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THE LEUKEMIAS. LEUKEMIAS-DEFINITION. Leukemias are neoplasms of the precurssors of the blood cells and are characterised by accumulation of abnormal white cells in the bone marrow. CLASSIFICATION OF LEUKEMIAS. Acute lymphoblastic leukemia Acute myeloid leukemia Chronic lymphocytic leukemia
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LEUKEMIAS-DEFINITION Leukemias are neoplasms of the precurssors of the blood cells and are characterised by accumulation of abnormal white cells in the bone marrow
CLASSIFICATION OF LEUKEMIAS Acute lymphoblastic leukemia Acute myeloid leukemia Chronic lymphocytic leukemia Chronic myeloid leukemia
FAB CLASSIFICATION OF AML M0 – Minimally differentiated AML M1- AML without differentiation M2- AML with differentiation M3- Acute promyelocytic leukemia M4- Acute myelomonocytic leukemia M5- Acute monocytic leukemia M6- Acute erythroleukemia M7- Acute megakaryocytic leukemia
WHO CLASSIFICATION AML with recurrent chromosome translocation AML with multilineage dysplasia AML therapy related AML not otherwise specified
AETIOPATHOGENESIS OF LEUKEMIA Ionizing radiation Chemicals Viruses Genetic disorders Acquired disorders Oncogenes Tumor suprresor genes
ACUTE LEUKEMIAS ACUTE MYELOID LEUKEMIA {AML} ACUTE LYMPHOID LEUKEMIA {ALL}
CLINICAL FEATURES • Due to bone marrow failure • Due to organ infiltration
Due to bone marrow failure • Anemia • Bleeding manifestations • Infections • Fever
Due to organ infiltration • Bone pain • Lymphadenopathy • Organomegaly • Renal failure • Gum hypertrophy • Meningitis • Chloroma
BLASTS IN LEUKEMIA LYMPHOBLAST MYELOBLAST Large cell with large nucleus Coarse chromatin Scanty cytoplasm 1-2 nucleoli No auer rods Large cell with large nucleus Open chromatin Moderate cytoplasm 2-5 nucleoli Auer rods sometime present
Diagnosis of Leukemias Peripheral blood picture Bone marrow examination Cytogenetics Cytochemistry Immunophenotyping Other investigations
MICROSCOPY OF AML • RBC - NORMOCYTIC NORMOCHROMIC • WBC - COUNT IS INCREASED AND PREDOMINANT CELLS SEEN ARE BLASTS(>20%)AUER RODS CAN BE SEEN • PLATELETS - REDUCED IN NUMBER (THROMBOCYTOPENIA)
IMMUNOPHENOTYPING AML CD-13, CD-33 AML-M7 CD-41,CD-42 AML/ALL M0,M1,M6,AND M7.
CYTOGENETICS M2 t(8;21)(q22;q22) M3 t(15;17) (q22;q21) M4 inv(16) M5 t(9;11)
Chronic leukemias Chronic myeloid leukemias (CML) Chronic lymphoid leukemias (CLL)
CHRONIC MYELOID LEUKEMIA • 3rd and 4th decade C/F • Anaemia • Hypermetabolism • Splenomegaly • Bleeding tendencies.
PHILADELPHIA CHROMOSOME 70% - 90% cases of cml Reciprocal translocation of parts of long arm of chromosome 22 to chromosome 9 t(9;22) Following this there is fusion of abl-bcr oncogenes which have a combined proliferative effect
MICROSCOPY OF CML • RBC -NORMOCYTIC NORMOCHROMIC • WBC - COUNT INCREASED. ALL PRECURSSORS OF WBC SEEN FROM BLASTS TO MATURE NEUTROPHILS BASOPHILS ARE INCREASED.BANDS ARE INCREASED • PLATELETS ARE INCREASED IN NUMBER • STAGES OF CML • CHRONIC PHASE • ACCELERATED PHASE • BLAST CRISIS
DIAGNOSIS Anaemia WBC-chronic, accelarated, blast Bone marrow examination Cytochemistry; NAP Other investigations
LEUKEMOID REACTION Occurrence of peripheral blood picture resembling that of leukemia in a patient who does not have leukemia
LEUKEMOID REACTION LEUKEMIA Clinical features diagnostic Blasts do not exceed 5% Platelets are normal Autopsy shows no features of infiltration Lap score is normal or high Clinical features diagnostic Numerous blasts Platelets are decreased Organ infiltration seen at autopsy Lap score is subnormal