Leukocyte Abnormalities Notes

Leucocyte Changes: General Terminology

  • [root]cytosis/[root]philia: Indicates an increase in the blood.
  • [root]penia: Indicates a reduction in the blood.
  • Important: These terms do not automatically indicate malignancy. For example, neutrophilia doesn't necessarily mean chronic myeloid leukemia.

Neutrophils

  • Make up 40-75% of white blood cells (WBC).
  • Absolute count: 2−8×109/L2-8 \times 10^9/L.
  • Develop from myeloblasts in the bone marrow.

Neutrophil Abnormalities

  • Quantitative: Refers to the number of neutrophils.
    • Neutrophilia: Increased neutrophil count.
    • Neutropenia: Decreased neutrophil count.
  • Qualitative: Refers to the characteristics or appearance of neutrophils.
    • Absence of components.
    • Granule abnormality.
    • Abnormal variants.

Ethnicity and Neutrophils

  • Reference ranges in Australian laboratories typically reflect Anglo-Saxon/Mediterranean populations.
  • It's important to use appropriate reference ranges where available.
  • If specific reference ranges aren't available, be aware of the potential differences due to ethnicity.
  • Reference: Porwit, McCullough, Erber. Blood and Bone Marrow Pathology. 2011

Age and Leucocyte Counts

  • Leukocyte counts vary with age; reference table provided for different age groups from cord blood to 18 years, including counts for leukocytes, neutrophils, eosinophils, basophils, lymphocytes, and monocytes.
  • Reference: Porwit, McCullough, Erber. Blood and Bone Marrow Pathology. 2011

Neutrophilia

  • Many causes, with reactive neutrophilia being the most common.
  • Multiple causes include:
    • Infection (bacterial, viral)
    • Acute inflammation
    • Stress, exertion
    • Pregnancy
    • Surgery, trauma, tissue damage or infarction
    • Steroids, cytokines

Reactive Neutrophilia

  • Count generally between 10−50×109/L10-50 \times 10^9/L.
  • Increased granulation/“toxic” changes.
  • “Left shift” – >10% band forms.

Reactive Neutrophilia - Döhle Bodies

  • Light blue-grey cytoplasmic inclusions.
  • Suggest (long-standing) bacterial infection.
  • May be residual endoplasmic reticulum.

Reactive Neutrophilia - Vacuolation

  • Common in sepsis.
  • Suggests bacterial infection.
  • Secondary to neutrophil phagocytosis; may occasionally contain stained bacteria.

Reactive Neutrophilia - Phagocytosed Bacteria

  • Seen only in bacterial sepsis.
  • Rarely seen outside the critically ill.
  • Frequently accompanied by other film abnormalities.

Reactive Neutrophilia - Cytokine Therapy

  • Recombinant G-CSF is used in mobilizing stem cells and to speed recovery from chemotherapy, resulting in granulocyte proliferation.
  • Appearances are almost always toxic; immature precursors are common.

Neutropenia

  • Severity:
    • Mild: 1.0−1.9×109/L1.0-1.9 \times 10^9/L
    • Moderate: 0.5−0.9×109/L0.5-0.9 \times 10^9/L
    • Severe: < 0.5 \times 10^9/L
  • Clinical Significance: Mild neutropenia is often not clinically significant if neutrophil function is preserved.

Neutropenia - Causes

  • Infection (viral, bacterial)
  • Medication/drugs (e.g., chemotherapy)
  • Autoimmune disease (e.g., SLE)
  • Immune neutropenia (e.g., anti-granulocyte antibodies)
  • Some hematological disorders

Qualitative Abnormalities

  • Inherited
    • May-Hegglin
    • Pelger-Huet
    • Chediak-Higashi
  • Acquired
    • Drugs
    • Alcohol
    • MDS (also quantitative)

Qualitative Abnormalities - Dysplasia

  • Dysplasia refers to abnormalities in appearance.
    • Hypo-/agranularity
    • Aberrant segmentation
    • Abnormal chromatin
  • Non-Specific Causes:
    • Drug effect
    • B12/folate deficiency
    • Congenital disorders
    • Acquired hematological disease (e.g., MDS)

Inherited Abnormalities - May-Hegglin Anomaly

  • MYH9 disorder.
  • Döhle bodies in cytoplasm.
  • Macrothrombocytopenia with preserved platelet volume.

Inherited Abnormalities - Pelger-Huet Abnormality

  • Bi-segmented nuclei.
  • Seen as an inherited abnormality.
  • “Pseudo-Pelger” neutrophils may be seen in dysplastic conditions.

Lymphocytes

  • Characterized by:
    • Round or slightly indented nucleus.
    • Mature chromatin.
    • Scant blue cytoplasm.
    • 7-12 m diameter.

Lymphocytes - Large Granular Lymphocytes

  • Characterized by:
    • Larger size.
    • More voluminous blue cytoplasm.
    • Presence of azurophilic granules.
  • Not always reflect a single lymphocyte set:
    • Usually NK cells (cytotoxic, innate immunity).
    • Occasionally T cells, including rare T cell disorders.

Age and Lymphocytes

  • Lymphocyte counts vary with age; a reference table is provided for different age groups from cord blood to 18 years, including counts for leukocytes, neutrophils, eosinophils, basophils, lymphocytes, and monocytes.
  • Reference: Porwit, McCullough, Erber. Blood and Bone Marrow Pathology. 2011

Lymphocytosis

  • Commonly seen in benign conditions:
    • Viral infection (EBV/CMV)
    • Pertussis
    • Hypoxia
    • Seizures
    • Hyposplenism
  • Morphology can be helpful in suggesting the cause but is rarely diagnostic.

Lymphocytosis - Viral Lymphocytes

  • Atypical ‘activated’ CD8 T cells; virus-infection B cells (EBV).
  • Can be seen in all viral infections (EBV/CMV/VZV/hepatitis).
  • Morphology:
    • Large cells.
    • Round/irregular nuclei.
    • Abundant cytoplasm; dark periphery.
    • Scalloping of RBC.

Lymphocytosis - Dengue vs Pertussis

  • Dengue: reactive lymphocytes with an eccentric nucleus; very basophilic cytoplasm.
  • Pertussis: mature (not activated) lymphocytes; impaired lymphocyte migration secondary to a bacterial factor.

Lymphocytosis - Malignant vs Benign

  • Malignant lymphocytosis is generally (but not always) monomorphic.

Plasma Cells

  • End-stage B cells that produce immunoglobulin; characterized by:
    • Eccentric nucleus.
    • Perinuclear hof.
    • Intensely basophilic cytoplasm.
  • “Not seen” in the blood – may occasionally be seen in chronic severe infection/HIV.
  • ‘Maturing’ (or “activated”) B cells may have some plasmacytoid features.

Monocytes

  • Characterized by:
    • ‘Horseshoe’ shaped nucleus.
    • Faint blue-grey cytoplasm.
    • Granules very uncommon.
    • Cytoplasmic vacuoles.
    • 15–30 m diameter.
  • Lifespan in blood: t1/2 ±70h.

Monocytosis

  • Relatively uncommon; transient finding in infection, particularly bacterial infection.
  • May be persistent in:
    • Chronic severe infection.
    • TB.
    • Malaria.
  • Persistent monocytosis can be seen in bone marrow disorders (e.g., MDS/CMML).

Monocytosis - Reactive

  • Monocytes are highly marginated, and a transient increase is usually due to demargination; typically resolves within a few days.
  • Reactive monocytosis is often accompanied by reactive neutrophil changes.

Monocytosis - Chronic Myelomonocytic Leukemia (CMML)

  • Persistent monocytosis seen in CMML has both proliferative and dysplastic features.

Eosinophils

  • Characterized by:
    • 2-3 nuclear lobes.
    • Granule-filled cytoplasm (red-orange on Romanowsky).
    • Different from neutrophil granules – eosinophils tend to be ‘packed’.
    • 12-17 m diameter.
  • Granules contain:
    • Phospholipases, histaminase
    • Ribonuclease, -glucuronidase
    • Cathepsin, collagenase

Eosinophilia

  • Most (but not all) eosinophilia is reactive:
    • Parasitic infection (common in children and those from remote/rural areas).
    • Skin infection.
    • Allergic reactions.
    • Drug therapy.
    • Allergic bronchopulmonary conditions (e.g., fungus exposure).
  • Eosinophilia may also be malignant (e.g., some myeloproliferative neoplasms).
    • Often (but not always!) a greater degree than reactive conditions.
    • Often associated with tissue damage from eosinophil granule release.

Eosinophilia - Reactive vs. Malignant

  • Distinguishing reactive from malignant eosinophilia morphologically is nearly impossible.

Basophils

  • Characterized by:
    • 2 nuclear segments.
    • Large round purple-black cytoplasmic granules.
    • Granules overlie the nucleus (unlike other granulocytes).
    • Approx. 12 m diameter.
  • Granules contain:
    • Histamine, tryptase, peroxidase
    • Mucopolysaccharides (chondroitin sulphate)
    • Chymase (a serine protease)

Basophilia

  • Rare; most often seen in myeloproliferative neoplasms such as CML.
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Summary

  • Leucocyte abnormalities can be considered as being:
    • Quantitative vs. qualitative
    • Inherited vs. acquired
  • Morphological features may give some clues as to the underlying (pathological) process.
  • “Benign” changes are much more common than malignant processes.