WBC DISORDERS

WBC DISORDERS

Neoplastic disorders

Bone marrow haematopoiesis

Releases only mature cells in peripheral bloodLeukemia Progressive, neoplastic disease of hematopoietic system . It is widespread within the marrow with involvement of peripheral blood (not always)

Unregulated proliferation of immature haemopoetic cells in the marrow

Classification Acute Rapid growth of immature blood cells ( blasts ) Rapid onset Very aggressive Mostly in children, young adults

Chronic Excessive build up of relatively mature blood cells Insidious in onset Less aggressive Mostly in older patientsClassificationLymphoid

Affects lymphocytes & plasma cells

Lymphocytic leukemia

Myeloid

Affects eosinophils, neutrophils,basophils

Myelogenous leukemia

Myeloid leukemiaArises from these cellsLymphoid leukemiaArises from these cells

EtiopathogenesisChromosomal translocation & acquired mutations

Inherited genetic factors

Viruses

Chronic immune stimulation

Iatrogenic factors

SmokingSymptoms of leukemia

Unregulated proliferation and invasion of immature blood cells in bone marrow and other tissues

BONE TENDERNESSHEPATOSPLENOMEGALYLYMPHADENOPATHY

Suppression of normal haemopoetic cells

- ANAEMIA - LEUKOPENIA- THROMBOCYTOPENIA

ACUTE LEUKEMIAALL & AML - proliferation of undifferentiated cells (BLASTS)

How do we differentiate myeloblast from lymphoblast ?

Morphology

Myelobalst

Lymphoblast Myeloblast Vs LymphoblastMyeloblastLymphoblastCytoplasm abundant scantGranules+-Auer rods+

-NucleusChromatinFine condensedNucleolus 2-3 , prominent inconspicuous17CytochemistryMyeloblastLymphoblastMyeloperoxidase+-Sudan Black+-PAS- +

Esterases-/+-Cytochemistry18ImmunophenotypingAntibodyMyeloblastLymphoblastCD13,CD33,CD65+-CD3-+(T)CD19-+(B)tDT-+19ACUTE MYELOID LEUKEMIADefinition Tumour of hematpoietic progenitors

Acquired oncogenic mutations

Impede differentiation

Accumulation of immature myeloid blasts in marrowDefinition Proliferation of immature myeloid cells

WHO classificationWHO classification incorporates morphological, immunophenotypic, genetic and clinical features.Defined by presence of >20% blasts in blood or bone marrow nucleated cells. (FAB > 30%)Diagnosis of AML can be made in blasts 20% Myeloblasts in the marrow Due to suppression of bone marrow Anemia Thrombocytopenia leucopenia

Due to infiltrationBony tenderness

Hepatosplenomegaly

AML-M3: Bleeding due to DIC AML M4/M5: Gum hyperplasia

Signs & Symptoms

Purpura

OrganomegalyPathogenesisGenetic alterations inhibit terminal maturationMarrow replaced by premature cellsBLOCKED MATURATION & SURVIVALAccumulating neoplastic cells - suppress normal hematopoietic cells anemia & thrombocytopenia

Cytogenetics AML M3: t (15;17)

AML M2: t(8;21)

AML M4: inv 16

AML M5: abnormalities of chromosome 11

Hematological findingsCBPHb TLC > 100,000Presence of myeloblastsPlatelets

Hematological findingsBone marrow aspiration

Hypercellular marrow

Erythroid, lymphoid & megakaryocytic cells supressed

>20% blasts seen

CytochemistryMPO +

Sudan Black +

PAS negative

Esterases -/+

MPO

SBB

AML M0

AML M1

AML M2

AML M3

Auer rodsNeedle like Cytoplasmic inclusions, red purple with Leishmans stainPositive staining with MPO & Sudan black Faggot cells(M3): formed by the fusion of primary granules

AML M3 hypogranular variant

AML M4

AML M5

AML M6

AML M7

Characteristic featuresM3--Young, better prognosis, retinoic acid, DIC

M4 , M5--lysozyme in urine, NSE+++, gum hypertrophy

M6--PAS++, Atypical erythroblasts

M7--marrow fibrosis, pancytopenia

ACUTE LYMPHOBLASTIC LEUKEMIA(ALL)Definition Malignant proliferation of immature lymphoid stem cells

Definition Neoplasms Immature B or T cells

85% - B-ALL childhood

T-ALL - adolescentsClinical features2-5 yrsAnemia, infections, bleeding symptomsLymphadenopathy, organomegalyMediastinal massBone pain-periosteal involvement

WHOClassificationPrecursor B-cell NeoplasmB cell lymphoblastic leukemia/ lymphoma (B-ALL)

Precursor T-cell NeoplasmT cell lymphoblastic leukemia/ lymphoma (T-ALL)

FAB ClassificationL1 - Small, homogenous (uniform ) lymphoblasts

FAB ClassificationL2 - Large, heterogenous (pleomorphic) lymphoblasts

FAB ClassificationL3 - Large,homogenous with vacuolated and deeply basophilic cytoplasm)- Burkitts type

Lab diagnosisCBCRBC count : edWBC count : ed with presence of >20% lymphoblastsPlatelet count : edBone marrow aspirationHypercellular>20% blasts seen

Lab diagnosisHistochemical markers

Myeloperoxidase negative

PAS positive

tdT positive

SIg -ve

Lab diagnosisCD markers

CD3 - T cell

CD19 - B cell

CD10 Pre B cell (CALLA)

Thank YouAcuteChronic

LymphoidALLCLL

MyeloidAMLCML

Organomegaly