QUALITATIVE DISORDERS OF WBC

•Presenter : Nabin Chaudhary

CONTENTS

• Lazy leukocyte syndrome• Chediak higashi syndrome• Infectious mononucleosis• Leukemia• Lymphoma

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

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• 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

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CLINICAL FEATURES

AGE Complications occur at the age of 1-2 years due to infections

SYMPTOMSMost common: Stomatitis, Otitis media and Bronchitis

RECURRENT INFECTIONSHigh Chance of Recurrent Infections

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ORAL MANIFESTATIONS

STOMATITIS (Most Common)

PERIODONTITIS

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DIAGNOSIS

CLINICAL DIAGNOSIS• Recurrent Infection, Periodontitis and Stomatitis

LABORATORY DIAGNOSIS• TLC slightly low• ANC as low as 100-200 cells/mm3

• Bone Marrow contains normal number of mature neutrophils

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MANAGEMENT

ANTIBIOTICS GIVEN TO CONTROL THE INFECTION

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CHÉDIAK-HIGASHI SYNDROME (BÉGUEZ CÉSAR SYNDROME, CHÉDIAK-STEINBRINCK-HIGASHI SYNDROME)

Described by Béguez Cesar (1943), Steinbrinck (1948), Chédiak (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 10Characterized by abnormal intracellular protein transport

LYST or CHS1 gene

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CLINICAL FEATURES

Affects all racesUsually appears soon after birth or in children <5 years

Characterized by immune deficient stateCharacteristic Clinical Feature:

Partial Oculocutaneous Albinism (Silvery Hair Syndrome)

Recurrent Infections of Respiratory tract and SinusesEasy bruisability and bleedingGastrointestinal disturbances Lymph Node enlargement (Cervical)May be associated with Malignant LymphomaProgressive Neurological Dysfunction

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

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ORAL MANIFESTATIONS

GILLIG AND CALDWELLUlcerations of the Oral MucosaSevere Gingivitis andGlossitis

HAMILTON AND GIANSANTIPeriodontitis (probably related to defective leukocyte function)

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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

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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

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INFECTIOUS MONONUCLEOSIS(GLANDULAR FEVER)

• Also known as EBV infectious mononucleosis/ Pfeiffer's disease / Filatov's disease

• Caused by Epstein Barr virus

• Drusenfieber (1889)

• First described by Sprunt and Evans in the John Hopkins Medical Bulletin(1920)

• 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”.

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CLINICAL FEATURES

Chiefly in Children and young adults15-20 year age groupNo sex or seasonal predilectionMost patients can be asymptomaticClinical syndrome consists of:

Fever Pharyngitis Adenopathy

Tonsillitis, Headache, Chills, Cough, Nausea or VomitingSplenomegaly and Hepatitis Enlargement of Cervical lymph node followed by the nodes of Axilla and Groin.

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Cervical lymphadenopathy Exudative pharyngitis

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ORAL MANIFESTATIONSFRASER 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)

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PETECHIAE ON THE PALATE WHITE OR GRAY MEMBRANE

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)

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MANAGEMENT

No specific treatment

Bed rest and adequate diet

Short-term steroid therapy occasionally used

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LEUKEMIADisease characterized by the progressive over production of WBCs which

usually appear in the circulating blood in an immature formConsidered 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 monthsChronic: Survival of over 1 yearSubacute: Survival duration lies between 6-12 months

Classification of leukemiasTwo 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)

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

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

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

• Auer rods in AML • ALL

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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.

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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.

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ALL AML

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.

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CML CLL

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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 / Ecchymoses leading to nodular lesions–skin

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LABORATORY FINDINGS

Acute leukemia

• Anemia and thrombocytopenia• Bleeding and

clotting time are prolonged.• The leukocyte

count rises in terminal stage to 1,00,000/mm3.

Chronic leukemia

• Anemia and thrombocytopenia.• Leukocytosis upto

5,00,000/mm3 and a very low white blood cells are also reported

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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

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GINGIVAL HYPERPLASIA

GINGIVAL HYPERTROPHY

GINGIVAL ENLARGEMENT

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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

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Ulceration of palate

Crusting of lip

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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

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.

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

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TUMORS OF LYMPHOID TISSUE

TWO TYPES:

HODGKIN’S LYMPHOMA

NON-HODGKIN’S LYMPHOMA

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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

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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

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DIAGNOSIS

• CLINICAL DIAGNOSISRubbery consistency of the enlarged lymph node

• LABORATORY DIAGNOSISDifferentiated from Non-Hodgkin’s Lymphoma by

the presence of cell known as Reed-Stenberg Cells

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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

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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 2nd and 3rd division of Vth cranial nerve

• Signs:• Necrotic proliferation, ulceration and discolouration of Palate

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NON-HODGKIN’S LYMPHOMA OF GINGIVA

Non Hodgkin’s lymphoma in hard palate

HL NHL1. A relatively homogeneous

disease process2. Neoplastic cells are only

< 1% of the total cell population in the lesion - rest are reactive normal cells.

3. LOCALIZED to start with – CONTIGUOUS spread from one nodal region to another.

1. Extremely heterogeneous

2. With very rare exception, neoplastic cells are always the predominant cell population often up to 100%.

3. SYSTEMIC to start with – NON-contiguous spread.

HL NHL4. Rare extra-nodal

involvement.5. Rare GI / Waldeyer’s

involvement.6. BM involvement –

significant therapeutic importance.

7. Associated with T-cell mediated immune deficiency – mycobacteria, fungal, viral, protozoal infections.

8. Always treated – localized cases may receive only RT.

4. Relatively common.

5. Relatively common.

6. Not significant in many cases.

7. Associated with humoral immune deficiency – bacterial infections.

8. Indolent cases may remain untreated for years – when treated, it is systemic CT – RT only adjunctive.

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