INVESTIGATIONS

I. BLOOD PICTURE
1. Anaemia→
• severe, progressive and normochromic.
• moderate reticulocytosis up to 5% and a few nucleated red
cells may be present.
2. Thrombocytopenia
• The platelet count is usually moderately to severely
reduced (below 50,000/μl) .Acute promyelocytic leukaemia
(M3) may be associated with a serious coagulation
abnormality, disseminated intravascular coagulation (DIC).
3. White blood cells The total WBC count ranges from
subnormal-to-markedly elevated values.
• exceed 100,000/μl
• Myeloblasts with Ayur rods present

Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
V.CYTOCHEMISTRY

• 1. Cellularity Typically, the marrow is hypercellular

2. Leukaemic cells
• The bone marrow is generally tightly packed with
leukaemic blast cells.
• The diagnosis of AML is based on finding that

myeloidblasts make up more than 20% of the cells in the
marrow
• Auer rods (Represent abnormal azurophilic granule) are

also present in myeloblasts and their presence is taken to
be definite evidence of myeloid differentiation.Dr. PRIYANKA SACHDEV
• 3. Erythropoiesis Erythropoietic cells are reduced.
Dyserythropoiesis,megaloblastic features and ring
sideroblasts
• 4. Megakaryocytes They are usually reduced or

absent.

Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
V.CYTOCHEMISTRY

III. Cytogenetics
• i) M3 cases have t(15;17)(q22;q12).
• ii) M4 have inv(16)(p13q22).

Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
V.CYTOCHEMISTRY

IV Immunophenotyping
• AML cells express CD13 and CD33 antigens.
• M7 shows CD41 and CD42 positivity.

Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
V.CYTOCHEMISTRY

V. CYTOCHEMISTRY
• 1. Myeloperoxidase (MPO) Positive in immature myeloid

cells containing granules and Auer rods but negative in M0
myeloblasts.
• 2. Sudan Black Positive in immature cells in AML.
• 3. Non-specific esterase (NSE) Positive in monocytic series

(M4 and M5).
• 4. Periodic acid-Schiff (PAS) Negative.
• Positive in erythroleukaemia (M6).
• 5. Acid phosphatase Negative.

• Diffuse reaction in monocytic cells (M4 and M5).

Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
V.CYTOCHEMISTRY

VI. BIOCHEMICAL INVESTIGATIONS
• 1. Serum muramidase Serum levels of lysozyme (i.e.

muramidase) are elevated in myelomonocytic (M4) and
monocytic (M5) leukaemias.
• 2. Serum uric acid raised.

Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
V.CYTOCHEMISTRY

Revision of types

OVERVIEW
• Introduction
• Age
• Pathogenesis
• Classification
• Lab diagnosis
• Treatment
• Prognosis
Treatment
I. TREATMENT OF ANAEMIA AND HAEMORRHAGE
• Anaemia and haemorrhage are managed by fresh blood
transfusions and platelet concentrates.
• Patients with severe thrombocytopenia (platelet count

below 20,000/μl) require regular platelet transfusions
since haemorrhage is an important cause of death in
these cases.

2. CYTOTOXIC DRUG THERAPY
• The most effective treatment of AML is a combination

of 3 drugs:
1. Cytosine arabinoside
2. Anthracyclines (daunorubicin, adriamycin)
3. 6-thioguanine
• Promyelocytic leukaemia (M3) is treated with tretinoin

(retinoic acid)
3. BONE MARROW
TRANSPLANTATION
Bone marrow (or stem cell) transplantation from
suitable allogenic or autologous donor (HLA and mixed
lymphocytes culturematched) is increasingly being used
for treating young adults with AML in first remission.

Prognostic factors of AML

REMEMBER

POLLS 6


A

D

D

C

D

A

B

B

C

• CML
• AML
• ALL
• CLL
LYMPHOID NEOPLASMS

• CML
• AML
• ALL
• CLL
Acute lymphoblastic leukemia/lymphoma
• Lymphoid malignancy originating from precursor

series of B or T cell (i.e. pre-B and pre-T)
• Acute lymphoblastic leukemia (ALL) encompasses a

group of neoplasms composed of immature,
precursor B (Pre-B) or T (Pre-T) lymphocytes referred
to as lymphoblast.
LYMPHOID SERIES

TYPES
1. Pre B-cell ALL

2. Pre T-cell ALL

AGE
• Peak incidence of Pre B-cell ALL is evident between 3-
5 years and ALL is the most common childhood
cancer.
• Pre T-cell ALL occurs in adolescent male.

OVERVIEW
• Introduction
• Age
• Pathogenesis
• Classification
• Lab diagnosis
• Treatment
• Prognosis
Pathogenesis
• Leukaemic blasts in pre-B-cell ALL show characteristic
cytogenetic abnormality of t(9;22) i.e. Philadelphia
positive-ALL

REMEMBER

LYMPHOID SERIES

FAB CLASSIFICATION
• 1) L1 lymphoblasts: It is most common type and has
better prognosis. Cells have scanty cytoplasm and
inconspicuous nuclei.
• 2) L2 lymphoblasts: Cells are large and more pleomorphic

in size with abundant cytoplasm and prominant nucleus.
• 3) L3 lymphoblasts: It is least common type. It is identical

to Burkitt’s lymphoma, i.e. Mature B-cells
• L1 ALL is the Commonest type of ALL having the
best prognosis.
• L3 ALL is the rarest type of ALL having the worst

prognosis

OVERVIEW
• Introduction
• Age
• Pathogenesis
• Classification
• Lab diagnosis
• Treatment
• Prognosis
Clinical Features

mouth, throat, skin, respiratory, perianal and other
sites.
II. DUE TO ORGAN INFILTRATION
→
1. Bone pain and tenderness
• Resulting from marrow expansion and infiltration of
the subperiosteum.
2. Generalized lymphadenopathy, splenomegaly and

hepatomegaly
• Caused by neoplastic infiltration of these tissues.
• More common in ALL than AML.
3.Symptoms related to compression of large mediastinal
vessels or airway → In Pre-T ALL of thymus.
4.CNS manifestation
• Due to meningeal involvement.
• Headache, vomiting, nerve palsies.
• More common in ALL than in AML.
5. Testicular involvement is also more common in ALL than in

AML.
Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
V.CYTOCHEMISTRY

1. Blood examination
• Anaemia
• Thrombocytopenia
• Leucopenia to- normal TLC to leucocytosis.
• DLC shows large number of circulating lymphoblasts
(generally in excess of 20%) having round to
convoluted nuclei, high nucleo-cytoplasmic ratio and
absence of cytoplasmic granularity.
Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
V.CYTOCHEMISTRY

2. Bone marrow examination
• The FAB diagnostic criteria for acute leukemia is the
presence of > 30 % blasts in bone marrow (normal <
5%).
• According to WHO classification, blasts should be >

20% blast in bone marrow for diagnosis of acute
leukemia.

Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
V.CYTOCHEMISTRY

3. Cytochemistry
• i) Periodic acid-Schiff (PAS): Positive in immature
lymphoid cells in ALL.
• ii) Acid phosphatase: Focal positivity in leukaemic blasts
in ALL.
• iii) Myeloperoxidase: Negative in immature cells in ALL.
• iv) Sudan Black: Negative in immature cells in ALL.
• v) Non-specific esterase (NSE): Negative in ALL.

Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
V.CYTOCHEMISTRY

Immunophenotyping
• TdT (terminal deoxynucleotidyl transferase) is
expressed by the nuclei of both pre-B and pre-T stages
of differentiation of lymphoid cells.
• Pre-B-cell type: Typically positive for pan-B cell

markers CD19, CD10, CD9a.
• Pre-T-cell type: Typically positive for CD1, CD2, CD3,
CD5, CD7.
Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
V.CYTOCHEMISTRY

Cytogenetic analysis
• Leukaemic blasts in pre-B-cell ALL show characteristic
cytogenetic abnormality of t(9;22) i.e. Philadelphia
positive-ALL

Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
V.CYTOCHEMISTRY

OVERVIEW
• Introduction
• Age
• Pathogenesis
• Classification
• Lab diagnosis
• Treatment
• Prognosis
Treatment
I. TREATMENT OF ANAEMIA AND HAEMORRHAGE
• Anaemia and haemorrhage are managed by fresh
blood transfusions and platelet concentrates.
• Patients with severe thrombocytopenia (platelet

count below 20,000/μl) require regular platelet
transfusions since haemorrhage is an important
cause of death in these cases.

2. CHEMOTHERAPY
• combination of
1. vincristine
2. prednisolone
3. anthracyclines (daunorubicin, adriamycin)
4. L-asparaginase

3. BONE MARROW TRANSPLANTATION
• Bone marrow (Stem cell) transplantation from
suitable allogenic or autologous donor (HLA and
mixed lymphocytes culture-matched) is used in preB
and pre-T cell ALL in adults with relapses. Bone
marrow transplantation has resulted in cure in about
half the cases.

REMEMBER
• The common sites of relapse of ALL after complete
remission are: Bone marrow , CNS and testis.

• CML
• AML
• ALL
• CLL
• CML
• AML
• ALL
• CLL
CHRONIC LYMPHOCYTIC LEUKAEMIA/
SMALL LYMPHOCYTIC LYMPHOMA (B-CELL
CLL/SLL)
• CLL and SLL are identical neoplasms/arise due to an

abnormal neoplastic proliferation of B cells.
• CLL is a tumor of mature B-ceIls
• CLL involves primarily bone marrow and blood,

while SLL involves lymph nodes.
LYMPHOID SERIES

AGE
• CLL/SLL occurs more commonly in middle and older
age groups (over 50 years of age) with a male
preponderance (male-female ratio 2:1).

OVERVIEW
• Introduction
• Age
• Pathogenesis
• Classification
• Lab diagnosis
• Treatment
• Prognosis
Pathogenesis

Clinical Features

causing spontaneous bruises, petechiae, bleeding
from gums and other bleeding tendencies.
mouth, throat, skin, respiratory, perianal and other
sites.
• 4. Enlargement of superficial lymph nodes is a very
common finding. The lymph nodes are usually
symmetrically enlarged, discrete and non-tender.
• 5. Splenomegaly and hepatomegaly are usual.

Laboratory Findings
I. BLOOD PICTURE
III.Cytogenetics
V.CYTOCHEMISTRY

BLOOD PICTURE
• 1. Anaemia Anaemia is usually mild to moderate and

normocytic normochromic in type. Mild
reticulocytosis may be present.
• 2. . Platelets The platelet count is normal or

moderately reduced as an autoimmune phenomenon

• 3. White blood cells Typically, there is marked
leukocytosis but less than that seen in CML (50,000-
200,000/ μl).
• Usually, more than 90% of leucocytes are mature

small lymphocytes.
• Smudge or basket cells (degenerated forms) are

present due to damaged nuclei of fragile malignant
lymphocytes. Dr. PRIYANKA SACHDEV
REMEMBER

• 1. Increased lymphocyte count (25-95%).

• 2. Reduced myeloid precursors.
• 3. Reduced erythroid precursors.

3. Immunophenotyping
• CLL is a tumor of mature B-ceIls
• Therefore it expresses the B-cell markers such as CD19

,CD20 and surface IgM and IgD,
• In addition CD 23 and CD5 are also present
• Low-level expression of surface Ig (usually IgM or IgM

and IgD) is also typical.
4. LYMPH NODE BIOPSY
• Cases with lymphadenopathy at presentation show
replacement of the lymph node by diffuse proliferation
of well-differentiated, mature, small and uniform
lymphocytes without any cytologic atypia or significant
mitoses .
• These cells are of monoclonal B-cell origin having
immunologic features of mantle zone B-cells.

Treatment
• Unlike other leukaemias, none of the available drugs
and radiation therapy are capable of eradicating CLL
and induce true complete remission.
• Treatment is, therefore, palliative and symptomatic

• These approaches include:
1. Alkylating drugs (e.g. chlorambucil,
cyclophosphamide), corticosteroids
2. Radiotherapy.
3. Splenectomy

REVISION

• CML
• AML
• ALL
• CLL
MYELOID SERIES

• CML
• AML
• ALL
• CLL
LYMPHOID SERIES

• CML
• AML
• ALL
• CLL
CML

AML

ALL

CLL

REMEMBER


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HAEMATOLOGY

Disorders of Leucocytes and Lymphoreticular Tissues

DR. PRIYANKA SACHDEV , MD

Dr. PRIYANKA SACHDEV

1. The red cells (erythrocytes)

Dr. PRIYANKA SACHDEV

• Depending upon the colour and content of granules,

Dr. PRIYANKA SACHDEV

• The Agranulocytes are 2 types of lymphocytes:

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

1. Lymphoid (immune system) stem cells→ develop into T, B

a. Granulocyte-monocyte progenitors (producing neutrophils,

Lymphoid stem cells Myeloid (trilineage) stem cells

Granulocyte-monocyte p. Erythroid p Megakaryocytes

T, B and NK cells Neutrophils RBC Platelet

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

MYELOID SERIES MONOCYTE-MACROPHAGE SERIES

Neutrophil Monocyte Lymphocyte

Dr. PRIYANKA SACHDEV

MYELOID SERIES MONOCYTE-MACROPHAGE SERIES

Neutrophil Monocyte Lymphocyte

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

• Specific or secondary granules appear at MYELOCYTE

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

MYELOID SERIES MONOCYTE-MACROPHAGE SERIES

Neutrophil Monocyte Lymphocyte

• Myemonoloblast (most primitive precursor)

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

MYELOID SERIES MONOCYTE-MACROPHAGE SERIES

Neutrophil Monocyte Lymphocyte

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

• Smaller and more numerous

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

‘Shift-to-right’ is appearance of hypersegmented (more than 5

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

• Round or slightly indented nucleus with coarsely-clumped

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV