The lecture discusses leukocytic disorders, focusing on acute and chronic leukemia, including acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL). It covers their diagnosis, clinical manifestations, etiology, and morphological characteristics, emphasizing the importance of blood and marrow morphology in diagnosis. The document also highlights the incidence rates, risk factors, and common genetic lesions associated with leukemia.
The lecture discusses leukocytic disorders, focusing on acute and chronic leukemia, including acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL). It covers their diagnosis, clinical manifestations, etiology, and morphological characteristics, emphasizing the importance of blood and marrow morphology in diagnosis. The document also highlights the incidence rates, risk factors, and common genetic lesions associated with leukemia.
Original Description:
Don’t come at me I’m just a broke med student who needs notes
The lecture discusses leukocytic disorders, focusing on acute and chronic leukemia, including acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL). It covers their diagnosis, clinical manifestations, etiology, and morphological characteristics, emphasizing the importance of blood and marrow morphology in diagnosis. The document also highlights the incidence rates, risk factors, and common genetic lesions associated with leukemia.
The lecture discusses leukocytic disorders, focusing on acute and chronic leukemia, including acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL). It covers their diagnosis, clinical manifestations, etiology, and morphological characteristics, emphasizing the importance of blood and marrow morphology in diagnosis. The document also highlights the incidence rates, risk factors, and common genetic lesions associated with leukemia.
The objective of the lecture is to discuss acute and chronic leukaemia
Topic outcomes At the end of the lecture, students should be able to
21.1. diagnose the types of acute myelogenous leukaemia (AML) by relating it to the aetiology, clinical manifestation, blood and marrow morphology. 21.2. diagnose the types of acute lymphoblastic (ALL) by relating to the aetiology, clinical manifestation, blood, and marrow morphology. 21.3. diagnose chronic lymphocytic leukaemia (CLL) by relating to the aetiology, clinical manifestation, blood and marrow morphology Malaysia incidence rate Leukemia: 2.9 per 100,000 population Leukemia
Leukemia is a malignant disorder of white blood cells caused
by acquired oncogenic mutations that impede the differentiation, leading to the accumulation of immature or matured cells in the bone marrow and peripheral blood. Classification of Leukaemia Pathogenesis of Leukaemia Leukaemia: Major Subtypes Morphologic characteristics of the blast cells Acute Myeloid Leukemia (AML) Acute myeloid leukemia (AML) is a tumor of hematopoietic progenitor cells caused by acquired oncogenic mutations that impede differentiation, leading to the accumulation of immature myeloid blasts in the marrow
Diagnosis of AML: FAB: 30% or more blast cells in bone marrow WHO: >20% blasts in the bone marrow
Peripheral WBC count frequently increased, but can be
syndrome (MDS), Myeloproliferative disease (MPD) 2. Congenital syndrome: Down’s syndrome Fanconi anaemia 3. Chemotherapeutic agents: used in treatment of cancer 4. Radiation: Therapeutic radiotherapy, nuclear reactor accidents 5. Chemical exposure: occupational exposure to benzene at work place 6. Smoking: AML linked to cigarette smoking which contains Benzene and other known carcinogens Pathogenesis of AML FAB Classification of AML Based on • The type of cell from which the leukemia developed • The level of morphology and maturity of the leukemic cells FAB Classification of AML WHO Classification of AML Clinical Presentation of AML Clinical symptoms are result of bone marrow failure or organ infiltration or both
Anemia: fatigue, dyspnea on exertion, dizziness
Neutropenia: fever, risk of infection depending on degree of neutropenia Thrombocytopenia: bleeding gums, nose, GIT petichae, ecchymosis. Symptoms of organ infiltration: bone pain, hepato- splenomegaly, Lymphadenopathy, gum swelling and bleeding and gingivitis Diagnostic Approach for AML Peripheral Blood Film in AML
• Total leukocyte count: variable, leucocytosis to leukopenia
• Increased number of blasts: 0-100%. • Absence of blast: (aleukaemic) • Platelets: ↓ • Hb: ↓ • RBC: Generally normocytic normochromic anemia Bone Marrow: Acute Myeloid Leukemia
Normal BM BM AML
• BM is hypercellular and shows a diffuse infiltration by
immature myeloid cells: Myeloblasts • More then > 20-30% myeloblasts, in marrow. Normal bone marrow contains 0-5% blasts. • Megakaryocytes decreased or absent • Erythroid series suppressed Classification of Lymphoid Neoplasm Acute Lymphoblastic Leukaemia (ALL)
• ALL is malignant disease of the lymphopoietic system that
is manifested by the uncontrolled growth of abnormal, poorly differentiated lymphoid cells. • ALL is a primary disease of young children (peak 2-5 years). • The malignant lymphocytes replace normal hematopoietic tissue in the bone marrow, spleen and liver. • The predominant cell in the bone marrow and peripheral blood are lymphoblasts Morphological Classification (FAB) of ALL
• ALL-L1: Children 2-15 years
• ALL-L2: Older children and adult • ALL- L3: Patients with leukemia secondary to Burkitt's lymphoma.
The types are defined based on two criteria
(1) the occurrence of individual cytologic features
2) the degree of heterogeneity among the leukemic cells
based on cell size, chromatin, nuclear shape, nucleoli, and degree of basophilia in the cytoplasm and the presence of cytoplasmic vacuolation. Morphological (FAB) Classification of ALL Morphological (FAB) Classification of ALL ALL-L1
L1: Homogenous (small cell):
• Homogenous cells • Small cells predominant, nuclear shape is regular with occasional cleft. • Best prognosis. • Accounts 70% of patients. • Common in children, with 75% of cases occurring below 15 years of age or younger ALL-L2: Heterogenous (Large Cell):
• Large cells with an irregular nuclear shape
• One or more large nucleoli are visible. • Cytoplasm varies in colour and nuclear membrane irregularities. • L2 accounts 27% of ALL patients. • Approximately 66% of seen in patients older than 15 years ALL-L3: Burkitt's Lymphoma Type
• Cells are large and homogenous in size
• Nuclear shape is round or oval. • 1-3 prominent nucleoli are present. • Cytoplasm is deeply basophilic with vacuoles. • Patients with L3 have a poor prognosis • By immunologic markers, these are B-cell malignancies. • L3 cells exhibit high mitotic index WHO Classification of ALL Etiology-ALL Most of the time, no clear cause can be found for ALL
The following risk factor have been identified
1. Radiation Exposure: high level radiation, X ray exposure in first few
month of development
2. Chemical Exposure: Hair dye, Benzene, chemotherapeutic agents
3. Viral Infection: HTLV, EBV
4. Genetic syndromes: Down syndrome, Bloom syndrome, Fanconi anemia
5. Race & gender: In males more common
Caucasian more than blacks
6. Others: Environmental pollution, Cigarette smoking, long exposure to
gasoline, diesel, pesticides ALL-Clinical features
Symptoms are related to direct infiltration of BM or other organs
by leukemic cells or symptoms produced by decreased production of normal cells.
• Fever: most common with or without any evidence of infection.
• Anemia: fatigue, dizziness, palpitation, dyspnea upon mild exertion. • Bleeding: result of thrombocytopenia due to marrow infiltration • Lymphadenopathy in B ALL; large mediastinal mass in T ALL. • Bone pain: Due to infiltration of marrow • Splenomegaly: Left upper quadrant fullness and early satiety due to splenomegaly. PB Picture in ALL
• Peripheral blood generally shows anemia, thrombocytopenia,
and leukocytosis. • DLC (differential leukocyte count) shows large number of circulating lymphoblasts (generally in excess of 20%) having round to convoluted nuclei, high nucleo-cytoplasmic ratio and absence of cytoplasmic granularity. BM (Bone marrow)-ALL
• Bone marrow examination shows 20-95% malignant
undifferentiated lymphoblasts
• Megakaryocytes are usually reduced or absent.
Chronic Lymphocytic Leukaemia (CLL)
• Common in older age group, rare under the age of 35.
• More common in men. • Characterized by proliferation of small, abnormal, mature B lymphocytes, often leading to decreased synthesis of immunoglobulin and depressed antibody response. • The number of mature lymphocytes in peripheral blood smear and bone marrow are greatly increased Morphological Classification of CLL Risk Factors: CLL
• Age. Most people diagnosed with chronic lymphocytic
leukemia are older than 60. • Sex. Men are more likely than are women to develop chronic lymphocytic leukemia. • Race. Whites are more likely to develop chronic lymphocytic leukemia than are people of other races. • Family history of blood and bone marrow cancers. A family history of chronic lymphocytic leukemia or other blood and bone marrow cancers may increase your risk. • Exposure to chemicals. Certain herbicides and insecticides, including Agent Orange used during the Vietnam War, have been linked to an increased risk of chronic lymphocytic leukaemia. CLL: Clinical Features
• Asymptomatic, except lymphocytosis
• Discovered incidentally. • Superficial lymphadenopathy and splenomegaly are common especially late in the disease • Hypogammaglobulinemia is also common late in the disease course with an associated increased susceptibility to infection. • Abour 10% patients have an IgM monoclonal gammopathy • Anemia and thrombocytopenia may indicate marrow replacement or autoimmune destruction • Skin Lesions-Herpes zoster Lab findings in CLL 1. Peripheral Blood A. Anemia: mild to moderate normocytic normochromic anemia B. Thrombocytopenia: mild C. White blood cells: marked leukocytosis (50,000-200,000/ul), more than 90% of them are matured lymphocytes. 2. Bone marrow examination: A. Increased lymphocyte count ( 25-95%) B. Decreased myeloid precursors C. Decreased erythroid precursor 3. Immunophenotyping: Pre-B cell CLL: positive for B cell markers CD19, CD10, CD9a Pre-T cell CLL: positive for T cell markers CD1, CD2, CD3, CD5 and CD7 4. Lymph node involvement: infiltration of lymph node with matured lymphocytes PB Picture in CLL
• Anaemia is mild to moderate and normocytic normochromic in type.
• Mild reticulocytosis may be present. • There is marked leucocytosis. Usually, more than 90% of leucocytes are mature small lymphocytes. • Smudge cells are present due to damaged nuclei of fragile malignant lymphocytes. • The absolute neutrophil count could be within normal range. • Granulocytopenia occurs when disease is fairly advanced. CLL-Bone Marrow
• The bone marrow is often replaced by small lymphocytes. Lymphocytes
consist of more than 40% of all nucleated cells. • Three patterns of lymphocyte infiltration, Diffuse, Nodular or Interstitial could be seen. • The diffuse infiltration suggests a worse prognosis Common Genetic Lesions Linked to Leukemia
