8 Leukocyte- Disorders PDF

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LEUKOCYTE DISORDERS I. II. Morphological Abnormalities of Leukocytes Non Malignant Leukocyte Disorders Malignant Leukocyte Disorders MORPHOLOGICAL ABNORMALITIES OF LEUKOCYTES 6. Basket Cell Net like nucleus from ruptured white blood cell especially 2o PMN. Seen in: Chronic Lymphocytic Leukemia Impro...

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LEUKOCYTE DISORDERS I. II. III.

Morphological Abnormalities of Leukocytes Non – Malignant Leukocyte Disorders Malignant Leukocyte Disorders

MORPHOLOGICAL ABNORMALITIES OF LEUKOCYTES 1. Hypersegmented Neutrophil a. Polycyte  Has a normal size but with 4 – 6 lobes in the nucleus.  Found in stage of recovery from infection. b. Macropolycyte  Larger than normal neutrophil and has 5 – 10 nuclear lobes.  Seen in: o Pernicious anemia o Megaloblastic Anemia 2. Pyknocyte  Nucleus becomes smaller and denser; nuclear segments disappear leaving several balls of dense chromatin. 3. Virocyte or Atypical Lymphocyte  Also called:  Downey Type Cell  Turk Irritation Cell  Cell has a chromatin arrangement which gives the cell a “moth – eaten” or “tunneled” appearance or “swiss – cheese”.  Cell has prominent azurophilic granules.  Seen in:  Infectious mononucleosis  Viral hepatitis  Viral pneumonia  Herpes simplex infections 4. Rieder Cell  Myeloblast that is characterized by having a nucleus with deep indentions often suggesting lobulations.  Seen in:  Acute Myeloid Leukemia 5. Vacuolated Cell  Cell with holes or vacuoles in the cytoplasm.  Signs of degeneration in severe infections, chemical poisoning and leukemia.

6. Basket Cell/Smudge Cell  Net like – nucleus from ruptured white blood cell especially 2o PMN.  Seen in:  Chronic Lymphocytic Leukemia  Improper Smearing 7. Lupus Erythematosus Cell (LE Cell)  A PMN which had engulfed the nuclear material of another PMN or a lymphocyte.  Digests / destroys the engulfed material  It has 2 nuclei: a. Nucleus of Phagocyte  Flattened in periphery b. Ingested Nucleus  Absent and replaced by a purplish homogenous round mass. 8. Tart Cell  A monocyte with an engulfed nucleus usually of a lymphocyte or maybe the whole lymphocyte itself.  Exhibits nucleophagocytosis.  Preserves and collects the engulfed material. 9. Hairy Cell  Lymphocytes with hair like cytoplasmic projections surrounding the nucleus.  Seen in:  Hairy Cell Leukemia. HCL Trap (Tartrate Resistance Acid Phosphate) 10. Sezary Cell  Rough lymph cell with nucleus that is grooved or convoluted.  Presence of hyperconvoluted cell  Cancer of the skin (Cutaneous lymphoma)  Seen in:  Sezary Syndrome  Mycosis fungoides LAP score  Used to differentiate LR (Leukemoid Rxn) from CML

ABNORMAL INCLUSION BODIES IN LEUKOCYTES 1. Auer Bodies/Rods  Are linear or spindle – shaped red purple inclusions in myeloblasts and monoblasts.  Derivatives of azurophilic granules.  Caused by unusual development of lysosomes.  Seen in: Chronic Lymphocytic Leukemia 2. Toxic Granules  Dark blue to purple cytoplasmic granules in the metamyelocyte, band or in neutrophil stage.  Characteristics of bacterial infections and are frequently seen in Aplastic anemia and also in myelosclerosis. 3. Dohle – Amato Bodies  Small round or oval bodies up to 2 – 3um.  Stain blue gray usually seen in the periphery of the cytoplasm of neutrophils.  Feature: Remnants of free ribosomes from an earlier stage of development.  Seen in:  Bacterial Infections  Severe Burns  Exposure to Cytotoxic agents  Complicated pregnancies 4. Snapper – Scheid Bodies  Found in cytoplasm of multiple myeloma and plasma cells (predominant cell) after therapy with amidine drugs. 5. Russell or Fuch’s Bodies  Gamma globulins bodies in the cytoplasm of plasma cells and inflamed tissue.  Bodies which gave a grape or berry or modula cell appearance. Two Groups of Leukocyte Disorders A. Non – Neoplastic Disorders  Not tumor related disorders B. Neoplastic and Related Disorders  Tumor related disorders

NON – MALIGNANT DISORDERS OF LEUKOCYTES A. Granulocytes DISORDER OF NUCLEUS

Defect or Change

Associated Conditions

Others

Hypersegmented Neutrophil

Abnormal DNA synthesis

Megaloblastic Anemia

Shift to the right

Pelger – Huet Anomaly (PHA)

Decreased segmentation in neutrophil “pinceness appearance” Mutation of Lamin B

PseudoPelger – Huet Anomaly

Has less dense nuclei with hypogranular cytoplasm

DISORDER OF CYTOPLASM

Defect or Change

Alder – Reily Anomaly

Accumulation of degraded mucopolysaccharides

Chediak – Higashi Syndrome

May – Hegglin Anomaly

Jordan’s Anomaly Alius – Grignashi Anomaly

Has large peroxidase lysosomes inclusions that are deficient in enzymes for phagocytosis Characterized by Dohle bodies, thrombocytopenia, giant platelets and leucopenia Caused by: Mutation of Non – Muscle Myosin Heavy Chain Type 2A gene (MYH9) Vacuolization of leukocytes Peroxidase depletion in PMN and monocytes

1. Chronic Myeloid Leukemia (CML) 2. Myelodysplastic Syndrome (MDS) 1. 2. 3. 4. 5. 6. 7.

Burns Drug reactions Infections MDS CML Acute Leukemia Chemotherapy

Associated Conditions 1. Hunter’s Syndrome (Type II) 2. Hurler’s Syndrome (Type I)

Albinism

Hyposegmentation Autosomal dominant disorder Decrease in lobulation Eye glass Dumbbell Shape Peanut Shape

Clinically significant acquired phenomena

Others Autosomal recessive disorder Very short life expenctancy Autosomal recessive Increase susceptibility to infection Autosomal dominant platelet disorder Mutation of MYH9 seen also in: 1. Sebastian 2. Fechtner 3. Epstein Barr Syndrome

Autosomal recessive

FUNCTIONAL DISORDER

Job’s Syndrome

Lazy Leukocyte Syndrome

Chronic Granulomatous Disease

Congenital C3 Deficiency

Myeloperoxidase Deficiency

Defect or Change Random movement of phagocytes is normal, but directional motility is impaired Both random and directed movement of the cells are defective Intracellular killing mechanism of granulocyte is defective Caused by mutation of Nicotinamide adenine di nucleotide phosphate – reduced form (NADPH) oxidase genes Asymptomatic carriers have half the normal C3 activity (heterozygous)

Associated Conditions

Others Hyperimmunoglobulin E Cells respond slowly to chemotactic factors

Recurrent mucous membrane infections

Disease usually seen in childhood

Phagocytes ingest but can’t kill catalase + organisms because of lack of appropriate respiratory burst (neutrophil) X - linked

Results in repeated infections

Homozygous carriers fail to opsonize bacteria MPO is decreased or absent in PMN and monocytes

Rare autosomal recessive trait Problems in opsonization of bacteria

Without MPO, bacterial killing is slowed

Caused by mutation of MPO genes  Chromosome 17

B. Monocyte – Macrophage Disorder Gaucher’s Disease - Most common of lysosomal lipid storage disease Type I Type II Type III

Defect or Change

Associated Conditions

Deficiency of glucocerebrosidase enzyme

Effects the bone marrow, spleen and liver

Non – neuropathic Acute neuropathic Sub – acute neuropathic

Adult type Infancy type Childhood type

Deficiency of Sphingomyelinase Niemann – Pick Disease

Caused by mutations of SMPD1 genes

Others GAUCHER CELL Macrophages are with wrinkled – looking cytoplasm (onion-skin like) and with small eccentric nucleus

Autosomal recessive Abnormal accumulation of sphingomyelin and cholesterol in body cells

Type A Acute Neuropathic manifested during infancy (2–4 months) Involves brain Hepatosplenomega ly Type B Chronic Form w/o CN involvement Type CD Chronic Neuropathic Type E Adult Non – Neuropathic Schuller – Christian Disease

Macrophage with cholesterol overload due to increase in foam cells

Hyperlipidemia

C. Lymphocytes Disorder

Defect or Change

Tay – Sachs Disease

Deficiency of hexosaminidase A

Bruton Agammaglobulinemia

Reduced Ig production in blood

B cell deficiency

Common Variable Hypogammaglobulinemi a

Reduced production of Ig due to overactivity of T8 cells

B cell deficiency

Nezelof’s Syndrome

Underdevelopment of the thymus

T cell deficiency

Di George’s Syndrome

Deletion of a small piece of Chromosome 22 (Philadelphia Chromosome)

T cell deficiency

Swiss – Type Agammaglobulinemia Wiskott – Aldrich Syndrome (WAS)

Associated Conditions

Severe combined immunodeficiency disorders Failure of T cell response 1. Severe combined immunodeficiency Only IgA and IgG are disorders present; IgM is absent 2. Bleeding Loss of both T and B cells function

Others Autosomal recessive Vacuolated lymphocytes  Inherited infantile sex – linked  Usually affects males

 Autosomal recessive  Congenital immunodeficiency

Autosomal recessive

Inherited as rare x – linked recessive Caused by mutation of

Ataxia Telangiectasia

Decreased T cell production

3. Recurrent Infection gene encoding a protein 4. Eczema  WASp  Rare childhood Characterized as having progressive loss of dse. muscular coordination  Affects the brain and other parts of the body...