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CLINICAL PATHOLOGY

WHITE BLOOD CELL DISORDERS

First Shift: August 21, 2018

TABLE OF CONTENTS II. LEUKOCYTES


 Function: Protection from non-self cells and altered self-cells.
I. Hematopoiesis Review……………………………………………………………. 1
II. Leukocyte/White Blood Cell…………………………………………………... 1
CLASSIFICATION OF LEUKOCYTES
A. Classification……………………………………………………………………… 1
 Phagocytes (NEBM) vs Immunocyte (L)
B. Neutrophil Development………………………………………………….... 1
III. Methods of Counting WBC…………………………………………..……..... 1 o Phagocytes
IV. Leukocytosis vs Leukopenia…………………………………………………. 2  Granulocytes
V. Neutrophils …………………………………………………………………………... 2  Neutrophils/Segmenters/Polymorphonuclear (N)
A. Neutrophilia …..………………………………………………………………….. 2 o do not exhibit affinity to acidic or basic stain
B. Neutropenia …………………………………………………………………….... 3  Eosinophils (E)
VI. Lymphocytes. …….……………………………………………………………….... 4 o With granules containing basic proteins that stain with
A. Lymphocytosis…………………………………………………………………… 4
acid stain (eosin)
B. Lymphocytopenia. …………………………………………………………….. 4
 Basophils (B)
VII. Monocytes …..……………………………………………………………………... 4
A. Monocytosis ……………………………………………………………………… 4 o With granules that are acidic and stain with basic stain
VIII. Eosinophils …..…………………………………………………………………….. 5 (Methylene Blue)
A. Eosinophilia ………………………………………………………………………. 5  Monocytes (M)
IX. Basophils………………………………………………………………………………. 5 o Macrophages in the bloodstream
A. Basophilia………………………………………………………………………….. 5 o Immunocytes
X. Leukemia……………………………………………………………………………….. 6  T-lymphocytes (involved in antigen-presenting cells)
A. Classification of Leukemia…………………………………………………. 6
 B-lymphocytes: Plasma cells (antibody production
B. Generalities of Leukemia…………………………………………………… 6
XI. Acute Myeloid Leukemia………………………………………………………. 6
 Granulocyte (NEB) vs. Agranulocyte (LM)
XII. Acute Lymphoblastic Leukemia…………………………………………… 10  Polymorphonuclear (NEB) vs. Mononuclear
XIII. Methods for Diagnosis……………………………………………………….. 10
XIV. Chronic Myelogenous Leukemia………………………………………… 11 NEUTROPHIL DEVELOPMENT
XV. Chronic Lymphocytic Leukemia…………………………………………… 11  Proliferative or mitotic pool (actively dividing):
o Progenitor cells, Myeloblasts, Promyelocytes, Myelocytes
 Post-mitotic/storage pool (not capable of cell division):
I. HEMATOPOIESIS o Metamyelocytes, Bands, Segmenters

METHODS OF COUNTING WBC


 Units of WBC
o SI Unit: 4.0-11.0x 109/L
o Conventional unit: 4,000 -11,000/mm3

TOTAL WBC COUNT


Age Group Normal Values

Adults 4.0-11.0x 109/L

Neonates 10.0-25.0 x 109/L

1 year 6.0 – 18.0 x 109/L

4-7 years 6.0 – 15.0 x 109/L

8-12 years 4.5 – 13.5 x 109/L

NORMAL DIFFERENTIAL WBC COUNT


PROPORTIONAL ABSOLUTE COUNT (x
Cell
RELATIVE COUNT (%) 109/L)
 All cells inside the box: seen in Peripheral circulation 38-80 Adult:1.8 – 7.0
 All others: Exclusively in Bone Marrow Neutrophil
Pedia: 1.0-8.5
o Presence of these immature cells in the blood may be 10-50 Adult: 1.5-4.0
Lymphocytes
indicative of a disease. Pedia: 1.5-8.8

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Monocytes
0-12 0.03-0.90 V. NEUTROPHILS

1-9.5 0.00-0.67
Eosinophils
0-2.5 0.00-0.20
Basophils

 Relative Count
o Gives the number of specific WBC type per 100 WBCs
o # of specific WBC type x 100
100 Cells Counted 

FACTORS INFLUENCING NEUTROPHIL COUNT


 Absolute Count
 Rate of inflow of cells from the marrow (mitosis/proliferation,
o Gives the number of specific WBC type per mm3 of blood
maturation/storage release)
o Relative Count (%) x WBC Count
 Proportion of neutrophils between the marginal (cells
adhering to vessels walls) granulocytic pool and the circulating
CLINICAL CORRELATES: ABSOLUTE COUNT VS RELATIVE
(non-adhering cells) granulocytic pool
COUNT
 Rate of outflow of neutrophils from the blood (migration from
In the laboratory, only the Total WBC count and WBC
and through vessels into tissues, both randomly and at sites of
Proportional count are included in the CBC. For example:
inflammation, infection, etc.
 Host factors that can modify degree of neutrophil response:
Remarks
o Age: children respond more intensely than adults
WBC count 5.7 x 109/ L Normal
o Virulence of infecting agent
Neutrophil 35% Below Normal
o Hematinic deficiency &/or marrow failure
Lymphocyte 65% Above Normal
o Primary or metastatic nonhematological neoplasms
 Calculation of Absolute Count for each WBC is encouraged
occasionally manifests with neutrophilia (GI and hepatic
o Use of absolute values has made the definition of
tumors, Hodgkin’s lymphoma, renal cell carcinoma)
normal range more precise and provides best value for
determining abnormality
A. NEUTROPHILIA
 Absolute Neutrophil count >7.5 x 109/L
Total WBC Count: 5.7 x 109/ L
o Composed of bands and neutrophils
WBC Proportional Remarks Absolute Remarks
count Count Count
PATHOPHYSIOLOGIC MECHANISM
Neutro 35% Below 1.995 x 109/ L NORMAL
 Increased cell production
Normal
Lympho 65% Above 3.705 x 109/ L NORMAL
 Accelerated release of cells from marrow
Normal  Shift of marginal to circulating pool
 Reduced egress of neutrophils from blood tissues
 Combination of above factors
IV. LEUKOCYTOSIS VS LEUKOPENIA
MECHANISM OF PRODUCTION OF NEUTROPHILIA
Leukocytosis Leukopenia
Mechanism Possible Triggers
Increases in WBC above upper Decrease in WBC below lower limit
limit of normal for sex and age of normal for age and sex Chronic disorders: Infections, tumors,
Neutrophilia, Eosinophilia, Neutropenia inflammation, endocrinopathies,
Increased production
Basophilia, Lymphocytosis, Lymphocytopenia myeloproliferative disorders
Monocytosis
Not usually clinically relevant; but if Increased production and
Chronic Myelogenous Leukemia
severe, it may indicate peripheral cell survival
immunosuppression (e.g. HIV/AIDS, Stress, intoxication, infections,
Accelerated release from the
chemotherapy) inflammation, corticosteroids,
marrow
endotoxins
Increased shift from
Stress, intoxication, hypoxia,
marginal pool to circulating
infections, exercise, adrenalin
pool
Decreased egress from
Corticosteroids
circulating pool

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ETIOLOGY OF NEUTROPHILIA
DEGREES OF NEUTROPENIA
KEY CAUSES OF NEUTROPHILIA Degree Absolute Neutrophil Count
Classification Examples
Normal > 1.5 x 109/L
Acute Inflammation CTD, Vasculitis, Arthritis
Mild 1.0-1.5 x 109/L
Acute Infections Bacterial, some viral, fungal, parasitic Moderate
Steroids, growth factors, uremia,  Some increased risk for
Drugs, Toxins, Metabolic 0.5-1.0 x 109/L
ketoacidosis infection
disorders
Severe
Tissue necrosis Burns, trauma, MI, hemolysis
 Significant risk for

Physiologic response Stress, smoking, exercise, pregnancy


infection < 0.5 x 109/L
 May cause pancytopenia
Solid tumors and myeloproliferative
Neoplasms
neoplasms

 “Shift to the left” MECHANISMS FOR PRODUCTION OF NEUTROPENIA


o Increase in immature peripheral blood granulocytes, usually  Decreased flow of neutrophils from the marrow due to lack of
seen in acute infection production or ineffective production (i.e., proliferation or
 “Leukemoid reaction” production defect)
o Reactive and excessive leukocytosis usually characterized by  Increased removal of neutrophils from the blood (survival
release of immature cells (myeloblasts, promyelocytes, defect)
myelocytes)  Altered distribution between circulating and marginal
o WBC >50 x 109/L with shift to the left granulocytic pools
o Conditions: severe and chronic infection, severe hemolysis,  Combination of factors
metastatic CA
o High leukocyte alkaline phosphatase (LAP) score: CAUSES OF NEUTROPENIA
The degree of reactivity is determined by scoring neutrophils Classification Examples
according to the amount of precipitated dye present
Bone marrow failure
(intensity of staining). Zero being the lowest and 4 being the  Aplastic anemia; leukemia;
highest. myelodysplasia;
More brown= higher score Part of general pancytopenia myelofibrosis; marrow
Higher score= more matured cells infiltrations; megaloblastic
anemia
LAP Score Principle: High reactivity of neutrophils to the dye Splenomegaly
seen if they have undergone normal growth Viral
 Hepatitis, Influenza, HIV
Infections
Fulminant bacterial infections
 Useful in differentiating Chronic Myelogenous Leukemia from
 Typhoid, military TB
Leukemoid Reaction
o Chronic Myelogenous Leukemia : Low LAP Score Immune Mediated Collagen Vascular Disorders, RA, AIDS
o Leukemoid Reaction: High LAP Score See DRUGS ASSOCIATED WITH
Drug-induced
NEUTROPENIA
Toxins Alcohol, aromaticcompounds
B. NEUTROPENIA
Megaloblastic anemia,
 Absolute Neutrophil Count: <1.5 x 109/L
Hematologic Myelodysplasia, Marrrow failure or
 Risk of infection depends on 3 factors Marrow replacement
o Absolute neutrophil count (ANC) Fanconi’s anemia, Kostman’s
Intrinsic Defects
o Neutrophil reserve in bone marrow. Normal in the ff: syndrome
 No prior cytotoxic therapy
Others Starvation
 Appropriate ANC increases in response to infections or
stress
 Normal bone marrow biopsy
o Duration of neutropenia
 Periodic or episodic (e.g. post chemo)
 Chronic

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DRUGS ASSOCIATED WITH NEUTROPENIA Monoclonal Polyclonal
Classification Examples
Lymphoproliferative disorders Acute infections
Anti-inflammatory Aminopyrine, Phenylbutazone Chronic lymphocytic leukemia Rubella
Non-Hodgkin’s lymphoma Pertussis
Chloramphenicol, Sulfas, Penicillin,
Antibacterial Acute lymphocytic leukemia Mumps
Cephalosporin
Infectious mononucleosis
Anticonvulsants Phenytoin, Phenobarbital Chronic infections
Tuberculosis
Antithyroids Carbimazone Brucellosis
Infective hepatitis
Phenothiazines Chlorpromazine, Promethazine
Syphilis
Antiarrhythmics, Digoxin, Diuretics, Immune mediated
Cardiac medicines
ACE Inhibitor Drug sensitivity
Vasculitis
Chemotherapy
Graft rejection
Tolbutamide, Phenidione, H2 Grave’s disease
Miscellaneous
antagonists, Antivirals vs AIDS Sjogren’s syndrome
Stress
Acute, transient
VI. LYMPHOCYTES

B. LYMPHOCYTOPENIA
 Absolute count:
o Adults < 1.0 x 109 cells/L
o Children <2.0 x 109 cells/L

CAUSES OF LYMPHOCYTOPENIA
Classification Examples

Destructive Radiation, chemotherapy, corticosteroids

 In adults, they constitute about 20% to 40% of all leukocytes Starvation, aplastic anemia, terminal cancer,
o 1.5 to 4.0 x 109 cells/L Debilitative
collagen vascular disease, renal failure
Viral hepatitis, influenza, typhoid fever,
A. LYMPHOCYTOSIS Infectious
tuberculosis
 Absolute count > 4.0 x109/L HIV cytopathic effect, nutritional imbalance,
AIDS-associated
 May be categorized as either monoclonal or polyclonal drug effect
 Often occurs in infants and young children in response to Congenital
Wiskott-Aldrich syndrome
infections that produce neutrophil reactions in adults immunodeficiency
Intestinal lymphangiectasia, obstruction,
Abnormal lymphatic
thoracic duct drainage/rupture, congestive
REVIEW OF PERIPHERAL SMEAR circulation
heart failure
 Reactive lymphocytes seen in viral infections
 Large granular lymphocytes in large granular lymphocytic
VII. MONOCYTES
leukemia
 Smudge cells in CLL
 Blasts of acute leukemia

MONOCLONAL VS POLYCLONAL LYMPHOCYTOSIS


 Monoclonal lymphocytosis is due to underlying
lymphoproliferative disorders
o Lymphocytes are increased due to an intrinsic defect in the
expanded lymphocyte population
 Polyclonal lymphocytosis is transient, reactive, and benign
o Secondary to factors extrinsic to the lymphocyte such as
infection or inflammation A. MONOCYTOSIS
 Absolute count > 0.8 x109/L
CAUSES OF LYMPHOCYTOSIS  Favorable sign when present during the recovery stage from
acute infection and agranulocytosis
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 > 50% due to hematologic disorders (e.g. AML, MDS, Pulmonary eosinophilic syndromes (Löffler’s,
lymphoma) Respiratory tropical pulmonary eosinophilia), Churg-
 10% inflammatory and immune disorders Strauss syndrome
MPN with translocation of PDGFRA/B or
 8% malignant diseases
FGFR1, CML, mastocytosis, Hodgkin
Neoplastic
lymphoma, T cell lymphomas, lymphocytic
CAUSES OF MONOCYTOSIS
HES
Classification Examples Idiopathic
Tuberculosis, subacute bacterial endocarditis, hypereosinophilic ---------
Infectious
syphilis, protozoal, rickettsial syndromes
Recovery from Certain drugs, hematologic and visceral
---------
neutropenia Others malignancies, GI inflammatory diseases,
Leukemias, myeloproliferative disorders, sarcoidosis, Wiskott-Aldrich syndrome
Hematologic
lymphomas, multiple myeloma
Collagen vascular disease, chronic ulcerative PRIMARY HYPEREOSINOPHILIC SYNDROME
Inflammatory colitis, sprue, myositis, polyarteritis, temporal
CRITERIA
arteritis
Solid tumor, immune thrombocytopenic
Others >1.5 x 109/L for more than 6 months
purpura, sarcoidosis

Absence of an underlying cause of eosinophilia despite extensive


VIII. EOSINOPHILS evaluation
Presence of end-organ damage or dysfunction related to eosinophilia:
skin, heart, nervous system

IX. BASOPHILS

A. EOSINPHILIA
 Mild < 1.5 x109 cells /L
 Moderate 1.5 to 5.0 x109 cells /L A. BASOPHILIA
 Severe > to 5.0 x109 cells/L  Absolute count > 0.2 x109/L
 Most common causes are parasitism and allergic disease
CAUSES OF BASOPHILIA
CAUSES OF EOSINOPHILIA
Classification Examples
Classification Examples
Myeloproliferative CML- Hyperleukocytosis, left-shifted
Allergic diseases Urticaria, hay fever, asthma diseases maturation, high eosinophil, and basophil

Allergic Food, drugs, foreign proteins


Parasitic diseases Trichinosis, filariasis, schistosomiasis

Recovery from acute Infectious Variola, varicella


---------
infectiom Chronic haemolytic
Psoriasis, pemphigus, dermatitis, Especially post-splenectomy
anemia
Certain skin diseases herpetiformis, urticarial, angioedema, atopic
Inflammatory Collagen vascular disease, ulcerative colitis
dermatitis
Inflammatory Eosinophilic fasciitis, Churg-Strauss syndrome
Non-parasitic Systemic fungal, scarlet fever, chlamydial
infections pneumonia of infancy

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X. LEUKEMIA LABORATORY FEATURES
 Group of disorders characterized by accumulation of  Anemia
malignant WBC’s in the bone marrow and blood.  Thrombocytopenia
 Cause symptoms from bone marrow failure and organ  Leukocyte count
infiltration. o May be low, normal, high
A. CLASSIFICATION OF LEUKEMIA o <5000/uL in half of patients
 Acute myelogenous leukemia (AML) o “absolute lymphocytosis”
o Most common leukemia in Children <1 yr. and Adult o High WBC count with High Lymphocyte %
 Acute lymphocytic leukemia (ALL) *Can present with Pancytopenia*
o Most common leukemia in Children  Myelogenous vs Lymphocytic
 Chronic myeloid leukemia (CML) o Difficult to differentiate based on clinical manifestations and
o Prototype of Myeloproliferative Neoplasm simple morphology (Wright-Giemsa stain)
o Eventually becomes Acute Leukemia XI. ACUTE MYELOGENOUS LEUKEMIA
o Incidence increases with age until mid-forties where it A. CLASSIFICATION OF AML
raises rapidly  Molecular Analysis
 Chronic lymphocytic leukemia (CLL) o Prognosis of patient depends on genotype
o Most common leukemia in Older adults  11q23 = bad prognosis, high chance relapse
o Most prevalent leukemia in Western countries. o Somehow give different clinical setups for patients having
B. GENERALITIES OF ACUTE LEUKEMIA same types of AML
ACUTE LEUKEMIA
 Characterized by accumulation of malignant immature WBC’s
(blast) in the blood and bone marrow
 Presence of >20% blasts in the blood and/or bone marrow
(WHO criteria)
o Very large cells: 4-5x the size of RBC’s
o High N:C ratio
o Open chromatin
o Prominent nucleoli
o Contains Auer rods (Myeloid only)
SYMPTOMS AND SIGNS AT PRESENTATION
 Marrow failure
o Anemia: fatigue, shortness of breath
o Granulocytopena: fever, focal infections
o Thrombocytopenia: Petecchiae, bruising, bleeding
 Tissue involvement or Organ infiltration
o Bone pain, tenderness
o Mild splenomegaly, hepatomegaly, lymphadenopathy,
mediastinal mass
o Gingival hyperplasia (common in M5: acute monoblastic
leukemia)
o CNS and cranial nerve dysfunction
o Visual changes (retinal involvement, hemorrhage,
papilledema)
o Testicular involvement
o Sweet syndrome (febrile neutrophilic dermatosis- skin lesion
full of leukocyte on histologic examination)
o Chloromas (extramedullary manifestation; solid collection of
leukocytes outside the bone marrow)

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FRENCH-AMERICAN –BRITISH CLASSIFICATION OF AML
Subtype Description Picture
M0: AML Minimally  Bone aspirate: 90% blast,
differentiated  <3% Myeloperoxidase (MPO) (+)
 Infants and older adults
 < 5 % of AML cases
 No clear evidence of cellular maturation

M1: AML without  Bone aspirate: 90% blast (contain Auer rods)
Maturation  < 10% promyelocytes or beyond
 >3% MPO (+)
 Middle aged persons

M2: AML with Maturation  Bone aspirate: <90% blast


 >10% maturing cells of neutrophil lineage
 <20% precursors with monocytic lineage
 Most common AML
 Auer rods present
All age group

M3: Acute  Promyelocyte accumulates


Promyelocytic Leukemia o Smear: Cytoplasm > Myeloblast
 Auer rods abundant
 Disseminated intravascular coagulation
(DIC) is common
 PML RARA (retinoic acid receptor alpha)
translocation (t15;17)
 Vitamin A during chemotherapy to decrease
risk for DIC

M4: Acute  20% Myeloblast,


Myelomonocytic  80%> monoblast >20%
Leukemia  Smear of Monoblast:
o Usually 3 nuclei
o Cytoplasm > myeloblast
 Auer rods common
 Gingival hyperplasia
 20% AML case

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M5: Acute Monoblastic  >80% Monoblast
Leukemia / Schilling  Younger patients
Leukemia  Auer rods rare
 <5% AML cases
 Extramedullary involvement (cutaneous &
gingival infiltration)
 Bleeding disorders
 DIC is common

M6: Acute Erythroid  Prominent erythropoietic proliferation


Leukemia / Di  >50% erythroid precursors
Guglielmo Syndrome  Aggressive clinical course

M7: Acute  50% blast megakaryocytic


Megakaryocytic  Auer rods rare
Leukemia

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XII. ACUTE LYMPHOBLASTIC LEUKEMIA (+)
Non-specific Esterase (-)
 >20% Lymphoblast for M4, M5
(+)
Periodic acid- Schiff (+)
A. CLASSIFICATION OF ALL fine blocks in M6
(+)
 FAB Classification Acid phosphatase (+)
in M6
o L1: Best prognosis
o L2
o L3: Burkitt type of leukemia; poor prognosis  Myeloperoxidase (MPO) – primary granules of myeloid cells
(lineage specific)

 Immunologic Markers
o B lymphoblastic leukemia
o T lymphoblastic leukemia
 Cannot be differentiated by morphology, but by markers in
flow cytometry

XIII. DIAGNOSTIC METHODS C. IMMUNOPHENOTYPING BY FLOW CYTOMETRY


 Important for different course of chemotheraphy  Antibodies labeled with different flurochromes recognize the
 Myelogenous VS Lymphocytic pattern and intensity of expression of the different antigens on
o May be difficult to differentiate based on clinical the surface of normal and leukemic cells
manifestations and simple morphology (Wright-Giemsa
stain)
 Other tests:
 Cytochemical stains
 Immunophenotyping by flow cytometry

A. SIMPLE MORPHOLOGY
 Wright-Giemsa Stain
 Immature granulocytes = Myelocytic
 Blast and lymphocyte = Lymphocytic
 Cell size and presentation may be in between of myeloblast
and lymphoblast which results to a difficult diagnosis
o Generally, Myeloblasts are larger than Lymphoblasts
Development of three cell lineages from pluripotent stem cells giving rise to
the three main immunological subclasses of acute leukemia
B. CYTOCHEMICAL STAINS FOR ACUTE LEUKEMIA
AML VS. ALL
Stain AML ALL
Myeloperoxidase (+) (-)
Sudan black (+) (-)

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D. KARYOTYPE ANALYSIS B – Promyelocyte (L), Myelocyte (R)
 Direct morphological analysis of chromosomes from tumor C – Metamyelocyte (with nuclear indentation)
cells under the microscope D – Band
 Requires tumor cells to be in metaphase and so cells are E – Basophils
cultured to encourage cell division prior to chromosomal
preparation  “Peripheral Blood Smear of the patient”
 One of the main determinants of prognosis o Very high WBC count + Left shift + very high eosinophils and
basophils = worry about Chronic Myelogenous Leukemia
XIV. CHRONIC MYELOGENOUS LEUKEMIA  Platelet count frequently increased but maybe normal or
 Clonal disorder of a pluripotent stem cell decreased
 Characteristic presence of the Philadelphia chromosome  Leucocyte Alkaline Phosphatase is low
–t(9.22) resulting to a chimeric BCR-ABL gene which codes for o Differentiate leukemia and infection
fusion protein with a tyrosine kinase activity o Leukemoid: very high WBC >50
o Chromosome 9 - ABL gene o Infection: high
o Chromosome 22 - BCR gene o CML: low
 Bone marrow is hypercellular with myeloid hyperplasia
CLINICAL FEATURES  Ph chromosome on cytogenetic analysis
 Symptoms related to hypermetabolism o Using conventional karyotype analysis or FISH
o Weight loss  Serum uric acid is usually elevated
o Lassitude
o Anorexia XV. CHRONIC LYMPHOCYTIC LEUKEMIA
o Night sweats
 Splenomegaly with associated abdominal discomfort, pain,
fullness, early satiety
 Features of anemia, abnormal platelet function
 Gout or renal impairment caused by hyperuricemia from
excessive purine breakdown
 Visual disturbances, priapism
 Up to 50% of case diagnosis is made incidentally from a
routine blood count
 Leucocytosis: usually >50 x109/L and sometimes >500 x 10 9/L

LABORATORY FEATURES
 A complete spectrum of myeloid cells in the peripheral blood
(WBC’s in all stages of maturation). The levels of neutrophils
and myelocytes exceed those of blasts and promyelocytes  Most common leukemia in the Western world but rare in the
 Increased basophils Far East
 Normochromic, normocytic anemias o Not common in the Philippines
 Occur in elderly patients more than 60 y/o, males
o Male to Female ratio 2:1
o Sevenfold increased risk for relatives of patients
 No higher incidence after previous chemotheraphy or
radiotheraphy
 Generally incurable but tend to run a chronic fluctuating course
 Most cases discovered on routine exam

CLINICAL FEATURES
 High lympocytosis: “If you see lymphocytosis in elderly, make
sure if its monoclonal or polyclonal”
o Monoclonal is worrisome. It is one of the most common
lymphoma at that age
 Multiple lymphadenopathy
o Symmetrical enlargement of cervical, axillary or inguinal
lymph nodes is the most frequent clinical sign
 Anemia and thrombocytopenia maybe present
A – Myeloblast
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 Splenomegaly and, less commonly, hepatomegaly are common
in the later stages
 Immunosupression is a significant problem resulting from
hypogammaglobulinemia and cellular immune function

LABORATORY EVALUATION
 Main Criteria: Absolute lymphocytosis of >5 x109/L
monoclonal B cells with CLL immunophenotype (CD5,
CD23) in the peripheral blood
 Absolute neutrophil count is variable
 Anemia or thrombocytopenia
 Autoimmune Complications
o 35% positive Coombs Test
o 15% to 20% Immune thrombocytopenia
 Pure Red Cell Aplasia observed less frequently
 Hypogammaglobulinnemia: common in CLL
o Defect in specific antibody response to infection and to
immunization
 Bone marrow: hypercellular or normocellular
o Characteristic feature: >30% mature lymphocytes
o Bone marrow cellularity is dependent on age
 Rule of 100: Expected % cellularity = 100 – age (in years)
 No characteristic abnormality of blood chemistry profile
 LDH, 2 microglobulin, BUA elevated in advanced diseases

References: RMT Notes, D2020 Trans, Lecture, and Henry’s 23 ed.


(Chapter 33)

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