QUALITATIVE DISORDERS

  Inherited & acquired, permanent & transient

  INHERITED -> asymptomatic (asx) of life threatening

  ACQUIRED -> in response to circumstances & are

interpreted as indicators of disease states
Hindi siya tlga sakit pero an indication na there is an
undergoing disease process

ACQUIRED
  Toxic granulations
  Dohle bodies
  Cytoplasmic vacuolations
TOXIC GRANULATIONS
GENETICS
is not a disease but an indication
Nuclear WHERE: severe inflammatory states & cytokine administration
o Pelger-Huet anomaly
o Hypersegmentation WHAT: larger, darker(azurophilic) more prominent than the
normal specific granules seen in differentiated myeloid forms
Cytoplasmic
o Lazy leukocyte syndrome
o Chronic Granulomatous Disease SEEN: promyelocyte, metamyelocyte, band, and segmented
stages
o May-Hegglin Anomaly
o Alder-Reilley Anomaly
o Chediak-Higashi Anomaly DUE: impaired cytoplasmic maturation in the effort to rapidly
o Jordan’s Anomaly generate large numbers of granulocytes.

Toxic granules are dark blue to purple cytoplasmic granules in

Bakit natin kailangan na malaman ang mga ito even though
the metamyelocyte, band, or neutrophil stage.
they are not a specific disease they are just an indicator of the
disease?
Peroxidase-positive; less peroxidase activity may be seen in
toxic than in normal neutrophils.
1. To establish diagnoses
2. To prognosticate
3. To evaluate therapy In order to check if talagang toxic granulation nga, you can do
a “PEROXIDASE TEST”. Positive indicates Toxic Granulation
MORPHOLOGIC ALTERATIONS

1. Nucleus
o   Pelger Huet (hereditary)
o   Hypersegmentation (hereditary)
2. Cytoplasm
o   Toxic Granulations (acquired)
o   Cytoplasmic Vacuolations (acquired)
o   Dohle bodies (acquired)
o   May-Hegglin (hereditary)
o   Alder-Reilly (hereditary)
o   Chediak-Higashi (hereditary)
o   Lazy leukocyte (hereditary)
o   Jordan’s anomaly (hereditary)

a lot of very coarse granules in the cytoplasm

CYTOPLASMIC VACUOLATIONS
  Degeneration begins to acquire holes or as a result
of active phagocytosis
  May reflect increase lysosomal activity
  Found in septicemia
  More reliable than granulations
A lot of vacuoles more reliable indicator that a patient has a
sepsis compared to your toxic granulation
A. DOHLE BODIES (acquired)
  Single or multiple blue cytoplasmic inclusions
  Remnants of RER with RNA from earlier maturational stages
  Associated with myeloid “left shifts”
  Seen in conjugation with toxic granulations
  PAS-positive
  Small, oval inclusions in the peripheral cytoplasm of
polymorphonuclear neutrophils (stain pale blue withWright’s
stain)
Figure 1. Dohle bodies
B. MAY-HEGGLIN ANOMALY (hereditary)
  Inclusion bodies particularly in the neutrophils but
also in monocytes, eosinophils, and basophils.
 Large (>5μm), spindle-shaped, pale, blue-staining
bodies consist of ribosomes, segments of
endoplasmic reticulum and microfilaments
 Periphery of the cytoplasm and resemble Dohle
Bodies.
 Mutation in MYH-9 (myosin Heavy Chain gene) in
chromosome 22.
 Autosomal dominant
 Examples are leukopenia, purpura and bleding
 PAS-negative
TRIAD
1. Inclusion body
2. Giant Platelets
3. 3. thrombocytopenia
May Hegglin Anomaly vs. Dohle Bodies
 True Dohle bodies are made up of lamellar rows of
rough endoplasmic reticulum, whereas MHA
inclusions consist of randomly placed rods in an
amorphous background
 In addition, Dohle bodies are found only in
neutrophils, whereas MHA inclusions are seen in
neutrophils, eosinophils, basophils, and monocytes
 MHA inclusions may stain a very pale color with
Wright stain and may be missed in monocytes whose
cytoplasm is also blue-grey.
C. OTHER DISORDERS IN PLATELET FUNCTIONS
Figure 2. May-Hegglin Anomaly
D. ALDER-REILLY ANOMALY
 Dense, azurophilic granules but mostly in clusters
resembles toxic granulations
 Not related to infections and not transient in nature
 Autosomal recessive
 Deposition of mucopolysaccharides (lipid)
 Associated with mucopolysaccharidosis (ex. Hurler
Syndrome, Hunter syndrome, Maroteaux-Lamy
polydystrophic dwarfism)
 Seen in all leukocytes (cell function is normal)
 More in bone marrow than in peripheral blood smear
 The Alder-Reilly anomaly may be found in healthy
individuals or in those with mucopolysaccharidoses, in
which granules are metachromatic.
E. CHEDIAK-HIGASHI SYNDROME
 Autosomal recessive disorder characterized by partial
oculocutaneous albinism, photophobia, immune
deficiency, abnormally large granules in leukocytes
and other granule- containing cells, neurologic
defects, and frequent pyogenic infections.
 Granulocytes, monocytes, and lymphocytes contain
giant granules which appear to be abnormal
lysosomes.
 The pathogenesis of this disorder is linked to an
abnormality of granule maturation, causing
enlargement and apparent fusion of granules and
vesicles (such as lysosomes, melanosomes, and
platelet dense granules) in all cell types.
  Chromosomal mutation at 1q43 effecting the LYST infections. Ichthyosis is a skin disease na parang fish like
gene. The product of this gene regulates lysosomal scaling (excessive scaling).
trafficking.
 In Chediak-Higashi syndrome, the neutropenia usually
is mild, and susceptibility to infection is attributed to
neutropenia and defective microbial activity of the
phagocytes.
 All cells with the lysosomal granules are affected
 Melanosomes of skin and eyes, hypopigmentation of
platelets, lack granules, prolonged BT, giant granules
in WBC
 Chemotaxis and phagocytosis defective cause Figure 5.1 Jordan’s Anomaly in peripheral leukocyte
neutropenia


Figure 4. Chediak Higashi Syndrome (abnormality of Figure 5.2 Jordan’s Anomaly

granule maturation, causing enlargement and
apparent fusion of granules and vesicles)
In the picture, you can see here a neutrophil with a cytoplasmic
vacuolations (the white circles).
F. LAZY LEUKOCYTE SYNDROME (SCHWACHMAN
SYNDROME) DDx OF VACUOLATED NEUTROPHILS

  Children Vacuoles/Vacuolization: Sign of Activation, Active Phagocytosis, or

  Defects in the: Some Types of Cancers.

o Chemotactic activity of leukocytes Sometimes due to prolong standing of blood, d naproprocess agad
o Production of C5a of complement nagkakaroon ng degenerative changes thus showing a cytoplasm with
vacuolations.
o Cytoskeleton of the leukocyte which prevents it from being
able to move around cannot accumulate at the site of an
infection. 1. Bacterial infection
o Subject to recurrent bacterial infections. 2. Fungal infection
3. Poisoning
4. Burns
Tamad sila because of their cytoskeleton. Since kulang ang 5. Chemotherapy
pumupunta na neutrophils at the site of injury thus they are 6. Artifact
subject to recurrent bacterial infections, kasi mga tamad ang
mga neutrophils nila.
H. NUCLEAR ABNORMALITIES
G. JORDAN’S ANOMALY
PELGER-HUET ANOMALY (PHA)

 PBS (Peripheral Blood Smear): persistent cytoplasmic

vacuolations in granulocytes, monocytes and rarely  An autosomal dominant disorder resulting in
lymphocytes. decreased nuclear segmentation.
 BM (Bone Marrow): cytoplasmic vacuoles found in the  Most common genetic disorder of leukocytes.
cytoplasm of promyelocytes, myelocytes,
metamyelocytes and rarely in plasma cells. Not
 Mutation of the lamin B receptor. The lamin B receptor
is an integral protein in the inner nuclear membrane.
observed in blasts or in red cells and thrombocytes
PHA is one of a large number of so-called
and their precursors.
laminopathies ranging from a type of muscular
 Presence of cytoplasmic vacuolations + Ichthyosis + dystrophy to premature aging.
Muscular dystrophy/cardiomyopathy/storage
disease = jordan’s anomaly.

CYTOCHEMICAL STAINS

The cytoplasmic vacuolations should be associated with the

clinical findings of the Ichthyosis, Muscular
dystrophy/cardiomyopathy/storage disease because if wala,
the vacuolations maybe related to sepsis or systemic 
 Figure 6. Pelger -Huet Anomaly (PHA)

Figure 8. Hypersegmented Neutrophils

Figure 7. Heterozygous and homozygous (PHA)
MORPHOLIC ALTERATIONS IN NEUTROPHILS SUMMARY
  Heterozygous PHA (segmented only once).
  Homozygous PHA (no segmentation).
 TOXIC GRANULATION - azurophilic cytoplasmic
Is the function affected? NO granules seen in severe infections, other toxic
conditions, and reactive conditions
 CYTOPLASMIC VACUOLES - seen in infection,
HEREDITARY HYPERSEGMENTATION
indicating phagocytosis
 DÖHLE BODIES - pale blue, oval cytoplasmic
  4 or more lobes in neutrophils remnants of ribosomes seen in infection and other
 Autosomal dominant toxic conditions
 No megaloblastic changes  MAY-HEGGLIN ANOMALY - rare autosomal
 Normal function dominant condition with pale blue cytoplasmic
 Myeloid “right shift” – more mature type of cells ribosomal inclusions resembling Döhle bodies
 Seen in Iron Defiency Anemia (IDA)  ALDER-REILLY ANOMALY - prominent azurophilic
granulation not related to infection
 PELGER-HUËT ANOMALY - bilobed or rounded
NORMAL SEGMENTATION nuclei with pince-nez shape
 CHÉDIAK-HIGASHI SYNDROME - autosomal
o Neutrophils 3 lobes recessive disorder with giant granules, likely
o Eosinophils <4lobes representing giant fused lysosomes, and abnormal
o Basophils <3lobes leukocyte function

HYPERSEGMENTED NEUTROPHILS (THE RIGHT SHIFT)

 Presence of neutrophils with six or more lobes or the

presence of more than 3% neutrophils with at least 5 lobes.

Causes

1) Diagnostic feature of megaloblastic anemia but not

pathognomic.

Also seen in:

1) Uremia
2) Patients on methotrexate or hydroxycarbimide therapy
3) Iron Defiency Anemia (yes IDA too can show
hypersegmented neutrophil)

Mechanism: Still not clear; that is what “wintrobe” says!

  It is one of the earliest marker of megaloblastic anemia.

  First to appear and last to disappear in megaloblastic anemia

Note:
  The normal number of neutrophils with 5 lobes is less than
0.5
  The normal number of neutrophils with 6 lobe is zero