Myeloid neoplasms: myeloproliferative neoplasms

10 ASCP MLS practice questions on Myeloid neoplasms: myeloproliferative neoplasms, part of Hematology. The first 10 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Hard

   A 32-year-old woman who takes an oral contraceptive has abdominal pain and new ascites, and imaging shows hepatic vein thrombosis. Results: Hb 13.6 g/dL [136 g/L], Hct 41% [0.41 L/L], WBC 9.6 × 10^3/µL [9.6 × 10^9/L], platelets 362 × 10^3/µL [362 × 10^9/L] and reticulocytes 1.2%; the spleen is enlarged. LD and haptoglobin are normal, PNH flow cytometry finds no GPI-deficient cells, factor V Leiden and prothrombin G20210A are not detected, and antiphospholipid antibodies are negative. JAK2 V617F is detected at an allele burden of 9%. What is the best interpretation of these results?

   1. AUnderlying myeloproliferative neoplasm
   2. BParoxysmal nocturnal hemoglobinuria
   3. CA false-positive JAK2 result
   4. DThrombosis from the contraceptive alone

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   Answer: A · Underlying myeloproliferative neoplasm

   JAK2 V617F is found in a large share of patients with hepatic or portal vein thrombosis, and in this setting it points to an underlying myeloproliferative neoplasm even when the blood counts look normal. The counts can be held down by an enlarged spleen that pools cells, by the larger plasma volume of portal hypertension, and by bleeding or iron deficiency, so the usual raised hematocrit or platelet count may be missing. A negative PNH test, a normal LD and haptoglobin and negative inherited and antiphospholipid tests make the JAK2 result the key finding. An oral contraceptive adds risk but does not explain a clonal JAK2 mutation, and low allele burdens are typical in this setting. A marrow biopsy then helps classify the neoplasm.

   • B: PNH flow cytometry finds no GPI-deficient cells, and there is no hemolysis.
   • C: A 9% allele burden is a real clonal result; low burdens are typical in splanchnic vein thrombosis.
   • D: The contraceptive adds risk, but it does not explain a clonal JAK2 mutation.

2. Question 2 · Hard

   A 47-year-old man has Hb 20.1 g/dL [201 g/L] and Hct 61% [0.61 L/L], with normal WBC and platelet counts. Serum erythropoietin is low, and JAK2 V617F is not detected. Which test should be done next?

   1. AQuantitative BCR::ABL1 RT-PCR
   2. BMPL exon 10 sequencing
   3. CCALR exon 9 sequencing
   4. DJAK2 exon 12 sequencing

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   Answer: D · JAK2 exon 12 sequencing

   A raised hemoglobin with low erythropoietin points to polycythemia vera, a primary erythrocytosis. About 95% of PV cases carry JAK2 V617F, and nearly all the rest carry mutations in JAK2 exon 12. Exon 12 cases often present with isolated erythrocytosis, as here, without high white cell or platelet counts. CALR and MPL mutations are found in ET and PMF but not in PV.

   • A: BCR::ABL1 defines CML, which does not present as isolated erythrocytosis.
   • B: MPL mutations occur in ET and PMF, not in PV.
   • C: CALR mutations occur in ET and PMF, not in PV.

3. Question 3 · Hard

   A man treated for chronic myeloid leukemia for 4 years now has 42% blasts in the blood. The blasts are MPO negative and express CD19, CD10, CD34 and TdT. The best interpretation is:

   1. ACML in accelerated phase
   2. BCML in myeloid blast phase
   3. CCML in B-lymphoid blast phase
   4. DNew T-lymphoblastic leukemia

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   Answer: C · CML in B-lymphoid blast phase

   With 20% or more blasts, CML has progressed to blast phase. About 70% of blast phases are myeloid, but 20% to 30% are lymphoid, mostly B-lineage, as shown here by CD19, CD10 and TdT without MPO. Lymphoid blast phase matters because it is treated with ALL-type therapy plus a tyrosine kinase inhibitor. The blasts still carry BCR::ABL1, often with additional genetic changes.

   • A: Accelerated phase, where still used, has 10% to 19% blasts; 42% is blast phase.
   • B: Myeloid blasts would be MPO positive or express CD13, CD33 or CD117.
   • D: CD19 and CD10 mark B-lineage cells, not T-lineage cells.

4. Question 4 · Hard

   A 58-year-old woman has platelets of 980 × 10^3/µL [980 × 10^9/L] on repeated testing, a normal hemoglobin, and WBC 11.0 × 10^3/µL [11.0 × 10^9/L] without basophilia. Iron studies and CRP are normal, and JAK2, CALR and MPL are all negative. Which test is needed to exclude another myeloproliferative neoplasm that can mimic ET?

   1. ABCR::ABL1 testing
   2. BHemoglobin electrophoresis
   3. COsmotic fragility testing
   4. DSerum erythropoietin

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   Answer: A · BCR::ABL1 testing

   CML can present with marked thrombocytosis and few other changes, and its treatment is completely different. WHO criteria for ET therefore require BCR::ABL1-positive CML to be excluded, by FISH or RT-PCR. A triple-negative result does not rule out ET, since about 10% to 15% of cases lack all three driver mutations. A marrow biopsy is also needed to separate ET from prefibrotic myelofibrosis.

   • B: Hemoglobin electrophoresis looks for hemoglobin variants and thalassemia.
   • C: Osmotic fragility testing is for hereditary spherocytosis.
   • D: Erythropoietin helps evaluate erythrocytosis, and the hemoglobin here is normal.

5. Question 5 · Medium

   In primary myelofibrosis, the blood shows teardrop cells, nucleated red cells and immature granulocytes mainly because:

   1. AIron deficiency distorts red cell shape
   2. BAutoantibodies damage the red cell membrane
   3. CFibrosis moves blood formation into the spleen
   4. DFibrin strands in vessels cut the red cells

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   Answer: C · Fibrosis moves blood formation into the spleen

   In PMF, cytokines from abnormal megakaryocytes drive reticulin and collagen fibrosis of the marrow. Blood formation shifts to the spleen and liver, and these sites, with the distorted marrow, release nucleated red cells and immature granulocytes early. Red cells deformed while squeezing through the fibrotic marrow and spleen become teardrop cells (dacrocytes). This leukoerythroblastic picture with dacrocytes and a dry tap is the classic pattern.

   • A: Iron deficiency gives microcytic, hypochromic cells, not a leukoerythroblastic picture.
   • B: Autoantibodies cause spherocytes in immune hemolysis.
   • D: Fibrin strands in small vessels cause schistocytes in microangiopathic hemolysis.

6. Question 6 · Easy

   The Philadelphia chromosome of chronic myeloid leukemia is formed by a translocation between chromosomes:

   1. A8 and 21
   2. B15 and 17
   3. C8 and 14
   4. D9 and 22

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7. Question 7 · Medium

   In essential thrombocythemia and primary myelofibrosis without a JAK2 mutation, the most common driver mutation is in:

   1. ABCR::ABL1
   2. BCALR
   3. CMPL
   4. DSF3B1

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8. Question 8 · Medium

   Why are tyrosine kinase inhibitors such as imatinib so effective in chronic myeloid leukemia?

   1. AThe drugs make promyelocytes mature
   2. BCML cells have lost a working TP53 gene
   3. CCML depends on an always-active BCR::ABL1 kinase
   4. DThe drugs switch off mutant JAK2 signaling

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9. Question 9 · Hard

   After 12 months of imatinib for CML, the BCR::ABL1 level is 0.08% on the International Scale (IS). This result is best described as:

   1. AAbove the 12-month target (warning)
   2. BDeep molecular response (MR4.5)
   3. CTreatment failure
   4. DMajor molecular response

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10. Question 10 · Medium

    Which finding best supports chronic myeloid leukemia rather than a leukemoid reaction?

    1. AA left shift during a severe infection
    2. BToxic granulation and Döhle bodies
    3. CA high neutrophil alkaline phosphatase score
    4. DThe BCR::ABL1 fusion with an absolute basophilia

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