Benign disorders of WBCs By/ Mr. Waqqas Elaas; M.Sc; MLT

References For theory : Essential Haematology, John Wiley & Sons Ltd ,6th Edition,Victor Hoffbrand. For practical : Practical Haematology, Churchill Livingstone, Eighth edition, John V. Dacie, S. M. Lewis, Internet site(s): http://www.essentialhaematology6.com/default.asp = MCQs http://www.hematologyatlas.com/ http://pathy.med.nagoya-u.ac.jp/atlas/doc/atlas.html Final Theoretical exam : 40 Final Practical exam : 20 (including written questions) 1st Periodic exam : 10 theory, 5 Practical 2nd Periodic exam : 10 theory, 5 Practical Homework and class activities : 5 Theory, 5 Practical Total : 100 Marks

Objectives To differentiate between the qualitative & quantitative WBCs benign disorders. To understand the etiology and pathology of reactive changes in the number and morphology of granulocytes. To understand the etiology and pathology of reactive changes in the number and morphology of lymphocytes and monocytes. To know the definition & causes of Infectious Mononucleosis. To know the definition & causes of Leukemoid reactions. To be able to differentiate between Eosinophilia & Hypereosinophilic syndromes.

Phagocytes Immunocytes (Granulocytes) (A granulocytes) Leucocytes (WBCs) Phagocytes Immunocytes (Granulocytes) (A granulocytes) Neutrophils Lymphocytes Eosinophils small & Large Basophils B & T Lymphocytes Monocytes* *sometimes Monocytes are considered as A granulocytes

Normal leucocytes morphology

LEUCOCYTES BENIGN DISORDERS Quantitative Change in number Terminology Cytosis / philia Increase in number Cytopenia/penia Decrease in number Qualitative Morphologic changes Functional changes

LEUCOCYTES BENIGN DISORDERS Quantitative changes Relative & Absolute values To make an accurate assessment, consider both relative and absolute values. For example a relative value of 70% neutrophils may seem within normal limits; however, if the total WBC is 20,000, the absolute value (70% of 20,000) would be an abnormally high count of 14,000.

Normal reference range (adults) LEUCOCYTOSIS Definition Raised TWBC above 11.0 x 109/L in adults, due to elevation of any of a single lineage. Note: elevation of the minor cell populations can occur without a rise in the total white cell count. Normal reference range (adults) 4.5 -- 11.0 x 109/L

LEUCOPENIA Definition TWBC lower than 4.5 x 109/L in adults Leucopenia may affect one or more lineages and it is possible to be severely neutropenic or lymphopenic without a reduction in total white cell count.

Increase in the count of all or one of the granulocytic component: (contd.) Granulocytosis Increase in the count of all or one of the granulocytic component: Neutrophils Basophils Eosinophils

NEUTROPHILIA Definition Increase in the number of neutrophils and / or its precursors In adults count >7.5 x 109/L but the counts are age dependent Increase may results from alteration in the normal steady state of Production Transit Migration Destruction

Causes of Neutrophilia NEUTROPHILIA (contd.) Causes of Neutrophilia Infection Bacterial Inflammatory conditions Autoimmune disorders Gout Neoplasia Metabolic conditions Uraemia Acidosis Haemorhage Corticosteroids Marrow infiltration/fibrosis Myeloproliferative disorders

Leukemoid reactions Excessive reactive leucocytosis. Applied to chronic Neutrophilia with marked leucocytosis (>20 x 109/L) The usual feature is the shift to the left of myeloid cells Causes include Infections Marrow infiltration Systemic disease (e.g.: Acute liver failure) (Left shift : indicates that the neutrophils present in the blood are at a slightly earlier stage of maturation than usual. The Band and the stages before. This is often seen in acute infections). (Right shift : an increase in the percentage of multilobed neutrophils).

NEUTROPENIA Neutropenia is an absolute reduction in the number of circulating neutrophils Mild (1- 1.5 x 109/L) Moderate (0.5 – 1 x 109/L) Severe (<0.5 x 109/L) Symptoms are rare with the neutrophil count above 1 x 109/L Bacterial infections are the commonest. Fungal, viral and parasitic infection are relatively uncommon.

(NEUTROPENIA) contd. Causes of Neutropenia Racial Congenital Marrow aplasia Marrow infiltration Megaloblastic anemia Acute infections Typhoid, Miliary TB, viral hepatitis Drugs Irradiation exposure Immune disorders HIV SLE Neonatal isoimmune and autoimmune neutropenia Hyperslplenism

The causes of eosinophilia can be considered under following headings Increase in the eosinophil count must prompt for further investigation (>0.6 x 109/L) The causes of eosinophilia can be considered under following headings Allergy Atopic, drug sensitivity and pulmonary eosinophilia Infection Parasites, recovery from infections Malignancy Hodgkin’s disease, NHL and myeloproliferative disorders Drugs Skin disorders Gastrointestinal disorders Hypereosinophilic syndrome

Hypereosinophilic syndrome (EOSINOPHILIA) Contd. Hypereosinophilic syndrome Criteria of diagnosis Peripheral blood eosinophil >1.5 x 109/L Persistence of counts more than 6 months End organ damage Absence of any obvious cause for eosinophilia Organ most commonly involved Heart Lung Skin Neurological

Absolute monocyte count is age dependent (MONOCYTOSIS) Absolute monocyte count is age dependent Count rarely exceeds >1.0 x 109/L Have no marrow reserves Causes of monocytosis can be grouped as Infections Chronic infection (TB, typhoid fever, infective endocarditis) Recovery from acute infection Malignant disease MDS, AML, HD, NHL Connective tissue disorders Ulcerative colitis, Sarcoidosis, Crohn’s disease Post splenectomy

(BASOPHILIA) Basophils are least common of the granulocytes Reference range for adult is 0 – 0.2 x 109/L Most commonly associated with hypersensitivity reactions to drugs or food Inflammatory conditions e.g RA, ulcerative colitis are also sometime associated with basophilia Myeloproliferative disorders Chronic myeloid leukemia

(LYMPHOCYTOSIS) The blood contain only few percent of total body lymphocytes The most consistent variation is seen with age Alteration of lymphocyte counts can result from The redistribution of lymphocytes Absolute increase of lymphocyte number Loss of lymphocytes Combination of these

Non-malignant causes of lymphocytosis Infections Viral infections Infectious mononucleosis CMV Rubella, hepatitis, adenoviruses, chicken pox,dengue Bacterial infections Pertussis Healing TB, typhoid fever Protozoal infections Toxoplasmosis Allergic drug reactions Hyperthyroidism Splenectomy Serum sickness

Infectious Mononucleosis (LYMPHOCYTOSIS) Infectious Mononucleosis Epstein-Barr virus Saliva from infected person is the main contagion Virus infect epithelial cells and B cells Infection in children under the age of 10 does not cause illness and result in life long immunity Clinical features Fever, malaise, fatigue, sore throat, splenomegaly Blood picture shows leucocytosis ( 10 – 20 x 109/L) due to absolute increase in lymphocytes Diagnosis is by serological tests There is no specific treatment

Qualitative changes (MORPHOLOGY) Congenital acquired Pelger-Huet anomaly Toxic granulation Neutrophil hyper-segmentation Dohle bodies May-Hegglin anomaly Pelger cells Alder’s anomaly Hypersegmented neutrophils Chediak-Higashi syndrome

LEUCOCYTES BENIGN DISORDERS Qualitative changes (MORPHOLOGY) Congenital Pelger-Huet anomaly Bilobed and occasional unsegmented neutrophils Autosomal recessive disorder

LEUCOCYTES BENIGN DISORDERS Qualitative changes (MORPHOLOGY) contd. Neutrophil hyper-segmentation Neutrophil function is essentially normal May-Hegglin anomaly Neutrophils contain basophilic inclusions of RNA Occasionally there is associated leucopenia, Thrombocytopenia and giant platelet are frequent

LEUCOCYTES BENIGN DISORDERS Qualitative changes (MORPHOLOGY) contd. Alder’s anomaly Granulocytes, monocytes and lymphocytes contain granules which stain purple with Romanowsky stain Granules contain mucopolysaccharides

LEUCOCYTES BENIGN DISORDERS Qualitative changes (MORPHOLOGY) contd. Chediak-Higashi syndrome Giant granules in granulocytes, monocytes and lymphocytes Depressed migration and degranulation Recurrent pyogenic infections Lymphoproliferative syndrome may develop Treatment is BMT

LEUCOCYTES BENIGN DISORDERS Qualitative changes (MORPHOLOGY) contd. Acquired Toxic granulation Dohle bodies Pelger cells Hypersegmented neutrophils

Homework (1) Case : A 20-year-old student presented with a 7-day history of fever, sore throat, lethargy and tender enlarged glands in the neck. Physical examination reveals fever, mild jaundice, inflamed pharyngeal mucosa and cervical adenopathy. Blood results Hb; 12.5 g/dl, wbc 18.0x109/l , differential 30% neutrophils 40% lymphocytes 30% abnormal lymphocytes. Platelets 100 x109/l. Throat swab: No bacterial growth HIV test negative Does the student has Neutrophilia OR Lymphocytosis? Explain your answer in Q1 What is the probable diagnosis? (2) Design a table containing the 5 types of leucocytes with their normal ranges in adults.