LEUKEMIA

CLASSIFICATION
A. Acute. . . . . 3 months, Bone Marrow:
Primitive Blast Cells
B. Subacute .. 3-12 months, BM cells-
Intermediate
C, Chronic. . .. 1 year or more

CYTOLOGIC CATEGORIES
A. Myeloid: Acute or Chronic
B. Lymphoid: Acute or Chronic
 FAB CLASSIFICATION
A. M1 ( Myeloblastic without maturation) . .
3% blast cells

B. M2 ( Myeloblastic with maturation). .

30% -blast cells

C. M3 (Hypergranular Promyelocytic). .
Promyelocytes with Auer rods
 ACUTE MYELOBLASTIC
LEKEMIA: M1,M2 & M3

CHARACTERISTICS
1. Deficient granulation
2. Pseudo-Pelger Huet anomaly
3. Cytochemistry:
Napthol AS-D Cloroacetate ( + )
Alpha Napthyl Acetate Esterase (-)
B. Monocytic Component
M4(Myelomonocytic). . 20%
myeloid/monoblasts
20% promonocytes/monocytes
( lysozyme)

M5 (Monocytic). . Poorly differentiated

20% abnormal granulocytic
precursors
Characteristics
1. NaptholASD Chloroacetate(-)
2. Alpha Napthyl Acetate Esterase (+)
3. Alpha Napthyl Butyrate “ (+)
C. ERYTHROCYTIC COMPONENT
M6 Erythroleukemia . . . 50% erythroid
-30% erythroid with 10% bizarre
- Auer Rods (+) or (-)
- Megakaryocytes (=) or (-)
Abnormal Megakaryocytes
Atypical Platelets
- Cytochemistry
Alpha Napthyl Acetate Esterase
PAS- (+)- Strongly positive
D. MEGAKARYOCYTIC COMPONENT
M7 Acute Megakaryocytic Leukemia
- Blast cells: Undifferentiated
- Cytochemistry
Sudan Black (-)
Peroxidase (-)
Butyrate Esterase (-)
Acetate Esterase (+)
Acid Phosphatase (+)
PAS (+) for megakaryocytes
(-) for megakaryoblasts
ANLL ( not in FAB) . . . Mo
1. ANLL . . . Primitive Blast Cells
2. Acute Mast Cell Leukemia
3. Acute Basophilic Leukemia
4. Hypoplastic Acute Myeloid Leukemia
5. Mixed Leukemia: Lymphoid,
Myeloid, Myelodysplastic
 CHRONIC
MYELOPROLIFERATIVE
DISORDERS
a. CML (Chronic Myeloid (myelogenous)
Leukemia
1. WBC Count: 300 X 10 9/L
2. Myeloblastic: few less l0%
3. Myelocytes/Neutrophils: Exceed
4. Basophilia 7. Anemia
5. Eosinophilia 8. LAP decreased
6. thrombocytosis 9. Ph chromosome
B. PV (POLYCYTHEMIA VERA)
1. Panmyelosis: Increased Erythroid
“ Granulocytic
“ Megakaryocytic
2. Red Cell Survival: Decreased
3. Erythropoietin excretion in the urine
4. Splenomegaly
C. Myelofibrosis with Myeloid Metaplasia
1. Chronic Progressive Panmyelosis
2. Fibrosis
3. Splenomegaly
4. Extramedullary Erythropoiesis
5. Normocytic Normochromic
6. Moderate Anisocytosis
7. Marked Poikilocytosis
- Tear Drop Cells
- Elliptocytes
8. NAP: Increased
D. THROMBOCYTHEMIA
1. Platelet Count: 3X normal
2. Blood Picture: Like PV,
Myelogenous leukemia,
myelofibrosis, myeloid metaplasia
3. Hypochromic Microcytic RBCs:
due to chronic blood loss
4. NAP test: Normal
E. MYELODYSPLASTIC SYNDROME
(MDS)
Characteristics
1 - over 50 years
- Anemia refractory to hematins
- Liver and Spleen: enlarged
- with or without Neutro & Thrombo
- Preleukemias
Characteristics
2. Dyserythropoiesis
- Nuclear fragmentation
- Irregular Staining
- Basophilic Stippling
- Ringed Sideroblasts
3. Dysgranulopoiesis
- Retarded Nuclear Maturation
- Distorded Cytoplasm
- Azurophilic granules (unstained)
4. Dysmegakaryopoiesis
- Large megakaryocytes with
unsegmented nuclei
- Micromegakaryocytes
- Some Mega: 2 or more
unsegmented nuclei
 TYPES OF MDS
1. RA with Anemia, Reticulocytopenia
2. RA with Ring Sideroblasts
3. RA with Excess Blasts (RAEB)
- 5% blasts
- Cytopenia in 3 lines
4. CMML ( Chronic Myelomonocytic
Leukemia
- Neutrophilia
- Monocytosis
- 5% Blasts
5. RAEB with greater than 5% blasts
- 20 to 30% blasts in the marrow
- with Auer Bodies
 OTHER FORMS OF
LEUKEMIA
1. Acute Undifferentiated (Stem Cell)
Leukemia
- Blast cells cannot be identified using
cytochemical or immunologic methods
2. Chloroma: formation of tumors
originating from skull, nasal sinuses,
ribs and vertebrae
3. Granulocytic Sarcoma ( Myeloblastic
Sarcoma): localized tumor of myeloblasts
4. Eosinophilic Leukemia: persistent
eosinophilia
- immature eosininophils
5. Basophilic Leukemia
6. Neutrophilic Leukemia: segmented
granulocytes
7. Megakaryocytic Leukemia (Acute
myelofibrosis)
- megakaryoblasts
- pancytopenia
- Blast cells
PAS (+)
Alpha Napthyl Acetate Esterase(+)
Alpha Napthyl Butyrate Esterase(+)
 ACUTE LYMPHOBLASTIC
LEUKEMIA
SUBTYPES (MARKERS)
1. T cell. . . . . E rosette; Hu Thy Ag,Tdt
2. Common Cell: C all antigen
3. Null Cell . . . . . Tdt (Terminal
Deoxynucleotidyl transferase)
4. Pre B Cell . . . . Tdt (+) or (-)
5. B Cell . . . . . . . SMIg
 CHRONIC LYMPHOCYTIC
LEUKEMIA
Characteristics
1. Lymphadenopathy
2. Asymptomatic
3. Symptomatic
Weakness Fatigue Anorexia
Weight Loss Enlarged Lymph Nodes
4. Leukocytes: 80 to 90% are small
lymphocytes
5. Anemia: slight
6. Thrombocytopenia: Slight
7. Marker: Surface Bound Ig
 HAIRY CELL LEUKEMIA
Ewalds Description: Reticulosis
- Reticulum Cell Leukemia
- Hairy Cell: Hair Like Ruffled
projections-numerous cytoplasmic
projections
- Ultrastructure appearance of the
cells
 3. Anemia, Pancytopenia
4. Bleeding
5. Infections
6. Paraneoplastic complications
7. Autoimmune Syndrome
8. Paraproteinemia
9. Common: 5 years old 1 patient-27 yrs
10. B cell Marker
11. Fibrotic Marrow
 LYMPHOMAS
1. Hodgkin Disease ( HD)
2. Non Hodgkin Disease (NHD)
Characteristics of HD
1. Cellular infiltrate: more variable
2. Cells in Node: Many are normal
Minor: Neoplastic
3. Neoplastic: Multigiant Cell (Reed-Sternberg
Cell)
4. Causes
- Genetic
- Environmental Hazards
- Infectious Agent (IM)
5. Frequency : 25%
6. Sex Affected: Both
NHD
1. Cellular Infiltrate: Variable
2. Cells in Nodes : Neoplastic B Cell

5% T Lymphocytes
3. Neoplastic Cells: B Cells
4. Causes
- RA
- IgA deficiency
- Wiskott Aldrich
- Ataxia Telangiectasia
AIDS
5. Frequency: 75%
6. Sex Affected: More Men than Women
 PLASMA CELL DYSCRASIAS
A. Multiple Myeloma ( Plasma Cell
Myeloma)
1. Most Common PCD: 50 to 75 yrs old
2. Etiology: Unknown
3. Beliefs: Genetic Factor; Chronic
antigenic Stimulation
4. Clonal Proliferation of Malignant
Plasma Cells
5. Proteins
IgG: 50%
IgA: 20%
IgD, IgE and IgM: rare
Bence Jones Proteins: 15%
6. Rouleaux: Blood Films
7. ESR: Increased
8. Normochromic Normocytic Leukemia
9. Myeloma Cells: Large with clumped
chromatin, pale/dark depending on RNA
10. Cellular Interactions: Intranuclear (Dutcher
Bodies ( crystalline)
Russell Bodies are globular
 PLASMA CELL LEUKEMIA
Characteristics
1. Found in younger patients
2. Less BM pain
3. Less Osteolysis
4. Greater Lymphadenopathy
5. Hepatomegaly
6. Pancytopenia
7. Leukoerythroblastic Findings
8. Elevated ESR
9. Plasma Cells are small (little cytoplasm)
 WALDENSTROM’S
MACROGLOBULINEMIA
1. Lymphoproliferative Disorder
2. Large Conc. Of Monoclonal IgM
3. Abnormal “B” Lymphocytes, Large
Plasmacytoid Lymphocytes and Plasma
Cells
4. IgM 15% gamma globulins
5. ESR: Increased
6. Normochromic Normocytic Anemia
 AMYLOIDOSIS
1. Proteinaceous deposits of amyloid
2. Types
a. Primary Amyloidosis: associated
with monoclonal gammopathies (
Plasma cell Lymphoma)
b. Secondary: Chronic Illness-
unrelated to Ig
 ERYTHROCYTE
ABNORMALITIES
ANEMIA- decrease in Hgb, Hct and RBC
count/direct result of decreased oxygen
carrying capacity.
POLYCYTHEMIA- increased PCV etc,
hypervolemia and hyperviscosity.
CLASSIFICATION OF ANEMIAS
1 Hypoproliferative 3. Hemolytic
2. Maturation Disorders 4. Blood Loss
PHYSIOLOGIC RESPONSE
1. Chemical/Physical Response
- reduction in the oxygen carrying capacity of
the blood
- Hypoxia
- Shift to the right of the oxyhemoglobin
dissociation curve
- Increased DPG
- Increased release of O2 into the tissues
- Increased cardiac output that will lead to
cardiac stress
II. Hematologic Response
- Triggering increase in red cell production
- Tissue hypoxia with increased erythropoietic
marrow stimulation
- Shift of reticulocytes or “immature red cells
in the peripheral blood
- Increase RC and increased RPI
WINTROBE’S CLASSIFICATION
1. Normocytic Normochromic
2. Microcytic Hypochromic
3. Microcytic Normochromic
4. Macrocytic Hypochromic
5. Macrocytic Normochromic
 MCV- represents the mean size of a
given heterogenous red cell population

RDW- size distribution measurement

generated from red cell Histogram
This provides a measure of
homogenecity(normal RDW) or
heterogenecity (high RDW)
Hypoproliferative Anemias- decreased RPI
1. with normal RCM and normal RDW
- BM failure (hypoplastic BM)
- decreased BM stimulation: Endocrine,
Renal and anemia of chronic diseases.
2. With abnormal RCM and RDW
- presence of oval macrocytes- BM
with hyperplasia, megaloblastoid or
Dysmyelopoietic BM
- Dacrycytes (Tear Drop Cells)
myelopthisic ( myeloid metaplasia- bone
marrow is fibrotic and neoplastic ;
Metastatic Cancer- BM is fibrotic and
neoplastic
BLOOD LOSS: RPR higher than 3
1. With normal RBC morphology
Acute Blood Loss
Chronic Blood Loss: becomes
microcytic hypochromic

MATURATION DISORDERS
1. Microcytic: MCV lower than 80 fl.
 Increased RDW Normal RDW
- dimorphic microcytes -Uniform microcytes
( Target Cells)
- Sideroblastic Anemias - Heterozygous
Thalassemia
(Mitochondrial Iron) - (Cytoplasmic iron)
- Microcytic Hypo - Uniform microcytes
- Uniform Normocytes
- Iron deficiency - Anemia of Chronic
diseases
- Serum iron decreased – Serum iton decreased
- Serum iron/ferrtin dec. - Serum iron/ferritin
Normal/Inc.
HEMOLYTIC ANEMIA: RPI over 3
1. Predominance of 1 morphologic
variants
- Hereditary spherocytosis_ OFT
and Autohemolysis)
- Hereditary elliptocytosis
- Hereditary stomatocytosis
- Hereditary acanthocytosis
- Hereditary pyropoikilocytosis
2. Presence of Target Cells
Hemoglobinopathies
Hgb C and other Variant Combination
3. With normal RBC; presence of
spiculated spherocytic RBC
4. + Coombs Test - Coombs Test
Autoimmune HA Enzyme Disorders
- Warm anttibody RBC enzyme Assay
1. Idiopathic
2. Secondary
Unstable Hemoglobin
- Cold antibody
- Cold Agglutinin Hypersplenism
disease
- PCH PNH
- Isoimmune
(HTR, HDN, Drug Induced)
5. Presence of RBC Fragments
- Microangiopathic HA
- Renal Disease
- Malignancy
- Infections
- DIC
- Cardiac Hemolytic Anemia
- Infectious Hemoytic Anemia
- Burns
 ERYTHROCYTOSIS
Relative Absolute
(normal RBC mass) (Increased RBC mass

Relative Primary
Erytrhocytosis Erythrocytosis
-Dehydration -Polycythemia vera
- Stress/Spurious (Erythremia)
(Gaisbocks syndrome)(with inc.erythropoietin)
- Tobacco Polycythe
mia
2. Secondary Polycythemia
- high altitude
- cardiac disease
- pulmonary disease
3. Smoker’s Polycythemia
- Kidney Disease
(tumors)
- Idiopathic (Essential
erythrocytosis)
 ANEMIA OF BONE MARROW
FAILURE
1. Aplastic Anemia: Pancytopenia,
Hypoplastic
2. Classification
- Primary Anemia
a. Acquired
b. Congenital ( Fanconi Anemia:rare)
- Secondary
a. Drugs/Chemicals
Chloramphenicols
Chlordane (Insecticides)
Chlorophenotane (DDT)
- Gold Preparations
- Hydantoins
- Sulfonamides
2. Radiation
- Radiotherapy
- Radioactive Isotope Administration
3. Immune Mechanisms
4. Infections
- NANB Hepatitis
- Military tuberculosis
- Brucelosis
- Parasitism
• Pure red cell aplasia (PRCA) or
erythroblastopenia refers to a type of
anemia affecting the precursors to
red blood cells but not to white blood cells.
In PRCA, the bone marrow ceases to
produce red blood cells.
PURE RED CELL APLASIA
Kinds of Pure Red Cell Aplasia
1. Acquired
a. Primary( idiopathic, Immune)
b. Secondary
- benign thymomas
- Drugs
- Chemicals
- Infections
- Hemolytic Anemia
2. Congenital-Diamond Blackfan Anemia
-with normal WBC
- Platelet Count- Normal
- Unresponsiveness of patients’ bone
marrow even with erythropoietin
 ANEMIA OF SYSTEMIC
DISORDER
1. Anemia of Endocrine Disorders
- Hypothyroidism: Metabolic Rate Dec
- Hypopituitarism: Pituitary glands
controls thyroid, gonad and adrenals)
- Hypogonadism : retarded growth
and sexual development
2. Anemia of chronic Disease (renal
failure: dec production of erythropoietin
3. Anemia of Pregnancy
- Iron deficiency
- Folate deficiency
 ANEMIA OF ABNORMAL
NUCLEAR DEVELOPMENT
MEGALOBLASTIC
1. Vitamin B12 Deficiency
(cobalamine):required for DNA synthesis
Sources:
a. Meat
b. Fish
c. Eggs
d. milk
2. Folate deficiency
Folic acid, pteroylglutamic acid:
required for DNA synthesis, Purine
Synthesis, pyrimidine synthesis
Sources
- green leafy vegetables, liver, kidney,
cereals, yeasts, fruits
3. Others
- Dietary deficiency
- Castle’s Intrinsic factor deficiency
- Gastrectomy
- Intrinsic Factor Molecular defect
- Bacterial Outgrowth
- Fistulae
- Achorhydria
- Diverticulosis
Peripheral Blood Changes
- MCV . . . . . 110 fl.
- MCH . . . . . 33-36 pg.
- MCHC . . . Normal
- WBC Ct. 1-3 X 10 9/L
- RBC Ct. .086 x 10 12/L
- Platelet Ct. Decreased
- Anisocytosis RDW: increased
- Macroovalocytosis
Biochemical Differentiation
1. Vitamin B12 deficiency
Serum B12: : markedly decreased
Serum Folic acid : Normal or Increased
Erythrocyte Folate: moderately dec.
2. Folic Acid
Serum B12 : normal or decreased
Serum Folic Acid : markedly decreased
Erythrocyte Folate: markedly decreased
3. Combined B12 and Folic Acid: all
decreased
ANEMIA OF ABNORMAL IRON
METABOLISM
1. Iron Deficiency Anemia
a. Increased Physiologic demand
(Rapid Growth, Pregnancy and
Lactation)
b. Inadequate Intake (iron deficient
loss, inadequate absorption
(Achlorhydria)
c, Chronic Blood Loss
3. Chronic Blood Loss
a. Mentrual Flow
b. GI bleeding
c. Regular Blood Donation
d. Chronic Hemolysis
2. Sideroblastic Anemia
a. Hereditary ALA Synthase deficiency
b. Acquired Siderablastic Anemia
-Primary
- Acute Myeloid Leukemia
- Myelodysplastic
- Myeloma
- Secondary
- alcoholism
- Lead Poisoning
- Cloramphenicols
- Drugs (TB medicines like Isoniazid,
Cycloserine
Pyrazinamide)
3. Anemia of Chronic Disorders
4. Lead Intoxication
 ANEMIA OF GLOBIN
DEVELOPMENT
1. Sickle Cell Anemia ( Hb SS)
- Point mutation for the sixth amino acid
in beta chain in which one nucleotide
base is substituted for valine
- Hb S migrates slower than Hb A
toward the + pole in electrophoresis
- decreased oxygen> Sickling> Oxygen
is released
 - polymerization of Hb molecule leading to
tactoids or crystals
- Cells are rigid, chronic hemolysis and the
patient exhibits fatigue, weakness and pallor.
2. Sickle Cell Trait (Hb AS)
- Hb A is higher than Hb S
- No symptoms
- Anemia: not present
- RBC : normal
- Target cells: few
- Sickle cells: occasional
3. Hemoglobin S/Thalassemia
- Mutant genes for Hb S and
Thalassemia are inherited
4. Hemoglobin C
- Amino acid substitution of lysine at
position 6
- Hemoglobin CC tends to crystalize
when dehydrated ( Hgb C crystals)
5. Hemoglobin C trait ( Hb.AC)
- hypochromia
- target cells
- Hb A is higher than Hb C
- Hb C suggests Hb C and
Thalassemia
6. Hemoglobin SC disease
- Clinical Symptoms: milder
- Hb SC crystals
- Blood Viscosity causes death
7. Hemoglobin D
- migrate in the same position as Hb S does
not cause sickling
8. Hemoglobin SD
- Sickle Cell Solubility Test (+)
- Citrate Agar electrophoresis: separates SD
from SS
9. Hemoglobin E
- Glutamic acid at position 26: lysine
- Microcytic Normochromic Hemolytic Anemia
- Red Cell Survival: Slightly decreased
- Increased RBC with Target Cells
10. Hemoglobin O
- Gl;utamic Acid at position 121 is
replaced by lysine
- rare
- Homozygous Hb OO with
splenomegaly
11. Hemoglobin C Harlem
- 2 amino acid substitution
- sixth and 73rd position replaced by valine
12. Hemoglobin G Philadelphia
- only alpha chain variant
- replacement of asparagines by
lysine
13. Hemoglobin I
- alpha and beta chains
affected/replaced by various
positions
14. Hemoglobin Gun Hill
- deletion of 5 beta chains amino acid ( B 91
and 95)
15. Hemoglobin CS (Constant Spring)
- elongated alpha chain ( plus 31 amino
acids)
 THANK YOU FOR LISTENING

ZENAIDA C. CAJUCOM, RMT, MA

ED.MGT, FPAMET