CHAPTER 29

NONMALIGNANT
LEUKOCYTE
DISORDERS
QUALITATIVE DISORDERS
OF LEUKOCYTES

Morphologic abnormalities with

and without functional defects
 PELGER-HUET ANOMALY
 Also known as true or  The disorder is a result of
congenital PHA. a mutation in the lamin ß-
receptor gene.
 Autosomal dominant
disorder characterized by
decreased nuclear
segmentation
(bilobed,unbilobed) and a
characteristic coarse
chromatin clumping
pattern potentially
affecting all leukocytes.
 Thelamin ß-receptor is an inner nuclear
membrane protein that combines ß-type lamins
and heterochromatin and plays a major role in
leukocyte nuclear shape changes that occur
during normal maturation.

 The mutation in the lamin ß-receptor gene result

in the morphologic changes characteristics of
PHA, although the exact pathological
mechanisms are not known.
PSEUDO- OR ACQUIRED PELGER-
HUET ANOMALY

 Neutrophilswith PHA morphology can be

observed in patients with hematologic
malignancies such as;

 Acutemyeloid leukemia
 myelodys -aplastic syndromes

 Chronic myeloproliferative neoplasms

 Pseudo-PHA neutrophils can also be seen in patients with;

 HIV patients
 Tuberculosis
 Mycoplasma pneumonia
 And severe bacterial infections

 Drugs known to induce pseudo-PHA includes;

 Mycophenolate mofetil
 Valproate
 Sulfisoxazole
 Ganciclovir
 Ibuprofen
 And chemotherapies such as, Paclitaxel and Docetaxel.
 NEUTROPHIL
HYPERSEGMENTATION
 Contain three to five Segmented Neutrophil
lobes that are
separated by
filaments.

 Most often associated

with the
megaloblastic
anemia's where the
neutrophils is also
larger than normal.
 NEUTROPHIL
HYPERSEGMENTATION
 Canalso be seen in the myelodysplastic
syndromes and represent a form of myeloid
dysplasia.

 Myelokathexis - refers to an rare hereditary

condition characterized by normal granulocyte
production.

 WHIM – a syndrome in which warts,

neutropenia, hypogammaglobulinemia,
infections and myelokathexis are common
findings.
 ALDER- REILLY ANOMALY
 Transmittedas a recessive trait and is
characterized by granulocytes with large, darkly
staining metachromatic cytoplasmic granules.

 Some patients with Alder-Reilly Anomaly, the

granules are found in lymphocytes and
monocytes, ruling out toxic granulation, which is
exclusive for neutrophils.
 ALDER- REILLY ANOMALY
 Two neutrophils from a
 Reilly bodies are most patient with Alder-Reilly
commonly associated anomaly.
with;

 Hurler syndrome
 Hunter syndrome

 Maroteaux-Lamy
polydystrophic dwarfism
CHEDIAK-HIGASHI SYNDROME
 A rare, fatal, autosomal recessive disease.

 The disease is characterized by abnormal fusion

of granules in most cells that contain granules
throughout the body.

 Hematologic findings includes giant lysosomal

granules in granulocytes, monocytes and
lymphocytes.
A. Neutrophil with large dark B. Monocyte with large azure
lysosomal granules. granules.

C. Lymphocyte with one large

azure granules.
 MAY-HEGGLIN ANOMALY
 Autosomal dominant platelet disorder
characterized by variable thrombocytopenia,
giant platelets and large Dohle body-like
inclusions in neutrophil, eosinophil's, basophils
and monocytes.

 Caused
by a mutation in the MYH9 gene on
chromosome.

 Dohlebodies are composed of lamellar rows of

rough endoplasmic reticulum.
 CHRONIC GRANULOMATOUS
DISEASE
 Inherited disorder caused by the decreased
ability of phagocytes to produce superoxide and
reactive oxygen species.
 LEUKOCYTE ADHESION
DISORDERS
 Recruitmentof leukocytes to the site of
inflammation involves capture of leukocytes
from peripheral blood.

 Rare autosomal recessive inherited disorders that

result in the ability of neutrophils and monocytes
to adhere to endothelial cells and to transmigrate
from the blood to the tissues.

 Leukocyte adhesion disorders have been divided

into three subcategories;
 LAD I- is caused by a mutation in exons 5 to 9 in the
gene responsible for ß2 integrin subunits resulting in
either a decreased or truncated.

 LAD I- is considerably rarer than LAD 1 and presents in

a similar manner.

 There are molecular defects in SLC35C1, which codes

for a focuse transporter that moves fucose from the
endoplasmic reticulum to the Golgi region.

 Fucose- is needed for post translational fucosylation of

glycoconjugates which is required for synthesis of select
in ligands.
 LAD II patients have growth retardation, a coarse face
and other physical deformities.

 LAD III- is very rare autosomal recessive disease.

Leukocytes and platelets have normal expression of
integrin's, but there is failure in response to external
signals that would normally result in leukocyte
activation.

 Clinically LAD III patients, experience a mild LAD I-

like immunodeficiency with recurrent bacterial and
fungal infections.
 MISCELLANEOUS GRANULOCYTE
DISORDERS

 Myeloperoxidase (MPO) deficiency- is characterized

by a deficiency in myeloperoxidase in the primary
granules of neutrophils and lysosomes of monocyte.

 Normally stimulates production of hypochlorite and

hypochlorous acid which are agents that attack
phagocytized microbes.

 The disorder is inherited in an autosomal dominant

manner with a prevalence of approximately 1 in 2000
individuals.
 Most patients do not experience problematic recurring
infections because compensatory pathways are utilized
for microbe killing that do not involve myeloperoxidase.

 Acquired myeloperoxidase deficiency can present in

association with hematologic neoplasms and lead
poisoning.

 In the hematology lab MPO deficiency can be easily

detected by the Siemens Advia analyzer, which uses
myeloperoxidase to identify cells in the automated
differential.
 MONOCYTE/ MACROPHAGE
LYSOSOME STORAGE DISEASE
 They represent inherited enzyme deficiencies or defects
that the result in flawed degradation of phagocytized
material.

 Mucopolyssacharidoses – are a family of inherited

disorders of GAG degradation.

 MPS caused by deficient activity of an enzyme necessary

for the degradation of dermatan sulfate, keratin sulfate
and chondroitin sulfate.

 Subdivided into mucopolysaccharide storage diseases

and lipid storage disease:
 Lipidstorage diseases – inherited
disorders in which lipid catabolism is
defective .

 Gaucher disease - the most common of

the lysosomal lipid storage disease. It is
autosomal recessive disorder caused by a
defect or deficiency in the catabolic
enzyme.
 REACTIVE CAUSES OF
MONOCYTES
 Infection  Recovery from acute
 Tuberculosis infection. Recovery from
neutropenia.
 Viral
Immunologic/Autoimmune.
 Malaria
 Brucellosis
 Systemic lupus erythematous
 Leishmaniasis
 Rheumatoid arthritis
 Fungal
 Autoimmune neutropenia
 Sub acute bacterial
 Inflammatory bowel disease
endocarditis
 Myositis
 Syphilis
 sarcoidosis
 Protozoal
 Hematologic
 Acute/chronic neutropenia
 Cyclic neutropenia
 Wiskott-Aldrich syndrome
 Drug-induced neutropenia
 Hemolysis
 Immune thrombocytopenia
 Drugs
 Colony-stimulating factors
 Olanzapine
 Carbamazepine
 Phenytoin
 Phenobarbital
 Valproic acid
 Cancer  Splenectomy
 Carcinoma Gastointestinal disease
 Sarcoma

 Plasma cell dyscrasias  Alcoholic liver disease

 Lymphoma  Sprue

 Stress
 Trauma

 Myocardial infarction

 Intense exercise
 CAUSES OF NONMALIGNANT
LYMPHOCYTOSIS

Reactive Morphology

 Infection
 Infectious mononucleosis
 Miscellaneous
 Cytomegalovirus infection
 Hepatitis
 Acute HIV infection
 Idiosyncratic drug reactions
 Adenovirus  Post vaccination
 Chickenpox
 Herpes influenza  Sudden onset of stress from
 Paramyzovirus (mumps) myocardial infarction
 Rubella (measles)
 Hemolytic streptococci  Allergic reaction
 Brucelliosis  Hyperthyroidism
 Paratyphoid fever
 Toxoplasmosis  malnutrition
 Typhoid fever
 Listeria
 Mycoplasma syphilis
CAUSES OF NONMALIGNANT
LYMPHOCYTOPENIA

Inherited Acquired
 Aplastic anemia infections
 Congenital  Acquired immunodeficiency syndrome
immunodeficiency  Severe acute respiratory syndrome
diseases  West nile
 Hepatitis
 Influenza
 Severe combined  Herpes
immunodeficiency disease  Measles
 Tuberculosis
 Common variable  Typhoid fever
immunedeficiency  Pneumonia
 Rickettsiosis
 Ataxia- telangictasia  Ehrichiosis
 Wiskott- aldrich syndrome  Sepsis
 Malaria
 others
 Latrogenic
 Immunosuppresive agents
 Stevens johnson syndrome
 Chemotheraphy
 Radiation
 Platelet
 Major surgery
 Systemic Disease
 Autoimmune disease
 Hodgkin lymphoma
 Carcinoma
 Primary myelofibrosis
 Protein-losing enteropathy
 Renal failure
 Nutritional/Dietary
 Ethanol abuse
 Zinc deficiency