Hematology Lecture Notes PDF

HEMATOPATHOLOGY : Hawler Medical University College of Medicine Department: Pathology SESSION THREE: ACUTE LEUKEMIAS CHRONIC LEUKEMIAS Hawler Medical University College of Medicine Department: Patho...

HEMATOPATHOLOGY : Hawler Medical University College of Medicine Department: Pathology SESSION THREE: ACUTE LEUKEMIAS CHRONIC LEUKEMIAS Hawler Medical University College of Medicine Department: Pathology Renewal Differentiation  Myeloblast Promyelocyte Myelocyte Metamyelocyte Band Segmented DIAGNOSIS  Clinical features. Anemia Infection Bleeding Tissue Infiltration  CBC Hb WBC count Platelet count BM Biopsy & Aspiration  Special Tests. Special stains: SBB&PAS Immunological study, Cytogenetic analysis, Molecular study ACUTE MYELOID LEUKEMIA Clinical Assessment Symptoms: Fatigue, fever, bleeding, infections. Risk factors: Chemotherapy, toxins, genetic syndromes. ________________________________________ Laboratory Evaluation CBC + Differential: Anemia, thrombocytopenia, blasts. Peripheral Smear: Blasts ± Auer rods. ________________________________________ Bone Marrow Examination ≥20% blasts (WHO criteria). Myeloblasts, monoblasts, megakaryoblasts, Erythroblast. ________________________________________ Flow Cytometry Myeloid markers: CD13, CD33, CD117, MPO. Monocytic markers: CD14, CD64. Exclude lymphoid markers.  Genetic Testing  Cytogenetics: t(8;21), inv(16), t(15;17).  Molecular: FLT3, NPM1, IDH1/2, CEBPA.  ________________________________________  Risk Stratification  Favorable: t(8;21), inv(16), NPM1+/FLT3-ITD(-).  Adverse: Complex karyotype, FLT3-ITD(+).  ________________________________________  APL Subtype  t(15;17)/PML-RARA.  High DIC risk—start ATRA.  ________________________________________  Other Tests  Coagulation: Rule out DIC.  Imaging: Infections, extramedullary disease.  ________________________________________ ALL DIAGNOSIS:  Clinical Assessment  - Symptoms: Fatigue, fever, infections, bleeding, bone pain.  - Findings: Lymphadenopathy, hepatosplenomegaly, mediastinal mass.  --- Laboratory Evaluation  -CBC + Differential: Anemia, thrombocytopenia, leukocytosis/leukopenia, blasts.  Peripheral Smear: Lymphoblasts.  Bone Marrow Examination - ≥20% blasts (WHO criteria).  Flow Cytometry  - B-lineage markers: CD10, CD19, CD20, TdT.  - T-lineage markers: CD3, CD7, CD2.  - Exclude myeloid markers.  Genetic Testing  - Cytogenetics: t(9;22) (BCR-ABL), t(12;21), hyperdiploidy.  Risk Stratification  Standard Risk: Hyperdiploidy, t(12;21).  - High Risk: t(9;22), MLL rearrangement, hypodiploidy. -  - CNS Involvement  - CSF cytology: Blasts in cerebrospinal fluid.  - Imaging: CNS masses or meningeal disease.  Other Tests  - Coagulation: Rule out coagulopathy. - Imaging: Mediastinal mass, organomegaly. ACUTE LYMPHOBLASTIC LEUKEMIAS (ALL): FAB CLASSIFICATION Acute Lymphoblastic Leukemias (L1): Small, monomorphic lymphoblasts. Nuclei are round & regular. Nucleoli not visible. Cytoplasm is scanty. Acute Lymphoblastic Leukemias (L2): Large & heterogeneous lymphoblasts. Irregular nuclear outline. Nucleoli prominent. Usually abundant amount of cytoplasm. Acute Lymphoblastic Leukemias (L3): Large very uniform in size and shape. Deeply basophilic and vacuolated cytoplasm. Called burkit’s type. ALL L1 ALL - L1 ALL L2 ALL L3 ACUTE MYELOID LEUKEMIAS (AML): FAB CLASSIFICATION: M0 Acute Undifferentiated Myeloid Leukemia M1 Acute Myeloid Leukemia without maturation M2 Acute Myeloid Leukemia with maturation M3 Acute Hypergranular Promyelocytic Leukemia M4 Acute Myelomonocytic Leukemias M5 Acute Monoblastic Leukemias M6 Erythroleukemia M7 Acute Megakaryoblastic Leukemia AML Auer rod can be seen in AML only AUER ROD ACUTE MYELOGENOUS LEUKEMIA, WITH MINIMAL MATURATION.  Five leukemic myeloblasts. Each contains several nucleoli some of which are very large. High nuclear to cytoplasmic ratio. Agranular cytoplasm. ACUTE MYELOGENOUS LEUKEMIA, WITH MINIMAL MATURATION.  Three leukemic myeloblasts. Each contains several nucleoli. High nuclear to cytoplasmic ratio. Agranular cytoplasm.  Prominent Auer rod in the blast in the center.  ACUTE MYELOGENOUS LEUKEMIA, WITH MINIMAL MATURATION Marrow film:  A cluster of leukemic myeloblasts. Each contains large nucleoli.  Note Auer rods in six of the blast cells. ACUTE PROMYELOCYTIC LEUKEMIA M3. t(15;17) DIC Marrow film: Leukemic promyelocytes. Virtually every cell has cytoplasmic reddish-purple granules ranging from few to numerous. Each cell contains nucleoli, often very large. Note small lymphocyte compressed among leukemic cells. AML M7: Acute megakaryocytic leukemia. Dysmorphic megakaryocytes. On left a micromegakaryocyte with shedding cytoplasm. On right a dysmorphic cell with atypical nuclear lobulation and scant cytoplasm with shedding cytoplasm. QUESTIONS? WHAT IS YOUR DIAGNOSIS HOW DO YOU CONFIRM THE DIAGNOSIS? CHRONIC LEUKEMIAS:  Chronic leukemias are caused by abnormal, uncontrolled & widespread proliferation of white blood cells.  THERE IS PROLIFERATION OF MATURE AND MATURING WHITE CELLS. TWO TYPES OF CHRONIC LEUKEMIAS: Depending on whether it is the myeloid line or the lymphoid line that is proliferating  Chronic myeloid leukemia (CML): Results from proliferation of the mature and maturing granulocytes.  Chronic lymphocytic leukemia (CLL): Results from increased numbers of mature lymphocytes. DIAGNOSIS OF CHRONIC MYELOID LEUKEMIA (CML)  Clinical Assessment  1. Symptoms: Fatigue, weight loss, night sweats, early satiety (due to splenomegaly), bleeding, or asymptomatic (incidental finding).  2. Physical Examination: Splenomegaly, hepatomegaly.  ________________________________________  Laboratory Tests  1. Complete Blood Count (CBC): Leukocytosis, anemia, thrombocytosis or thrombocytopenia. Basophilia and eosinophilia.  2. Peripheral Blood Smear: Granulocytic hyperplasia: Increased immature myeloid cells (myelocytes, metamyelocytes). Basophils present.  Confirmatory Testing  1. Cytogenetics: Detect Philadelphia chromosome (t(9;22)).  2. Molecular Testing: Identify BCR-ABL1 fusion gene by RT-PCR or FISH.  ________________________________________  Additional Tests  1. Bone Marrow Aspiration and Biopsy: Hypercellular marrow with granulocytic hyperplasia.  2. Lactate Dehydrogenase (LDH): Elevated in proliferative phases.  CHRONIC PHASE blast less than 5% BLAST CRISIS ACCELERATED blast more PHASE than 20% blast 5-19% CML Myeloblast Promyelocyte Neutrophil Myelocyte Band Metamyelocyte DIFFERENTIAL DIAGNOSIS: Exclude Differential Diagnoses 1. Reactive Leukocytosis: Rule out infection or inflammation. 2. Other Myeloproliferative Neoplasms (MPNs): Assess JAK2 mutation status if necessary. DIAGNOSIS OF CHRONIC LYMPHOCYTIC LEUKEMIA (CLL):  Clinical Assessment  1. Symptoms: Fatigue, weight loss, night sweats, recurrent infections, or asymptomatic (incidental finding).  2. Physical Examination: Lymphadenopathy, splenomegaly, hepatomegaly.  ________________________________________  Laboratory Tests  1. Complete Blood Count (CBC): Absolute lymphocytosis (>5 × 10⁹/L).  2. Peripheral Blood Smear: Mature small lymphocytes with scant cytoplasm. Smudge cells (fragile lymphocytes).  3. Flow Cytometry  Markers: CD19, CD20(dim), CD23, CD5.  Monoclonality: κ/λ light chain restriction.  4. Genetics  FISH: del(13q), del(17p).  TP53 mutation, IGHV status.  5. Bone Marrow  Lymphoid infiltration (if needed).  Differentials  Reactive lymphocytosis.  Other B-cell disorders. Basophilia in CML CML CML Blast crises CLL CLL QUESTIONS: 60 YEARS OLD MAN WITH ABSOLUTE LYMPHOCYTOSIS; WHAT ARE RECOMMENDED INVESTIGATIONS?