1.7 Hematology: Lymphoproliferatrive and Myeloproliferartive Disorders

Repeated phlebotomy in patients with polycythemia vera (PV) may lead to the development of:

A. Folic acid deficiency

B. Sideroblastic anemia

C. Iron deficiency anemia

D. Hemolytic anemia

C. Iron deficiency anemia

C The most common treatment modality utilized in PV is phlebotomy. Reduction of blood volume (usually 1 unit of whole blood—450 cc), can be performed weekly or even twice weekly in younger patients to control symptoms. The Hct target range is less than 45% for men, less than 42% for women. Iron deficiency anemia is a predictable complication of therapeutic phlebotomy because approximately 250 mg of iron is removed with each unit of blood.

A. Increased in number and functionally abnormal

A In essential thrombocythemia, the platelet count is extremely elevated. These platelets are abnormal in function, leading to both bleeding and thrombotic diathesis.

In essential thrombocythemia, the platelets are:

A. Increased in number and functionally abnormal

B. Normal in number and functionally abnormal

C. Decreased in number and functional

D. Decreased in number and functionally abnormal

D. Reed-Sternberg cells

D The morphological common denominator in Hodgkin's lymphoma is the Reed-Sternberg (RS) cell. It is a large, binucleated cell with a dense nucleolus surrounded by clear space. These characteristics give the RS cell an "owl's eye" appearance. Niemann-Pick cells (foam cells) are histiocytes containing phagocytized sphingolipids that stain pale blue and impart a foamlike texture to the cytoplasm. Flame cells are plasma cells with distinctive red cytoplasm. They are sometimes seen in the bone marrow of patients with multiple myeloma.

Which of the following cells is considered pathognomonic for Hodgkin's disease?

A. Niemann-Pick cells

B. Reactive lymphocytes

C. Flame cells

D. Reed-Sternberg cells

C. Teardrop cells

C The marked amount of fibrosis, both medullary and extramedullary, accounts for the irreversible red cell morphological change to a teardrop shape. The red cells are "teared" as they attempt to pass through the

fibrotic tissue.

In myelofibrosis, the characteristic abnormal red blood cell morphology is that of:

A. Target cells

B. Schistocytes

C. Teardrop cells

D. Ovalocytes

D. Absolute increase in total red cell mass

D The diagnosis of PV requires the demonstration of an increase in red cell mass. Pancytosis may also be seen in about two thirds of PV cases. The plasma volume is normal or slightly reduced, and the arterial oxygen saturation is usually normal.

PV is characterized by:

A. Increased plasma volume

B. Pancytopenia

C. Decreased oxygen saturation

D. Absolute increase in total red cell mass

A. Splenomegaly

A Splenomegaly is a feature of PV but not characteristic of secondary polycythemia. The red cell mass is increased in both primary polycythemia (PV) and secondary polycythemia. Erythropoietin is increased and oxygen saturation is decreased in secondary polycythemia.

Features of secondary polycythemia include all of the following except:

A. Splenomegaly

B. Decreased oxygen saturation

C. Increased red cell mass

D. Increased erythropoietin

B. Decreased plasma volume of circulating blood

B Relative polycythemia is caused by a reduction of plasma rather than an increase in red blood cell volume or mass. Red cell mass is increased in both PV and secondary polycythemia, but erythropoietin levels are high only in secondary polycythemia.

The erythrocytosis seen in relative polycythemia occurs because of:

A. Decreased arterial oxygen saturation

B. Decreased plasma volume of circulating blood

C. Increased erythropoietin levels

D. Increased erythropoiesis in the bone marrow

B. Pancytosis

B PV is a myeloproliferative disorder characterized by uncontrolled proliferation of erythroid precursors. However, production of all cell lines is usually increased. Panhyperplasia is a term used to describe the cellularity of the bone marrow in PV.

In PV, what is characteristically seen in the peripheral blood?

A. Panmyelosis

B. Pancytosis

C. Pancytopenia

D. Panhyperplasia

C. 137

C One hundred mature neutrophils are counted and scored. The LAP score is calculated as: (the number of 1+ cells × 1) + (2+ cells × 2) + (3+ cells × 3) + (4+ cells × 4). That is, 48 + 76 + 9 + 4 = 137. The reference range is approximately 20-130.

The leukocyte alkaline phosphatase (LAP) stain on a patient gives the following results

10(0) 48(1+) 38(2+) 3(3+) 1(4+)

Calculate the LAP score.

A. 100

B. 117

C. 137

D. 252

A. CML: low LAP; leukemoid: high LAP

A CML causes a low LAP score, whereas an elevated or normal score occurs in a leukemoid reaction. CML cannot be distinguished by WBC count because both CML and leukemoid reaction have a high count.

CML is distinguished from leukemoid reaction by which of the following?

A. CML: low LAP; leukemoid: high LAP

B. CML: high LAP; leukemoid: low LAP

C. CML: high WBC; leukemoid: normal WBC

D. CML: high WBC; leukemoid: higher WBC

D. All of these options

D Anemia, fibrosis, myeloid metaplasia, thrombocytosis, and leukoerythroblastosis occur in idiopathic myelofibrosis.

Which of the following occurs in idiopathic myelofibrosis (IMF)?

A. Myeloid metaplasia

B. Leukoerythroblastosis

C. Fibrosis of the bone marrow

D. All of these options

B.The prognosis is better if Ph1 is present

B Ninety percent of patients with CML have the Philadelphia chromosome. This appears as a long arm deletion of chromosome 22, but is actually a translocation between the long arms of chromosomes 22 and 9. The ABL oncogene from chromosome 9 forms a hybrid gene with the bcr region of chromosome 22. This results in production of a chimeric protein with tyrosine kinase activity that activates the cell cycle. The prognosis for CML is better if the Philadelphia chromosome is present. Often, a second chromosomal abnormality occurs in CML before blast crisis.

What influence does the Philadelphia (Ph1) chromosome have on the prognosis of patients with chronic myelocytic leukemia?

A. It is not predictive

B.The prognosis is better if Ph1 is present

C.The prognosis is worse if Ph1 is present

D.The disease usually transforms into AML when Ph1 is present

D. An increase in basophils

D CML is marked by an elevated WBC count demonstrating various stages of maturation, hypermetabolism, and a minimal LAP staining. An increase in basophils and eosinophils is a common finding. Pseudo Pelger-Huët cells and thrombocytosis may be present. The marrow is hypercellular with a high M:E ratio (e.g., 10:1).

Which of the following is (are) commonly found in CML?

A. Many teardrop-shaped cells

B. Intense LAP staining

C. A decrease in granulocytes

D. An increase in basophils

D. CML

D Chronic myelogenous leukemia shows the least LAP activity, whereas the LAP score is slightly to markedly increased in each of the other states.

In which of the following conditions does LAP show the least activity?

A. Leukemoid reactions

B. Idiopathic myelofibrosis

C. PV

D. CML

C. Presence of granulocytes at different stages of development

C The WBC count in CML is often higher than 100 × 109/L, and the peripheral smear shows a granulocyte progression from myeloblast to segmented neutrophil.

A striking feature of the peripheral blood of a patient with CML is a:

A. Profusion of bizarre blast cells

B. Normal number of typical granulocytes

C. Presence of granulocytes at different stages of development

D. Pancytopenia

D. Splenomegaly

D Splenomegaly is seen in more than 90% of CML patients, but it is not a characteristic finding in AML. Infections, hemorrhage, and elevated WBC counts may be seen in both CML and AML.

Which of the following is often associated with CML but not with AML?

A. Infections

B. WBCs greater than 20.0 × 109/L

C. Hemorrhage

D. Splenomegaly

D. Osteolytic lesions

D Osteolytic lesions indicating destruction of the bone as evidenced by radiography are seen in multiple myeloma but not in Waldenström's macroglobulinemia. In addition, Waldenström's gives rise to a lymphocytosis that does not occur in multiple myeloma and differs in the morphology of the malignant cells.

Multiple myeloma and Waldenström's macroglobulinemia have all the following in common except:

A. Monoclonal gammopathy

B. Hyperviscosity of the blood

C. Bence-Jones protein in the urine

D. Osteolytic lesions

C. Rouleaux

C Rouleaux is observed in multiple myeloma patients

as a result of increased viscosity and decreased albumin/globulin ratio. Multiple myeloma is a plasma cell dyscrasia that is characterized by an overproduction of monoclonal immunoglobulin.

What is the characteristic finding seen in the peripheral smear of a patient with multiple myeloma?

A. Microcytic hypochromic cells

B. Intracellular inclusion bodies

C. Rouleaux

D. Hypersegmented neutrophils

D. Philadelphia chromosome

D The Ph1 chromosome is a diagnostic marker for CML. Osteolytic lesions, monoclonal gammopathy, and bone marrow infiltration by plasma cells constitute the triad of diagnostic markers for multiple myeloma.

All of the following are associated with the diagnosis of multiple myeloma except:

A. Marrow plasmacytosis

B. Lytic bone lesions

C. Serum and/or urine M component (monoclonal

protein)

D. Philadelphia chromosome

C. Benign monoclonal gammopathy

C Benign monoclonal gammopathies have peripheral blood findings similar to those in myeloma. However, a lower concentration of monoclonal protein is usually seen. There are no osteolytic lesions, and the plasma cells comprise less than 10% of nucleated cells in the bone marrow. About 30% become malignant, and therefore the term monoclonal gammopathy of undetermined significance (MGUS) is the designation used to describe this condition.

Multiple myeloma is most difficult to distinguish from:

A. Chronic lymphocytic leukemia

B. Acute myelogenous leukemia

C. Benign monoclonal gammopathy

D. Benign adenoma

D. All of these options

D Mutated plasmablasts in the bone marrow undergo clonal replication and expand the plasma cell mass. Normal bone marrow is gradually replaced by the malignant plasma cells leading to pancytopenia. Most malignant plasma cells actively produce immunoglobulins. In multiple myeloma, the normally controlled and purposeful production of antibodies is replaced by the inappropriate production of even larger amounts of useless immunoglobulin molecules. The normally equal production of light chains and heavy chains may be imbalanced. The result is the release of excess free light chains or free heavy chains. The immunoglobulins produced by a clone of myeloma cells are identical. Any abnormal production of identical antibodies is referred to by the general name of monoclonal gammopathy. Osteoclasts are bone cells active in locally resorbing bone and releasing calcium into the blood. Nearby osteoblasts are equally active in utilizing calcium in the blood to form new bone. Multiple myeloma interrupts this balance by the secretion of at least two substances. These are interleukin-6 (IL-6) and osteoclast-activating factor (OAF). As its name implies, OAF stimulates osteoclasts to increase bone resorption and release of calcium, which leads to lytic lesions of the bone.

The pathology of multiple myeloma includes which of the following?

A. Expanding plasma cell mass

B. Overproduction of monoclonal immunoglobulins

C. Production of osteoclast activating factor (OAF) and other cytokines

D. All of these options

A. Lymphoplasmacytoid cells

A Waldenström's macroglobulinemia is a malignancy of the lymphoplasmacytoid cells, which manufacture IgM. Although the cells secrete immunoglobulin, they are not fully differentiated into plasma cells and lack the characteristic perinuclear halo, deep basophilia, and eccentric nucleus characteristic of classic plasma

cells.

Waldenström's macroglobulinemia is a malignancy of the:

A. Lymphoplasmacytoid cells

B. Adrenal cortex

C. Myeloblastic cell lines

D. Erythroid cell precursors

C. Hairy cell leukemia

C A variable number of malignant cells in hairy cell leukemia (HCL) will stain positive with tartrateresistant acid phosphatase (TRAP+). Although this cytochemical reaction is fairly specific for HCL, TRAP activity has occasionally been reported in B-cell and rarely T-cell leukemia.

Cells that exhibit a positive stain with acid phosphatase and are not inhibited with tartaric acid are characteristically seen in:

A. Infectious mononucleosis

B. Infectious lymphocytosis

C. Hairy cell leukemia

D. T-cell acute lymphoblastic leukemia

D. CML

D The JAK2(V617F) mutation is negative in patients with CML. It may be positive in patients with idiopathic myelofibrosis (35%-57%), polycythemia vera (65%-97%), and essential thrombocythemia

(23%-57%).

The JAK2(V617F) mutation may be positive in all of the following chronic myeloproliferative disorders except:

A. Essential thrombocythemia

B. Idiopathic myelofibrosis

C. PV

D. CML

D. Sustained platelet count >600 × 109/L

D The criterion for the 2001 WHO diagnosis of essential thrombocythemia (ET) was a platelet count ≥600 x 109/L. This was changed in the 2008 WHO criteria to ≥450 x 109 /L. Diagnosis of essential thrombocythemia requires meeting all four major 2008 WHO diagnostic criteria, which also includes: megakaryocyte proliferation with large and mature morphology and no or little granulocyte or erythroid proliferation; not meeting WHO criteria for CML, PV, IMF, MDS, or other myeloid neoplasm; and demonstration of JAK2(V617F) mutation or other clonal marker, or no evidence of reactive thrombocytosis.

All of the following are major criteria for the 2008 WHO diagnostic criteria for essential thrombocythemia except:

A. Platelet count >450 × 109/L

B. Megakaryocyte proliferation with large and mature morphology, and no or little granulocyte or erythroid proliferation

C. Demonstration of JAK2(V617F) or other clonal marker

D. Sustained platelet count >600 × 109/L