KEVIN U.

DAUILA MLS3G
Non-malignant and Malignant Disorders of WBCs
Non-malignant Disorders of WBCs
A. Qualitative Disorders of Leukocytes
B. Quantitative Abnormalities of Leukocytes
C. Epstein-Barr Virus (EBV)-Related Infections
A. Qualitative Disorders of Leukocytes
a1. Morphologic Abnormalities with and without Functional Defect
Disorder
Pelger-Hut
Anomaly

Signs and
Symptoms
Abnormality of the
teeth
Depressed nasal
bridge
Failure to thrive
Foot dorsiflexor
weakness
Frontal blossing
Generalized tonicclonic seizures
Gingival
overgrowth
Hypertelorism

Description
Nucleus does not
segment beyond the
two-lobed staged
resulting to bilobed or
rounded nuclei with
pincenaz/dumbbell/peanutshape

Lab Results
Nuclei of PelgerHut neutrophils
may appear round,
oval, or peanutshaped.
PHA cells are
mature, so
cytoplasm is nearly
colorless, except for
the color imparted
by normal
cytoplasmic

Disease
Correlation
Benign, inherited
anomaly.
Acquired or
pseudoPelger-Hut
is seen in
Myelodysplastic
syndrome (MDS), or
Myeloproliferative
Disorders (MPD)

 Intellectual
disability

Neutrophil
hypersegmentation

Warts
Neutropenia

Hypogammaglobulin
emia
Infections
Myelokathexis

Alder-Reilly Anomaly Clinical findings, if

present, are due to
associated condition

granulation.

Larger than normal

neutrophils with six or
more nuclear segments

Granulocytes with large,

darkly staining
metachromatic
cytoplasmic granules
composed primarily of
partially digested

Neutrophil
hypersegmentation,
hypercondensed
chromatin, and
pyknotic changes
Neutrophils with six
or more nuclear
segments
Granulocytes,
lymphocytes and
monocytes have
heavy azurophilic
granulation

Megaloblastic
Anemia
Myelodysplastic
syndromes
WHIM
Vitamin B12 and
Folate deficiency

Hurler syndrome
Hunter syndrome
Maroteaux-Lamy
polydystrophic
dwarfism

mucopolysaccharides.

Chediak-Higashi
Syndrome

Albinism
Photophobia
Poor resistance to
infection
Mild bleeding
tendencies

Abnormal infusion of
granules in most cells
that contain granules
throughout the body

Prominent dark
staining, coarse
cytoplasmic
granules.
Giant lysosomal
granules in
granulocytes,
monocytes, and
lymphocytes.
Neutrophil shows
giant gray-green
cytoplasmic
granules

May-Hegglin
Anomaly

Asymptomatic but
may develop mild
bleeding tendencies
related to the degree
of thrombocytopenia

Blue, Dohle-like
cytoplasmic inclusions
in all granulocytes

Leukocyte
dysfunction and
recurrent pyogenic
infections
Bleeding due to
abnormal dense
granules in platelets

Lymphocytes and
monocytes show red
granule in
cytoplasm
Neutrophils may
Bleeding tendency
have blue staining
from associated
May-Hegglin
thrombocytopenia
inclusions: resemble
Dohle bodies
Inclusions can also
be found in

monocytes and
lymphocytes
Thrombocytopenia
with giant platelets
(abnormal, bizarre
appearing platelets)

a2. Normal Morphology with Functional Abnormalities

Disorder
Chronic Granulomatous
Disease

Signs and Symptoms

Granulomas in many
organs, sites of chronic
infection

Description
Lab Results
Defective respiratory
Normal WBC
burst; cells engulf but do morphology
not kill microorganisms
Number of WBC
increased

Disease Correlation
Mutation(s) in NADPH
oxidase genes leads to
failure of neutrophil
respiratory burst
following phagocytosis
of organism
Recurrent bacterial and
fungal infection

Leukocyte Adhesion
Disorder I

Leukocyte Adhesion
Disorder II

Leukocyte Adhesion
Disorder III

Lymphadenopathy
Splenomegaly
Skin lesions
Gingivitis
Perirodontitis
Inflammation of the
umbilical cord
(omphalitis) in infants

Absence of cell surface

adhesion proteins
affecting multiple
functions

Facial dysmorphism
depressed nasal bridge
Severe growth delay
short stature
Severe intellectual
deficit
severe periodontitis

Absence of cell surface

adhesion proteins
affecting multiple
functions

LAD-I life threatening

infections
Glanzmann
thrombastehenia-like
bleeding disorder
Lack of pus in infected

Absence of cell surface

adhesion proteins
affecting multiple
functions

Expression of integrin
is absent or abnormal
Mutation in CD18

Neutrophilic
leukocytosis
Flow cytometric
analyses reveal CD18
expression on
leukocytes
Genetic analyses of
mutations in the ITGB2
gene confirm the
diagnosis
Leukocytosis with
neutrophilia
Presence of Bombay
blood group in blood
typing

Impaired expression of
selectin ligands CD15

CD18 and CD15 are

Leukocytosis with
neutrophilia
Platelet aggregation
assays and genetic
analysis confirm the
diagnosis

Recurrent infections
IRAK-4 deficiency
Chronic granulomatous
disease
Primary
immunodeficiencies
Leukemoid Reaction

Physical growth
retardation
Coarse face, and/or
other physical
deformities
Neurological defects
Recurring infections
Absent blood group H
antigen
Defect in fucose
metabolism
Recurrent bacterial and
fungal infections
Decreased platelet
integrin GPIIb, resulting
in bleeding

areas

Miscellaneous
Granulocyte disorders

Most patients do not

experience problematic
recurring infections
because compensatory
pathways are utilized for
microbe killing that do
not involve
myeloperoxidase

normally expressed
Defect in Integrin
activation
Characterized by a
deficiency in
myeloperoxidase in the
primary granules of
neutrophils and
lysosomes od monocyte

MPO deficiency can be

easily detected by
Siemens Advia analyzer,
which uses
myeloperxodase to
identify cells in the
automated differential

Hematologic neoplasms
Lead poisoning

Lab Results
Peripheral blood smear
may appear normal;
however, metachromatic
Reilly bodies may be
seen in neutrophils,
monocytes, and
lymphocytes
Bone marrow may
reveal macrophages
with large amounts of

Disease Correlation
Hurler Syndrome (MPS ISevere)
Scheie Syndrome (MPS Iattenuated)
Hunter Syndrome (MPS
II-Severe)
Sanfillipo Syndrome type
A, B, C (MPS III)
Morquio Syndrome Type
A, B (MPS IV)

a3. Monocyte/Macrophage Lysosomal Storage Diseases

Disorder
Mucopolysaccharidoses

Signs and Symptoms

Coarse or rough facial
features
Dwarfism
Dysplasia
Thickened skin
Enlarged organs such
as liver or spleen
Excessive body hair
growth

Description
Deficient activity of an
enzyme necessary for
the degradation of
dermatan sulfate,
heparin sulfate, keratan
sulfate, and/or
chondroitin sulfate

Gaucher Disease

Neurologic symptoms
Hypersplenism
Anemia
Thrombocytopenia

Defect or deficiency in
the catabolic enzyme glucocerebrosidase,
which is necessary for
glycolipid metabolism

Niemann-Pick Type A

Failure to thrive
Hepatosplenomegaly
Rapid
neuerodegenerative
decline

Deficient activity of
sphingomyelinase, a
lysosomal enzyme
encoded by the SMPD1
gene located on
chromosome 11. The
enzyme defect results in
pathologic accumulation
of sphingomylein and
other lipids in the
monocyte-macrophage
system, the primary site
of pathology in patients

metachromatic material
Hepatomegaly
Gaucher cells in the
bone marrow
Increase in serum
phosphatase
Macrophages with
blue-gray cytoplasm
appear striated or
wrinkled (onion-skin like)
Chitotriosidase:
determines level of
storage
glucocerebrosidase
Macrophages contain
foamy cytoplasm packed
with lipid-filled
lysosomes that appear
as vacuoles after
staining
Acid sphingomyelinase
activity level
distinguishes type A vs.
B

Thalassemia
Chronic Myelogenous
Leukemia
Acute Lymphoblastic
Leukemia

Interstitial lung disease

Psychomotor regression

Niemann-Pick Type B

Little or no
neurological symptoms,
but many experience
severe and progressive
hepatosplenomegaly

Niemann-Pick Type C

Systemic, neurologic
and psychiatric
symptoms
Ataxia
Inability to move the
eyes vertically
Poor muscle tone

with NPD.
Deficient activity of
sphingomyelinase, a
lysosomal enzyme
encoded by the SMPD1
gene located on
chromosome 11. The
enzyme defect results in
pathologic accumulation
of sphingomylein and
other lipids in the
monocyte-macrophage
system, the primary site
of pathology in patients
with NPD.
Characterized by an
inability of the body to
transport cholesterol
and other fatty
substances (lipids)
inside of cells.

Macrophages contain
Heart disease
foamy cytoplasm packed Pulmonary insufficiency
with lipid-filled
lysosomes that appear
as vacuoles after
staining
Acid sphingomyelinase
activity level
distinguishes type A vs.
B

Macrophages contain
Severe liver disease
foamy cytoplasm packed Interstitial lung disease
with lipid-filled
lysosomes that appear
as vacuoles after
staining
Gene sequencing to
screen for NPC1
mutations (95% of
cases) or NPC2 (5% of
cases)

B. Quantitative Abnormalities of Leukocytes

Signs and Symptoms
Neutrophils
Neutrophilia

Neutropenia

Hypothermia
Bleeding leading to
hypotension,
tachycardia and most
probably sepsis
Tachypnea and
Dyspnea

Low-grade fever
Sore mouth
Odynophagia
Gingival pain and
swelling
Skin abscesses
Recurrent sinusitis and
otitis
Symptoms of
pneumonia
Perirectal pain and
irritation
Eosinophils
Eosinophilia

Wheezing and

Description
An increase in
neutrophils can be
related to several
factors, including
catecholamine-induced
demargination or a shift
in neutrophils from the
marginal pool to the
circulating pool
The presence of
abnormally few
neutrophils in the blood,
leading to increased
susceptibility to
infections.

Refers to the condition

Lab Results
Increase in neutrophils
above 7.0x109/L in
adults and 8.5x109/L in
children

Decrease in absolute
neutrophil count (ANC)
below 2.0x109/L in white
adults and 1.3x109/L in
black adults

Absolute eosinophil

Disease Correlation
Myocardial infarction
Autoimmune Disease
Metabolic ketoacidosis
Acute hemorrhagae
Pancreatitis and
Vasculitis
Sjogren syndrome
Felty Syndrome
Rheumatoid arthritis
Dyskeratosis congenital
Fanconi anemia
Copper deficiency
Reticular dysgenesis
Chediak-Higashi
Syndrome

Acute Myelogenous

breathlessness
Abdominal pain
Diarrhea
Fever
Cough and rashes

in which abnormally high count above 0.4x109/L

amounts of eosinophils
are found in blood and in
body tissues

Eosinopenia

Basophils
Basophilia

Basopenia

Diarrhea
Abdominal pain
Fever
Cough and rashes

Number of eosinophil
granulocytes is lower
than expected

Splenomegaly
Weakness
Persistent fatigue
Headache
Hypothyroidism

Condition in which there

is abnormally high
amount of basophils
circulating in the blood
stream

Fatigue
Fever
Malaise
Oral Ulcerations

Absolute eosinophil
count of less than
0.09x109/L

Absolute basophil count

above 0.15x109/L

Absolute basophil count

of less than 0.01x109/L
A form of
agranulocytosis

Leukemia
Ascariasis
Asthma
Atopic dermatitis
(eczema)
Churg-Strauss syndrome
Marrow hypoplasia
Autoimmune disorders
Sepsis
Acute inflammatory
States
Aftermath of acute
bacterial/viral infection
Chronic myelogenous
leukemia
Myeloproliferative
neoplasms
Carcinoma
Lymphoma
Allergy
Chronic Inflammatory
Conditions
Iron Deficiency
Hyperlipidemia

associated with a
deficiency of basophils

Monocytes
Monocytosis

Monocytopenia

Lymphocytes
Lymphocytosis

Fatigue
Weakness
Fever
Overall feeling of
being ill

The presence of
abnormally high
amounts of monocytes
in the blood stream

Weakness
Fatigue and tiredness

Number of monocytes is
lower than expected

Fever
Skin, Temperature,
Nerve symptoms

An abnormal increase in
the number of
lymphocytes in the

Chronic myelogenous
leukemia
Small pox and Chicken
pox
Polycythemia vera
Ulcerative colitis
Absolute monocyte
count of greater than
1.0x109/L in adults and
greater than 3.5x109/L in
neonates

Absolute monocyte
count of less than
0.2x109/L

Absolute lymphocyte
count of greater than
10.0x109/L in children

Tuberculosis
Syphilis
Systemic Lupus
Erythematosus
Rheumatoid Arthritis
Wiskott-Aldrich
Syndrome
Inflammatory Bowel
Disease
Malaria
Subacute bacterial
endocarditis
Epstein-Barr Virus
Hemodialysis
Sepsis
Infectious Mononucleosis
Cytomegalovirus
Infection

 Lymphocytopenia

Pain
Lymphadenopathy

blood

Lymphadenopathy
suggesting cancer or HIV
infection
Cough, runny nose,
feve
Painful swollen joints
and rash
Small tonsils

Absolute lymphocyte
An abnormal decrease in count of less than
Stevens-Johnsons
9
the number of
2.0x10 /L in children and Syndrome
lymphocytes in the
1.0x109/L in adults
Ataxia-telangiectasia
blood
Severe acute respiratory
syndrome
Hodgkin Lymphoma
Protein-losing
enteropathy

C. Epstein-Barr Virus (EBV)-Related Infections

Infectious Mononucleosis
Signs and Symptoms
Common
Sore throat
Dysphagia
Chills
Fever
Cervical lymphadenopathy
Fatigue
Headache

Less common
Hepatomegaly
Elevated transaminases
Splenomegaly
Hemolytic Anemia
Thrombocytopenia

and 4.5x109/L in adults

Paratyphoid and Typhoid

Fever
Toxoplasmosis

Description
Infectious mononucleosis is an infection commonly caused by the Epstein-Barr virus. The virus spreads through saliva, which is why
its sometimes called kissing disease.
Lab Results
WBC: 10-30 x 109/L due to an absolute lymphocytosis
Reactive lymphocyte morphology
Positive heterophile antibody test
Positive EBV specific antigen and antibody tests
Disease Correlation
Hemolytic Anemia
Aplastic Anemia in mild cases
Thrombotic Thrombocytopenic purpura
Dessiminated Intravascular Coagulation
Hemolytic Uremic Syndrome
Guillain-Barre Syndrome

Malignant Disorders of WBCs

Hodgkin lymphoma

Signs and Symptoms

Painless swelling of
lymph nodes in neck,
armpits or groin
Persistent fatigue

Description
It is a cancer of the
lymphatic system. Cells
in the lymphatic system
grow abnormally and

Lab Results
CBC - low RBC count,
lymphopenia,
neutrophilia,
eosinophilia

Disease Correlation
Epstein-Barr Virus
Infection
Classical Hodgkin
Lymphoma

 Fever and chills

Night sweats
Unexplained weight
loss
Loss of appetite
Itching

Non-Hodgkin
Lymphoma

Painless swelling of
lymph nodes in neck,
armpits or groin
Abdominal pain or
swelling
Chest pain, coughing
or trouble breathing
Fatigue
Fever
Night sweats
Weight loss

Burkitt lymphoma

Fatigue
Unexplained Fever
Night sweats

may spread beyond the

system. Characterized
by Reed-Sternberg cells
which originate from B
cells in the germinal
center of lymph nodes.

Positive warmagglutinin on a Coombs

test
Elevated ESR
Elevated Lactate
dehydrogenase
Serum creatinine may
be elevated

Lymphocyte-rich
classical Hodgkin
Lymphoma
Nodular sclerosis
Hodgkin Lymphoma
Mixed cellularity
Hodgkin Lymphoma
Lymphocytedepleted Hodgkin
Lymphoma
A cancer that starts in
High lymphocyte count AIDS-related lymphomas
cells called lymphocytes, in the lymph and
Anaplastic Large-cell
which are part of the
marrow
lymphoma
bodys immune system. Lactate
Angioimmunoblastic
In Non-Hodgkin
dehydrogenase
lymphoma
lymphoma, tumors
elevated
Cutaneous T-cell
develop from
Bone marrow biopsy lymphoma
lymphocytes.
presence of lymphoma
Follicular Lymphoma
cells
Marginal zone lymphoma
Ultrasound tumors
Mantle cell lymphoma
may produce echoes
Diffuse large B-cell
that are different from
lymphoma
the echoes made by
Nasal T-cell lymphoma
healthy tissues
A form of non-Hodgkins Lactate
lymphoma in which
dehydrogenase
cancer starts in immune elevated

 Weight loss
Loss of appetite

Chronic Myeloid
Leukemia

Fever
Tiredness
Get bruises
Night sweats
Weight loss
Shortness of breath
Feel less hungry
Swelling or pain on the
left side of the body
Pain in bones

Acute Myeloid
Leukemia

Fatigue
Fever
Weight loss
Loss of appetite
Night sweats
Shortness of breath
Petichiae

cells called B-cells

It is a tumor of the jaw in
African children and
young adults which is
associated with
Plasmodium falciparum
infection
A type of cancer that
affects the blood and
bone marrow. In CML,
the bone marrow
produces too many
white blood cells, called
granulocytes. These
cells, sometimes called
blasts, gradually crowd
the bone marrow,
interfering with normal
blood cell production
A type of blood cancer.
AML usually develops
from cells that turn into
WBCs (other than
lymphocytes). The bone
marrow makes abnormal
myeloblasts, RBCs, or

Presence of immature
WBCs, and decreased
amounts of RBCs and
platelets
Having at least 20%
blasts in the marrow or
blood is generally

Acute Lymphoblastic
Leukemia

Hairy Cell Leukemia

Easy bruising or
bleeding

platelets

Bleeding from the

gums
Bone pain
Fever
Frequent infections
Frequent or severe
nosebleeds
Lumps caused by
swollen lymph nodes in
and around the neck,
underarm, abdomen or
groin
Pale skin
Shortness of breath
Weakness, fatigue or a
general decrease in
energy
Some people have no
signs and symptoms.

Also known as acute

lymphocytic leukemia, it
type of cancer of the
blood and bone marrow.

Others may experience

required for the

diagnosis of AML
Cytochemistry stain
causes the granules of
most AML cells to
appear as black spots
Down Syndrome
Neurofibromatosis Type
1
Bloom Syndrome
Fanconi Anemia
Ataxia-telangiectasia
Li-Fraumeni Syndrome

The bone marrow makes

too many immature
lymphocytes

A rare slow growing

cancer of the blood in
which the bone marrow
makes too many B-cells.

Presence of hairy
lymphocytes
Low WBC count
Low platelet count

Mutations in the DNA

cause bone marrow
stem cells to create tool
many WBCs that dont

S/S:
Fatigue
Easy bruising
Recurring infections
Weakness
Weight loss
A feeling of fullness in
abdomen that may
make it uncomfortable
to eat more than a little
at a time

These B-cells are

abnormal and look
hairy under a
microscope.

Low RBC count

work properly.
Infections
Bleeding
Anemia