Acute Leukemias

Question 1

1. Auer rods may be seen in all of the following except:
   A. Acute myelomonocytic leukemia (M4)
   B. Acute lymphoblastic leukemia (ALL)
   C. Acute myeloid leukemia without maturation (AML:M1)
   D. Acute promyelocytic leukemia (PML; M3)

Answer 1

B - Auer rods are not seen characteristically in lymphoblasts. They may be seen in myeloblasts, promyelocytes, and monoblasts.

Question 2

2. 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

Answer 2

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 a microcytic, hypochromic, or megaloblastic process.

Question 3

3. In leukemia, which term describes the peripheral blood finding of leukocytosis with a shift to the left, accompanied by NRBCs?
   A. Myelophthisis
   B. Dysplasia
   C. Leukoerythroblastosis
   D. Megaloblastosis

Answer 3

C - The presence of immature leukocytes and NRBCs 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.

Question 4

4. 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

Answer 4

D - A normal physiological response to anemia would be an increase in the kidney’s production of erythropoietin. The accumulation of leukemic cells in bone marrow leads to marrow failure, which manifests as anemia, thrombocytopenia, and granulocytopenia.

Question 5

5. 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

Answer 5

D - Acute monocytic leukemia has an incidence of 1% to 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.

Question 6

6. In which age group does ALL occur with the highest frequency?
   A. 1–15 years
   B. 20–35 years
   C. 45–60 years
   D. 60–75 years

Answer 6

A - ALL usually affects children from ages 1 to 15 years 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.

Question 7

7. 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 (PML)
   C. Acute myelomonocytic leukemia
   D. Acute monocytic leukemia

Answer 7

B - In patients with acute PML, the azurophilic granules in the leukemic promyelocytes contain thromboplastic substances. When released from promyelocytes, these activate soluble coagulation factors causing DIC.

Question 8

8. An M:E ratio of 10:1 is most often seen in:
   A. Thalassemia
   B. Leukemia
   C. Polycythemia vera (PV)
   D. Myelofibrosis

Answer 8

B - A disproportionate increase in the myeloid component of bone marrow is usually the result of a leukemic state. The normal M:E ratio is approximately 4:1 in adults with normal cellularity.

Question 9

9. Which of the following is a characteristic of Auer rods?
   A. They are composed of azurophilic granules
   B. They stain positive on periodic acid–Schiff (PAS) staining
   C. They are predominantly seen in chronic myelogenous leukemia (CML)
   D. They are nonspecific esterase positive

Answer 9

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.

Question 10

10. SITUATION: The following laboratory values are seen:

WBC = 6.0 × 109/L
RBC = 1.90 × 1012/L
PLT = 130 × 109/L
Hgb = 6.0 g/dL
Hct = 18.5%
Serum vitamin B12 and folic acid: normal

WBC Differential
6% PMNs
40% lymphocytes
4% monocytes
50% blasts

Bone Marrow
40% myeloblasts 60% promegaloblasts
40 megaloblastoid NRBCs/100 WBCs

These results are most characteristic of:
A. Pernicious anemia
B. Acute myeloid leukemia, without maturation
C. Acute erythroid leukemia
D. Acute myelomonocytic leukemia

Answer 10

C - In acute erythroid leukemia, greater than 50% of nucleated bone marrow cells are erythroid and greater than 30% nonerythroid cells are blasts. Pernicious anemia results in pancytopenia and low vitamin B12 concentrations.

Question 11

11. A 24-year-old man with Down syndrome presents with fever, pallor, lymphadenopathy, and hepatosplenomegaly. His CBC results are as follows:
    WBC = 10.8 × 109/L
    RBC = 1.56 × 1012/L 8%
    PMNs Hgb = 3.3 g/dL
    25% lymphocytes
    67% PAS-positive blasts
    Hct = 11%
    PLT = 2.5 × 109/L

These findings are suggestive of:
A. Hodgkin lymphoma
B. Myeloproliferative disorder
C. Leukemoid reaction
D. Acute lymphocytic leukemia

Answer 11

D - Common signs of ALL 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.

Question 12

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. ALL

Answer 12

A - AML blasts stain positive for SBB and peroxidase. Usually, less than 10% blasts are found in peripheral blood smears from 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.

Question 13

13. In myeloid cells, the stain that selectively identifies phospholipid in the membranes of both primary and secondary granules is:
    A. PAS
    B. Myeloperoxidase
    C. SBB
    D. Terminal deoxynucleotidyl transferase (TdT)

Answer 13

C - Phospholipids, neutral fats, and sterols are stained by SBB. 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. TdT is a DNA polymerase found in thymus-derived lymphocytes and some bone marrow–derived lymphocytes.

Question 14

14. Sodium fluoride may be added to the naphthyl ASD acetate (NASDA) esterase reaction. The fluoride is added to inhibit a positive reaction with:
    A. Megakaryocytes
    B. Monocytes
    C. Erythrocytes
    D. Granulocytes

Answer 14

B - NASDA stains monocytes (and monoblasts) and granulocytes (and myeloblasts). The addition of fluoride renders monocytic cells (and blasts) negative, thus allowing for differentiation from granulocytic cells, which remain positive.

Question 15

15. Leukemic lymphoblasts reacting with anti–common acute lymphoblastic leukemia antigen (anti-CALLA) are characteristically seen in:
    A. B-cell ALL
    B. T-cell ALL
    C. Null-cell ALL
    D. Common ALL

Answer 15

D - The majority of non-T, non-B ALL blast cells display the 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 compared with other immunologic subtypes of B-cell ALL.

Question 16

16. Which of the following reactions are often positive in ALL but are negative in AML?
    A. TdT and PAS
    B. Chloroacetate esterase and nonspecific esterase
    C. SBB and peroxidase
    D. New methylene blue and acid phosphatase

Answer 16

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). TdT is positive in all types of ALL except L3. Both TdT and PAS are negative in AML.

Question 17

17. A patient’s peripheral blood smear and bone marrow both show 70% blasts. These cells are negative on SBB staining. Given these data, which of the following is the most likely diagnosis?
    A. AML
    B. Chronic lymphocytic leukemia (CLL)
    C. Acute PML
    D. ALL

Answer 17

D - SBB stains phospholipids and other neutral fats. It is the most sensitive stain for granulocytic precursors. Lymphoid cells rarely stain positive with SBB. Because 70% lymphoblasts would never be seen in CLL, the correct response is ALL.

Question 18

18. Which of the following leukemias are included in the 2008 World Health Organization classification of myeloproliferative neoplasms (MPN)?
    A. CML
    B. Chronic neutrophilic leukemia (CNL)
    C. Chronic eosinophilic leukemia (CEL)
    D. All of these options are classified as MPN

Answer 18

D - The WHO classification system includes the following disorders under MPN: CML, CNL, CEL, essential thrombocythemia (ET), PV, primary (idiopathic) myelofibrosis, hypereosinophilic syndrome, mast cell disease, and MPNs unclassified.

Question 19

19. In addition to morphology, cytochemistry, and immunophenotyping, the WHO classification of myelo- and lymphoproliferative disorders is based on which characteristic?
    A. Proteomics
    B. Cytogenetic abnormalities
    C. Carbohydrate-associated tumor antigen production
    D. Cell signaling and adhesion markers

Answer 19

B - In addition to morphology, cytochemical stains, and flow cytometry, the WHO classification relies heavily on chromosomal and molecular abnormalities.

Question 20

20. The WHO classification requires what percentage for the blast count in blood or bone marrow for the diagnosis of AML?
    A. At least 30%
    B. At least 20%
    C. At least 10%
    D. Any percentage

Answer 20

B - The WHO classification of AML requires that 20% or greater of nucleated bone marrow cells be blasts, whereas the French–American-British (FAB) classification generally requires 30% or greater. The WHO classifies AML into five subgroups: 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.

Question 21

21. What would be the most likely designation by the WHO for AML M2 by the FAB classification?
    A. AML with t(15;17)
    B. AML with mixed lineage
    C. AML with t(8;21)
    D. AML with inv(16)

Answer 21

C - AML with t(8;21) is classified under the category “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.

Question 22

22. What would be the most likely designation by the WHO for AML M3 by the FAB classification?
    A. AML with t(15;17)
    B. AML with mixed lineage
    C. AML with t(8;21)
    D. AML with inv(16)

Answer 22

A - AML with t(15;17) is classified under the category “AML with Recurrent Genetic Abnormalities” by the WHO. Acute PML (known as M3 under the FAB system) is composed of abnormal promyelocytes with heavy granulation, sometimes obscuring the nucleus, and abundant cytoplasm. Acute PML 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.

Question 23

23. Which AML cytogenetic abnormality is associated with AML M4 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)

Answer 23

D - AML with inv(16) has pericentric inversion of chromosome 16 and is associated with M4 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.

Question 24

24. What would be the most likely classification by the WHO for AML M7 by the FAB classification?
    A. Acute myeloid leukemias with recurrent genetic abnormalities
    B. Acute myeloid leukemia with multilineage dysplasia
    C. Acute megakaryoblastic leukemia classified under AML (not otherwise categorized)
    D. Acute leukemias of ambiguous lineage

Answer 24

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 is distinct from myeloperoxidase and is specific for the megakaryocytic cell line. Acute megakaryoblastic leukemia is defined as an acute leukemia in which 50% or greater of the blasts are of megakaryocytic lineage. In the WHO 2016 revision, it is classified under “AML (not otherwise categorized).”