Question 1

The presence of which of the following in the bone marrow would lead a clinician to the diagnosis of a myeloproliferative disorder rather than an acute leukemia?

Accepted Answer

Myeloproliferative disorders are characterized by the overproduction of mature myeloid cells, leading to increased numbers of these cells in the bone marrow and peripheral blood. In contrast, acute leukemias are characterized by the presence of increased numbers of young, dividing cells in the bone marrow. Therefore, the presence of high numbers of proliferating mature cells in the bone marrow would suggest a myeloproliferative disorder.

Question 2

The major cell line involved in the pathogenesis of PMF is which of the following?

Accepted Answer

PMF is a myeloproliferative neoplasm that primarily affects the megakaryocytic cell line. Megakaryocytes are increased in number and size, leading to thrombocytosis and bone marrow fibrosis. Erythrocytic and myelocytic cell lines may also be affected, but megakaryocytic lineage is the major cell line involved in the pathogenesis of PMF. Fibroblasts play a secondary role and contribute to the development of bone marrow fibrosis.

Question 3

What substance(s) is(are) primarily responsible for stimulating the growth and proliferation of fibroblasts in PMF?

Accepted Answer

PDGF is a potent mitogen for fibroblasts and is the primary growth factor responsible for stimulating their growth and proliferation in PMF.

Question 4

A physician strongly suspects CML in a patient and has already ordered a bone marrow differential and cytogenetic analysis for the Philadelphia chromosome. What other test would help confirm the CML picture for this patient?

Accepted Answer

Confirmatory testing for CML would include a molecular assay to detect the BCR/ABL1 fusion gene, which is characteristic of CML. The Philadelphia chromosome (detected by cytogenetic analysis) and bone marrow differential may suggest CML, but confirmation requires identification of the BCR/ABL1 fusion gene. Immunophenotyping with flow cytometry (choice B) may help to differentiate CML from other hematologic malignancies but is not confirmatory. Molecular testing for JAK2 kinase (choice A) is used to diagnose myeloproliferative neoplasms other than CML. PAS staining (choice D) can be used to identify abnormal blasts but is not specific for CML.

Question 5

Increased sensitivity to which cytokine(s) is thought to be partially responsible for the increased megakaryocyte proliferation of ET?

Accepted Answer

Increased sensitivity to IL-3 and IL-6 has been shown to be partially responsible for the increased megakaryocyte proliferation in ET. GM-CSF, EPO, SCF, IL-4, MPL, and CSF-G have not been found to have a significant role in ET pathogenesis.

Question 6

How would you confirm a variant of CML?

Accepted Answer

BCL/ABL fusion is a hallmark of CML, and FISH analysis is a reliable method for confirming its presence in suspected cases. Bone marrow aspirate, cytochemical staining, and drug history may provide additional information but are not specific for confirming the variant of CML.

Question 7

Which is found in >90% of cases of PV and promotes EPO receptor activation?

Accepted Answer

JAK2(V617F) is found in over 90% of cases of PV and promotes EPO receptor activation, leading to the proliferation of erythrocyte precursors and the overproduction of red blood cells. Bcl-x₁ is not relevant to PV. BCR/ABL1 is associated with chronic myeloid leukemia (CML) and RAS mutations are associated with other myeloproliferative neoplasms such as chronic myelomonocytic leukemia.

Question 8

Which of the following are criteria for systemic mastocytosis?

Accepted Answer

All three criteria are necessary for a diagnosis of systemic mastocytosis. Atypical morphology in >25% of mast cells, >25% of all mast cells in the bone marrow immature or atypical, and presence of KIT point mutation in mast cells are all diagnostic criteria for systemic mastocytosis.

Question 9

Explain the significance of the Philadelphia chromosome in ALL.

Accepted Answer

The answer of Explain the significance of the Philadelphia chromosome...

Question 10

The myeloproliferative disorder best described by increased leukocytes, immature granulocytes, and decreased LAP with the Philadelphia chromosome present is which of the following?

Accepted Answer

The description matches Chronic Myelogenous Leukemia (CML), characterized by the Philadelphia chromosome and increased leukocytes, including immature granulocytes. Decreased LAP is also seen in CML. CIMF (Chronic Idiopathic Myelofibrosis), PV (Polycythemia Vera), and ET (Essential Thrombocythemia) may have increased leukocytes but are not associated with the Philadelphia chromosome.

Question 11

Which is a characteristic of ET that would help distinguish it from reactive thrombocytosis?

Accepted Answer

Splenomegaly is a characteristic of ET that distinguishes it from reactive thrombocytosis. ET often results in splenomegaly due to the overproduction of platelets, while reactive thrombocytosis does not typically cause spleen enlargement.

Question 12

A 45-year-old patient visits his physician for a routine examination to address his hypertension. The patient has prominent splenomegaly and rosy cheeks. He is also a smoker. Lab values are: EPO: elevated WBC count: 18.4 × 10⁹/L4 RBC: 6.84 × 10¹²/L PLT: 705 × 10⁹/L Based on these findings, what would you expect to find in the bone marrow?

Accepted Answer

The patient's elevated EPO level and elevated RBC count suggest erythroid hyperplasia in the bone marrow, likely due to chronic hypoxia from smoking-induced lung disease. The high WBC count could be due to a secondary infection or inflammation, but it does not necessarily indicate myeloid hyperplasia. Panmyelosis, or a hyperplastic response involving all bone marrow elements, is not consistent with the patient's lab and clinical findings.

Question 13

Which of the following tests would help differentiate ET from other causes of thrombocytosis?

Accepted Answer

Platelet function tests can help differentiate essential thrombocythemia (ET) from other causes of thrombocytosis by assessing the functionality of the platelets, which may be abnormal in ET.

Question 14

Which of the following genes is associated with clonal hypereosinophilia?

Accepted Answer

PDGFRA gene mutations are associated with clonal hypereosinophilia, a condition characterized by the overproduction of eosinophils, a type of white blood cell.

Question 15

Which of the following assays differentiate CNL from CML?

Accepted Answer

LAP (leukocyte alkaline phosphatase) staining is used to differentiate CNL (chronic neutrophilic leukemia) from other myeloproliferative disorders, including CML (chronic myeloid leukemia). In CNL, LAP score is elevated, while in CML, it is low. Hematocrit, WBC count, and bone marrow fibrosis are not specific assays to differentiate between CNL and CML.

Question 16

The key factor to distinguish relative and absolute polycythemia is that a relative polycythemia is caused by:

Accepted Answer

Relative polycythemia is caused by a decreased amount of serum, which leads to an increase in the concentration of red blood cells in the blood. This can be due to dehydration or loss of fluids, which causes a relative increase in the number of red blood cells. In contrast, absolute polycythemia is caused by an increase in the production of erythrocytes, either due to a primary disorder of the bone marrow or a secondary response to increased production of erythropoietin. The options A, C, and D are all potential causes of absolute polycythemia.

Question 17

Which of the following test results is most consistent with a diagnosis of PMF?

Accepted Answer

Dacryocytes (teardrop cells) are often seen in the peripheral blood of patients with primary myelofibrosis (PMF), and are part of the diagnostic criteria for the disease. A high percentage of blasts in the peripheral blood (answer A) is more commonly seen in acute myeloid leukemia, and although high white blood cell (WBC) count (answer B) and high platelet (PLT) count (answer D) can be seen in PMF, they are not specific to the disease.

Question 18

An abundance of blasts and some mature forms with an apparent decrease in the intermediate maturational stages is referred to as:

Accepted Answer

Leukemic hiatus refers to the observation in blood smears where there is a presence of a large number of immature cells (blasts) and some mature forms, but a noticeable absence of intermediate stages of cell maturation. This pattern is indicative of certain types of leukemia, where the normal maturation process of blood cells is disrupted.

Question 19

What laboratory finding distinguishes leukemoid reaction from CML?

Accepted Answer

In leukemoid reaction, the leukocyte alkaline phosphatase (LAP) score is typically elevated, while in chronic myeloid leukemia (CML), LAP score is low. Other distinguishing factors include the presence of Philadelphia chromosome and increased basophils in CML, which are not seen in leukemoid reaction.

Question 20

The role of PDGF in PMF is to:

Accepted Answer

PDGF (Platelet Derived Growth Factor) promotes the proliferation of bone marrow fibroblasts in PMF (Primary Myelofibrosis), which leads to the deposition of collagen fibers and the formation of fibrosis in the bone marrow.

Quiz 24: Myeloproliferative Neoplasms