LEUKEMIA DR. AYESHA JUNAID MBBS,MCPS,FCPS. Professor of Pathology Consultant Haematology Incharge Blood Transfusion Services-SIH Leukemia OBJECTIVES What is leukemia? What is the Pathogenesis of Leukeima? How do we classify leukemia? (WHO 2008 classification) Leukemia OBJECTIVES What is their clinical presentation? How do we diagnose leukemia in laboratory? What are the basic principles of management? Leukemia vs Leukemoid Reaction Leucocytosis Neutrophilia,Eosinophilia,Lymphocytes Leucopenia Leukemoid Reaction Leukemia Leukemia Myeloid cells Mitotic pool (blast to myelocytes) Maturation pool (ends with the mature neutrophil) Storage pool (Mature neutrophils residing in the bone marrow) LEUKEMIA Leukemia is a disease resulting from the neoplastic proliferation of hemopoeitic or lymphoid cells LEUKEMIA It results from the mutation in a single stem cell The progeny of which form a clone of leukemic cells LEUKEMIA Genetic events contributing to malignant transformation include Inappropriate expression of oncogenes Loss of function of TSG LEUKEMIA CLASSIFICATION LINEAGE & DEGREE OF MATURATION MORPHOLOGY CYTOCHEMICAL CYTOGENETICS IMMUNOPHENOTYPICAL IMMUNOHISTOCHEMISTRY MOLECULAR GENETICS LEUKEMIA CLASSIFICATION WHO 2008 Evidence based classification for daily therapeutic decisions. Provides a flexible framework for integration of new data LEUKEMIA Acute leukemia Chronic leukemia Acute Myeloid Leukemia Acute Lymphoid Leukemia Chronic Myeloid Leukemia Chronic Lymphoid Leukemia ACUTE LEUKEMIA Heterogeneous group of clonal disorders arising from • Pluripotent stem cells • Clinical course • Response to therapy ACUTE LEUKEMIA Acute leukemia accounts for approximately 10% of all human cancers Is the leading cause of cancer deaths in adults younger than 35 years of age BONE MARROW TREPHINE HIGH AND LOW POWER CYTOCHEMISTRY It identifies diagnostically useful enzymes or other cytoplasmic substances of hemopoietic cells Particularly useful for identification of immature cells in leukemia SUDAN BLACK B PERIODIC ACID SCHIFF(PAS) ACID PHOSPHATASE Leukemia AML/ALL MORPHOLOGY Differentiation on morphological grounds alone is not possible Morphological features favoring lymphoid derivation include Blasts including relatively condensed chromatin Absence of conspicuous nucleoli Presence of scanty agranular cytoplasm CYTOCHEMISTRY CYTOCHEMISTRY PAS ACUTE LEUKEMIA ALL AML ACUTE LEUKEMIA CLINICAL FEATURES ONSET Abrupt, acute Insidious, slowly progressive Bone marrow malfunction Anemia, infection & bleeding ACUTE LYMPHOBLASTIC LEUKEMIA CLINICAL FEATURES Bone pain & tenderness Lymphadenopathy Splenomegaly Hepatomegally CNS manifestations Testicular involvement Skin LEUKEMIA LABORATORY EVALUATION Anemia Leukocytosis/leukopenia/normal TLC Thrombocytopenia Bone marrow examination Aspirate & biopsy LABORATORY EVALUATION LEUKEMIA