LEUKEMIAS LEUKEMIAS Dr Mehboob Khan Pathologist. Leukemias are malignancies of hemtopoietic cells or...
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Transcript of LEUKEMIAS LEUKEMIAS Dr Mehboob Khan Pathologist. Leukemias are malignancies of hemtopoietic cells or...
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LEUKEMIAS
Dr Mehboob KhanPathologist
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Leukemias are malignancies of hemtopoietic cells or tissues in which there is abnormal proliferation of hemopoietic cells with infiltration of bone marrow and lymphatic tissues
ETIOLOGY:1. Molecular biology of leukemogenesis- oncogenes2. Abnormalities of the chromosomes- translocation
deletions3. Radiation4. Chemicals5. Viruses6. Genetic factors-Down syndrome
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CLASSIFICATION1. LYMPHOID• ACUTE LYMPHOID LEUKEMIA (ALL)• CHRONIC LYMPHOID LEUKEMIA (CLL)2. MYELOID• ACUTE MYELOID LEUKEMIA (AML)• CHRONIC MYELOID LEUKEMIA (CML)
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ACUTE MYELOID LEUKEMIA
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AML -NOT OTHERWISE CLASSIFIED MORPHOLOGIC CLASSIFICATION
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MYELOBLASTWITH AUER ROD
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MYELOBLAST
NORMOBLASTS
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AML-M4AML-M5
AML-M6 MEGAKARYOBLASTS
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HYPERCELLULAR BONE MARROW (ALL)
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CLINICAL FEATURES OF ACUTE LEUKEMIA:1. COMMON• Anemia• Fever• Malaise• Hemorrhages, bruising and petechiae2. LESS COMMON:• Infections of mouth and pharynx• Pains in bones and joints• URTI (children)• Superficial lymph node enlargement (children in ALL)3. OCCASIONAL:• Abdominal pain• Skin rashes• Gum hypertrophy• Mediastinal obstruction
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CLINICAL FEATURES DUE TO ORGAN INFILTRATION:• Tender bones• Superficial lymphadenopathy (ALL)• Splenomegaly, hepatomegaly (ALL)• Gum hypertrophy and infiltration, rectal ulceration
and skin involvement (AML- myelomonocytic and and monocytic type)
• Meningeal syndrome (ALL)• Testicular swelling and mediastinal compression
(ALL)
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BLOOD PICTURE:1. Normocytic and normochromic anemia2. Total WBC count may be increased upto 500 x 10 /L3. Thrombocytopenia4. Peripheral blood smear- myeloblasts, promyelocytes, myelocytes ,
metamyelocytes, agranular neutrophils, stab cells, myelomonocytes and normoblasts
5. Bone marrow- hypercellular with plenty of blast cells (>75% of the marrow cell population)
THERE SHOULD BE AT LEAST 30% BLASTS IN BONE MARROW (FAB ) 20% BLASTS IN BONE MARROW (WHO)6. Tests for DIC will be positive in Promyelocytic leukemia
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3. CYTOCHEMISTRY• Myeloperoxidase- positive in immuture myeloid cells
containing granules and auer rods but negative in M0 myeloblasts
• Sudan black- positive in immature cells in AML• Non specific esterase (NSE)- positive in monocytic series
(M4 and M5)• Periodic acid Schiff (PAS)- positive in immature lymphoid
cells and in erythroleukaemia (M6)
• Acid phosphatase – focal positive in leukaemic blasts in ALL and diffuse reaction in monocytic cells (M4 and M5)
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MYELOBLAST (MYELOPEROXIDASE POSITIVE)
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4. IMMUNOPHENOTYPING• AML cells express CD13 and CD33 antigens• M5 shows CD41 and CD42 positivity• ALL is positive for CD10, CD19 in Pre B ALL (90%); B
cell ALL (50%); • ALL T cell type are positive for CD1,CD2, CD5, CD7
5. OTHER INVESTIGATIONS• Serum muramidase- elevated in M4 and M5 AML• Serum uric acid- frequently elevated
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COURSE AND PROGNOSIS IN AML:1. GOOD PROGNOSIS• Age <40 year• M2,M3 and M4 types• Blast cells with Auer rods• Total WBC <25,000/cumm• Tranlocation and inversion• Leukemia without preceding Myelodysplastic syndrome (MDS)
2. BAD PROGNOSIS:• Age<2 years and >55 years• M0,M6,M7 types• Total WBC >100,000/cumm• Deletions• Leukemia with preceding MDS
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ACUTE LYMPHOBLASTIC
LEUKEMIA(ALL)
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• ALL is the commonest leukemia seen in childhood• The predominant cell seen in ALL is LYMPHOBLAST• Lymphoblast has coarse nuclear chromatin and 1-2
nucleoli, high nucleus:cytoplasmic ratio (N:C), stain positve for PAS (periodic acid Schiff) and TdT (terminal deoxynucleotidyltransferase)
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LYMPHOBLASTS (ALL)
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MYELOBLASTS LYMPHOBLASTS
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LYMPHOBLASTS in peripheral blood smear (ALL)
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FAB CLASSIFICATION OF ALL1. L1 ALL• Commonest type• Best prognosis• Lymphoblasts have coarse chromatin with small nucleoli and scanty
cytoplasm
2. L2 ALL• Lymphoblasts have heterogenous chromatin with 1-2 nucleoli,
moderate cytoplasm with few vacuoles
3. L3 ALL• Rare and worst prognosis• Homogenous chromatin with 1-2 prominent nucleoli, abundant
cytoplasm and vacolues positive for Oil O Red
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WHO IMMUNOLOGICAL CLASSIFICATION OF ALL1. B CELL• More common• CD19 and Cd20 positive• Associated with pancytopenia2. T CELL• Less common• CD1, CD2, CD7 positive• Associated with mediastinal mass, lympadenopathy and
splenomegaly
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(Adolescent males/ Lymphomas/Thymic mass)
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CLINICAL FEATURES:• Same as AML • With lymphadenopathy, hepatsplenomegalyBLOOD PICTURE:• Elevated total WBC count upto 500,000/cum• Anemia, neutropenia• Thrombocytopenia• Lymphoblasts >30% in bone marrowBIOCHEMICAL CHANGES:• Elevated uric acid, LDH levels• Elevated serum phosphate levels• Hypocalcemia
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PROGNOSIS IN ALLGOOD PROGNOSIS• Age 2-8 years• Females• L1 type• Pre-B cell• Absence of mediastinal mass• Hyperdiploidy or translocations
BAD PROGNOSIS• Age < 2 year , >10 years• Male• L2 and L3 type• Pre T cell• Mediastinal mass• Ph chromosome
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