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1|Page Lasanthi Aryasinghe

• Abrupt stormy onset (days-wks)


• Depression of BM causes:
- Fatigue (due to anemia) 90% of ALLs have
•Immature, precursor
Lymphoblasts (LN): Immunostaining for numerical or
B or T lymphoctyes • 85% are pre-B-cell - Infection (absent mature WBC) Aggressive chemotherapy +
Terminal structural changes:
Lymphoblasts childhood acute • Little cytoplasm prophylactic treatment of
- Bleeding (due to  platelets) deoxynucleotidyl-
leukaemia (4 yrs) (Agranular) • Hyperploidy CNS  90% Remission
• Bone pain (marrow expansion) Cytochemistry: transferase (TdT)
• Distinction between • Large nuclei • Polyploidy
(+ve 95% of ALL)
Acute pre-B & pre-T ALLs • 80% of childhood • Generalized lymphadenopathy • PAS stain block +ve
Lymphoblastic done by Immuno- leukaemias  B- ALL • Delicate, finely stippled • t(12;21) Poor Prognosis:
• Splenomegaly & hepatomegaly chromatin Pre-B-ALL:
Leukaemia/ phenotyping • t(9;22): • Age <2yrs
due to neoplastic infiltration • Acid Phosphatase CD: 19, 22, 10
Lymphoma • Less common: • Absent / inconspicuous Philadelphia
stain +ve  T-ALL • Adolescence or adulthood
(ALL) • FAB Classification: Pre-T-cell • Pre-T ALL thymus involved  nucleoli chromosome
Pre-T-ALL:
- L1ALL, L2ALL, L3ALL “lymphomas” in compression of mediastinal • MPO –ve in ALL • PB blast counts >100, 000
• Nuclear membrane CD: 1, 2, D5, 7 • t(4;11)
Blast size, cytoplasm adolescents w/ structures (high tumor burden)
characteristics & thymic shows subdivisions
• Translocations of
• Testicular involvement (ALL) “lobulated” appearance Early pre-T cells: • Philadelphia chromosome
nuclear:cytoplasmic involvement (11q23)- MLL gene
-ve for CD: 3, 4, 8
ratio • CNS (headache, vomiting, nerve • High mitosis rate rearrangements
palsies) due to meningeal
• “Starry Sky”:
spread, more common in ALL
interspersed benign
than AML
macrophages that have
ingested debris of dying
neoplastic cells

Peripheral Blood Film:

• Peripheral B-cell
Neoplasm /
Lymphoma
•Leucocytosis
• SLL 4% of all NHLs
• Absolute
• Morphologically, lymphocytosis:
phenotypically & >5×109/L
genotypically • Symmetrical superficial LN
indistinguishable • Small, round Variable and dependent on
enlargement: discrete and Lymph Node Biopsy: Chromosomal
lymphocytes with clinical stage
• CLL & SLL differ nontender scanty cytoplasm Tumor cells express: translocations are
only in the degree of • Architecture: effaced
Chronic • Splenomegaly + hepatomegaly CD: 5, 20, 23 & low rare Poor Prognosis:
peripheral blood • Smudge/ Smear cells
Lymphocytic level expression of
• Features of : Anaemia, fragile lymphocytes • Predominant Deletions of : • Deletions of 11q & 17p
Leukaemia lymphocytosis Surface Ig (IgM &D)
Thrombocytopaenia, Immune disrupted during population: small •13q14
(CLL) • Older subjects, smearing lymphocytes 6-12 µm •11q23
deficiency (association w/
& rare <40yrs Herpes zoster) containing: Immunoperoxidase •17p CLL/SLL can transform to
Staging of CLL: • Normochromic
- Round, slightly irregular staining shows more aggressive lymphoid
Small • Rai Classification • <<Males; 2:1 • Hypogammaglobulinemia Normocytic anaemia
nuclei tumor cells are •Triosomy 12q neoplasms:
Lymphocytic - Lymphocytosis (normal Ig)   susceptibility - Autoimmune monoclonal due to
- Condensed chromatin • Prolymphocytic
Lymphoma - Lympadenopathy to infections haemolytic anaemia : expression of one Ig genes of some
- Scanty cytoplasm transformation (B CLL/
(SLL) - Enlarged liver/ Round spherocytic form of light chain CLL/SLL are
• Auto-antibodies against RBCs PLL)
spleen RBCs either κ or λ somatically
or platelets (Autoimmune • Variable numbers of
- Anemia - BM failure hypermutated • Large B-cell lymphoma
haemolytic anaemia / large prolymphocytes
(Hb<10mg/dl) - Hypersplenism (Richter syndrome)
thrombocytopaenia can occur) (high mitotic rate)
- Thrombocytopenia gathered together
(<100 x 109/L) Serum Protein
forming loose agregates
Electrophoresis:
“proliferation centers”
• Binet et al: Hypogammaglobulina
PATHOGNOMIC of
- Stages A, B, C emia
CLL/SLL
- Organ areas 0-5
- Anemia BM Biopsy/Aspirate:
- Thrombocytopenia Lymphocyte infiltrate
of normal elements

Tumor cells infiltrate


spleen and hepatic
portal tracts.

Pheripheral Blood:
Lymphocytosis
(<20,000 per mm3)
seen in only 10% cases • Incurable, however it has
Tumor cells express: an indolent waxing &
BM CD: 19, 20, 10 and t(14;18): waning course
Involved in 85% of Surface Ig Juxtaposition of IgH
• Median survival: 7 to 9 yrs
cases: paratrabecular Neoplastic cells: locus on
lymphoid aggregates Unlike CLL/SLL & chromosome 14 & • Not improved by
• Resemble normal mantle lymphoma BCL2 locus on aggressive therapy, hence,
• Painless, generalized germinal center B cells
• Peripheral B-cell Spleen FL does not express chromosome 18 clinical approach is to
lymphadenopathy
Follicular Lymphoma • Middle age • Predominately nodular CD5 but expresses (overexpression of palliate patients with low
Lymphoma • Involvement of extranodal sites or nodular and diffuse BCL2 protein in BCL2) dose chemotherapy or
• Accounts for 45% of • Males = Females
as GIT, CNS or testis is relatively growth pattern >90% of cases radiation when they
adult lymphomas
uncommon. Uncommonly, may develop symptoms
• Two principal cell types: Almost all tumors lack t(14;18) &
- Majority: small cells w/ express BCL6 instead have
Prominent nodules irregular cleaved nucleus (transcriptional rearrangement of • Histologic transformation
represent white pulp & scanty cytoplasm - repressor- regulates BCL6 gene on in 30%-50% of cases to:
follicles expanded by centrocytes germinal center B chromosome 3q27 - Diffuse Large B-cell
follicular lymphoma - Larger cells with open Lymphoma
cell development)
cells nuclear chromatin, - Burkitts lymphoma (Rare)
several nucleoli &
Hepatic Portal triads modest amount of
also involved cytoplasm - centroblasts
2|Page Lasanthi Aryasinghe

• 30%:
Dysregulation of
Neoplastic cells: BCL6 (regulator
Unlike low grade lymphomas, pts
•Relatively large cell size for formation of
• Peripheral/Mature w/ present:
(4-5 times x diameter of germinal center)
B-cell Lymphoma • Rapidly enlarging often a small lymphocyte) Tumor cells express:
• 10%: t(14;18) and
• Heterogeneous symptomatic, mass at a single Diffuse pattern of CD: 19, 20 & Surface
cREL amplification
group of tumors, nodal or extranodal site (e.g. growth Ig
in a subset Aggressive fatal tumor- if
Diffuse large B- skin & GIT)
• 20% of all NHL • Slightly <Male • Nuclei are round or untreated
cell lymphoma Variable expression
• Can arise at any site; Waldeyer Spleen oval, appear vesicular
(DLBCL) • 60%-70% of • 60 yrs of germinal center Intensive chemotherapy in
ring, oropharngeal lymphoid Presence of isolated due to chromatin Oncogenic viruses:
aggressive lymphoid markers CD10 & 60-80%  Remission
tissues (tonsils & adenoids) large mass is typical margination at nuclear HIV/EBV:
neoplasms BCL6
commonly involved (while indolent B-cell membrane can Immunodeficiency
• “High grade” • 1° or 2° involvement of liver & lymphomas produce sometimes be large All are TdT negative associated large B-
lymphoma spleen in the form of destructive multifocal expansion multilobated or cleaved cell lymphoma
masses of white pulp) • 1-3 Prominent Nucleoli
HIV or KSHV/HHV8
• Cytoplasm moderately Body cavity large
abundant: pale or cell lymphoma
basophilic
• Anaplastic tumours may
contain multinucleated
cells with large
inclusions like nucleoli

Lymph Node Biopsy:


Involved tissue effaced
by diffuse infiltrate
(sheets) of intermediate-
Most manifest at extranodal sites sized lymphoid (10-
25µm) cells: In virtually every
Largely in children • Endemic tumor: presents as a
• Containing round to case the C-MYC
and young adults: mass (lympadenopathy) in the
oval nuclei with coarse oncogene on
mandible with involvement of chromosome 8 is
• Peripheral B-cell African (endemic) chromatin Mature B-cells of
abdominal viscera (particularly translocated to an • Very agressive but
Lymphoma • <<Males 5-10 yrs the tumor express:
the kidneys, ovaries, and adrenal •Lack of nuclear variation Ig gene: responds well to short
• Lymphomatous • EBV 95% of cases glands) in shape & size gives a • CD: 19, 20, 10 term, high dose chemo.
Burkitt’s correlate of Acute monotonous apearance • t (14;8)
• Surface IgM • Most children and young
Lymphoma Lymphoblastic Sporadic • Sporadic tumor: present as • t (2;8)
• Several nucleoli • BCL6 adults can be cured, but
Leukaemia (ALL) • <<Males abdominal mass involving
ilioceacum & peritoneum • Moderate amt of faintly • t (8;22) the outcome is more
• 30% of childhood • EBV 20% of cases • Monotypic κ or λ
basophilic cytoplasm guarded in older adults
NHLs light chain
Subset of aggressive • High mitotic index & • Essentially all
lymphoma Involvement of BM & peripheral apoptotic tumor cell endemic tumors
• Individuals w/ HIV blood is uncommon. death is typical  have latent EBV
numerous pale Tingible
body macrophages with
ingested nuclear debris
“Starry sky pattern”

BM aspirated cells:
• Slightly clumped
chromatin
• 2-5 distinct nucleoli
• Blue cytoplasm with
multiple, clear vacuoles

• Predominant tumor
cell resemble
normal Marginal Tumors acquire
Zone B-cell (mature) chromosome
Tumors are localized, extranodal: aberrations
• Heterogeneous
Gastric MALT • Arise within tissue with pre- t(11;18) or t (1;14)
group of tumors that
lymphoma is most exisiting chronic inflammatory Splenic Marginal Zone @ extranodal sites
arise within LN,
Marginal zone common form; disorders of autoimmune or Lymphoma (Benign):  makes tumor
spleen or extranodal
Lymphomas/ preceded by infectious etiology Massive Splenomegaly nonresponsive to
tissue
Tumors of Helicobacter Pylori w/circulating monoclonal antibiotic therapy
MALT: • Association with • Remain localized for long, may
gastritis B-cells w/ a villous
Maltoma inflammation spread late in their course Translocations 
appearance
suggests that these • May regress if the inciting agent tumor progression
neoplasms lie b/w (e.g. H. pylori) is eradicated independent of
reactive lymphoid original extrinsic
hyperplasia and full- stimuli e.g. H.pylori
blown-B-cell
lymphoma
3|Page Lasanthi Aryasinghe

BM showing abnormal BM Aspirate:


plasma cells:

Marrow cells largely


replaced by plasma cells,
• Monoclonal protein
incl forms w/ multiple
(paraprotien) - IgG in
nuclei, prominent
⅔ & IgA in ⅓ of nucleoli & cytoplasmic
• Bone pain pathological factures cases; in serum droplets containing Ig
 hypercalcemia: confusion, and/or urine
• Multifocal destructive Occasional pts w/ “indolent
weakness, lethargy, constipation • Immuneparesis:
• Plasma cell bone tumors composed myeloma” can survive for
and polyuria normal serum Ig
neoplasm: of plasma cells many years
proliferation of B- • Features of anemia levels (IgG, A, M)  (plasmacytoma)
cell clone secretes • Recurrent infections • Urine contains Bence throughout the skeletal Chemo w/ eg Melphalan
and synthesizes a • 98% of cases system (axial) alkylating agents induce
Jones proteins in 2/3 Karyotypic
single homogenous >40yrs • Protineaceous deposits from remission in 50%-70% pts,
heavy Bence-Jones protienuria, • Plasma cells in BM abnormalities are: but the median survival still
Ig or its fragments • Peak incidence in
Multiple hypercalcemia, uric acid & (>20%) w/ abnormal >30% of bone cellularity : only 3 yrs
7th decade • Deletions of 13q
Myeloma • IL-6: potent growth amyloid  Renal failure forms
factor for myeloma • Plasma cells with a • t(14q32) involving
• << Men (myeloma kidney) • Bone lesions appear perinuclear hallow (due Ig heavy chain Poor Prognosis:
• Myeloma cells • <<African descent • Abnormal bleeding tendancies: radiographically as to prominent Golgi app)
secrete: osteoclast- punched-out defects, •  Serum IL-6
Myeloma protein interferes w/ & eccentric nucleus
activating factor platelet fn & coagulation factors usually 1 to 4 cm • Monosomy chrom 13
(OAF), TNF & IL-1  • Plasmablasts
 RBCs to stick to one another • Normochromic,
osteolytic lesions • Pts with bony  lesions
in linear arrays (rouleaux) • Bizarre multinucleated
normocytic or macro-
cells • Untreated: 6-12 months
• Amyloid disease  diarrhea, cytic anemia
macroglossia & carpal tunnel • Russell bodies
• Rouleux formation:
(cytoplasmic inclusions)
• Dutcher bodies (nuclear
inclusions)

Dysregulated synthesis &


• High ESR
secretion of Ig 
cytological variants:
• Serum calcium • Flame cells
levels in 25% of cases • Mott cells
•  Serum IL-6 in
pts w/ active disease Grossly: gelatinous, soft,
red tumor masses

• t(2;5)(p23; q35)
Lymph Node Biopsy: • Associated with
ALK gene
Follows an aggressive course, • Often comprises large rearrangements
Anaplastic anaplastic cells on chromosome 2
• T-cell or null cell • Common in characterized by systemic
Large Cell CD 30 +ve T-cells  formation of a
phenotype children symptoms and extranodal
Lymphoma • Some cells contain chimeric gene
involvement
horse-shoe shaped encoding the ALK
nuclei & voluminous fusion proteins
cytoplasm (behave as active
Tyrosine Kinases)

Acute presentation as: Combination of


HTL V-1 endemic in
chemotherapy may be
Adult T-Cell parts of Japan & • Lymphadenopathy
tried, however the
Leukaemia/ the Caribbean;
• Hepatosplenomegaly Consistent CD4+ • Associated with prognosis is poor
Lymphoma • Mature T-cell disease is rare in
phenotype HTLV-1 infection
people who have • Skin lesions (cutaneous
(ATLL) not lived in these infiltration) ATLL-1 lymphocytes:
Antiretroviral drugs may
areas • Hypercalcemia Bizarre morphology with have a valuable role
a convoluted, clover-leaf
(flower cells) nucleus

Mycosis Fungiodes & SS:


Chronic cutaneous lymphoma Disease progression • Indolent tumors
presents with: characterized by
extra-cutaneous • Variety of treatment
• Severe pruritis
• Chronic cutaneous spread, commonly to Skin Biopsy: available including chemo,
• Psoriasis- like lesions radiotherapy & a photo-
CD4+ Helper T cell LN, spleen, liver & BM
Infiltration of the activable drug (psoralens)
Mycosis lymphoma
epidermis and upper combined with UV-A light
Fungoides Peripheral Smear: CD4+ T-cells
• Characterized by a Clinically, cutaneous lesions show dermis by neoplastic T (PUVA)
In 25% of cases small
marked predilection three distinct stages: cells with characteristic
number of tumor cells • Median survival: 8-9 yrs
to involve the skin cerebriform nuclei
1- Inflammatory premycotic can be seen leading to
overlap between • Transformation to large
2- Plaque phase cell lymphoma of T-cell
Mycosis fungoides &
3- Tumor phase Sezary syndrome type occasionally occurs as
a terminal event
4|Page Lasanthi Aryasinghe

Peripheral Smear:
Shows circulating T
lymphoma cells
• CD4+ Helper T cell “Sezary cells” with
tumor Variant in which skin involvement characteristic deep
is manifested as: nuclear clefting:
• Leukaemic Skin Biopsy:
Sézary manifestation of • Generalized pruritic, exfoliative cerebriform nuclei
Shows lymphocytic CD4+ T-cells *SEE Mycosis Fungioides*
Syndrome Mycosis fungoides erythroderma affecting palms,
soles, face- Red Man syndrome Sensitive molecular infiltration
Characterized by a analyses have shown
marked predilection • Generalized lymphadenopathy that tumor cells are
to involve the skin found early in the
disease course in the
blood, BM, and LN (in
Mycosis Fung also)

Bimodal incidence: Clinical S/S:


• Young adulthood • Nontender, asymmetrical, firm, Classical Reed- Sternberg Cells
RS Cells are activated (age 15–35) discrete enlargement of LNs (activated B- cells):
B-cell w/ Ig gene • >55 years old
• Constitutional symptoms:
rearrangements
• <<HIV - Fever 30%: continuous or cyclic
Distinctive neoplastic
giant cells: Reed- • <<Men except - Pruritis 25%: often severe
Sternberg cells with Nodular sclerosis
- Alcohol-induced pain in areas • Large (15-45 μm)
reactive lymphocyte, variant <<women Lympho-histiocytic
where disease is present • Binucleate (mirror image nuclei)
histiocytes and (L& H cells): Cure rate in stage I & IIA is
HL <1% of cancer • Large pink-staining nucleoli- owl’s eyes
granulocytes - Weight loss close to 90%
worldwide 1/25000 • Abundant cytoplasm
1) Localised to single - Profuse sweating • NLPHL best prognosis
LN or chain of nodes followed by MC
- Weakness, fatigue • Normochromic,
Normocytic Anemia Variants RS Cells: • NS & LR are slowly
2)Orderly contiguous - Anorexia & cachexia
• NF-ĸB up Mononuclear: progressing and prognosis
spread: adjacent LNs • Eosinophilia
Hodgkin’s  Spleen  Hepatic regulation depends on stage
Lymphoma common to EBV • Leucocytosis (
disease Finally BM Ann Arbor Staging (I-IV, A,B,E): • Polypoid nuclei (popcorn • LD type has the worse
involvement & extra- positive and Predictive of prognosis and neutrophils)
cells) prognosis
negative HL
nodal disease-Staging guides the choice of therapy •  Serum Lactate De- • Specific to Lymphocyte
3) Less peripheral A- Absence of symptoms in B hydrogenase (LDH) predominant HL
• 1 round nucleus Long-term survivors of
involvement • LMP-1 protein • Large inclusion-like nucleolus chemo and radiotherapy
(Latent membrane B- Presence of 1 or more of foll: Pleomorphic have an increased risk of
protein-1) of EBV, Lacunar:
Classical HL: •Unexplained fever >38°C • Multiple, irregular nuclei developing second cancer
has transforming
• Seen in Lymphocyte
1- Nodular sclerosing activity •Night sweats depletion HL
2- Mixed cellularity •Loss of >10% body wt w/in 6mts
3- Lymphocyte-rich • Cytokines
secreted by RS E- Localized extranodal (ie tissue • Folded or multilobate nuclei
4- Lymphocyte- cells cause other than LN, thymus, spleen, • Surrounded by abundant pale
depletion accumulation of Waldeyer’s Ring, appendix or cytoplasm
reactive cells like Peyer’s patch) extension from • Predominantly in Nodular Sclerosis
IL-6, IL-13, TNF mass of nodes

• Lacunar variant of RS
cells

• Commonly occurs
RS cells:
in adolescents and • Involves lower cervical,
Nodular Most common type • +ve: CD15 & 30
young adults supraclavicular and mediastinal Prognosis is excellent
Sclerosing type 65-70% of HLs • -ve: CD 45, B & T-
• Rarely associated LN cell markers
with EB virus
• Collagenous (fibrotic)
bands dividing the LN
parenchyma into
nodules

• Classical RS cells and


Mononuclear cells are
plentiful Identical to NS:
• << Males,
Mixed • Older age group • Usually present with systemic • Diffuse effacement by a RS cells:
20-25% of HLs heterogeneous cellular • +ve: CD15 & 30 Strong EBV assoc Prognosis is very good
Cellularity type symptoms and advanced stage
• Strong EBV infiltrate: • -ve: CD 45, B & T-
association - Small lymphocytes, cell markers
- Eosinophils
- Plasma cells
- Benign macrophages

• Frequent (40%) • Diagnostic or Classical


Lymphocyte- Very good to excellent
Uncommon form association w/ RS cells & Mononuclear
Rich type prognosis
EBV cells frequently present

• Predominantly in
older patients • Paucity (shortage) of Overall prognosis is poor as
Lymphocyte lymphocytes & relative pt presents in advanced
Least common type • <<HIV-positive
Depletion Type abundance of RS cells or stage with systemic
• Often EBV Pleomorphic variants symptoms
associated

In contrast to all
• Nodular infiltrate
Nodular other forms of HL;
Excellent prognosis
Lymphocyte • << Young males • Typical RS cells are
L&H variants show:
Predominance extremely difficult to
Uncommon • No EBV •B cell marker: CD20
Hodgkin's find
association •Germinal center A small number of cases
Lymphoma
• L&H or popcorn RS cells cell-specific transform to:
(NLPHL)
seen transcriptional
Large B cell lymphoma
factor: BCL6
5|Page Lasanthi Aryasinghe

BM aspirate:
Dyserythropoiesis

•Acquired neoplastic
disorders of multi- Nucleated red cell
potent hemato- progenitors with
poietic stem cells multilobulated or multiple
nuclei
BM aspirate shows:
Characterized by: • Dyserythropoiesis
• Ineffective haemo-
• Dygranulopoiesis
poiesis In most cases • Anemia – nonresponsive to
• Peripheral blood disease arises de treatment (Refractory Anemia) • Dymegakaryopoeisis
cytopaenias novo (1° MDS), but • Sometimes neutropenia &
• Single or multiple in a significant Ring sideroblasts w/ Fe • Partial or total loss of
thrombocytopenia may be
lineage dysplasia proportion chemo Blood Film shows: laden mitochondria chromosomes 5,7 or Y
present w/out anemia
and/or radio- (Refractory cytopenia) • Pancytopaenia: RBCs (Prussian Blue or Perl’s)-
therapy has been are macrocytic or perinuclear granules
• It is preleukaemic given for another • Recurring infections: granulo- • Trisomy 8
dimorphic • 5q-Syndrome:
Myelodysplastic & may progress to hematological cytes are  and show impaired
Syndromes chemotatic, phagocytic & • Reticulocyte count Dygranulopoiesis Good prognosis
AML, although disease, lymphoma • 20% RAS oncogene
death often occurs or solid tumor adhesive function •  Granulocytes w/ mutation (N-RAS)
before (2° MDS) • Spontaneous bruising or lack of granulation
bleeding • Pelger abnormality:
• 50% pts >70yrs • 15% FMS mutation
FAB Classification: • May be asymptomatic single or bilobed
• <25% are <50yrs granulocyte nuclei
• Based proportion • In CMML: splenomegaly, gum Pseudo-Pelger-Huet cells
• <<Males hypertrophy, lymphadenopathy • Platelets may be
of cells in PB & BM neutrophils with only two
large or small lobes ( normal 3 to 4)
• Refractory Anemia,
•Single or multilineage
Ring Sideroblasts/
Excess Blasts, RAEB dysplasia
Dymegakaryopoeisis
in transformation,
Chronic Myelomon-
ocytic Leukemia
(CMML)

Megakaryocytes with
multiple nuclei instead of
normal single
multilobated nucleus

Group of conditions
4 Types of MPDs:
arising frm pluri-
potent stem cell • Splenomegaly • Chronic Myeloid
Leukaemia (CML)
• Cellular phase: Hypercellular
BM with PB cytosis • Polycythaemia Rubra
Characterized by:
Vera (PCV)
Chronic Myelo- • Fibrotic and/or leukaemic
•Clonal proliferation << Middle aged -
proliferative phase: progressive BM fibrosis • Essential
of one or more Elderly individual
Disorders Thrombocythaemia
haemopoietic
(ET)
components in the
BM, PB, liver,spleen ONLY CML shows low NAP • Myelofibrosis (MF)
• Slow indolent scores; PCV & MF have high NAP
PCV, ET & MF are non-
progression
leukemic MPDs
(relative to ALL)

Clonal disorder of
the pluripotent CML characterized by
stem cells Philadelphia chromosome
Peripheral Blood Smear
Peripheral Blood: • Reciprocal translocation
CML is triphasic: t(9;22)(q34;q11)
• Leucocytosis >50,000
1- Chronic (Stable)
Phase) • Full spectrum of • Abelson proto-oncogene
 Total body myeloid cell mass myeloid cells(Neutro, ABL moved to the BCR
2- Accelerated  clinical features: Baso, Eosino, Pro/ gene on 22 + part of 22
Phase: meta/myelocytes) moves to 9
• Hypermetabolism (weight loss,
Anaemia, thrombo- lassitude, nightsweats, anorexia) Neutrophils in different • BCR-ABL chimeric fusion
•Normochromic
cytopenia,  baso- stages of maturation gene
• Massive splenomegaly normocytic anaemia
phils, eosinophils or • < 40-60 years
Chronic • Chimeric gene encodes
blast cells in PB &/or • Anaemia (pallor, dyspnoea and
Myeloid BM • < Atom bomb  chimeric protein with
tachycardia) BM exam: Bone Marrow Biopsy
Leukaemia survivors in Japan tyrosine kinase activity
(CML) • Bleeding: impaired platelets Hypercellular with
3- Blast crises: granulopoeitic • Ph +ve reduce the
• >20% blasts in
function (bruising, epistaxis,
predominance adherence of CML
blood &/or BM menorrhagia)
progenitor cells to the
• Gout/renal impairment due to • NAP Score: low BM stromal layers
• Enlarged spleen &
fibrotic marrow hyperuricaemia from excessive compared to their normal
purine breakdown • Ph chromosome: is cell counterparts 
• New chromosome +ve on cytogenetic autonomous proliferation
abnormalities (eg analysis of blood/BM of CML progenitors due
Hypercellular with
double Ph chrom) •  Serum Uric acid to their premature
granulopoeitic dominance
• Transformation/ escape from physiological
Metamorphosis to inhibitory influences in
AML (70% of cases) the stem cell niche
or ALL (30%)
6|Page Lasanthi Aryasinghe

Alterations in genes
encoding for critical
transcription factors 
arrest of terminal
Bone Marrow hypercellular  • PB Morphology:
differentiation
replaced with leukaemic blasts - Blast count >20% = Most common:
which leads to: Acute leukemia
• t(8;21) - CBF complex
FAB Classification: • General - Bone pain, fever - Blast type:
Myeloblast- AML • AML-M4 Eo:
° of maturation • All age groups • BM failure Cytopaenias: Myelomonocytic with
Lymphobast- ALL
(M0-M3) and (Anaemia, Thrombocytopaenia, abnormal eosinophils:
• 80% of adult
lineage of leukaemic Neutropaenia) Delicate chromatin,
leukaemias • BM Morphology inv (16) - CBF 1β gene Poor Prognosis:
blasts (M4-M7) prominent nucleoli, and
taken into account, • 10- 15% of •Extramedullary organ infiltration fine azurophilic • Translocations
• Cytochemistry:
using morphology childhood monocytic component AML-M5: cytoplasmic granules with an 11q23
- MyeloPeroxidase • AML-M3: Promyelocytic
and cytochemistry leukaemias - Gingival hypertrophy breakpoint and
Acute (MPO) stain
- Skin infiltration AML M1: t(15;17) (PML; RARA) - MLL gene
Myelogenous +ve myeloid
- Meningeal leukaemia CD 34, 64, 33 Retinoic acid receptor –α rearrangement
Leukaemia Can arise de novo -ve  lymphoid
WHO Classification: - Solid tumor mass (chloroma) gene (RAR α) fuses to a •Therapy related:
(1° AML), but can - PAS stain protein PML  chimeric
Cytogenetic, Alkylating agents &
develop from MDS, • Lymphadenopathy “block positivity” in gene block in myeloid
morphologic and Topoisomerase II
chemo and/or lymphoid differentiation
clinical features • Hepatomegaly, Splenomegaly inhibitors
radio-therapy or
(prior haematologic All trans retinoic acid
hematological • Coagulopathy: DIC in Acute • Immunophenotyping AML M3 - BM shows
disorders) in (ATRA) used for
disease Promyelocytic Leukaemia (AML- (Flow Cytometry) neoplastic promyelocytes
defining disease treatment
M3) from tissue thrombplastin • Cytogenetic analysis with abnormally coarse
entities
(Chromosomal and numerous azurophilic
Banding) granules. Needle like Auer
M6: Erythroleukaemia • FLT3 Mutations 
• Molecular genetic rods
(DiGuglielmo's disease) activates tyrosine kinase
analysis (FISH)
This synergistic genetic
“hits”  cellular
proliferation along with
block in differentiation

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