WBC Exam
On what basis can B and T lymphocytes be distinguished? A. Differences in nuclear shape B. Monoclonal antibody reactions to surface and cytoplasmic antigens C. Cytoplasmic granularity and overall cell size D. Chromatin pattern in the nucleus
B. Monoclonal antibody reactions to surface and cytoplasmic antigens Morphologic criteria such as cell size, nuclear shape, and chromatin pattern or cytoplasmic granularity cannot be used to identify lymphocyte subtypes. Monoclonal antibodies (CD surface markers) to specific surface and cytoplasmic antigens can distinguish lymphocyte subpopulations and identify the development stage. For example, blood lymphocytes that are B cells express CD19 and CD20 markers, T cells express CD2 and CD3 and either CD4 or CD8 markers. NK cells express CD56. NK cells often exhibit large granular lymphocyte morphology.
Cells that produce immunoglobulins in response to antigenic stimulation are designated A. NK cells B. Plasma cells C. Virocytes D. Thymocytes
B. Plasma cells Plasma cells are the mature end stage of the B lymphocyte, producing immunoglobulins in response to activation by a specific antigen. The antibody produced bya single plasma cell is of one immunoglobulin type. NK cells recognize and kill tumor cells or cells infected with virus through direct contact. Virocytes are reactive lymphocytes, and thymocytes are immature T cells. T lymphocytes provide cellular immunity.
A 60-year old patient presents with extreme fatigue. Her blood and bone marrow findings are as follows: severe anemia with a dual RBC population, 3% marrow blasts, and numerous ringed sideroblasts. This information is most consistent with A. Refractory anemia (RA) B. Refractory anemia with ringed sideroblasts (RARS) C. Refractory anemia with excess blasts (RAEB) D. Chronic myelomonocytic leukemia (CMML)
B. RARS Refractory anemia with ringed sideroblasts is a myelodysplastic syndrome that may also be referred to as primary or idiopathic sideroblastic anemia. The main findings that characterize this type of MDS include refractory anemia with a heterogenous population of red cells, a hypercellular bone marrow with < 5% blasts, and the presence of >15% ringed sideroblasts in the marrow. RA and RARS are the least likely MDS types to progress to acute myelogenous leukemia.
Which of the following is not a characteristic of T lymphocytes? A. Secrete cytokines B. Synthesize antibody C. Comprise majority of cells in the blood lymphocyte pool D. Regulate the immune response
B. Synthesize antibody Antibodies are synthesized by plasma cells, which are end-stage B lymphocytes that have transformed to plasma cells following stimulation by antigen. An end product of T cell activation is the production of cytokines such as interleukins and colony-stimulating factors. T cells are surveillance cells that normally comprise the majority (about 80%) of lymphocytes in the blood. T cells regulate the immune response by helping (T helper or inducer cells) or suppressing (T suppressor cells) the synthesis of antibody by plasma cells.
The presence of CD2, CD5, CD7 and the absence of CD10 (CALLA) are associated with A. B lymphocytes B. T lymphocytes C. Myeloid cells D. Monocytic cells
B. T lymphocytes CD 2,5,7 are found on T cells. CALLA is the common acute lymphoblastic leukemia antigen and is found in early pre-B cells.
A "shift to the left", when used to describe a cell population, refers to A. Increased cells in the blood due to a redistribution of blood pools B. An increase in immature blood cells following release of BM pools C. A cell production "hiatus" or gap D. A higher percentage of lymphocytes than neutrophils
B. an increase in immature blood cells following release of BM pools A shift to the left means an increase in immature neutrophilic cells in the blood caused by BM release of cells in response to infection or tissue damage. A redistribution of the blood pools because of emotional or physical stimuli is characterized by an increased WBC count without a left shift. A cell "hiatus" refers to a population of cells in which there is a gap in the normal maturation sequence. A cell hiatus is most often seen in acute leukemia, in which there are many blasts and a few mature cells but no intermediate stages.
Antigen-dependent lymphopoiesis occurs in secondary lymphoid tissue located in the A. Liver and kidney B. Spleen and lymph nodes C. Lungs and Peyer's patches D. Thymus and bone marrow
B. spleen and lymph nodes Antigen-independent lymphopoiesis occurs in primary lymphoid tissue located int he thymus and bone marrow. The formation of immunocompetent T and B cells from the lymphoid progenitor cell is influenced by environment and several interleukins. Antigen-dependent lymphopoiesis occurs in secondary lymphoid tissue (spleen, lymph nodes, Peyer's patches) and begins with antigenic stimulation of immunocompetent T and B cells. Lymphocytes are the only white cells that recirculate (return to blood from the tissues).
Which of the following is not classified as a myeloproliferative disorder? A. Polycythemia vera B. Essential thrombocythemia C. Multiple myeloma D. Chronic myelogenous leukemia
C. Multiple myeloma Multiple myeloma is a malignant lymphoproliferative disorder characterized by a clonal proliferation of plasma cells and multiple bone tumors. Myeloproliferative disorders are characterized by a proliferation of BM cells (granulocytic, monocytic, erythrocytic, megakaryocytic), with usually one cell type primarily affected. For example, the main cell type affected in PV is the erythrocyte, and the platelet is mainly affected in essential thrombocythemia. Transformation among the myeloproliferative disorders is frequent.
Production of primary granules ceases and production of secondary granules commences with what cell stage? A. Myeloblast B. Promyelocyte C. Myelocyte D. Metamyelocyte
C. Myelocyte The first precursor cell that can first be recognized as granulocytic is the myeloblast and which has no granules. Primary or nonspecific granule production begins and ends during the promyelocytic stage. The granules are redistributed between daughter cells as mitotic divisions occur. Secondary or specific granule production begins with the myelocyte stage and continues during succeeding cell stages with the synthesis of products specific to the function of the particular granulocyte (neutrophil, eosinophil,or basophil).
The most mature granulocyte precursor that can undergo mitosis is the A. Myeloblast B. Promyelocyte C. Myelocyte D. Metamyelocyte
C. Myelocyte The last stage in the granulocytic series that divides is the myelocyte. Cells before and including this stage constitute the BM mitotic pool and undergo multiple cellular divisions. Nuclear chromatin progressively clumps and nucleoli are no longer present in the nondividing metamyelocyte stage that follows the myelocyte.
8 year old girl has a fever, sore throat, bruising, petechiae, and pallor. WBC 110 x 10^9/L, RBC 1.70 x 10^12/L, Hb 55 g/L, Hct 16%. Differential shows 93% blasts, 7% lymphocytes and BM has 85% blasts. All the blasts are small with no variation in their appearance. Which of the following cytochemical stains would be positive in the blast cells of this patient? A. MPO B. LAP C. PAS D. NSE
C. Periodic acid-Schiff stain PAS stains glycogen in lymphoblasts. MPO is positive for myeloid cells, NSE for monocytes. LAP is useful in diagnosing CML.
Functionally, white blood cells are divided into A. Granulocytes, nongranulocytes B. Polymorphonuclears, mononuclears C. Phagocytes, immunocytes D. Granulocytes, lymphocytes
C. Phagocytes, immunocytes The major function of leukocytes is defense either by phagocytosis or by immune mechanisms. The phagocytic cells are the granulocytes and monocytes. The immune response is mediated by lymphocytes, however, monocytes play a role in immunity as antigen-presenting cells. Leukocytes may be classified according to granularity as granulocytes and nongranulocytes or divided based on nuclear segmentation as polymorphonuclears (PMNs) and mononuclears.
Which of the following is not a mechanism by which neutropenia may be produced? A. Hypersplenism B. Marrow injury or replacement C. Recent strenuous exercise D. Drug-induced antibodies
C. Recent strenuous exercise Recent strenuous exercise or other physical and emotional stimuli cause a transient increase in the leukocyte count. This is due to a redistribution of the blood pools. Marrow injury to stem cells or marrow replacement by malignant cells causes neutropenia of varying degrees. Neutropenia may be caused by immune mechanisms (antibodies) or an overactive spleen that sequesters neutrophils. Chemotherapeutic drugs also suppress bone marrow production of neutrophils.
Of the following, an absolute neutrophil count of 1.0*10^9/L would be associated with A. Shortness of breath B. Bleeding tendencies C. Risk of infection D. No clinical symptoms
C. Risk of infection Neutropenia is associated with a risk of infection. The degree of neutropenia correlates with the infection risk from high susceptibility (<1.0*10^9/L) to great risk (<0.5*10^9). Infection increases with the degree and duration of the neutropenia. Shortness of breath and bleeding tendencies are clinical symptoms associated with severe anemia and thrombocytopenia, respectively.
What is the initial laboratory technique for the diagnosis of monoclonal gammopathies? A. Immunologic markers of marrow biopsy cells B. Cytochemical staining of marrow and peripheral blood cells C. Serum and urine protein electrophoresis D. Cytogenetic analysis of marrow cells
C. Serum and urine protein electrophoresis Serum and urine protein electrophoresis detects the presence of an M spike, the first essential step in establishing the disorder as a monoclonal gammopathy such as multiple myeloma or Waldenstrom disease. This can be followed by immunoelectrophoresis to determine the class of immunoglobulin or chain type. Immunologic markers, cytochemical stains, and/or cytogenetics are used in conjunction with cell morphology to diagnose malignant conditions.
Which of the following statements about Hodgkin disease is false? A. Peak incidence occurs in young adults B. Staging determines extent of disease and treatment course C. Stage IV has the best prognosis D. Almost a 2:1 male predominance over females is characteristic
C. Stage IV has the best prognosis The prognosis is poor for patients with Stage IV Hodgkin disease, in which there is widespread disease including bone marrow involvement. Stage I or II Hodgkin disease has a very good prognosis for cure. The clinical course and treatment varies with the extent of disease and morphologic subtype (Rye classification). The peak incidence for Hodgkin lymphoma occurs in young adults (late twenties). Men have a 50% higher incidence of the disease than women. The CRP level and ESR are increased during active disease and can be used to monitor remission status.
Auer rods present in blasts A. Excludes a diagnosis of acute myelogenous leukemia B. Stains positive with leukocyte alkaline phosphatase (LAP) C. Stains positive with myeloperoxidase (MPO) D. Identifies the cell as a malignant lymphoblast
C. Stains positive with myeloperoxidase (MPO) A malignant blast cell with an Auer rod (composed of fused primary granules), stains positive with both myeloperoxidase and Sudan black B. Auer rods are not seen in lymphoblasts and their presence can be diagnostic of AML such as acute myeloblastic leukemia (M1 and M2) or acute myelomonocytic leukemia (M4). Multiple Auer rods may be seen in APML (M3). Auer rods stain negatively with LAP, which detects the enzyme alkaline phosphatase in neutrophil granules.
Which of the following statements about macrophages is incorrect? A. They are mature tissue forms of blood monocytes B. They serve as antigen-presenting cells to the immune system C. Their quantity of lysosome and acid hydrolases decreases during maturation D. They remove damaged or dying cells and cellular debris
C. Their quantity of lysosome and acid hydrolases decreases during maturation Acid hydrolases and the number of lysosomes increase as the blood monocyte matures into a tissue macrophage. Macrophages are widely dispersed in body tissues and organse of the reticuloendothelial system. Macrophages have receptors for IgG and complement, and they serve as phagocytes by ingesting debris and dead cells at sites of inflammation. Macrophages act in the immune response as antigen-presenting cells by ingesting and exposing antigens for recognition by lymphocytes. Monocytes/macrophages secrete complement components and cytokines, including colony stimulating factors and interleukins.
An adult has a total WBC count of 4x10^9/L. The differential count is as follows: PMNs 25%, bands 5%, lymphocytes 65%, monocytes 5%. The absolute reference range for lymphocytes is 1-4x10^9/L. Which of the following is true? A. The percentage of lymphocytes is normal B. There is an absolute lymphocytosis C. There is a relative lymphocytosis D. There is both an absolute and a relative lymphocytosis
C. There is a relative lymphocytosis Absolute values for cell types are obtained by multiplying the percentage of the cell type by the total number of cells. In this case 4x.65=2.6*10^9/L which is within the normal absolute count for lymphocytes. Normal percentage of lymphocytes is 20-44% so there is a relative lymphocytosis but the absolute lymphocyte value is normal.
What markers are found on pre-B cells?
CD10, CD19, CD22, CD24
t(9;22) is the gene mutation associated with what disease?
CML
Which of the following is characteristic of primary granules? A. Coated with a phospholipid membrane B. Called azurophilic or specific granules C. Contain myeloperoxidase and lactoferrin D. Present in the promyelocyte stage only
A. Coated with a phospholipid membrane Primary granules, which appear in the promyelocyte stage, may be called azurophilic or nonspecific granules. Specific or secondary granules (neutrophilic, eosinophilic, basophilic) appear in the myelocyte stage. Primary granules contain hydrolytic enzymes (myeloperoxidase, lysozyme, acid phosphatase) and are coated with a phospholipid membrane. Lactoferrin is a component of neutrophil granules. Primary granules are visible in the myelocyte stage, but in later stage cells the primary granules, although present, are less visible by light microscopy under normal conditions.
In which of the following are eosinophils not increased? A. Cushing syndrome B. Allergic disorders C. Skin disorders D. Parasitic infection
A. Cushing syndrome Eosinophils are decreased in Cushing syndrome, in which the adrenal glands secrete large amounts of adrenocorticosteroids. Eosinophils are increased in allergic disorders, various skin diseases, and certain types of parasitic infections (especially those due to intestinal and tissue-dwelling worms). Eosinophilia is also seen in chronic myelogenous leukemia and Hodgkin lymphoma.
What is the term for cell movement through blood vessels to a tissue site? A. Diapedesis B. Opsonization C. Margination D. Chemotaxis
A. Diapedesis Diapedesis is the movement of cells from the blood stream into the tissues by squeezing through endothelial cells of the vessel wall. Chemotaxis is the movement of cells directed by chemotactic stimuli such as bacterial products, complement components, or injured tissue. Opsonization is the coating of an organism or foreign particle by IgG or complement for recognition and phagocytosis by neutrophils or monocytes. The ingestion of red cells, often coated with IgG or complement, is called erythrophagocytosis. Margination is the attachment of neutrophils to the endothelial lining of the blood vessels.
Which of the following is the least likely to be expressed by early B cell precursors? A. SIgM, a surface membrane immunoglobulin B. CD34, a hematopoietic stem cell marker C. TdT (terminal deoxynucleotidyl transferase), a nuclear enzyme D. CD10 (CALLA), a surface antigen
A. SIgM Early B cell precursors would be expected to express TdT, CD10, and CD34. TdT and the stem cell marker CD34 are present on the earliest B or T lymphoid cells. Surface immunoglobulin SIgM can only be detected on B cells at later stages of development. TdT can be used to differentiate the leukemic cells of acute lymphoid leukemia from acute myeloid leukemia. CALLA is a marker found in precursor types of B cell ALL.
Which of the following statements about neutrophils is false? A. Suppress allergic reactions caused by basophils B. Have surface receptors for IgG and complement components C. Contain alkaline phosphatase and muramidase D. Act in nonspecific phagocytosis and are destined to die
A. Suppress allergic reactions caused by basophils A function of the eosinophil is to modify the severe allergic reactions caused by degranulation of the basophil. Neutrophils have receptors for the opsonins IgG and complement and are the most important cell in the initial defense against acute bacterial infection. Neutrophils are nonspecific phagocytes, ingesting bacteria, fungi, dead cells, etc., and they contain hydrolytic enzymes, including muramidase (lysozyme) and alkaline phosphatase. Neutrophils die in the performance of their function and are removed by macrophages.
Which of the following statements is correct? A. Hypersegmented neutrophils have four nuclear lobes B. Auer rods are composed of fused primary granules C. Toxic granules are prominent secondary granules D. Dohle bodies are agranular patches of DNA
B. Auer rods are composed of fused primary granules. Auer rods are seen in the cytoplasm of malignant cells, most often myeloblasts, and are composed of fused primary granules. Hypersegmented neutrophils have five lobes or more and are associated with vitamin B12 or folate deficiency. Toxic granules are primary granules with altered staining characteristics that stain in late-stage neutrophils due to toxicity. Dohle bodies are agranular patches of RNA present in neutrophil cytoplasm and associated with toxic states.
Which of the following gene mutations correlates with the t(9;22) that is present in Philadelphia chromosome positive chronic myelogenous leukemia? A. MYC/IGH B. BCR/ABL C. PML/RARA D. JAK2
B. BCR/ABL The Philadelphia chromosome, t(9;22), is detected in almost all cases of CML (depends on detection method) and results in a mutated BCR/ABL fusion gene. The resulting fusion protein causes increased tyrosine kinase activity, which promotes cell proliferation. Imatinib mesylate (Gleevec) is a therapeutic agent that targets the molecular defect by blocking tyrosine kinase activity and is now a first-line drug used in the chronic phase of CML. The t(15;17) that is diagnostic of promyelocytic leukemia results in a PML/RARA fusion gene that blocks maturation. Many PML patients respond to retinoic acid therapy, which induces promyelocyte differentiation. Nearly all cases of Burkitt lymphoma have t(8;14), which is a translocation of the MYC gene from chromosome 8 to the Ig heavy chain (IgH) region on chromosome 14. JAK2 is a point mutation in a gene regulating cell proliferation and it is present in over 90% of PV cases and approximately 50% of those with ET and myelofibrosis. Detection of cytogenetic and molecular mutations has diagnostic and prognostic significance and is an important tool in monitoring response to treatment.
Which of the following infections does not cause reactive lymphocytes to appear in the peripheral blood? A. EBV B. Bordetella pertussis C. CMV D. Toxoplasma gondii
B. Bordetella pertussis (whooping cough) A striking lymphocytosis may be seen in children with pertussis, but normal lymphocytes rather than reactive lymphocytes, are present. A relative and/or absolute lymphocytosis with reactive lymphocytes in various stages of activation is characteristic of infection caused by EBV, CMV, and toxoplasmosis. A positive heterophile antibody test can help distinguish infectious mononucleosis caused by EBV from conditions with a similar blood picture. EBV is also linked to Burkitt and Hodgkin lymphomas.
A child has acute lymphoblastic leukemia that is precursor B cell type and CALLA positive. Analysis by flow cytometry would likely show cells that immunophenotype for A. CD2, CD7 B. CD10, CD19 C. CD13, CD33 D. CD14, CD34
B. CD10, CD19 The CALLA positive, precursor B ALL malginant cells would be expected to express CD10, the common ALL antigen marker; the B cell lineage marker CD19; and TdT, a marker on early lymphoid cells. Precursor T ALL would express TdT and the T cell makers CD2 and CD7. CD13 and CD33 are myeloid markers, and CD14 is a marker for monocytic cells.
Which of the following statements about basophils is false? A. Morphologically, basophils resemble tissue mast cells B. Membrane receptors bind IgG C. Basophilic granules contain heparin and histamine D. Granules are water soluble
B. Membrane receptors bind IgG Basophils and tissue mast cells have receptors for IgE and complement components, which trigger degranulation when appropriate antigens are present and are responsible for severe hypersensitivity reactions (anaphylaxis). Basophils and tissue mast cells have morphologic similarities but represent distinct cell types. Basophils possess water-soluble granules that contain, among other substances, heparin and histamine (a vasodilator and smooth muscle contractor). Basophils have a segmented nucleus, and the granules, although often scanty, overlie the nucleus. The mast cell has a single round nucleus, contains many more granules than the basophil, and can be found in the BM.
Which of the following can differentiate metamyelocytes from other stages of granulocyte maturation? A. Presence of specific granules B. Indentation of nucleus C. Absence of nucleoli D. Color of cytoplasm
B. Indentation of nucleus Indentation of the nucleus (kidney shape) is the feature that characterizes the metamyelocyte stage. Specific granules begin forming in the myelocyte and persist through later stages. Cytoplasmic color is not a reliable feature, because it is variable and may not differ significantly from the myelocyte or band stage. Nucleoli are absent in metamyelocytes and may not be visible in myelocytes (they may be indistinct).
A bone marrow with 90% cellularity and myeloid:erythroid (M:E) ratio of 10:1 is most characteristic of A. Chronic myelogenous leukemia B. Primary polycythemia C. Beta-thalassemia major D. Aplastic anemia
A. Chronic myelogenous leukemia A hypercellular bone marrow and high M:E ratio are most characteristic of the excessive granulocyte production that occurs in CML. Polycythemia vera typically has a hypercellular marrow with panhyperplasia and a normal or low M:E ratio. Beta-thalassemia major is a severe hemolytic anemia in which RBC hyperplasia of the bone marrow is pronounced and a low M:E ratio is usual. Aplastic anemia is associated with a hypocellular marrow with a reduction of all cell lines and a normal M:E ratio.
A Gaucher cell is best described as a macrophage with A. "Wrinkled" cytoplasm due to accumulation of glucocerebroside B. "Foamy" cytoplasm filled with unmetabolized sphingomyelin C. Pronounced vacuolization and deposits of cholesterol D. Abundant cytoplasm containing storage iron and cellular remnants
A. "Wrinkled" cytoplasm due to accumulation of glucocerebroside Gaucher disease is a lipid storage disorder in which there is an accumulation of glucocerebroside in the macrophages because of a genetic lack of glucocerebrosidase, an enzyme required for normal lipid metabolism. Gaucher cells are found in the liver, spleen, and bone marrow. Niemann-Pick disease is caused by a deficiency of sphingomyelinase in which "foamy" macrophages, called Niemann-Pick cells, are filled with sphingomyelin. Normal macrophages may contain iron and other cellular debris.
Lymphocyte concentrations in the peripheral blood are greatest during what age interval? A. 1-4 years B. 4-15 years C. 16-40 years D. 40-70 years
A. 1-4 years Young children have the highest peripheral lymphocyte concentrations rangin from 4.0-10.5*10^9 cells/L at 1 year and declining to 2-8*10^9 cells/L by 4 years of age. Lymphocyte counts decrease with age because of a decrease in lymphocyte stimulation and processing of antigens, ranging from 1-4*10^9 cells/L in adults. In addition to the difference in lymphocyte number in children, the normal morphology of childnre's lymphocytes differs from that of adults. Patient age should be considered when deciding between normal and abnormal lymphocytes.
8 year old girl has a fever, sore throat, bruising, petechiae, and pallor. WBC 110 x 10^9/L, RBC 1.70 x 10^12/L, Hb 55 g/L, Hct 16%. Differential shows 93% blasts, 7% lymphocytes and BM has 85% blasts. All the blasts are small with no variation in their appearance. Which of the following would you expect to most accurately reflect the child's platelet count? A. 10x10^9/L B. 100x10^9/L C. 200x10^9/L D. 400x10^9/L
A. 10x10^9
8 year old girl has a fever, sore throat, bruising, petechiae, and pallor. WBC 110 x 10^9/L, RBC 1.70 x 10^12/L, Hb 55 g/L, Hct 16%. Differential shows 93% blasts, 7% lymphocytes and BM has 85% blasts. All the blasts are small with no variation in their appearance. What is the child's most probably diagnosis? A. ALL B. AML C. HCL D. MDS
A. ALL Blast percent indicates presence of acute leukemia. Triad of symptoms seen in acute leukemia is neutropenia, anemia, and thrombocytopenia. ALL is most likely to be found in this age group. HCL does not present with blasts and MDS has less than 20/30% (WHO/FAB) blasts in the BM.
A patient who has a "packed" bone marrow with predominantly immature blast cells and few normal precursor cells most likely has a A. Acute leukemia B. Chronic leukemia C. Myelodysplastic syndrome D. Aplastic anemia
A. Acute leukemia This bone marrow is most indicative of a patient with acute leukemia. Although chronic leukemias usually have a hypercellular marrow, the malignant cells are more mature or differentiated. Myelodysplastic syndromes are associated with a hypercellular bone marrow, but the marrow blast percent is less than 20%. Aplastic anemia is characterized by a hypocellular bone marrow with few cells.
Which of the following would be least helpful in distinguishing chronic myelogenous leukemia (CML) from a neutrophilic leukemoid reaction? A. An extreme leukocytosis with increased neutrophilic bands, metamyelocytes, and myelocytes B. Leukocyte alkaline phosphatase score C. Presence of marked splenomegaly D. Neutrophils with Dohle bodies and toxic granulation
A. An extreme leukocytosis with increased neutrophilic bands, metamyelocytes, and myelocytes The blood profile of both CML and neutrophilic leukemoid reaction is characterized by extremely high leukocyte counts with immature neutrophils. Splenomegaly is a manifestation of the malignant disease process and associated with CML rather than a leukemoid reaction. The presence of toxic granules and Dohle bodies would be typical of a leukemoid reaction caused by a severe bacterial infection. The LAP score is low in CML and high in a neutrophilic leukemoid reaction.
The most common type of chronic lymphocytic leukemia (CLL) in the U.S. involves the A. B cell B. NK cell C. T cell D. Plasma cell
A. B cell B cell chronic lymphocytic leukemia (CLL) is by far the most common type found in the U.S. Immune dysfunction because of hypogammaglobulinemia occurs in later stages of the disease, as does thrombocytopenia. Development of WAIHA is a frequent occurrence in patients with CLL. Treatment for B cell CLL is conservative and aimed at controlling symptoms. T cell CLL is a rare and is a more aggressive disease.
Based on the WHO classification system, B cell ALL (L3) and __________ represent different clinical presentations of the same disease entity. A. Burkitt lymphoma B. Hodgkin lymphoma C. Mycosis fungoides D. Small lymphocytic lymphoma
A. Burkitt lymphoma The lymphoid cells of B cell acute lymphoblastic leukemia (L3) are morphologically identical to the malignant B cells of Burkitt lymphoma (large cells with basophilic cytoplasm and cytoplasmic lipid vacuoles). Although the site of origin is the BM in B cell ALL and the tissues in Burkitt lymphoma, the WHO classifies them as the same disease entity with different clinical presentations. Both CLL and small lymphocytic lymphoma are malignant proliferations of small, mature lymphocytes and diagnosis is based on the predominant site of involvement. Mycosis fungoides and Sezary syndrome are different stages of a cutaneous T cell lymphoma in which the skin is the early site of involvement, with subsequent progression to the BM and blood.
Naphthol AS-D chloroacetate esterase (specific) is usually positive in _______ cells, and alpha-naphthyl acetate esterase (nonspecific) is useful for identifying blast cells of ______ lineage. A. Granulocytic; monocytic B. Monocytic; granulocytic C. Granulocytic; lymphocytic D. Monocytic; lymphocytic
A. Granulocytic; monocytic Naphthol AS-D chloroacetate esterase (specific) reacts strongly in granulocytic cells, and alpha-naphthyl acetate esterase (nonspecific) stains positively in monocytic cells. The esterase stains are used to distinguish between subtypes of AML. The cells of AML (M1 and M2) will stain positive with specific esterase and negative with nonspecific esterase. The cells of AML (M5) will stain positive with nonspecific esterase and negative with specific esterase. The cells of acute myelomonocytic leukemia (M4) will show positivity with both specific and nonspecific esterase. Stain results are correlated with cell morphology, immunophenotype, and karyotype for diagnosis.
What is the approximate amount of time a granulocyte spends in the circulation before migrating into the tissues? A. Less than 1 day B. About 3 days C. Up to 5 days D. More than 10 days
A. Less than 1 day After granulocytes are released from the BM, they remain in circulation one day or less. Their major function takes place in tissues. They migrate through vessel walls to reach areas of inflammation very soon after release. The life span of granulocytes is short; however eosinophils and basophils apepar to survive longer in the tissues than neutrophils.
Which of the following statements about non-Hodgkin types of lymphoma is true? A. Lymphadenopathy is the most common presenting symptom B. Initially, they present as a systemic disease rather than a localized tumor C. They are often associated with multiple bone lesions D. They are characterized by proliferation of malignant cells primarily involving the bone marrow
A. Lymphadenopathy is the most common presenting symptom Prominent lymphadenopathy is the most consistent finding in non-Hodgkin types of lymphoma at presentation, but lymphoma may also arise in the spleen, liver, or GI tract (abdominal tumor). Lymphomas begin as localized tumors involving lymphoid tissue that spread to the bone marrow and blood (depends on type). The malignant lymphoid cells are immunologically classified as B cell (most common) or T/NK cell. Clonality can also be established by demonstrating gene rearrangements via molecular analysis. Some common subtypes of non-Hodgkin lymphoma are small lymphocytic, Burkitt, follicular, and mantle cell lymphomas. Leukemias are initially systemic disorders primarily involving the bone marrow and blood at onset. Bone lesions are associated with multiple myeloma.
83-year old woman in ER complaining of fatigue and recent weight loss. WBC 2.6x10^9/L, RBC 2.79x10^12/L, Hb 92g/L, Hct 28%, MCV 100, RDW 23.5%, platelet 42x10^9/L. Differential shows 42% segs, 45% bands, 3% lymphs, 3% metas, 4% myelos, 3% blasts, 4 nRBC/100 WBC. Poor granulation and hyposegmentation of neutrophils, giant platelets with poor granulation, oval macrocytes, basophilic stippling, Cabot rings, Pappenheimer bodies, H-J bodies. Three micromegakaryocytes are seen per 100 WBCs. Serum B12/folate levels are normal. The peripheral blood findings are most consistent with A. MDS B. Degenerative left shift C. Megaloblastic anemia D. CML
A. MDS MDSs are pluripotential stem cell disorders characterized by one or more peripheral blood cytopenias. There are prominent maturation abnormalities in all three cell lines in the BM. Normal B12/folate rules out megaloblastic anemia.
The familial disorder featuring pseudo-Dohle bodies, thrombocytopenia, and large platelets is called A. May-Hegglin anomaly B. Chediak-Higashi syndrome C. Pelger-Huet anomaly D. Alder-Reilly anomaly
A. May-Hegglin anomaly May-Hegglin anomaly is an autosomal dominant disorder in which large blue cytoplasmic structures that resemble Dohle bodies are found in the granulocytes and possibly the monocytes. Leukocytes are normal in function. Platelets are decreased in number and abnormally large. About one-third of patients have mild to severe bleeding problems because of abnormal platelet function.
What does the granulocyte mitotic pool in the BM contain? A. Myeloblasts and promyelocytes B. Band and segmented forms C. The majority of marrow granulocytes D. Myelocytes and metamyelocytes
A. Myeloblasts and promyelocytes The granulocyte mitotic pool contains the cells capable of division, which are the myeloblasts, promyelocytes, and myelocytes. The post-mitotic pool, or reserve, is the largest BM pool and contains metamyelocytes, band, and segmented forms. This pool is available for prompt release into the blood if needed and its early release is the cause of a "left shift". If released, the BM mitotic pool can dramatically increase its activity to replenish this reserve.
What is the major phagocytic cell involved in the initial defense against bacterial pathogens? A. Neutrophil B. Eosinophil C. Basophil D. Monocyte
A. Neutrophil Although some phagocytic activity has been attributed to the eosinophil, it is the segmented neutrophil and monocyte that have the greatest phagocytic activity. The neutrophil is the most important because of numbers and its ability to respond quickly, especially against bacterial pathogens. Monocytes arrive at the site of injury after the neutrophil to "clean up".
In which anomaly is a failure of granulocytes to divide beyond the band or two-lobed stage observed? A. Pelger-Huet B. May-Hegglin C. Alder-Reilly D. Chediak-Higashi
A. Pelger-Huet True Pelger-Huet anomaly is a benign autosomal dominant trait characterized by hyposegmentation of granulocytes, coarse nuclear chromatin, and normal cytoplasmic granulation. The cells have no functional defect. It is of practical importance to recognize this anomaly so that it is not confused with a shift to the left due to infection. Acquired or pseudo Pelger-Huet is commonly associated with myeloproliferative disorders, myelodysplastic syndromes, or drug therapy. Pelgeroid cells are hyposegmented and the cytoplasm is frequently hypogranular.
Terminal deoxyribonucleotidyl transferase (TdT) is present in A. Precursor B and precursor T lymphoid cells B. Mature B and T lymphocytes C. Precursor B cells and mature B lymphocytes D. Precursor T cells and mature T lymphocytes
A. Precursor B and precursor T lymphoid cells TdT is a nuclear enzyme found in stem cells and precursor B/T lymphoid cells. High levels of TdT are found in 90% ALLs and 10% of AMLs (M0/M1). This enzyme is not found in mature cells.
What is the key diagnostic test for Hodgkin lymphoma? A. Bone marrow biopsy B. Lymph node biopsy C. Spinal tap D. Skin biopsy
B. Lymph node biopsy The test that would be the most beneficial for the diagnosis of Hodgkin lymphoma is a lymph node biopsy. Lymphadenopathy is the major clinical presentation of Hodgkin disease, and early stages do not have bone marrow involvement. A skin biopsy would be indicated for diagnosis of mycosis fungoides, a T cell lymphoma of the skin. A bone marrow exam and spinal tap are important to the diagnosis of acute leukemias.
Which of the following are indicators of a neutrophilic response to tissue damage or inflammatory stimuli? A. Toxic granules and Dohle bodies in the neutrophils B. Vacuoles and Barr bodies in the neutrophils C. Hypersegmented neutrophils and Auer rods D. Pyknotic neutrophils and Russell bodies
A. Toxic granules and Dohle bodies in the neutrophils The presence of toxic granules, Dohle bodies, and/or vacuoles in the cytoplasm of the neutrophils is indicative of a neutrophilic response to inflammation. The changes observed in the toxic neutrophil may occur in patients with severe burns, some malignancies, exposure to toxic drugs and chemicals, and acute infection. A Barr body is a drum-stick shaped body of nuclear material found in the neutrophils of females that represents the inactive X chromosome and is of no significance. Auer rods are seen in malignant myeloid cells, usually blasts. Hypersegmented neutrophils are associated with megaloblastic anemias but may be seen in long-term chronic infections. Pyknotic cells and vacuoles may be seen in overwhelming sepsis or in a degenerating blood specimen. Russell bodies are globular inclusions found in plasma cells that are composed of immunoglobulin.
90 year old man with blasts containing Auer rods that stain black with Sudan black B stain complains of fatigue and nosebleeds. Patient was febrile and had petechiae. WBC 20x10^9/L, RBC 2.58x10^12/L, Hb 77g/L, Hct 24%, platelet 32x10^9/L. Differential shows 75% blasts, 20% lymphocytes, and 5% segmented neutrophils. BM had an 80% cellularity with 80% blasts which were MPO and specific esterase positive, NSE/PAS negative. Cytogenetic studies would most likely reveal which chromosome abnormality? A. t(8;21) B. t(8;14) C. t(9;22) D. t(15;17)
A. t(8;21) t(8;21) - M2 t(15;17) - M3 Philadelphia chromsome t(9;22) - CML t(8;14) - Burkitt lymphoma
t(8;21) is the gene mutation associated with what disease?
AML (M2)
t(16;16) or inv(16) is the gene mutation associated with what disease?
AML (M4Eo variant)
11q23 is the gene mutation associated with what disease?
AML (M5)
t(15;17) is the gene mutation associated with what disease?
APL
In which of the following would an absolute monocytosis not be seen? A. Tuberculosis B. Recovery stage of acute bacterial infection C. Collagen disorders D. Infectious mononucleosis
D. Infectious mononucleosis Monocytes must be distinguished from reactive lymphocytes, which are the characteristic feature of infectious mononucleosis. Monocytosis occurring in the recovery stage of acute infections is considered a favorable sign. An increase in monocytes is associated with collagen disorders (eg. rheumatoid arthritis), tuberculosis, and malignant conditions such as myelodysplastic syndromes and monocytic leukemias.
Hypersegmented neutrophils are found in a leukemia patient following treatment. These findings are most suggestive of therapy with A. Corticosteroids (eg. prednisone) B. A folate antagonist (eg. methotrexate) C. Recombinant erythropoietin D. Chloramphenicol
B. A folate antagonist A drug-induced megaloblastic blood profile with macrocytic ovalocytes and hypersegmented neutrophils is a common finding in patients receiving antifolate chemotherapeutic drugs such as methotrexate. Recombinant EPO is associated with a reticulocyte response and used to treat a variety of conditions such as renal disease, ACD, or anemia caused by chemotherapy. Chloramphenicol is an antibiotic with a known assoc. for aplasia due to marrow suppression.
90 year old man with blasts containing Auer rods that stain black with Sudan black B stain complains of fatigue and nosebleeds. Patient was febrile and had petechiae. WBC 20x10^9/L, RBC 2.58x10^12/L, Hb 77g/L, Hct 24%, platelet 32x10^9/L. Differential shows 75% blasts, 20% lymphocytes, and 5% segmented neutrophils. BM had an 80% cellularity with 80% blasts which were MPO and specific esterase positive, NSE/PAS negative. What is this patient's most likely diagnosis? A. AML without maturation (M1) B. AML with maturation (M2) C. Acute monocytic leukemia (M5) D. MDS
B. AML with maturation (M2) BM blast percent is high, Sudan black B, MPO, and specific esterase stains are positive indicating presence of myeloid cell line. NSE is negative, indicating absence of monocytic cell line. BM blast percent is too low for M1 but is in range for M2.
Coarse PAS positivity may be found in the leukemic cells of A. Acute myeloblastic leukemia (M1) B. Acute lymphoblastic leukemia (L1) C. Acute myelomonocytic leukemia (M4) D. Acute monocytic leukemia (M5)
B. Acute lymphoblastic leukemia (L1) The periodic acid-Schiff (PAS) stain can be used to detect intracellular glycogen deposits in the lymphoblasts of acute lymphoblastic leukemia (ALL), in which coarse clumps of PAS positive material may be observed. Myeloblasts and monoblasts usually show a faint staining reaction. The immunophenotype has a much greater diagnostic value for ALL than the cytochemical stain results. The PAS may also be used to distinguish the malignant erythroid precursors of acute erythroleukemia, which show strong PAS positivity, from normal erythrocytic cells that stain negative.
Which type of leukemia is associated with the best prognosis for a cure? A. Chronic lymphocytic leukemia in the elderly B. Acute lymphoblastic leukemia in children C. Acute myelogenous leukemia in children D. Chronic myelogenous leukemia in young adults
B. Acute lymphoblastic leukemia in children Acute lymphoblastic leukemia (ALL) of children has the best prognosis. Other favorable factors include children between ages 3 and 7, mild to moderate increases in the peripheral white blood count prior to treatment, and precursor B ALL, CALLA positive type (rather than T cell ALL). Certain cytogenetic and molecular abnormalities are also associated with a better prognosis. Acute leukemia in adults is less favorable because remissions are shorter and more difficult to induce, especially in those over 70 years of age. Prognosis is poor in adults with ALL.
The PB from a 69-year old female shows lymphocytosis with smudge cells. WBC count was 83.0x10^9 cells/L (83x10^3/uL) and her platelet count was normal. Based on the cell morphology and this information, what is the most likely diagnosis? A. ALL B. CLL C. Waldenstrom macroglobulinemia D. Viral infection
B. CLL CLL is characterized by an absolute lymphocytosis and a predominance of small, mature lymphocytes with hyperclumped nuclear chromatin. Elevated leukocyte counts are usual, as are fragile, smudged lymphocytes. ALL typically occurs in children and is characterized by immature lymphoid cells. Plasmacytoid lymphocytes and red cell rouleuax may be found in the blood of individuals with Waldenstrom disease. Viral infections are associated with a lymphocytosis and the presence of reactive lymphocytes that are heterogenous in morphology. Reactive lymphocytes exhibit a variety of forms with regard to size and cytoplasmic staining intensity as compared to the homogenous cell populations present in malignant disorders such as CLL and ALL.
53-year old man comes in for a yearly physical feeling tired the last few months. Found splenomegaly. CBC showed WBC 80x10^9/L, RBC 4.1x10^12/L, Hb 123 g/L, Hct 37%, platelet 650x10^9/L. Differential showed 40% PMN, 18% bands, 5% metas, 7% myelos, 28% lymphs, 2% monos. No RBC/WBC abnormalities seen. The PB findings are most consistent with a diagnosis of A. Neutrophilic leukemoid reaction B. CML C. AML D. Regenerative left shift
B. CML CML is a myeloproliferative disorder, a malignant proliferation of leukocytes not in response to infection. No toxic changes found in CML. Thrombocytosis is seen in more than half of patients with CML. A neutrophilic leukemoid reaction represents a normal body response to a severe infection. It is a benign proliferation of WBCs with a high leukocyte count but usually less than 50x10^9/L. Toxic granulation, vacuolization, and Dohle bodies are present in NLR. Both CML and NLR display a left shift so they may be confused with one another.
What is the growth factor that is primarily responsible for regulating granulocyte and monocyte production? A. Erythropoietin B. Colony stimulating factor C. Interleukin D. Thrombopoietin
B. Colony stimulating factor The growth factor mainly responsible for regulating the production of granulocytes and monocytes is granulocyte/monocyte colony-stimulating factor (GM-CSF), which acts on the committed bipotential progenitor cell CFU-GM (colony forming unit-GM). GM-CSF stimulation of granulocyte or monocyte production increases in response to need and can also affect the production of erythrocytic and megakaryocytic lineages. G-CSF induces granulocyte differentiation, and M-CSF supports monocyte differentiation. EPO is a lineage-specific growth factor responsible for stimulating erythrocyte production, and TPO is mainly responsible for regulating platelet production. Interleukins, in particular IL-3, influence multiple cell lines including granulocytes and monocytes.
Which of the following statements does not correctly describe the WHO classification of hematopoietic neoplasms? A. Acute leukemia is defined as the presence of at least 20% bone marrow blasts B. Diagnosis is based on cellular morphology and cytochemistry C. It groups lymphoid disorders into B cell, T/NK cell, and Hodgkin lymphoma D. Diagnostic criteria include morphologic, cytochemical, immunologic, cytogenetic, and molecular features
B. Diagnosis is based on cellular morphology and cytochemistry The FAB classification of acute leukemias, myeloproliferative disorders, and myelodysplastic diseases was originally based on cellular morphology and cytochemistry (immunophenotyping was later added). Using FAB criteria, acute leukemia was defined as greater than 30% bone marrow blasts. The diagnostic criteria used by WHO includes morphologic, cytochemical, immunologic, cytogenetic, and molecular features, as well as clinical findings, to better characterize all hematologic maglinancies (myeloid and lymphoid) and predict disease course. The WHO classification defines acute leukemia as the presence of 20% or more bone marrow blasts and includes diagnostic categories with recurrent cytogenetic abnormalities. According to the WHO classification, lymphoid disorders are grouped into B cell, T/NK cell, and Hodgkin lymphoma. Further division of the B and T cell neoplasms considers site of involvement and precursor cell versus mature cell conditions.
Which of the following statements about eosinophils is false? A. They contain a type of peroxidase that is distinct from that of neutrophils B. Eosinophilic granules contain lysozyme C. Eosinophils are an important line of defense against parasites D. Major basic protein is a component of eosinophil granules
B. Eosinophilic granules contain lysozyme Eosinophils lack lysozyme which is present in neutrophils and monocytes and contain a distinctive peroxidase that differs biochemically from the myeloperoxidase of neutrophils and monocytes. Major basic protein is a component of the granules and is very important to the ability of eosinophils to control parasites. In addition, eosinophils play a role in modifying the allergic reactions caused by degranulation of basophils. Basophils release eosinophil chemotactic factor of anaphylaxis (ECF-A), which calls eosinophils to the site.
An adult patient with massive splenomegaly has mild anemia, a slightly elevated WBC count, and an LAP score of 170. The blood smear shows teardrop erythrocytes and leukoerythroblastosis. These findings are most consistent with A. Chronic myelogenous leukemia B. Idiopathic myelofibrosis C. Primary polycythemia D. Primary thrombocythemia
B. Idiopathic myelofibrosis The BM is progressively replaced by fibrotic tissue in myelofibrosis, a chronic myeloproliferative disorder. Attempts to aspirate BM usually result in a dry tap. A biopsy stain demonstrates increased fibrosis. The presence of teardrop-shaped RBCs is an important feature of myelofibrosis. In addition, abnormal platelets, a leukoerythroblastic blood profile and myeloid metaplasia in the spleen and liver are often associated with this disease. A high LAP score (ref 13-160) and increased RBC mass are found in polycythemia vera, but the LAP score is low in CML.
In a patient with fever of unknown origin, which of the following findings is not consistent with an inflammatory process? A. Increased CRP B. Increased albumin C. Increased fibrinogen D. Increased ESR
B. Increased albumin The overall reaction of the body to tissue injury or invasion by an infectious agent is known as inflammation. This response brings leukocytes to the site of infection or tissue damage and is associated with activation of inflammatory mediators, including cytokines (IL-1), molecules released by cells (histamine), and byproducts of plasma enzyme systems (complement, kinins, fibrin). The plasma concentration of positive acute-phase reactants such as CRP and fibrinogen, can increase dramatically in response to inflammation, and levels of albumin and transferrin will fall (negative APRs). The ESR will be elevated, primarily because of the rise in fibrinogen.
What percentage of neutrophils in the peripheral blood constitutes the circulating pool? A. 100% B. 80% C. 50% D. 30%
C. 50% Approximately 50% of the neutrophils in the PB are found in the circulating pool. This is the pool measured when a total WBC count is done. Another 50% are found adhering to vessel walls (marginal pool). These pools are in constant exchange. Emotional/physical stimuli can cause a shift of cells from the marginating to the circulating pool causing a transient rise in the total WBC count. The total WBC count can double but return to normal within several hours.
The presence of the chromosomal abnormality t(15;17) and a high incidence of DIC is diagnostic of A. AML without maturation (M1) B. AML with maturation (M2) C. APML (M3) D. AMML (M4)
C. APML (M3) The abnormal cells found in acute promyelocytic leukemia (M3) contain large numbers of azurophilic granules. These granules contain procoagulants that on release hyperactivate coagulation, resulting in DIC. Although other acute leukemias may trigger DIC, M3 is the one most frequently associated with this life-threatening bleeding complication. If DIC is resolved, many patients with APML respond favorably to therapy with retinoic acid, which causes maturation of the malignant promyelocytes. The presence of t(15;17) has diagnostic and prognostic significance, and APML is classified with acute myeloid leukemias with recurrent cytogenetic translocations by WHO. AML with t(8;21) is also included in this WHO category (M2).
Blast cells that are CD14 and CD33 positive, Sudan black B positive, specific esterase positive, and nonspecific esterase positive. Which type of acute leukemia is most consistent with the immunophenotyping and cytochemical staining results? A. Acute lymphoblastic leukemia, T cell type B. Acute erythroleukemia C. Acute myelomonocytic leukemia D. Acute monocytic leukemia
C. Acute myelomonocytic leukemia The acute leukemia indicated by these results is acute myelomonocytic leukemia (AMML), which has both granulocytic and monocytic features. CD14 is a monocytic marker and CD33 is a marker for primitive myeloid cells. The SBB shows positive staining in both granulocytic and monocytic cells, the specific esterase stains positive in granulocytic cells, and the nonspecific esterase is positive in monocytic cells.
In patients with IM, which blood cells are infected by the causative agent? A. Monocytes B. T lymphocytes C. B lymphocytes D. Histiocytes
C. B lymphocytes The EBV attaches to receptors on B lymphocytes, and the virus is incorporated into the cell. The infection generates an intense immune response of T cells directed against infected B cells. It is the activated T lymphocytes that comprise the majority of reactive lymphocytes seen in the blood of patients with IM. Other B cells produce nonspecific polyclonal antibody in response to the EBV infection.
Which of the following myeloproliferative disorders is characterized by the presence of a t(9;22) chromosome abnormality and the BCR/ABL oncogene? A. PV B. ET C. CML D. Chronic idiopathic myelofibrosis
C. CML The Philadelphia chromosome t(9;22) is found in precursor cells for erythrocytes, granulocytes, and platelets in at least 90% of cases of CML.
A patient with normal hemoglobin and WBC count values, a persistently elevated platelet count (>1000 x 10^9/L), increased marrow megakaryocytes, and a history of frequent bleeding and clotting episodes most likely has A. Polycythemia vera B. Chronic myelofibrosis C. Essential thrombocythemia D. Chronic myelogenous leukemia
C. Essential thrombocythemia Primary or essential thrombocythemia (ET) is a chronic myeloproliferative disorder in which the main cell type affected is the platelet. An extremely high number of platelets are produced, but abnormal platelet function leads to both bleeding and clotting problems. The BM shows megakaryocytic hyperplasia. The hemoglobin value and platelet count are increased in PV, and CML is characterized by a high WBC count. Malignant thrombocythemia must be differentiated from a reactive thrombocytosis seen in patients with infection or following surgery. In reactive causes, the platelet count is rarely over 1 million x 10^9/L, platelet function is normal, and thrombocytosis is transient.
Myeloid metaplasia refers to A. Displacement of normal marrow cells by fibrous tissue B. Hematopoietic failure C. Extramedullary hematopoiesis D. Tumors (neoplasms) of the bone marrow
C. Extramedullary hematopoiesis The production of hematopoietic cells in sites outside of the bone marrow can be referred to as myeloid metaplasia or extramedullary hematopoiesis. Hematopoiesis, with the exception of lymphopoiesis, is normally confined to the bone marrow during postnatal life. Production of erythroid, myeloid, and megakaryocytic elements can be established in the liver and spleen, similar to that which occurs during embryonic development. Myeloid metaplasia is frequently associated with myelofibrosis, a condition in which the marrow is gradually replaced by fibrotic tissue.
Which of the following would not cause a total WBC count of 62.2 x 10^9/L (62.2 x 10^3/uL) and toxic granulation with bands present in PB? A. Treatment with myeloid growth factors B. Gram-negative septicemia C. HIV D. Systemic fungal infection
C. HIV The elevated WBC count and toxic neutrophils indicate an extreme response to severe infection (bacterial septicemia, fungal) or treatment with recombinant myeloid growth factors. GM-CSF and G-CSF are used to increase cells for peripheral stem cell transplant and reduce infection in patients after high-dose chemotherapy or during transplant. A leukemoid reaction is one that mimics the type of blood picture seen in leukemia. It is associated with extremely high leukocyte counts (>50x10^9 cells/L) and is usually found in severe infection. The most common type of leukemoid reaction is neutrophilic, but lymphocytic leukemoid reaction also occur. HIV infection is associated with leukopenia and lymphocytopenia.
Which of the following statements about hairy cell leukemia is true? A. It is an acute disease, primarily affecting young adults B. Splenomegaly is an unusual finding C. Hairy cells contain tartrate-resistant acid phosphatase D. Hairy cells are abnormal T lymphocytes
C. Hairy cells contain tartrate-resistant acid phosphatase The malignant cells of HCL stain positive with acid phosphatase in the presence of tartaric acid; that is, hair cells contain tartrate-resistant acid phosphatase (TRAP). Normal cells stain acid phosphatase positive, but staining is inhibited by the addition of tartrate. HCL is a chronic disorder, mainly confined to the elderly. The spleen usually shows marked enlargement, but enlarged lymph nodes are very uncommon. Hairy cells are malignant B cells, and pancytopenia is usual at presentation.
Multiple myeloma is characterized by the presence in urine of large amounts of A. Cryoglobulins B. IgG heavy chains C. IgG light chains D. Beta microglobulins
C. IgG light chains The secretion of large amounts of monoclonal IgG or other immunoglobulin light chains by a malignant clone of plasma cells produces a characteristic M spike on serum and urine protein electrophoresis. In some cases, only the light chains are produced in excess. Because the light chains are easily cleared by the kidneys, they may appear only in the urine (Bence-Jones proteinuria). Renal impairment in multiple myeloma is associated with the toxic effects of filtered light chains. High levels of serum beta microglobulin correlate with the myeloma tumor burden. Cryoglobulins are proteins that precipitate in the cold and may be seen in multiple myeloma and Waldenstrom macroglobulinemia.
Which of the following is not a characteristic finding in polycythemia vera? A. Blood pancytosis B. Increase red cell mass C. Increased EPO level D. Increase blood viscosity
C. Increased EPO level Primary PV is a malignant myeloproliferative disorder characterized by autonomous marrow production of erythrocytes in the presence of low EPO levels. Usual findings include increased RBC mass, elevated hemoglobin values and variable degrees of leukocytosis and thrombocytosis. Splenomegaly, a high LAP score, thrombotic tendencies, and problems caused by blood viscosity are typical. Phlebotomy is done to reduce red cell mass.
Which of the following is not associated with neutrophilia? A. Staphylococcal pneumonia B. Crushing injury C. Infectious hepatitis D. Neoplasms (tumors)
C. Infectious hepatitis Acute viral hepatitis is associated with lymphocytosis. The major causes of neutrophilia are bacterial infection, neoplastic tumors, and inflammatory responses to tissue injury. "Toxic" neutrophils may be present (toxic granulation, Dohle bodies, vacuolization). Infection with organisms other than bacteria (fungi, some parasites, certain viruses) may also cause neutrophilia.
Which of the following characteristics would be least likely to distinguish reactive lymphocytes from monocytes? A. Sharp indentation of the cytoplasmic margin by adjacent red blood cells B. Presence of large azurophilic granules C. Irregular, indented nuclear shape D. Abundant, deeply basophilic cytoplasm
C. Irregular, indented nuclear shape The nucleus in both monocytes and reactive lymphocytes can be irregular in shape, with indentations, although a monocyte nucleus often has folds and lobulations. Reactive lymphocytes characteristically have an increased amount of dark blue cytoplasm, whereas monocyte cytoplasm is usually a blue-gray color. Lymphocytes lack the many fine granules that give monocytes a typical "ground glass" appearance of the cytoplasm, but monocytes can occasionally have larger granules. Sharp indentation of the cytoplasm by adjacent red cells and an increased number of large granules are features of reactive lymphocytes. Vacuoles, although more commonly present in monocytes, can also be seen in reactive lymphocytes.
Acute erythroleukemia (M6) is characterized by increased A. Promyelocytes and lysozyme activity B. Marrow megakaryocytes and thrombocytosis C. Marrow erythroblasts and multinucleated red cells D. Marrow monoblasts and immature monocytes
C. Marrow erythroblasts and multinucleated red cells More than 50% of the marrow cells are erythroid in acute erythroleukemia (M6). Giant erythroid precursors, bizarre and multinucleated red cells, and increased myeloblasts are found in the marrow and may appear in the blood. Acute erythroid leukemia is rare, and the disease typically evolves into acute myeloblastic leukemia (M1 or M2).
Vasodilation and bronchoconstriction are the result of degranulation by which of the following blood cells? A. Eosinophils B. Monocytes C. Neutrophils D. Basophils
D. Basophils Basophil granules contain histamine, a potent vasodilator and smooth muscle contractor that is responsible for the systemic effects seen in immediate hypersensitivity reactions, which are also termed anaphylaxis. Degranulation occurs when basophils are coated with an IgE type of antibody that recognizes a specific allergen, such as bee venom, certain plant pollens, or latex. The resulting anaphylactic shock can be life threatening.
In which of the following is progression to acute leukemia least likely? A. CML B. Refractory anemia with excess blasts (RAEB) C. Refractory anemia with ringed sideroblasts (RARS) D. CLL
D. CLL Progression to acute leukemia is a very unlikely event for patients with chronic lymphocytic leukemia, even though there is no cure. Patients with CML typically progress to blast crisis most often of myeloid type, unless treated with imatinib mesylate in the chronic phase. RAEB is the most likely type of myelodysplastic syndrome to develop AML. RARS is preleukemic but fairly stable.
In what disorder is significant basophilia most commonly seen? A. Hairy cell leukemia B. Plasma cell leukemia C. Acute lymphoblastic leukemia D. Chronic myelogenous leukemia
D. Chronic myelogenous leukemia Basophilia and eosinophilia is a typical finding in patients with chronic myelogenous leukemia (CML). A progressive increase in basophil number suggests transformation of the disease to a more accelerated phase. Myeloproliferative disorders such as CML, PV, or AML are often associated with peripheral basophilia, which is not a feature of lymphoproliferative disorders such as acute lymphoblastic leukemia, hairy cell leukemia, or plasma cell leukemia.
In what condition would an LAP score of 10 most likely be found? A. Bacterial septicemia B. Late pregnancy C. Polycythemia vera D. Chronic myelogenous leukemia
D. Chronic myelogenous leukemia Leukocyte alkaline phosphatase (LAP) scores are usually low in patients with CML. The LAP reflects alkaline phosphatase activity in neutrophils, and the score is usually elevated in conditions where neutrophils are activated and/or increased in number, such as late pregnancy, bacterial infection, and PV. The primary use of the LAP is to distinguish between the malignant cells of CML and a severe bacterial infection (leukemoid reaction). It may also be used to distinguish between CML and other chronic myeloproliferative disorders such as PV. The LAP may be called NAP (neutrophil alkaline phosphatase) stain).
Which of the following is characteristic of agranulocytosis? A. Neutrophils without granules B. Decreased number of granulocytes, red cells, and platelets C. Immature granulocytes in the peripheral blood D. Decreased numbers of granulocytes
D. Decreased numbers of granulocytes Agranulocytosis refers to an absence of granulocytes in both the peripheral blood and BM. A deficiency of granulocytes is found in cases of aplastic anemia, in which deficiencies in red cells and platelets also occur. The early release of cells from the BM will result in immature cells in the blood but is not referred to as agranulocytosis. Neutrophils that exhibit little or no granulation may be called hypogranular or agranular and are a sign of abnormal growth (dyspoiesis).
Which of the following is a typical finding in chronic leukemias at onset? A. Symptoms of infection and bleeding B. Significant thrombocytopenia C. Severe anemia D. Elevated leukocyte count
D. Elevated leukocyte count At presentation, patients with chronic leukemia (CML or CLL) consistently have elevated leukocyte counts, whereas individuals with acute leukemia may present with low, normal, or high leukocyte counts. The hallmark findings of anemia, thrombocytopenia, and neutropenia are often found in patients with acute leukemia at the time of diagnosis and are due to replacement of normal marrow hematopoietic cells by blasts. Patients with chronic leukemia may have few symptoms at onset, with anemia and thrombocytopenia developing during progression of the disease.
Which of the following is not among the diagnostic criteria used for classifying the myelodysplastic syndromes? A. Unexplained anemia refractory to treatment B. Hypogranular and hyposegmented neutrophils C. Abnormal platelet size and granulation D. Hypocellular bone marrow with 25% blasts
D. Hypocellular bone marrow with 25% blasts Myelodysplastic syndromes (MDSs) are characterized by a hypercellular bone marrow and up to 20% marrow blasts that distinguish MDS from acute leukemia (using WHO criteria). The blood and bone marrow blast percetages differ, and the risk of transformation to acute leukemia varies with the types of MDSs. These disorders are characterized by one of more peripheral blood cytopenias along with features of abnormal growth (dyspoiesis) in the bone marrow. A consistent feature in all types of myelodysplasia is unexplained and refractory anemia. Abnormalities may be morphologic and/or functional. Criteria that help define the types of myelodysplastic syndromes include megaloblastoid maturation of erythroid precursors, presence of multinucleated red cells, ringed sideroblasts, hypogrnaular and/or hyposegmented neutrophils, monocytosis, abnormal platelet morphology, circulating micromegakaryocytes, and degree of dyspoiesis.
Which of the following are characteristic findings in Waldenstrom disease? A. Increased IgA and hepatosplenomegaly B. Increased IgE and renal failure C. Increased IgG and hypercalcemia D. Increased IgM and blood hyperviscosity
D. Increased IgM and blood hyperviscosity Waldenstrom macroglobulinemia is caused by a proliferation of transitional B lymphocytes (lymphoplasmacytic or plasmacytoid lymphs) that secrete high amounts of monoclonal IgM. Because IgM is a macroglobulin, blood hyperviscosity is the cause of many of the symptoms found in this disease (bleeding and visual impairment). Plasmapheresis can reduce the IgM protein concentration. Hepatosplenomegaly is common in Waldenstrom disease (rather than bone lesions).
The presence of both immature neutrophils and nucleated erythrocytes in the peripheral blood is most accurately called a A. Neutrophilic left shift B. Regenerative left shift C. Neutrophilic leukemoid reaction D. Leukoerythroblastic reaction
D. Leukoerythroblastic reaction A leukoerythroblastic blood profile, which refers to the presence of both immature neutrophils and nucleated red cells, is most commonly associated with conditions involving BM infiltration by malignant cells (leukemia, cancer) or replacement by fibrotic tissue. A neutrophilic left shift is defined as presence of increased numbers of immature neutrophils in the blood without nucleated red cells. A regenerative left shift and a neutrophilic leukemoid reaction are characterized by varying degrees of leukocytosis and a neutophilic left shift, most often found in response to infection. In contrast, a degenerative left shift refers to leukopenia and a left shift that may occur if marrow pools are depleted in an overwhelming infection (use exceeds BM capacity to replace).
Which of the following is not commonly found in acute myelogenous leukemia? A. Neutropenia B. Thrombocytopenia C. Hepatosplenomegaly D. Lymphadenopathy
D. Lymphadenopathy Although a hallmark of acute lymphoblastic leukemias (ALL), lymphadenopathy is not associated with AML. ALL is also more liekly to have CNS involvement and the CNS is a potential site of relapse. Hepatomegaly and splenomegaly are associated with both types of acute leukemia, as well as with the presence of anemia, neutropenia, and thrombocytopenia. Common presenting symptoms are fatigue, infection, or bleeding. If untreated, both acute myelogenous and lymphoblastic leukemias have a rapidly fatal course.
What is the largest WBC normally found in the peripheral blood? A. Eosinophil B. Neutrophil C. Lymphocyte D. Monocyte
D. Monocyte Monocytes have a diameter up to 20um, making them the largest cells in the peripheral blood under normal conditions. Eosinophils and neutrophils have diameters of about 12um. The small lymphocyte is 8-9um in diameter, similar to the RBC which has a diameter of 6-8um. Large lymphocytes range in size from 11-16um in diameter.
Alder-Reilly anomaly is an abnormality of A. Lysosomal fusion B. Nuclear maturation C. Oxidative metabolism D. Mucopolysaccharide metabolism
D. Mucopolysaccharide metabolism Alder-Reilly anomaly is a hereditary autosomal recessive disorder caused by a deficiency of enzymes involved in the metabolism of mucopolysaccharides. Partially degraded mucopolysaccharides accumulate in various tissues, organs, and the leukocytes that are characterized by the presence of large azurophilic granules resembling toxic granulation. The inclusions do not affect leukocyte function and are referred to as Alder-Reilly bodies. The anomaly is often associated with facial and skeletal abnormalities, such as those seen in Hunter syndrome and Hurler syndrome. Lysosomal fusion with impaired degranulation is the defect in Chediak-Higashi syndrome and is associated with early death due to abnormal leukocyte function.
Which of the following is not produced by neutrophils during the respiratory burst? A. Hydroxyl radicals B. Hydrogen peroxide C. Superoxide anion D. Myeloperoxidase
D. Myeloperoxidase Myeloperoxidase is an enzyme present in the primary granules, regardless of the phagocytic activity of the cell. The products produced during the oxidative burst are generated in response to chemotactic activation and ingestion of microbes. Generation of oxygen metabolites is necessary for microbial killing.
Plasma cell myeloma is a clonal disease involving malignant end-stage B cells, in which overproduction of immunoglobulin is a hallmark and the presence of red cell rouleaux is a characteristic finding on the blood smear. A patient with plasma cell myeloma complains of fatigue and severe lower back pain. Which of the following would not be typical of this disease? A. Bone tumors of plasma cells B. Hypercalcemia C. Progressive renal impairment D. Normal sedimentation rate
D. Normal sedimentation rate Excessive amounts of monoclonal immunoglobulin result in the deposition of proteins on circulating red cells that causes red cell "coining". The erythrocyte sedimentation rate is extremely elevated because of spontaneous rouleaux formation. Multiple myeloma is characterized by bone pain and spontaneous bone fractures caused by tumors of plasma cells. Bone destruction leads to elevated calcium levels and renal impairment can result from damage by excess light chains. Plasma cells progressively crowd out normal bone marrow precursors and may be found in the blood circulation in advanced disease. Treatment with thalidomide has improved survival.
Which of the following represents the principal defect in chronic granulomatous disease (CGD)? A. Chemotactic migration B. Phagocytosis C. Lysosomal formation and function D. Oxidative respiratory burst
D. Oxidative respiratory burst Chronic granulomatous disease (CGD) is a hereditary disorder in which neutrophils are incapable of killing most ingested microbes. The disease is usually fatal because of defective generation of oxidative metabolism products, such as superoxide anions and hydrogen peroxide, which are essential for killing. Chemotaxis, lysosomes, phagocytosis and neutrophil morphology are normal. Several variants of CGD have been described, with specific enzyme defects and different modes of inheritance. The more common type of CGD has a sex-linked inheritance pattern.
Which of the following suggests a diagnosis of Hodgkin disease rather than other lymphoproliferative disorders? A. Presence of a monoclonal population of large lymphoid cells B. Predominance of immature B cells with irregular nuclear clefts C. Circulating T cells with a convoluted, cerebriform nucleus D. Presence of giant binucleated Reed-Sternberg cells with prominent nucleoli
D. Presence of giant binucleated Reed-Sternberg cells with prominent nucleoli The presence of Reed-Sternberg cells is the diagnostic feature of Hodgkin disease (lymphoma). The Reed-Sternberg giant cell is usually binucleated, and each lobe has a prominent nucleolus. Studies suggest that this neoplastic cell is of B cell lineage. It is not found int he blood but only in the tissues. Circulating T cells with a convoluted nucleus descirbe the Sezary cells seen in Sezary syndrome, the leukemic phase of mycosis fungoides. A monoclonal population of large lymphoid cells or immature B cells with nuclear clefts is most descriptive of lymphoma cells, present in certain types of peripheralized non-Hodgkin lymphoma, that have spread from the tissues to the BM and blood.
Which of the following factors is not associated with variations in the total WBC count? A. Age B. Exercise C. Emotional stress D. Sex
D. Sex The total WBC count reference ranges for males and females are equivalent. WBC counts do change with age, being higher in newborns and children than in adults. Any change from basal conditions, such as exercise or emotional stress, will cause a transient leukocytosis due to a redistribution of blood pools. WBC values are lower in the morning and higher in the afternoon (diurnal variation).
