486 qualitative disorders of wbc

qualitative disorders of WBC

1. QUALITATIVE DISORDERS OF WBC Presenter : Nabin Chaudhary

2. CONTENTS Lazy leukocyte syndrome Chediak higashi syndrome Infectious mononucleosis Leukemia Lymphoma

3. LAZY LEUKOCYTE SYNDROME (SCHWACHMAN SYNDROME) Defect in neutrophil chemotaxis and deficient random mobility of neutrophils Blood Neutrophils cannot migrate at the site of tissue injury Phagocytic and Bactericidal activities are normal 3

4. In vivo study demonstrated that the abnormalities in migration are intrinsic to the granulocyte Alteration in the structure or function of micro-filamentous proteinof the granulocyte membrane Disorder of membrane leading to altered deformability Disordered function of the micro filamentous protein of the cell membrane Excessive or undue rigidity of neutrophils Impaired mobility Failure of egress from the bone marrow

5. CLINICAL FEATURES AGE Complications occur at the age of 1-2 years due to infections SYMPTOMS Most common : Stomatitis, Otitis media and Bronchitis RECURRENT INFECTIONS High Chance of Recurrent Infections 5

6. ORAL MANIFESTATIONS STOMATITIS (Most Common) PERIODONTITIS 6

7. DIAGNOSIS CLINICAL DIAGNOSIS Recurrent Infection, Periodontitis and Stomatitis LABORATORY DIAGNOSIS TLC slightly low ANC as low as 100-200 cells/mm 3 Bone Marrow contains normal number of mature neutrophils 7

8. MANAGEMENT ANTIBIOTICS GIVEN TO CONTROL THE INFECTION 8

9. CHÉDIAK-HIGASHI SYNDROME (BÉGUEZ CÉSAR SYNDROME, CH ÉDIAK-STEINBRINCK-HIGASHI SYNDROME ) Described by Béguez Cesar (1943), Steinbrinck (1948), Ch é diak (1952) and Higashi (1954) Congenital Autosomal Recessive Immunodeficient defect of Granulocytes and Melanocytes Abnormal granules are seen in all blood granulocytes resulting in decreased chemotactic and bactericidal activity . The condition usually results in death of childhood before the age of 10 Characterized by abnormal intracellular protein transport LYST or CHS1 gene 9

10. CLINICAL FEATURES Affects all races Usually appears soon after birth or in children <5 years Characterized by immune deficient state Characteristic Clinical Feature : Partial Oculocutaneous Albinism (Silvery Hair Syndrome) Recurrent Infections of Respiratory tract and Sinuses Easy bruisability and bleeding Gastrointestinal disturbances Lymph Node enlargement (Cervical) May be associated with Malignant Lymphoma Progressive Neurological Dysfunction 10

11. SILVERY HAIR SYNDROME: Defect melanization of melanosomes i.e. autophagocytosis of melanosomes 11

12. ORAL MANIFESTATIONS GILLIG AND CALDWELL Ulcerations of the Oral Mucosa Severe Gingivitis and Glossitis HAMILTON AND GIANSANTI Periodontitis (probably related to defective leukocyte function) 12

13. DIAGNOSIS CLINICAL DIAGNOSIS Albinism Recurrent Infection Hepatosplenomegaly Oral Ulcerations and Periodontitis LABORATORY DIAGNOSIS Hematological studies show presence of giant abnormal granules in the peripheral circulating leukocytes, in their marrow precursors and in many other cells of the body. These granules are the hallmark of the syndrome . Thought to represent abnormal lysosomes 13

14. MANAGEMENT No specific treatment Often fatal Death occurring before child reaches 10 Antibiotics and drugs like Vincristine, Prednisolone and Ascorbic acid have been tried for the treatment 14

15. INFECTIOUS MONONUCLEOSIS (GLANDULAR FEVER) Also known as EBV infectious mononucleosis/ Pfeiffer's disease / Filatov's disease Caused by E pstein Barr virus Drusenfieber (1889) First described by Sprunt and Evans in the John Hopkins Medical Bulletin(1920) 15

16. Is transmitted by intimate contact with body secretions, primarily oro -pharyngeal secretions and through deep kissing or intimate oral exchange of saliva – so called as “ kissing disease ”.

17. CLINICAL FEATURES Chiefly in Children and young adults 15-20 year age group No sex or seasonal predilection Most patients can be asymptomatic Clinical syndrome consists of: Fever Pharyngitis Adenopathy Tonsillitis, Headache, Chills, Cough, Nausea or Vomiting Splenomegaly and Hepatitis Enlargement of Cervical lymph node followed by the nodes of Axilla and Groin . 17

18. 18 Cervical lymphadenopathy Exudative pharyngitis

19. ORAL MANIFESTATIONS FRASER AND MOODIE Acute gingivitis and stomatitis Appearance of white or gray membrane in various areas. Petechial hemorrhage of soft palate and occasional oral ulcers Edema of soft palate and uvula SHIVER AND ET. AL. ( Emphasized on the petechial COURANT AND SOBKOV hemorrhage of soft palate near the junction of hard palate SCHUMACHER AND BARCAY an early diagnostic sign ) 19

20. 20 PETECHIAE ON THE PALATE WHITE OR GRAY MEMBRANE

21. Laboratory Findings Atypical lymphocytes in the circulating blood,antibodies to EBV and increased heterophil antibody titre Positive Paul- Bunnell test( pathognomic and characteristic) Monospot test(highly specific test)

22. MANAGEMENT No specific treatment Bed rest and adequate diet Short-term steroid therapy occasionally used 22

23. LEUKEMIA Disease characterized by the progressive over production of WBCs which usually appear in the circulating blood in an immature form Considered true malignant neoplasm (uncoordinated and independent proliferation of WBC cells or their precursors) Classified based on Clinical Behavior (Acute, Subacute or Chronic) and the primary hematopoietic cell line affected (Myeloid or Lymphoid) Acute : Survival less than 6 months Chronic : Survival of over 1 year Subacute : Survival duration lies between 6-12 months 23

24. Classification of leukemias Two major types (4 subtypes) of leukemias Acute leukemias Acute lymphoblastic leukemia (ALL) Acute myelogenous leukemia (AML) (also "myeloid" or " nonlymphocytic ") Chronic leukemias Chronic lymphocytic leukemia (CLL) Chronic myeloid leukemia (CML) (Within these main categories, there are typically several subcategories)

25. Acute vs. chronic leukemia Acute leukemias : Young, immature, blast cells in the bone marrow (and often blood) More fulminant presentation More aggressive course Occurs more commonly in children and young adults • Chronic leukemias : Accumulation of mature, differentiated cells Often subclinical or incidental presentation In general, more indolent (slow) course Frequently splenomegaly Mature appearing cells in the B. marrow and blood Occurs in adults of middle age or older

26. Phladiphia chromosome Philadelphia chromosome is an acquired cytological abnormality in the leukemia cells in CML Present in >80% of those with CML. It is a hybrid chromosome comprising reciprocal translocation between the long arm of chromosome 9 and the long arm of chromosome 22—t(9;22) forming a fusion gene BCR/ABL on chromosome 22, which has tyrosine kinase activity

27. Distinguishing AML from ALL light microscopy AML: Auer rods, cytoplasmic granules ALL: no Auer rods or granules. flow cytometry special stains ( cytochemistry ) i.e AML:MPO + ve,SBB +VE,NSE +VE in M4,M5,M7,FINE PAS +VE IN M6,M7 ALL:BLOCK PAS +VE,ACID PHOSPHATASE +VE in T ALL

28. Auer rods in AML ALL

29. ETIOLOGY Viruses: Epstein Barr Virus , Herpes Virus and Human T-leukemia virus Radiation and Atomic Energy : When exposure is over the dose of 100 rads Chemical agents : Chronic exposure to aniline dyes, benzene and Phenylbutazone Anti-cancer drugs like Melphalan and Cholorambucil have an increased risk of developing leukemia especially Myelocytic variety. 31

30. ACUTE LYMPOID LEUKEMIA Affects the children younger than 15 years of age. Due to defect in lymphoid cells differentiation. More common in whites than non whites. M>F Do not have myeloperoxidase positive granules. ACUTE MYELOID LEUKEMIA Affects between the age of 15 to 39 years . Due to defect in myeloid cells differentiation. No such association. Have myeloperoxidase positive granules along with auer rods. 32

31. 33 ALL AML

32. CHRONIC MYELOID LEUKEMIA Malignancy involving myelocytes Associated with chromosomal abnormalities ie. Philadelphia chromosome. Occurs between the age of 30 to 60 years . Complete series of cells including myeloblast, promyelocyte, metamyelocyte and band cells are seen in peripheral smear. CHRONIC LYMPHOID LEUKEMIA Malignancy involving lymphocytes . No such association . M>F Occurs in the patients above 45 years of age. Smudge cells are the characteristic feature. 34

33. 35 CML CLL

34. CLINICAL FEATURES Acute leukemia Abrupt stormy in onset with pyrexia Weakness, fever, headache, generalized swelling of lymph node Petechial or ecchymotic hemorrhages of skin and mucous membrane Spleen, liver, kidney enlarged Chronic leukemia Insidious in onset Patient appears healthy or may exhibit features such as: anemic pallor and emaciation Lymph node enlargement is common in CLL than in CML Enlargement of salivary gland and tonsils resulting in Xerostomia Petechiae / E cchymoses leading to nodular lesions–skin 36

35. LABORATORY FINDINGS Acute leukemia Anemia and thrombocytopenia Bleeding and clotting time are prolonged. The leukocyte count rises in terminal stage to 1,00,000/mm 3 . Chronic leukemia Anemia and thrombocytopenia. Leukocytosis upto 5,00,000/mm 3 and a very low white blood cells are also reported 37

36. ORAL MANIFESTATIONS Oral lesions occur in both Acute and Chronic forms 80% of affected patient exhibit Gingival Hyperplasia in Acute Monocytic Leukemia Gingivitis, hemorrhage, petechiae and ulceration of the mucosa Gingivae are boggy, edematous and deep red Gingivae bleed easily 38

37. 39 GINGIVAL HYPERPLASIA GINGIVAL HYPERTROPHY GINGIVAL ENLARGEMENT

38. Purpuric lesions of the oral mucosa seen Rapid loosening of the teeth seen (due to necrosis of PDL) Destruction of alveolar bone Osseous changes in the jaw including alterations in developing tooth crypts, destruction of Lamina Dura, displacement of teeth 40

39. 41 Ulceration of palate Crusting of lip

40. TREATMENT According to type of leukemia Treatment consists of supportive care, Chemotherapy, Radiotherapy, Corticosteroid therapy or Bone marrow transplantation Chemotherapy includes three phases: Induction Consolidation Maintenance 45

41. Leukemoid Reaction A leukemoid reaction describes a high WBC count with neutrophilia,usually in response to infection. The WBC count may be as high as 50,000 /microL and can easily mimic CML or AML.

42. Features Suggesting Leukemoid Reaction Toxic granulation. High Neutrophil Alkaline P hosthotase (NAP) score. Presence of an obvious cause for the neutrophilia .

43. TUMORS OF LYMPHOID TISSUE TWO TYPES: HODGKIN’S LYMPHOMA NON-HODGKIN’S LYMPHOMA 48

44. HODGKIN’S LYMPHOMA Lymphoproliferative disorders arising from lymph nodes and from lymph components of various organs First described by British pathologist, Thomas Hodgkin in 1932 Characterized by painless enlargement of lymphoid tissue throughout the body Exact cause unknown 49

45. ORAL MANIFESTATIONS Incidence: Primary jaw lesion are uncommon Secondary effect : Seen in oral cavity in the form of infection due to reduced host immune response Appearance : Appear in the oral cavity as an ulcer or a swelling or as an intra – bony lesion 50

46. DIAGNOSIS CLINICAL DIAGNOSIS Rubbery consistency of the enlarged lymph node LABORATORY DIAGNOSIS Differentiated from Non- H odgkin’s Lymphoma by the presence of cell known as Reed-Stenberg Cells 51

47. NON-HODGKIN’S LYMPHOMA Also called ‘ LYMPHOSARCOMA ’ Neoplastic proliferation of lymphoid cells, usually affecting B-lymphocytes Involves not only the lymph nodes but also bone marrow, spleen and other tissues Early involvement of bone marrow is typical of this lymphoma 52

48. ORAL MANIFESTATIONS Site: Occurrence in oral cavity is rare; Found in tonsils, palate, buccal mucosa and gingiva Appearance: Palatal lesion are slow growing, painless, bluish soft tissue mass; often confused with minor salivary gland Symptoms : Paresthesia of MENTAL NERVE Pain and neuralgia of 2 nd and 3 rd division of V th cranial nerve Signs : Necrotic proliferation, ulceration and discolouration of Palate 53

49. NON-HODGKIN’S LYMPHOMA OF GINGIVA 54

50. Non Hodgkin’s lymphoma in hard palate

51. HL NHL A relatively homogeneous disease process Neoplastic cells are only < 1% of the total cell population in the lesion - rest are reactive normal cells. LOCALIZED to start with – CONTIGUOUS spread from one nodal region to another. Extremely heterogeneous With very rare exception, neoplastic cells are always the predominant cell population often up to 100%. SYSTEMIC to start with – NON-contiguous spread .

52. HL NHL Rare extra-nodal involvement. Rare GI / Waldeyer’s involvement. BM involvement – significant therapeutic importance. Associated with T-cell mediated immune deficiency – mycobacteria, fungal, viral, protozoal infections. Always treated – localized cases may receive only RT. Relatively common. Relatively common. Not significant in many cases. Associated with humoral immune deficiency – bacterial infections. Indolent cases may remain untreated for years – when treated, it is systemic CT – RT only adjunctive.

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