1.6 Acute Leukemias (H)

• Auer rods may be seen in all of the following except:

  
  

  A. Acute myelomonocytic leukemia (M4)

  B. Acute lymphoblastic leukemia

  C. Acute myeloid leukemia without maturation (M1)

  D. Acute promyelocytic leukemia (M3)

  B

  
  

  Auer rods are not seen characteristically in lymphoblasts. They may be seen in myeloblasts, promyelocytes, and monoblasts.
• Which type of anemia is usually present in a patient with acute leukemia?

  
  

  A. Microcytic, hyperchromic

  B. Microcytic, hypochromic

  C. Normocytic, normochromic

  D. Macrocytic, normochromic

  C

  
  

  Acute leukemia is usually associated with a normocytic normochromic anemia. Anemia in acute leukemia is usually present from the onset and may be severe; however, there is no inherent nutritional deficiency leading to either a microcytic, hypochromic, or megaloblastic process.
• In leukemia, which term describes a peripheral blood finding of leukocytosis with a shift to the left, accompanied by nucleated red cells?

  
  

  A. Myelophthisis

  B. Dysplasia

  C. Leukoerythroblastosis

  D. Megaloblastosis

  C

  
  

  The presence of immature leukocytes and nucleated red cells is called leukoerythroblastosis and frequently denotes a malignant or myeloproliferative process. Myelophthisis refers to replacement of bone marrow by a disease process such as a neoplasm. The development of abnormal tissue is called dysplasia.
• The basic pathophysiological mechanisms responsible for producing signs and symptoms in leukemia include all of the following except:

  
  

  A. Replacement of normal marrow precursors by

  leukemic cells causing anemia

  B. Decrease in functional leukocytes causing

  infection

  C. Hemorrhage secondary to thrombocytopenia

  D. Decreased erythropoietin production


  D

  
  

  A normal physiological response to anemia would be an increase in the kidney's production of erythropoietin. The accumulation of leukemic cells in the bone marrow leads to marrow failure, which is manifested by anemia, thrombocytopenia, and granulocytopenia.
• Which type of acute myeloid leukemia is called the true monocytic leukemia and follows an acute or subacute course characterized by monoblasts, promonocytes, and monocytes?

  
  

  A. Acute myeloid leukemia, minimally differentiated B. Acute myeloid leukemia without maturation

  C. Acute myelomonocytic leukemia

  D. Acute monocytic leukemia

  D

  
  

  Acute monocytic leukemia has an incidence of between 1%-8% of all acute leukemias. It has a distinctive clinical manifestation of monocytic involvement resulting in skin and gum hyperplasia. The WBC count is markedly elevated, and prognosis is poor.
• In which age group does acute lymphoblastic leukemia occur with the highest frequency?

  
  

  A. 1-15 years

  B. 20-35 years

  C. 45-60 years

  D. 60-75 years

  A

  
  

  Acute lymphoblastic leukemia (ALL) usually affects children from ages 1-15 and is the most common type of acute leukemia in this age group. In addition, ALL constitutes the single most prevalent malignancy in pediatric patients.
• Disseminated intravascular coagulation (DIC) is most often associated with which of the following types of acute leukemia?

  
  

  A. Acute myeloid leukemia without maturation

  B. Acute promyelocytic leukemia

  C. Acute myelomonocytic leukemia

  D. Acute monocytic leukemia

  B

  
  

  The azurophilic granules in the leukemic promyelocytes in patients with acute promyelocytic leukemia contain thromboplastic substances. These activate soluble coagulation factors, which when released into the blood, cause DIC.
• An M:E ratio of 10:1 is most often seen in:

  A. Thalassemia

  B. Leukemia

  C. Polycythemia vera

  D. Myelofibrosis

  B

  
  

  A disproportionate increase in the myeloid component of the bone marrow is usually the result of a leukemic state. The normal M:E ratio is approximately 4:1 in adults with normal cellularity.
• Which of the following is a characteristic of Auer rods?

  
  

  A. They are composed of azurophilic granules

  B. They stain periodic acid-Schiff (PAS) positive

  C. They are predominantly seen in chronic

  myelogenous leukemia (CML)

  D. They are nonspecific esterase positive

  A

  
  

  Auer rods are a linear projection of primary azurophilic granules, and are present in the cytoplasm of myeloblasts and monoblasts in patients with acute leukemia.
• SITUATION: The following laboratory values are seen:

  WBCs = 6.0 × 109/L

  RBCs = 1.90 × 1012/L

  Platelets = 130 × 109/L

  Serum vitamin B12 and folic acid: normal

  Hbg = 6.0 g/dL

  Hct = 18.5%

  
  

  WBC Differential - Bone Marrow

  6% PMNs - 40% myeloblasts

  40% lymphocytes - 60% promegaloblasts

  4% monocytes - 40 megaloblastoid NRBCs/100 WBCs

  50% blasts - n/a

  
  

  These results are most characteristic of:

  
  

  A. Pernicious anemia

  B. Acute myeloid leukemia without maturation C. Acute erythroid leukemia

  D. Acute myelomonocytic leukemia

  C

  
  

  In acute erythroid leukemia, more than 50% of nucleated bone marrow cells are erythroid and more than 30% nonerythroid cells are blasts. Pernicious anemia results in pancytopenia and low vitamin B12 concentrations.
• A 24-year-old man with Down syndrome presents with a fever, pallor, lymphadenopathy, and hepatosplenomegaly. His CBC results are as follows:

  
  

  WBCs = 10.8 × 109/L

  8% PMNs

  25% lymphocytes

  67% PAS-positive blasts

  RBCs = 1.56 × 1012/L

  Hgb = 3.3 g/dL

  Hct = 11%

  Platelets = 2.5 × 109/L

  
  

  THese findings are suggestive of:

  A. Hodgkin's lymphoma

  B. Myeloproliferative disorder

  C. Leukemoid reaction

  D. Acute lymphocytic leukemia

  D

  
  

  Common signs of acute lymphocytic leukemia are hepatosplenomegaly (65%), lymphadenopathy (50%), and fever (60%). Anemia and thrombocytopenia are usually present and the WBC count is variable. The numerous lymphoblasts are generally PAS positive.
• SITUATION: A peripheral smear shows 75% blasts. ese stain positive for both Sudan Black B (SBB) and peroxidase. Given these values, which of the following disorders is most likely?

  
  

  A. Acute myelocytic leukemia (AML)

  B. CML

  C. Acute undifferentiated leukemia (AUL)

  D. Acute lymphocytic leukemia (ALL)

  A

  
  

  AML blasts stain positive for Sudan Black B and peroxidase. Usually, fewer than 10% blasts are

  found in the peripheral smear of patients with CML, unless there has been a transition to blast crisis. The organelles in the cells of AUL are not mature enough to stain positive for SBB or peroxidase. Blasts in ALL are characteristically negative with these stains.
• In myeloid cells, the stain that selectively identifies phospholipid in the membranes of both primary and secondary granules is:

  
  

  A. PAS

  B. Myeloperoxidase

  C. Sudan Black B stain

  D. Terminal deoxynucleotidyl transferase (TdT)

  C

  
  

  Phospholipids, neutral fats, and sterols are stained by Sudan Black B. The PAS reaction stains intracellular glycogen. Myeloperoxidase is an enzyme present in the primary granules of myeloid cells and to a lesser degree in monocytic cells. Terminal deoxynucleotidyl transferase is a DNA polymerase found in thymus- derived and some bone marrow-derived lymphocytes.
• Sodium fluoride may be added to the naphthyl ASD acetate (NASDA) esterase reaction. e fluoride is added to inhibit a positive reaction with:

  
  

  A. Megakaryocytes

  B. Monocytes

  C. Erythrocytes

  D. Granulocytes

  B

  
  

  NASDA stains monocytes (and monoblasts) and granulocytes (and myeloblasts). The addition of fluoride renders the monocytic cells (and blasts) negative, thus allowing for differentiation from the granulocytic cells, which remain positive.
• Leukemic lymphoblasts reacting with anti-CALLA are characteristically seen in:

  
  

  A. B-cell ALL

  B. T-cell ALL

  C. Null-cell ALL

  D. Common ALL

  D

  
  

  The majority of non-T, non-B ALL blast cells display the common ALL antigen (CALLA) marker. Lymphoblasts of common ALL are TdT positive and CALLA positive but do not have surface membrane IgM or μ chains and are pre-B lymphoblasts. Common ALL has a lower relapse rate and better prognosis than other immunologic subtypes of B-cell ALL.
• Which of the following reactions are often positive in ALL but are negative in AML?

  
  

  A. Terminal deoxynucleotidyl transferase and PAS

  B. Chloroacetate esterase and nonspecific esterase

  C. Sudan Black B and peroxidase

  D. New methylene blue and acid phosphatase

  A

  
  

  PAS is positive in about 50% of ALL with L1 and

  L2 morphology but is negative in ALL with L3 morphology (B-cell ALL). Terminal deoxynucleotidyl transferase is positive in all types of ALL except L3. Both terminal deoxynucleotidyl transferase and PAS are negative in AML.
• A patient's peripheral blood smear and bone marrow both show 70% blasts. ese cells are negative for Sudan Black B stain. Given these data, which of the following is the most likely diagnosis?

  
  

  A. Acute myeloid leukemia

  B. Chronic lymphocytic leukemia

  C. Acute promyelocytic leukemia

  D. Acute lymphocytic leukemia


  D

  
  

  Sudan Black B stains phospholipids and other neutral fats. It is the most sensitive stain for granulocytic precursors. Lymphoid cells rarely stain positive for it. Because 70% lymphoblasts would never be seen in CLL, the correct response is ALL.
• Which of the following leukemias are included in the 2008 World Health Organization classification of myeloproliferative neoplasms?

  
  

  A. Chronic myelogenous leukemia (CML)

  B. Chronic neutrophilic leukemia (CNL)

  C. Chronic eosinophilic leukemia (CEL)

  D. All of these options are classified as myeloproliferative neoplasms (MPN)

  D

  
  

  The 2008 WHO classification system includes the following disorders under the myeloproliferative neoplasms (MPN): chronic myelogenous leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia (CEL), essential thrombocythemia (ET), polycythemia vera

  (PV), primary (idiopathetic) myelofibrosis, hypereosinophilic syndrome, mast cell disease, and MPNs unclassified.
• In addition to morphology, cytochemistry, and immunophenotyping, the WHO classification of myelo- and lymphoproliferative disorders is based upon which characteristic?

  
  

  A. Proteomics

  B. Cytogenetic abnormalities

  C. Carbohydrate-associated tumor antigen

  production

  D. Cell signaling and adhesion markers

  B

  
  

  In addition to morphology, cytochemical stains, and flow cytometry, the WHO classification relies heavily on chromosomal and molecular abnormalities.
• The WHO classification requires what percentage for the blast count in the blood or bone marrow for the diagnosis of AML?

  
  

  A. At least 30%

  B. At least 20%

  C. At least 10%

  D. Any percentage

  B

  
  

  The WHO classification of AML requires that ≥20% of nucleated bone marrow cells be blasts, while the FAB classification generally requires ≥30%. WHO classifies AML into five subgroups: These are acute myeloid leukemias with recurrent genetic disorders; acute myeloid leukemia with multilineage dysplasia; acute myeloid leukemia and myelodysplastic syndromes, therapy related; acute myeloid leukemia not otherwise categorized; and acute leukemia of ambiguous lineage.
• What would be the most likely designation by the WHO for the FAB AML M2 by the French-American-British classification?

  
  

  A. AML with t(15;17)

  B. AML with mixed lineage

  C. AML with t(8;21)

  D. AML with inv(16)

  C

  
  

  AML with t(8;21) is classified under the category of AML with Recurrent Genetic Abnormalities by the WHO. This translocation occurs in up to 15% of cases of AML and may be the most common translocation. The AML1-ETO translocation occurs chiefly in younger patients and often in cases of acute myeloblastic leukemia with maturation,

  FAB M2. The translocation involves the fusion of the AML1 gene on chromosome 21 with the ETO gene on chromosome 8.
• What would be the most likely designation by the WHO for the FAB AML M3 by the French-American-British classification?

  
  

  A. AML with t(15;17)

  B. AML with mixed lineage

  C. AML with t(8;21)

  D. AML with inv(16)

  A

  
  

  AML with t(15;17) is classified under the category of AML with Recurrent Genetic Abnormalities by the WHO. Acute promyelocytic leukemia (PML; known as M3 under the FAB system) is composed of abnormal promyelocytes with heavy granulation, sometimes obscuring the nucleus, and abundant cytoplasm. Acute promyelocytic leukemia (APL) contains a translocation that results in the fusion of a transcription factor called PML on chromosome

  15 with the alpha (α)-retinoic acid receptor gene (RARα) on chromosome 17.
• Which AML cytogenetic abnormality is associated with acute myelomonocytic leukemia with marrow eosinophilia under the WHO classification of AML with recurrent genetic abnormalities?

  
  

  A. AML with t(15;17)

  B. AML with mixed lineage

  C. AML with t(8;21)

  D. AML with inv(16)

  D

  
  

  AML with inv(16) has pericentric inversion of chromosome 16, and is associated with acute myelomonocytic leukemia with marrow eosinophilia, M4eo under the FAB system. The inv(16) results in the fusion of the CBFβ gene on 16q22 with the MYH11 gene on 16p13.
• What would be the most likely classification by the WHO for the FAB AML M7 by the French-American-British classification?

  
  

  A. Acute myeloid leukemias with recurrent genetic

  abnormalities

  B. Acute myeloid leukemia with multilineage

  dysplasia

  C. Acute myeloid leukemia not otherwise

  categorized

  D. Acute leukemias of ambiguous lineage


  C

  
  

  Acute megakaryoblastic leukemia, which is equivalent to FAB M7, is a relatively uncommon form of leukemia characterized by neoplastic proliferation of megakaryoblasts and atypical megakaryocytes. Recognition of this entity was aided by the use of platelet peroxidase (PPO) ultrastructural studies. PPO, which is distinct from myeloperoxidase, is specific for the megakaryocytic cell line. Acute megakaryoblastic leukemia is defined as an acute leukemia in which greater than or equal to 50% of the blasts are of megakaryocytic lineage.