Non-Malignant Granulocyte Disorders

WBC Reference Range

3.5-10.5 × 10⁹/L

Neutrophil Reference Range

1.7-7.0 × 10⁹/L

Lymphocyte Reference Range

0.9-2.9 x 10⁹/L

Monocyte Reference Range

0.3-0.9 x 10⁹/L

Eosinophil Reference Range

0.05-0.5 x 10⁹/L

Basophil Reference Range

0.0-0.3 x 10⁹/L

Causes of Neutrophilia

Bacterial Infection

Drug Intoxication

Stress Response

Malignancy

Tissue Destruction/Injury (Inflammation)

Left Shift

>6 bands, >1 metamyelocyte, or >0.5 myelocyte

Leukemoid Reaction

White count >25.0 with left shift

LE Picture

Left Shift + nRBCs

Toxic Granules

• Large, deep purple primary granules in the neutrophil cytoplasm

• Formed when the neutrophil releases its secondary granules, making the primary ones more visible

Dohle Bodies

Aggregates of ribosomal rER that appear in the peripheral cytoplasm of neutrophils

Blue-grey, rod-shaped, or oval inclusions

What are the three toxic changes seen in neutrophilia?

• Toxic Granules

• Dohle Bodies

• Vacuoles

Causes of Neutropenia

Bone Marrow Failure

Chemotherapy

Drug Intoxication

Immune Destruction

Pseudoneutropenia

• Caused by neutrophils clumping together

  • Results in falsely decreased white cell and neutrophil counts

Pelger-Huet Anomaly - Inheritance

Autosomal Dominant

Pelger-Huet Anomaly

The neutrophils function normally, but don’t segment beyond two lobes (hyposegmentation)

Nucleus may also appear round (mononuclear) with more mature chromatin

Alder-Reilly Anomaly

Large purple granules in the cytoplasm of all white cells

Alder = Abundance of granules

What disorders are associated with Alder-Reilly syndrome?

Decreased mucopolysaccharide production

(Hunter’s syndrome, Hurler’s syndrome)

How does Alder-Reilly Syndrome differ from toxic granulation?

All white cells are affected in Alder-Reilly syndrome

Chediak-Higashi Anomaly - Inheritance

Autosomal Recessive

Chediak-Higashi Anomaly

Fusion between primary and secondary granules in all white cells

How is function impacted in Chediak-Higashi anomaly?

• Granules do not function properly

• Reduced chemotaxis

  • Reduced bactericidal capabilities

What CBC findings are associated with Chediak-Higashi anomaly?

Neutropenia and Thrombocytopenia

May-Hegglin Anomaly

Giant (cigar-shaped) platelets and randomly distributed Dohle-like bodies in all white cells

May = Mega Platelets

What CBC finding is associated with May-Hegglin anomaly?

Thrombocytopenia

Chronic Granulomatosus Disease

Defect in the respiratory burst

Patients can phagocytize bacteria, but cannot form the superoxides needed to kill the bacteria

Bacteria survive; patients often have frequent infections

What test is used to confirm chronic granulomatosus disease?

Nitroblue Tetrazolium Dye Test

• Neutrophils are mixed with nitroblue tetrazolium dye and bacteria

• If they can take up the bacteria and initiate oxygen intake, the solution turns blue

  • In CGD patients, the solution will stay yellow

Myeloperoxidase Deficiency

Cells are deficient in myeloperoxidase

Neutrophils will show up on the PBS and appear morphologically normal

They will not show up on the automated CBC scatterplot

What disorders are associated with pseudo Pelger-Huet cells?

Myelodysplastic Disorders

Myeloproliferative Neoplasms

How can Pelger-Huet and Pseudo Pelger-Huet cells be distinguished?

In Pelger-Huet anomaly, all neutrophils will be hyposegmented

There will be a mix of “normal” and hyposegmented neutrophils in pseudo Pelger-Huet cases

Where are the findings in Alder-Reilly anomaly most prominent?

Cells of the bone marrow

Causes of Eosinophilia

Parasitic Infections

Hypersensitivity Reactions

Allergies

Malignancies

Hypereosinophilic Syndrome

An eosinophil count >1.5 × 10⁹/L with tissue infiltration and no apparent cause

Associated with Charcot-Leyden crystals & heart damage

How can HES and eosinophilic leukemia be distinguished?

• HES will generally involve mature eosinophils

  • EL will exhibit increased eosinophilic myelocytes and myeloblasts

Charcot-Leyden Crystals

Formed from eosinophil breakdown products (eosinophil granules + cytoplasm)

They are found in tissues or fluids where eosinophils migrate and then break down

Causes of Basophilia

Hypersensitivity Reactions

Chronic Myeloproliferative Disorders

Causes of Monocytosis

Malignancies

Inflammation

Immune Disorders

Chronic Infection

What malignancies are associated with monocytosis?

Acute monocytic and myelomonocytic leukemias

Chronic myelomonocytic leukemia

Gaucher Disease - Cause

Glucocerebrosidase deficiency

Macrophages can’t digest the stroma of ingested cells, and glucocerebrosidase accumulates

Gaucher Cells

20-80 microns

Small, eccentric nucleus

Wrinkled/striated “tissue paper” cytoplasm filled with lipid

Gaucher Disease - Inheritance

Autosomal Recessive

Gaucher Disease - Clinical Findings

Hepatosplenomegaly

Anemia

Leukopenia

Thrombocytopenia (& bleeding)

Elevated Serum Acid Phosphatase

Niemann Pick Disease

Missing/deficient sphingomyelinase

Niemann-Pick Cells

Lymphoid tissue and bone marrow

20-100 microns

Eccentric nucleus

Globular, foamy cytoplasm filled with lipid droplets

Niemann-Pick Disease - Inheritance Pattern

Autosomal Recessive

Associated with Ashkenazi Jewish populations

Niemann-Pick Disease - Clinical Characteristics

Leukopenia

Thrombocytopenia

Poor physical development

Fatal by age 3