Acute Leukemia PDF

Pathology: Hematology Dr Annamma Joseph Acute Leukaemia Learning outcomes Leukemia 1.Define leukaemia. 2. Classify leukaemia by WHO and FAB classification. Acute Leukaemia (AML, ALL) 1. Describe the aetiopathogenesis of AML & ALL. 2. Describe the clinical features of AML & ALL. 3. Analyse and descri...

Pathology: Hematology Dr Annamma Joseph Acute Leukaemia Learning outcomes Leukemia 1.Define leukaemia. 2. Classify leukaemia by WHO and FAB classification. Acute Leukaemia (AML, ALL) 1. Describe the aetiopathogenesis of AML & ALL. 2. Describe the clinical features of AML & ALL. 3. Analyse and describe the blood and bone marrow changes of AML & ALL. 4. Describe the clinical course and prognosis of AML & ALL. 2 Leukaemia (Definition) -Review Neoplastic proliferation of white blood cell precursors Leukaemias are a group of disorders characterized by the accumulation of malignant white cells in the bone marrow and blood. Acute Leukemia (Acute myeloblastic & Acute lymphoblastic leukemia) Characterised by >20% blasts in the blood and bone marrow 3 Classification of acute leukaemia WHO classification Based on lineage of blasts to myeloid or lymphoid Acute myeloblastic/myeloid leukaemia Acute lymphoblastic leukaemia FAB classification (AML- M0-M7 ; ALL- L1,L2,L3) Immunological classification for AML, ALL(B and T cell lineage). 4 Classification of AML based on FAB (French American British)  M0 – Undifferentiated AML  M1- AML without maturation  M2 – AML with maturation  M3 – Acute promyelocytic leukaemia  M4 – Acute myelomonocytic leukaemia  M5 – Acute Monoblastic leukaemia  M6 – Erythroleukaemia  M7 – Acute megakaryoblastic leukaemia 5 Classification of AML -FAB  M0 – Undifferentiated AML  M1- AML without maturation  M2 – AML with maturation AML without maturation AML with maturation  M3 – Acute promyelocytic leukemia  M4 – Acute myelomonocytic leukemia  M5 – Acute monoblastic leukemia 7  M6 – Erythroleukemia  M7 – Acute megakaryoblastic leukaemia 8 Acute lymphoblastic leukaemia(Summary) Accumulation of lymphoblasts(>20%) in the blood and bone marrow Most common malignant disease of childhood 75% of cases occur before the age of 6 years 85% of cases are of B‐cell lineage and 15% of T‐cell lineage. 9 Classification of ALL FAB classification based on morphology of blasts L1- Small homogenous blasts L2 - Heterogenous blasts L3 - Large homogenous blasts Based on immunological markers B cell and T cell lineage 10 FAB Classification of ALL L1 – Homogenous small blasts, L2 – Heterogenous blasts, variable cytoplasm, scanty cytoplasm, regular round irregular/cleft nucleus, large nucleoli nuclei, inconspicous nucleoli L3 – Large homogenous blasts, basophilic cytoplasm, round nucleus, prominent nucleoli, cytoplasmic vacuolation Clinical features Acute Myeloid Leukaemia Acute Lymphoblastic Leukaemia(ALL) Age Young adults. Rare in child Age Increasing with age(median age 65yrs). Children < 6years or old age Features Features Bone marrow failure Bone marrow failure Anemia Anemia Infections (fever + low WBC) Infections(fever + low WBC) Bleeding (Low platelets) Bleeding(Low platelets) Organ infiltration Organ infiltration Liver+ Spleen+(Mild),Lymph nodes Liver+ Spleen+ Other sites+(Testis,Meninges) 12 Other sites+(like gums) AML and ALL Infections of eye and foot (Low WBC) Hepatosplenomegaly Purpuric spots due to bleeding tendency Specific Clinical features Acute Myeloid Leukaemia Bleeding / DIC AML M3 Gum hypertrophy AML M4, M5 Acute Lymphoblastic Leukaemia Generalised lymphadenopathy Meningeal infiltration or testicular infiltration 14 AML M4 or M5 Gum hypertrophy Gum hypertrophy 15 Acute Lymphoblastic Leukemia (ALL) Child with cervical lymphadenopathy and mediastinal widening (Xray) 59- year- old male with meningeal infiltration 16 Diagnosis of acute leukemia (general) The diagnosis is made by Analysis of blood (hematological parameters and peripheral blood smear) Analysis of bone marrow Cytochemical stains Immunophenotyping Cytogenetic studies and molecular studies. Diagnosis helps guide the treatment and monitor for residual disease of individual cases. Cytogenetic and molecular abnormalities are used to classify and indicate prognosis. 17 Lab Diagnosis: AML and ALL 1.Haematological Parameters Hb low (4 –5 gm%) MCV and MCH normal (normocytic, normochromic anemia on peripheral smear) Total leucocyte count – increased and abnormal (10 – 300,000/mm3) Normal granulocytes are reduced Platelet count – decreased (thrombocytopoenia) 18 2.Peripheral smear Acute Myeloid Leukaemia Myeloblast ++ (>20%) Morphology according to subtype (M0-M7) Auer rod is characteristic of AML Acute Lymphoblastic Leukaemia Lymphoblast ++ (>20%) Granulocyte decreased Morphology according to subtypes(L1,L2,L3) 19 Auer rods in AML Linear rod like pink structures in the cytoplasm of myeloblasts. Aggregates of primary granules in the blasts In AML M3 ,multiple Auer rods are seen. They are called faggot cells. Faggot cell 20 Characteristic features of AML M3 Acute promyelocytic leukaemia 1.Can present with DIC 2.Multiple Auer rods (faggot cells) 3.Treatment with ATRA(All trans retinoic acid) 21 Characteristic features of AML M4,M5 Gum hypertrophy AML M5(Monoblastic Leukemia) AML M4 (Myelomonocytic leukemia) 22 AML Peripheral smear: RBCnormocytic normochromic anaemia WBC- More than 20% blasts Auer rods+. M0 - M7 Platelets - Reduced AML M1 AML M3 Maturation varies according to subtype (M0-M7) Students are not required to differentiate morphology of subtypes AML M2 AML M4 AML M5 AML M6 AML M7 23A ALL- Peripheral blood smear Peripheral smear: RBC- Normocytic normochromic anaemia WBC- More than 20% blasts.Blasts of L1, L2 or L3 types Platelets - Reduced FAB classification for ALL (review) L1 – Homogenous small blasts, scanty cytoplasm, regular round nuclei, inconspicous nucleoli 24 FAB classification for ALL (review) L2 – Heterogenous blasts, variable cytoplasm, irregular/cleft nucleus, large nucleoli L3 – Large homogenous blasts, basophilic cytoplasm, round nucleus, prominent nucleoli, cytoplasmic vacuolation Burkitt’s lymphoma 25 3.Bone Marrow Acute Myeloid Leukaemia Cellularity increased  Myeloblast predominant(>20%)  Erythroid elements and megakaryocytes decreased  Acute Lymphoblastic Leukaemia Cellularity increased  Lymphoblast predominant (>20%)  Erythroid elements and megakaryocytes decreased  26 Bone marrow in AML,ALL Bone marrow aspirate in ALL Bone marrow trephine biopsy –high-power magnification (AML) 27 4.Cytochemical stains AML *Myeloperoxidase *Sudan *PAS *Nonspecific esterase ALL +ve +ve -ve -ve -ve +ve (Block positivity) +ve in M5 -- 28 Cytochemical stains Myeloperoxidase +ve in blasts of AML Sudan black +ve in blasts of AML 29 Cytochemical stains Block positive in Periodic Acid Schiff (PAS) in the ALL blasts Leishman stain >90% ALL blasts 30 +ve Pink colour in blasts as block 5.Immunophenotyping AML CD 13 CD 33 CD117 ALL CD10 B cell- CD19, 20, 22 T cell- CD 2, 5, 7 Immunophenotyping -Technique used to study the protein expressed by cells by using monoclonal antibodies. CD-(cluster of differentiation) -cell surface molecules on leukocytes and other cells. 31 Methods of immunophenotyping 1.Immunostaining in biopsy 2.Flow cytometry 32 Immunological types of acute leukemia The 3 cell lineages from pluripotential stem cell giving rise to the immunological types of acute leukemia (AML,T ALL and B ALL) 33 Cytogenetic studies Cytogenetic abnormalities are common in leukemia AML ALL t (15:17) – M3 t (9:22) t (8:21) – M2 t (8:14) Inv. Ch. 16 - M4 Hyper diploid ALL Loss of Ch. 5/7 (Poor prognosis) Complex abnormalities ( Poor prognosis) Ch.is short form for chromosome 34 Prognosis Acute Myeloid Leukaemia Acute Lymphoblastic Leukaemia Overall prognosis is better Overall prognosis is poor With treatment modalities in >85% of children can now expect to be cured. the young, it is improving The cure rate in adults is 5% 5year survival is about 30% over the age of 70 years. AML M3, AML with 5year survival is 69% chromosomal abnormality like inv16, t(8:21)have favourable prognosis Hyper diploid ALL – favourable t(9:22)- poor prognosis 35 Summary of acute leukaemia  Classification based on lineage of blasts Blast morphology Cytochemical stains Immunophenotyping – membrane markers Cytogenetics and Molecular studies  Classification Based on WHO and FAB 36 References: Robbins and Cotran Pathologic Basis of Disease 10th Edition Underwood’s pathology: A clinical approach 7th edition Hoffbrand’s Essential Haematology 8th Edition THANK YOU 37