Chapter 11 Acute Leukemias Definition of Leukemia Leukemia mutation of stem cells that causes impaired production of normal RBCs WBCs and platelets Initial evaluation Symptoms CBC Cell lineage Cell maturity what stage of differentiation Acute blocking and differentiation takes place early Immature Chronic allowed to differentiate More mature Usually seen in adults Definition of Leukemia Neoplastic cells crowding bone marrow causes a decrease in platelets and red cell count Spleen becomes site of extramedullary hematapoeisis Leukemias categorized based on cell lineage and maturity Acute myeloid leukemias Acute lymphoblastic leukemias Chronic myelocytic leukemias Chronic lymphocytic leukemias Acute Myeloid Leukemia AML Usually caused by chromosomal translocation which causes abnormal oncogene expression May be caused by genetics or toxic exposure i e chemicals Diagnosis based on Cytochemical stains Electron microscopy Cytochemistry including flow cytometry Clinical Features of AL Cells are dysfunctional and may lead to Fever physiological response Infection Anemia occurs and leads to Fatigue Weakness Thrombocytopenia causes Easy bruising in capillaries Petechiae Mucosal bleeding Clinical Features of AML AML also leads to Headache Blindness Gum infiltration Joint pain i e rheumatory arthritis Heart palpitations Clincial Features of AML Peripheral blood Blood counts are variable Blasts are present depending on nature Auer rods monoblasts myeloblasts or promyelocyte inclusions May see anemia and giant platelets nRBCs present Pseudohyposegmentation Hypersegmentation of neutrophils Diagnosis of AML In order to diagnose AML 200 WBCs should be classified Hypercellular bone marrow 20 or greater myeloblasts found in marrow or blood Myeloblasts distinguished by Auer rods Cytochemical stains Surface markers clustered antigen binding profiles Cytochemical Stains Cytochemical stains used to classify acute leukemias and usually negative for lymphoid cells Usually performed on bone marrow smears Positive reactions that occur will be associated with a particular lineage Identified lipids or enzyme within blast population Cytochemical Stains Myeloperoxidase MPO Promyelocytes myelocytes metamyelocytes and band and segmented neutrophils will stain strongly positive Negative reaction differentiates ALL from AML Sudan Black B Stains phospholipids and other intracellular lipids Negative in lymphocytes Differentiates ALL from AML Sensitive for granulocyte precursors Cytochemical Stains Specific esterase naphthol AS D chloroacetate esterase Primary granules of myeloid cells Myeloblasts neutrophils basophils and mast cells stain positive Eosinophils monocytes and lymphocytes stain negative Cytochemical Stains Nonspecific esterase alpha naphthyl butyrate or alpha naphthyl acetate esterase Monocytes stain negative while other activity remains positive Used to identify monoblasts and monocytes in acute monoblastic leukemia and acute myelomonocytic leukemia Cytochemical Stains Terminal deoxynucleotidyl transferase Tdnt Intranuclear enzyme found in stem cells and immature lymphoid cells within the bone marrow Not found in mature B lymphocytes Immunophenotype Immunophenotyping used to classify the clone of leukemic blasts using antibodies against cell surface markers i e proteins Particular nomenclature for the type of leukemia based on Morphologic information Immunophenotypic information Cytochemical information Unique presentation carrier type analysis Classification Acute leukemias organized according to the cell line and stage of maturation that predominates French American British FAB group developed system of nomenclature Developed through the years Acute myeloid leukemias M0 M7 Acute lymphoid leukemias L1 L3 Not well defined for individual subtypes Requisite blast percentage for FAB classification is 30 in bone marrow Classification FAB had limitations World Health Organization WHO proposed new classification for the acute myeloid leukemias Four main WHO groups AML with recurrent cytogenetic abnormalities change in genetic profile is consistent AML with myelodysplasia 1 abnormal clone Therapy related AML and MDS AML not otherwise categorized Required blast percentage is 20 in blood or marrow Acute Myeloid Leukemia with Recurrent Recurrent Genetic Abnormalities Abnormalities Important features of group Recurrent genetic abnormality Favorable prognosis Commonly reciprocal translocations Acute Myeloid Leukemia with Recurrent Recurrent Genetic Abnormalities Abnormalities Acute myeloid leukemia with t 8 21 q22 q22 Most often in children or young adults Myeloblasts present Azurophilic granules Chediak Higashi granules Auer rods are common Maturation in the neutrophil lineage Acute Myeloid Leukemia with Recurrent Recurrent Genetic Abnormalities Abnormalities Acute myeloid leukemia with t 8 21 q22 q22 cont Dysplastic neutrophilic features Pseudo Pelger Huet Hyposegmentation Hypogranulation Eosinophils are often increased Monocyte percentages are usually decreased Acute Myeloid Leukemia with Recurrent Recurrent Genetic Abnormalities Abnormalities Acute myeloid leukemia with inv 16 p13q22 or t 16 16 p13 q22 Most often in younger patients Various stages of monocytic granulocytic and eosinophilic maturation Abnormally large granules in the immature eosinophils Most cases present with eosinophilia increased presence of eosinophils in the blood Monoblasts and promonocytes will stain positive for NSE Acute Myeloid Leukemia with Recurrent Recurrent Genetic Abnormalities Abnormalities Acute promyelocytic leukemia AML with t 15 17 q22 q12 Most often in middle aged patients Abnormal hypogranular promyelocytes Numerous Auer rods in myeloblasts and promyelocytes Bundles of Auer rods may be seen faggot cells Strong MPO reaction Acute Myeloid Leukemia with Recurrent Recurrent Genetic Abnormalities Abnormalities Acute myeloid leukemia with 11q23 Occurs more often in children Monoblasts and promonocytes predominate Monoblasts have abundant cytoplasm Often show pseudopodia Fine nuclear chromatin with one or more nuclei Azurophilic granules Cytoplasmic vacuoles NSE strongly positive MPO often negative AML with Myelodysplasia Primarily seen in adults Blast percentage is 20 Dysplasia in at least two cell lines Dysplastic feature in neutrophils Hypogranulation Hyposegmentation Pseudo Pelgeroid Bizarre segmented nuclei AML with Myelodysplasia Dysplastic feature in erythroid cells Nucleated red cells Megaloblastic features Ringed