QUALITATIVE DISORDERS OF LEUKOCYTES

Abnormal morphology with and without Functional

Defects
 Neutrophil Hypersegmentation
• Normal neutrophils contain (3 to 5) lobes.
• Hypersegmented neutrophils have more than five lobes
and are most often associated with the megaloblastic
anemias, where the neutrophil is also larger than normal.
• Hypersegmented neutrophils can also be seen in the
myelodysplastic syndromes.
• Much less frequently, hypersegmented neutrophils can be
found in hereditary neutrophil hypersegmentation. In this
disorder, patients are asymptomatic and have no signs of
megaloblastic anemia.
Toxic granulation
• Toxic granulation of neutrophils appears as dark, blue-black
granules in the cytoplasm of neutrophils: segmented, bands,
and metamyelocytes.
• Toxic granules are peroxidase positive and reflect an increase
in acid mucosubstance within primary, azurophilic granules
of neutrophils. The result is a lowered pH in phagolysosomes
that enhances microbial killing.
• There is a positive correlation between levels of C-reactive
protein (acute phase protein) and the percentage of
neutrophils with toxic granulation; therefore, the intensity of
toxic granulation is a general measure of the degree of
inflammation.
Toxic granulation

Toxic granulation Normal neutrophil Toxic granulation

 Döhle bodies
• Döhle bodies are cytoplasmic inclusions consisting of remnants of
ribosomal ribonucleic acid (RNA) .
• Döhle bodies are typically found in neutrophils and often in cells
containing toxic granulation.
• They appear as intracytoplasmic, pale blue round or elongated
bodies between 1 and 5 mm in diameter.
• They are usually located in close apposition to cellular membranes.
• A delay in preparing the blood after collection in EDTA tube may
affect Döhle body appearance in that they are more gray than blue
and, in some cases, may not be visible.
• Döhle bodies are relatively nonspecific. Their presence has been
associated with bacterial infections, sepsis, and normal pregnancy
Döhle bodies
Cytoplasmic vaculation
• Cytoplasmic vaculation is seen less often than toxic granules and Döhle
bodies. Vacuoles generally reflect phagocytosis.
• Phagocytosis can be induced by drugs such as sulfonamides and
chloroquine, Storage in EDTA (artefactual) for more than 2 hours.
Phagocytic vacuoles caused by either bacteria or fungi are often seen in
septic patients.
 Pelger-Huët Anomaly
Is an autosomal dominant disorder characterized by decreased nuclear
segmentation (bilobed, unilobed).
Potentially affecting all leukocytes.
Changes are most obvious in mature neutrophils.
• The nuclei may appear round, ovoid, .
• Bilobed forms-the characteristic spectacle like.
• In homozygous PHA, all neutrophils are affected
• In the heterozygote, 55% to 93% of the neutrophil
population are affected, and there is a mixture of all
of the aforementioned nuclear shapes.
• Neutrophils in Pelger-Huët anomaly appear to
function normally.
Pseudo- or Acquired Pelger-Huët Anomaly
Neutrophils with PHA morphology can be observed in:
hematologic malignancies such as:
Myelodysplastic syndromes ,Acute myeloid leukemia, and
chronic Myeloproliferative neoplasms.
Pseudo-PHA Neutrophils can also be seen in some infections:
HIV infection, tuberculosis, Mycoplasma pneumonia and severe
bacterial infections.

Drugs known to induce pseudo-PHA include :

Valproate, Ibuprofen, and chemotherapies…
Alder-Reilly Anomaly
• Alder-Reilly anomaly is transmitted as a recessive trait
• Characterized by granulocytes with large, darkly staining
cytoplasmic granules .
• The granules are referred to as Alder-Reilly bodies or Reilly bodies.
The morphology may resemble heavy toxic granulation.
• Also, in some patients with Alder-Reilly anomaly, the granules are
found in lymphocytes and monocytes, ruling out toxic granulation,
which is exclusive for neutrophils.
• Leukocyte function is not affected in Alder-Reilly anomaly.
Alder-Reilly Anomaly
 Chédiak-Higashi Syndrome
• Is a rare, autosomal recessive disease.
• In 2008, only 800 cases were reported worldwide.
• The disease is characterized by abnormal fusion of granules in most
cells that contain granules throughout the body.
• The fused granules are large and mostly dysfunctional.
• Disease manifestations can be found in hair, skin, adrenal and pituitary
glands, and nerve.
• Hematologic findings in Chédiak-Higashi syndrome include giant
lysosomal granules in granulocytes, monocytes, and lymphocytes.
• These fused granules result in leukocyte dysfunction and recurrent
pyogenic infections.
• Patients often have bleeding issues due to abnormal dense granules in
platelets.
Chédiak-Higashi Syndrome
May-Hegglin Anomaly
• Rare, autosomal dominant platelet disorder characterized by variable
thrombocytopenia, giant platelets, and large Döhle body-like
inclusions in neutrophils, eosinophils, basophils, and monocytes.
• The basophilic Döhle body-like leukocyte inclusions in May-Hegglin
anomaly are composed of precipitated myosin heavy chains.
• Clinically, the majority of individuals with May-Hegglin anomaly
are asymptomatic, but a few have mild bleeding tendencies that are
related to the degree of thrombocytopenia.
May-Hegglin Anomaly
Normal Morphology with Functional Abnormalities
Chronic Granulomatous Disease

• is a rare inherited disorder caused by the decreased ability of phagocytes to produce

superoxide and reactive oxygen species.
• Most patients experience bacterial and fungal infections of the lung, skin, lymph nodes, and
liver.
Leukocyte Adhesion Disorders
• Leukocyte adhesion disorders (LADs) are rare autosomal recessive inherited disorders that
result in the inability of neutrophils and monocytes to adhere to endothelial cells and to
transmigrate from the blood to the tissues.

• Recruitment of leukocytes to the site of inflammation involves capture of leukocytes from

peripheral blood, followed by rolling along a vessel wall. This process is mediated through
selectins, which interact with their ligands on the surface of leukocytes.

• The basic defect is a mutation in the genes responsible for the formation of cell adhesion
molecules
Myeloperoxidase (MPO) deficiency

ØCharacterized by a deficiency in myeloperoxidase in the primary

granules of neutrophils and lysosomes of monocyte.

ØMyeloperoxidase normally stimulates production of hypochlorite and

hypochlorous acid, which are oxidant agents that attack phagocytized

microbes. The disorder is inherited in an autosomal dominant manner.

Genetic B and T Lymphocyte Abnormalities

• Functional B and T lymphocyte abnormalities are genetic disorders that generally

result in the decreased production of B cells, T cells, or both. They are all associated
with an increased risk of infection and secondary malignancy.