Nonmalignant Disorders of Granulocytes and Monocytes

Student Learning Outcomes

• Differentiate between quantitative and qualitative disorders of granulocytes.

  • Examples depend on the primary function of the affected WBC.

• Differentiate between acute, intermediate, and chronic neutrophilia.

• Define leukemoid reaction and distinguish between leukemoid reactions and CML.

• Recognize eosinophilia, basophilia, and monocytosis in blood smears and match with causes.

• Define neutropenia and list at least 4 causes.

• Describe and recognize 3 types of abnormal nuclear morphology in neutrophils:

  • Hypersegmentation
  • Pelger-Huёt anomaly (hyposegmentation)
  • Pyknotic nucleus

• Describe and recognize 4 types of abnormal cytoplasmic morphology in neutrophils:

  • Toxic granulation
  • Döhle bodies
  • Ehrlichia
  • Vacuoles

• Describe 4 inherited neutrophil disorders with characteristic neutrophil morphology:

  • May-Hegglin anomaly
  • Chediak-Higashi syndrome
  • Alder-Reilly inclusions
  • Chronic Granulomatous disease (CGD)

• Explain why inherited abnormalities of neutrophils can also appear in monocytes.

• List at least 3 mechanisms causing qualitative granulocyte disorders.

• Describe lipid functions in the human body and the importance of corresponding enzymes.

• General characteristics of Lipid/Lysosomal Storage Diseases (LSDs) with diagnostic tests for confirmation.

• Match enzyme deficiencies with typical abnormal cells for LSDs:

  • Gaucher’s Disease
  • Niemann-Pick Disease
  • Tay-Sach’s Disease

• Differentiate between Glycosaminoglycan/Mucopolysaccharidosis disorders and Histiocytosis disorders.

Overview of Nonmalignant WBC Disorders

• Quantitative Disorders: Increase or decrease in leukocyte counts, often due to infections.
• Qualitative Disorders: Defective killing ability of leukocytes.
• Toxic challenges can affect granulocytes; cell type affected depends on infection.
  • Bacterial infections affect neutrophils.
  • Viral infections affect lymphocytes.
  • Parasitic infections affect eosinophils.
• Laboratory tests: CBC, WBC differential, ESR, Bone Marrow aspirations for suspected malignancies.

Quantitative Disorders

• Leukocytosis: Increase in leukocyte concentration in peripheral blood.
• Leukocytopenia: Decrease in total leukocyte count.
• Nonmalignant leukocytosis is common, caused by:
  • Increased immature cell movement from bone marrow.
  • Increased mobilization from maturation-storage compartments.
  • Decreased movement of mature cells into tissues.

Neutrophilia

• Definition: Absolute neutrophil count > 7.0 imes 10^9/L.

• Factors affecting concentration:

  • Bone marrow production and release.
  • Neutrophil migration into tissues.
  • Circulating vs. marginating neutrophils.

• Types of Neutrophilia:

  1. Immediate Neutrophilia: Redistribution from marginal to circulating pool (e.g., from stress).
  2. Acute Neutrophilia: Occurs 4-5 hours after a pathological stimulus.
  3. Chronic Neutrophilia: Follows acute neutrophilia as the bone marrow releases younger cells.

• Associated conditions:

  • Bacterial infections (most common): Absolute neutrophil count > 10-19 imes 10^9/L.
  • Severe infections may lead to neutropenia (e.g., typhoid fever).

Leukemoid Reaction vs. Chronic Myelocytic Leukemia (CML)

• Leukemoid Reaction: Extreme neutrophilia (WBC count > 30 imes 10^9/L), resembles CML but lacks Philadelphia chromosome (Ph+).
• Clinical parameters:
  • Leukocyte alkaline phosphatase (LAP) score increased in leukemoid reaction but decreased in CML.
  • Spleen size normal in leukemoid reaction, generally enlarged in CML.

Eosinophilia

• Definition: Absolute count > 0.6 imes 10^9/L.
• Causes:
  • Allergy and asthma (most common).
  • Parasitic infections, particularly helminths.
  • Drug hypersensitivity reactions.
  • Chronic inflammatory states and some malignancies.

Basophilia

• Definition: Absolute count > 0.15 imes 10^9/L.
• Features in CML and specific viral infections.
• Basophilia can signify other conditions such as ulcerative colitis and polycythemia vera.

Monocytosis

• Definition: Absolute count > 0.8 imes 10^9/L.
• Associated with chronic infections, inflammatory diseases, and certain malignancies.

Neutropenia

• Definition: Absolute neutrophil count < 1.5 imes 10^9/L.
• Caused by:
  • Decreased bone marrow production.
  • Increased cell loss due to infections or immune mechanisms (e.g., anti-leukocyte antibodies).
  • Pseudoneutropenia from sampling errors.

Summary of Quantitative Disorders

• Increased Neutrophilia: Inflammatory conditions, infections, physical stimuli, and some malignancies.
• Decreased Neutrophilia: Bone marrow damage, hypersplenism, starvation, and certain drugs.

Qualitative Abnormalities of Mature Granulocytes

• Nuclear Abnormalities: Hypersegmentation, Pelger-Huёt anomaly, pyknotic nucleus.
• Cytoplasmic Abnormalities: Toxic granulation, Döhle bodies, Ehrlichia, vacuoles.

Inherited Functional Abnormalities of Neutrophils

1. May-Hegglin Anomaly: Characterized by Döhle body-like inclusions and large platelets.
2. Chédiak-Higashi Syndrome: Large granules in leukocytes leading to frequent infections.
3. Alder-Reilly Inclusions: Mucopolysaccharides in neutrophil granules.
4. Chronic Granulomatous Disease (CGD): Neutrophils can phagocytize but can't kill due to oxidative burst defects.

Lipid Storage Diseases (LSDs)

• Overview: Caused by enzyme deficiencies leading to lipid accumulation in lysosomes.
• Types of LSDs: Gaucher's Disease, Niemann-Pick Disease, Tay-Sach’s Disease with specific enzyme deficiencies.

Glycosaminoglycans/Mucopolysaccharidoses (MPS)

• Rare diseases where specific enzyme deficiencies prevent degradation of mucopolysaccharides.
• Characterized by various symptoms, organomegaly, skeletal abnormalities, and specific WBC features.

Sea Blue Histiocytosis

• Not an enzyme deficiency but causes similar symptoms with increased histiocytes affecting immune response.

Case Studies and Clinical Examples

• Presented a case of Niemann-Pick disease with hepatosplenomegaly and abnormal cell findings.

Diagnostics

• Laboratory tests crucial in identifying leukocyte disorders and confirming diagnoses through enzyme assays and blood smears.
• Diagnostic characteristics for Gaucher's, Niemann-Pick, and other LSDs highlighted.