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Handout # 1

Acute leukemias
Leukemia type
Acute Myelogenous Leukemia (AML) Definition: A disorder of stem cell in the bone marrow. May involve different myeloid stem cells giving rise to different types of AML. For example: it may involve CFU GEMM --> AML M0 Granulocytic cell --> M1 to M3 CFU GM --> M4 Monocytic stem cell --> M5 Erythroid stem cell --> M6 Megakaryocytic stem cell --> M7 M0 : Minimally differentiated AML M1 : AML without maturation M2 : AML with maturation M3 : Acute promyelocytic leukemia *** M4 : Acute myelomonocytic leukemia M5 : Acute monocytic leukemia M6 : Acute erythroleukemia M7 : Acute megakaryocytic leukemia

Pathogenesis
Basically a malignant disorder of Stem cell in BM Risk factors: Irradiation Benzene Down syndrome

Clinical findings
Most common type of leukemia between 15-39 years of age. Majority present with bleeding (thrombocytopenia), Fever (infection), fatigue and bone pain.

Laboratory findings

CBC: Normocytic anemia WBC findings: Count: <10,000 to 100,000 Myeloblast commonly present AML M0 : no Auer rods in myeloblasts; only show positivity for Platelets: reduced (thrombocytopenia Bone marrow: myeloid CD markers Packed with myeloblasts AML M1: rare Auer Rods present in myeloblasts Blast count > 30% AML M3: Most common AML; Auer rods commonly found, associated with t(8;21) --> better prognosis A Typical Myeloblast: AML M3 : Numerous Auer rods and lots of cytoplasmic granules ; neoplastic cells are promyelocytes (considered as Has large nucleus with few nucleoli Contains cytoplasmic granules blasts) ' Most common leukemia associated with DIC; Characteristic translocation : t(15;17) ; 15 has PML gene, 17 Shows presence of Auer rods Stains positive for MPO and SBB has RAR alpha gene (codes for retinoic acid receptor). Stains Negativly for TdT and PAS Translocations disrupts this. High doses of vitamin A may CD markers: induce remission. Positive for myeloid markers CD13, 14,33 etc AML M4 : presence of both myeloblasts and Monoblasts Negative for CD 10, 19,20 (B cell markers) and CD 2,3,1 (T cell AML M5: majprity of cell are monoblasts (positive for non markers) specific esterase), gum infiltration is characterisitic AML M6: Erythroblasts and myeloblasts AML M7: megakaryoblasts

Acute Lymphoblastic leukemia (ALL) Definition: Stem cell disorder arising from lymphoid stem cells Classification: FAB classification: L1: L2: L3: leukemic form of Burkitt's lymphoma Immunological classification: B-ALL Early pre B : CALLA ag positive; MC type Pre B Mature B T-ALL : Tdt positive

Disorder of Lymphoid stem cells

ALL is most common leukemia and overall cancer in children. Most children <15 years (mean age 4 yrs) Accounts for 15% of adult leukemia Fever and bone pain Generalized lymphadneopathy Epistaxis and ecchymoses from thrombocytopenia Hepatosplenomegaly Testicular and CNS involvement T-ALL : presents as a mediastinal mass in young male boys of 15-20 yrs age.

CBC: Normocytic anemia WBC findings: Count: <10,000 to 100,000 Lymphoblast commonly present Platelets: reduced (thrombocytopenia Bone marrow: packed with lymphoblasts Blast count> 30% A Typical Lymphblast: Has large nucleus with inconspicous nucleoli Scant amount of cytoplasm No cytoplasmic granules Tdt positive PAS positive MPO and SBB negative Early pre B lymphoblast: CD 10 positive (CALLA) Pre B lymphoblast : CD 10 negative T lymphoblast: CD10 negative, CD 2,3,5 7 positive

Handout # 2

Definition
Chronic Myeloid Leukemia (CML) Definition: neoplastic proliferation of pluripotent stem cell. With predominant involvement of granulocytic series of cells.

Pathogenesis
Risk factors: Radiation (1945 atomic bomb) Benzene Chromosome abnormality: t(9;22) Translocation of abl from 9 to 22 with fusion at break point cluster region (bcr) Formation of bcr-abl fusion gene --> tyrosine kinase activity Chromosome 22 is called Philadelphia chromosome

Chronic leukemias Clinical findings


Common leukemia between 40-60 years of age. Signs of anemia: malaise, fatigue Hypermetabolic state: associated with hyperuricemia, fever, weight loss and sweating. Massive splenomegaly : Dragging sensation in abdomen ; Hepatomegaly Soft tissue collections of leukemic cells: called chloromas

Chronic lymphocytic leukemia (CLL): Most commonly arises from virgin B cells.

Neoplastic disorder of virign B cells (cannot differentiate into plasma cells --> hypogammaglobulinemia

Most common overall leukemia Most common leukemia in patients over 60 years. MC cause of generalized nonpainful lymphadenopathy in an elderly patient. 25% asymptomatic at presentation Generalized nonpainful lymphadenopathy Hepatosplenomegaly Increased incidence of autoimmune hemolytic anemia, autoimmune thrombocytopenia, hypogammaglobulinemia Most common in Japan and Caribbean Generalized lymphadenopathy Hepatosplenomegaly Skin infiltration Lytic lesion in bone --> hypercalcemia Most common in middle agen men Splenomegaly is the most common physical finding Lymphadenopathy is absent Increased incidence of Mycobacterium avium intracellulare

Adult T cell leukemia (ATCL) Definition: malignant T cell leukemia associated with HTLV-1 infection Hairy cell leukemia (HCL) Malignancy of B cells

Handout # 2

Laboratory findings
Normocytic normochromic anemia WBC findings: Marked increase in count (50,000 to 200,000) Mature and immature WBCs (myelocyte most abundant cell) Increased basophils and eosinophi. Myeloblast: less than 10% of total cells Platelets: thrombocytosis / thrombocytopenia (50/50) Bone marrow: hypercellular, increased M/E ratio, fibrosis common in late stages Chromosome studies: Philadelphia chromosome (positive in 95% cases), bcr-abl fusion gene (positive in 100% cases) LAP score: low WBC findings: absolute lymphocytosis (15,000 200,000) with smudge cells (fragile lymphoid cells). Platelets: thrombocytopenia Bone marrow: infiltrated by neoplastic lymphoid cells Miscellaneous: hypogammaglobulinemia

Lymphoblast with T cell marker. Tumor cells have flower shaped or 4 clover leaf shaped nucleus

Pancytopenia is characteristic WBC findings: malignant B cells with hairy projections. Positive Tartrate resistant acid phosphatase stain (TRAP stain) Bone marrow: packed with malignat cells that resemble fried eggs, with ample cytoplasm and small nucleus (yolk).

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