question

Name the terms that represent an increase or a decrease in the number of total white cells and for each of the specific cell lines found in normal peripheral blood.

answer

-osis, -ilia = increase enia = decrease

question

Calculate the absolute number of a given cell line.

answer

Percentage (from the differential) x total WBC=absolute count

question

State the reference intervals for absolute numbers for each of the white cell lines in the peripheral blood in adults.

answer

Lymphocytes: 1-4.0 x 10^9/L Neutrophils: 1.8-7.0 x 10^9/L Basophils: 0-0.2 x 10^9/L Eosinophils: 0-0.5 x 10^9/L Monocytes: 0.2-1.0 x 10^9/L

question

State the approximate percentages found in a normal differential white cell count in adults.

answer

Lymphocytes: 25-35% Neutrophils: 40-85% Basophils: 0-2% Eosinophils: 0-5% Monocytes: 2-10%

question

State deviations from adult numbers for total WBC and neutrophil/lymphocyte proportions in newborns and children.

answer

Leukocyte count: newborn: 9-30 x 10^9/L child: 4.5-13.5 x 10^9/L Neutrophil: newborn: 4.5-18 x 10^9/L Child: 1.5-8.5 x 10^9/L Lymphocyte: newborn: 2-11 x 10^9/L child: 2-8.8 x 10^9/L

question

leukemoid reaction

answer

WBC count >25 x 10^9/L with neutrophils predominating usually; caused by severe infections or extreme tissue damage

question

leukoerythroblastosis

answer

nucleated RBCs and immature granulocytes seen in the peripheral blood

question

"left shift"

answer

increase in the number of band forms, myelocytes, metamyelocytes

question

Pseudoneutrophilia

answer

redistribution of marginating granulocyte pool to circulating granulocyte pool rather than true increase; bands and segs are in normal proportions

question

Reactive neutrophilia

answer

peripheral blood >7.0 x 10^9/L neutrophils, usually reaction to infection

question

Benign

answer

a condition, tumor, or growth that is NOT cancerous. This means that it does not spread to other parts of the body and it does not change or destroy nearby tissue

question

Recognize neutrophilia, neutropenia, eosinophilia, basophilia, and monocytosis from hematologic data

answer

Neutrophilia: >7.0 x 10^9/L in white adults Neutropenia: <2 x 10^9/L in white adults Eosinophilia: 0.2 x 10^9/L Monocytosis: >1.0 x 10^9/L

question

Describe the mechanisms by which immediate, acute and chronic neutrophilias develop.

answer

Immediate: redistribution of MGP neuts to CGP Acute: immediate response to a pathologic process within 4-5 hours of stimulus; marrow release from maturation and storage compartment Chronic: stimulus continues for more than a few days, the mitotic and stem cell pools are stimulated and bone marrow production increases; M:E ration increased.

question

State conditions and infections associated with true and with pseudo neutropenias.

answer

True: aplastic anemia, megaloblastic anemia, leukemias, most viral infections, a few bacterial infections, overwhelming bacterial infections and sepsis, drugs, chemicals, chemotherapy. Pseudoneutropenia: stress and exercise

question

agranulocytosis

answer

Drugs and chemotherapy; aplastic anemia

question

two of the most common causes of eosinophilia, of basophilia, and of monocytosis

answer

Eosinophilia: parasitic infections and allergic conditions Basophilia: hypersensitivity reactions and myeloproliferative disorders Monocytosis: tuberculosis malignant disease

question

Toxic granulation

answer

Blue-black granules in segmented neutrophils Origin: azurophilic (primary) granules

question

Dohle bodies

answer

small, oval, pale blue inclusions. Origin: remnants or aggregates of free ribosomes or rough ER

question

Cytoplasmic vacuoles

answer

especially multiple vacuoles in one cell. Origin: end stage of digestion of phagocytized material or fat or other stored substances

question

Agranular or hypogranular forms

answer

gray or gray/dusty rose colored cytoplasm. Origin: decreased number of granules or decreased affinity of granules for stain

question

state the significance of "drumsticks" on neutrophil nuclei. Distinguish drumsticks from other nonspecific nuclear appendages/small clubs.

answer

Attached to a nuclear lobe by a filament, completely condensed with no chromatin pattern; inactivated X chromosome. Small clubs-no narrow filament, chromatin pattern similar to neutrophil.

question

Ring nuclei

answer

seen in dysmyelopoiesis

question

Hypersegmentation of neutrophils

answer

6 lobes

question

Necrobiotic forms of cells

answer

dead cells with shiny chromatin, fragmented nucleus

question

Pelger-Huet anomaly

answer

autosomal dominant; failure of normal segmentation of neutrophil nuclei. No more than 2 segments, increased number of bands; resemble spectacles; coarse chromatin, normal function.

question

Chediak Higashi syndrome

answer

autosomal recessive; partial albinism, photophobia, abnormal large granules in leukocytes=fused granules; functional abnormalities of leukocytes-prevents granules from being delivered to the phagosomes to participate in killing of ingested bacteria. Frequent pyogenic infections and early death

question

Alder-Reilly anomaly

answer

autosomal recessive; dense azurophilic granulation resembling toxic granules; partially degraded protein carbohydrate accumulates; can be in all leukocytes or just one line

question

May-Hegglin anomaly

answer

autosomal dominant; pale blue inclusions resembling Dohle bodies; giant platelets; thrombocytopenia; can be in all leukocytes or just one line

question

antigen independent lymphopoiesis

answer

Antigen independent-development into immunocompetent T and B lymphocytes (virgin lymphocytes). Location: PRIMARY LYMPHOID TISSUE: nonadult bone marrow, thymus, fetal liver and yolk sac, paraaortic region.

question

antigen dependent lymphopoiesis

answer

antigenic stimulation of immunocompetent T and B lymphocytes (T and B cells react and remember antigen). Location: SECONDARY LYMPHOID TISSUE: adult bone marrow, spleen, lymph nodes, gut-associated lymphoid tissue. CLP->pre B->B cell->plasma CLP->pret T->T cell->CD4, CD8

question

Define CD designation.

answer

Cluster of differentiation: refers to a group of monoclonal antibodies recognizing the same protein marker antigen on a cell. They are used to classify cell types and stages of maturation

question

List significant CD and other markers that identify each stage of lymphocyte development.

answer

Pro-B, pre-B (lymphoblast): TdT, MHCII (HLA-DR), CD34, CD10, CD19 Intermediate B lymph: acquires surface immunoglobulin SIgM Mature B lymphocyte: Lose CD10, acquire CD21, CD22 Pro-T: CD34, TdT Pre-T: (CD34+/-) Tdt, CD7,5,2 Post T: CD7, CD5, CD2 Mature T lymphs: CD4 or CD8

question

6. Identify the reference % of each type of mature lymphocyte found in adult peripheral blood.

answer

Lymphocytes: 25-35% WBC count T lymphocytes: 80%-60-80% CD4, 20-40% CD8 B lymphocytes: 20%

question

Define lymphocytosis numerically in infants, children, and adults

answer

Infants: >11 x 10^9/L Children: >8.8 x 10^9/L Adults: >4.0 x 10^9/L

question

Differentiate between relative and absolute lymphocytosis.

answer

Relative: increased percentage usually due to decrease of neutrophils Absolute: true increase of lymphocytes for age

question

List causes of lymphocytosis. Differentiate between conditions, which result in large numbers of reactive forms of lymphocytes, in smaller numbers of reactive forms or in normal morphology.

answer

Lymphocytosis with nonreactive, small mature lymphs: Infectious lymphocytosis, Pertussis "whooping cough" Lymphocytosis with increased reactive lymphs >20% (>1,000/uL): infectious mononucleosis, cytomegalovirus, infectious hepatitis, toxoplasmosis, certain drugs. Lymphocytosis with <20% reactive lymphocytes: viral infections in general

question

4. Describe the associated age group, general disease picture and blood picture associated with acute infectious lymphocytosis and Bordetella

answer

Occurs in children; increased white count 20-50 x 10^9/L , 60-97% mature lymphocytes; tests for mono negative; increase in eosinophils as leukocytosis recedes. Symptoms: mild or none; lasts 3-5 weeks

question

EBV-the blood picture as the disease develops

answer

Absolute lymphocytosis >5 x 10^9/L; 60-90% of WBC lymphs; leukocytosis; reactive lymphs >1x10^9/L; pleomorphism

question

changes in lymphocyte morphology that would lead you to describe a cell as a reactive lymphocyte

answer

Increased total cell size, increased amount of cytoplasm, basophilia in cytoplasm, chromatin less dense, possible visible nucleoli

question

4 or 5 conditions that have the same blood picture as infectious mononucleosis and explain how they can be separated

answer

Cytomegalovirus, infectious hepatitis, toxoplasmosis, certain drugs; negative heterophil/heterophile antibody test

question

Describe the blood picture seen in most viral conditions other than those describe in the above objectives

answer

Lymphocytosis with <20% reactive lymphocytes

question

Define lymphocytopenia numerically in different age groups.

answer

<1.0 x 10^9/L adults <2.0 x 10^9/L children

question

list 2-3 causes of lymphocytopenia

answer

Acquired immune deficiency disorders, disseminated neoplasms, chemotherapy, radiotherapy, corticosteroids, acute inflammatory disorders, chronic infection, stress, malnutrition

question

Neoplastic

answer

autonomous/unregulated growth or production of cells. The growth can be benign or malignant. In general, it means a tumor

question

Malignant

answer

uncontrolled growth resulting in cancer

question

Oncogenes

answer

altered cell genes that cause tumors

question

Proto-oncogenes

answer

normal unaltered cellular counterparts of oncogenes

question

Tumor suppressor genes

answer

suppress tumor growth (stop oncogenes)

question

Autonomous

answer

responding, reacting, or developing independently of the whole

question

Panmyelosis

answer

increase in all cell types of the bone marrow

question

Clonal

answer

resulting from clones of one or multiple cells

question

Blast crisis

answer

>20% blasts of any type

question

Distinguish malignant from reactive conditions.

answer

Reactive conditions are part of the normal regulatory mechanisms in response to infection or disease. Malignant conditions are uncontrolled, unregulated growth not related to any infection or disease.

question

three types of myeloid neoplastic disorders of the bone marrow

answer

Myeloproliferative neoplasms (MPN)/disorders (MPD) Meylodysplastic syndromes (MDS) Acute leukemias-malignancy

question

4 diseases in the classification of myeloproliferative disorders and the cell line most affected in each

answer

Chronic myelocytic leukemia-overproductive of granulocytes Polycythemia vera-overproduction of erythrocytes Essential thrombocythemia-overproduction platelets Primary myelofibrosis (PMF)-overproduction of fibrosis tissue

question

State current theories of the pathophysiology of myeloproliferative disorders in general and of chronic myelogenous leukemia, specifically

answer

Clonal defects in pluripotential stem cell-some mutations known, some unknow. The cells are capable of maturation so that the cell types that are presentn are more mature than the blast. Pathophysiology of CML-Philadelphia chromosome, which increases tyrosine kinase production

question

clinical findings in chronic myelogenous leukemia

answer

Middle age (30-50), splenomegaly with feelings of fullness in the abdomen.

question

Identify and describe the Philadelphia chromosome by morphologic and molecular means. State the significance of the Philadelphia chromosome and BCR/ABL fusion in the diagnosis of chronic myelocytic leukemia

answer

Philadelphia chromosome is a translocation of chromosome 9 and 22, exchange info. BCR.ABL fusion on chromosome 22; tyrosine kinase production increased. Unregulated growth of the abnormal clone.

question

Calculate and explain the calculation and significance of the result of the leukocyte alkaline phosphatase (LAP)/neutrophil alkaline phosphatase (NAP) stain in the diagnosis of chronic myelocytic leukemia

answer

Count 100 neutrophils and classify the activity of the LAP/NAP enzyme found in secretory vesicles, 0-4. Multiply the cell rating by # of cells, total # of cells-score. REFERENCE INTERVAL 13-130

question

typical findings in the blood smear and bone marrow morphology in chronic myelocytic leukemia

answer

Blood- Extreme leukocytosis: >100 x 10^9/L; all stages of neutrophil precursors with myelocyte and metamyelocytes in greatest number (flower garden), <5% blasts. Nucleated RBCs, basophilia, eosinophilia and micromegakaryocytes possible. Anemia, increased platelets. Bone marrow- 90-100% cellular (very hypercellular) with similar proportions of blasts and promyelocytes. Increased M:E ratio

question

Describe the disease course of chronic myelocytic leukemia (that is, the changes that may occur in the patient's blood, bone marrow, and clinical features).

answer

Increased splenomegaly, increased WBC, thrombocytopenia, worsening anemia, increased basophils, increased blasts, increased fibrosis of marrow

question

Describe clinical and laboratory features that distinguish chronic myelocytic leukemia from neutrophilic leukemoid reaction

answer

Leukemoid reaction-neutrophils predominate

question

Define primary myelofibrosis (PMF)/myelofibrosis and myeloid metaplasia (MMM)

answer

Myelofibrosis with extramedullary hematopoiesis; fibrous tissue in the bone marrow

question

Describe the secondary (reactive) nature of the development of fibrosis in this disease.

answer

Fibrosis tissue normal, just responding to abnormal growth factors

question

three classic findings on a peripheral blood smear and describe other findings that are usually present (especially LAP/NAP and JAK2

answer

1. Leukoerythroblastic reaction-increase in presence of immature granulocytes and presence of NRBCs in peripheral blood. 2. Teardrops 3. Abnormal platelets-hypogranular, agranular, giant "dry tap", fibrosis of the bone marrow; JAK2 positive 50% of the time; LAP/NAP variable

question

Identify the diagnostic findings in the bone marrow. State the special stain used for diagnosis and explain the results.

answer

Dry tap; fibrosis of bone marrow; silver stain for reticulin fibers

question

identify the features that distinguish PMF/MMM from other MPD

answer

Fibrosis of the marrow, extramedullary hematopoiesis causing splenomegaly and hepatomegaly, and leukoerythroblastosis and teardrops in the PB.

question

Define polycythemia.

answer

Increased red cells in the blood

question

Describe the typical peripheral blood counts, peripheral blood smear features and the diagnostic features in the bone marrow.

answer

Total red cell mass increased >25% absolute erythrocytosis for gender; RBC 6-10 x 10^12/L, increased hgb and hct; crowding, normocytic, normochromic, few NRBCs; platelets increased, abnormal forms/function; increased WBC. Bone marrow-hypercellular, increased NRBCs and megakaryocytes

question

Describe the course of PV

answer

Anemia->myelofibrosis or acute leukemia in 5-10% Survival 8-15 years

question

Define and differentiate secondary polycythemia, relative polycythemia, and absolute polycythemia

answer

Secondary polycythemia-underlying cause for it, EPO increased. Relative polycythemia- Absolute polycythemia-

question

Identify the lab features that distinguish PV from the other MPD.

answer

Increased RBC, increased hct, EPO decreased

question

Differentiate essential thrombocythemia from secondary thrombocythemia

answer

Essential thrombocythemia-stem cell disorder that primarily affects the megakaryocyte lineage, idiopathic causes. Secondary thrombocythemia-underlying cause of disease

question

State the distinguishing features of the peripheral blood and bone marrow in essential thrombocythemia

answer

Increased platelet count >600 x 10^9/L, abnormal platelets Bone marrow-increase in # megakaryocytes

question

Define leukemia

answer

Stem cell disorder characterized by malignant neoplastic proliferation and accumulation of immature and nonfunctional hematopoietic cells in the bone marrow (increase number of immature white blood cells

question

Distinguish leukemic conditions from reactive processes

answer

Monoclonal vs. polyclonal: all the products from one cell are the same; one cell line taking over. Anemia, thrombocytopenia vs. normal red cells and platelets (in reactive processes) reactive: body reacting to something body has been exposed to.

question

Describe morphologic and clinical criteria by which acute and chronic leukemias are differentiated

answer

Acute: rapid onset of symptoms, very short length of survival without treatment, BLAST CELLS Chronic: insidious onset of symptoms, longer survival time without treatment, IMMATURE CELLS

question

Describe the criteria of three systems that are currently in use for classifying and subclassifying acute leukemias

answer

1. Classification by cell origin: myeloid vs. lymphoid Acute myelocytic, chronic myelocytic, acute lymphocytic, chronic lymphocytic 2. FAB system: Acute lymphocytic leukemias (lymphoblastic) 3 subtypes by morphology L1-L3, acute myelocytic leukemias (acute nonlymphocytic leukemias) subdivided into 8 subtypes M0-M7 based on morphology, degree of maturation, and cytochemical results 3. WHO system: based on FAB system but added immunophenotyping and cytogenetics to differentiate the origin of the leukemic blast cells and classify the type of acute leukemia.

question

Describe general peripheral blood and bone marrow findings in acute leukemias.

answer

PB: anemia, thrombocytopenia, WBC variable, neutropenia, blasts of the cell type that is malignant, blast and neutrophils, leukemic hiatus. BM: NEED TO MAKE DIAGNOSIS; increase in number of cells of the type of leukemia (usually blast stage); >30% blasts FAB, >20% WHO; hyperplasia (hypercellularity), decreased number of normal cells

question

State the level of blast forms necessary for the diagnosis of acute leukemias

answer

>20% WHO >30% FAB

question

State the importance of bone marrow examination for the diagnosis of leukeimas.

answer

Required to make diagnosis and differentiate from other conditions that present with similar blood and clinical findings.

question

Identify the stem cells involved in the origin of acute myeloid leukemias (AML).

answer

CFU-GEMM or CFU-GM

question

Recognize synonyms for acute myeloid leukemias

answer

Acute myelocytic leukemia Acute myelogenous leukemia Acute granulocyte leukemia Acute non-lymphocytic leukemia Acute myelobastic leukemia

question

Describe peripheral blood findings in AML in general (WBC count, differential, abnormal WBC morphology, RBC parameters and morphology, platelet number and morphology) and bone marrow findings.

answer

WBC varies; BLASTS present; Auer rods ONLY FOUND IN AMLs; may or may not have more mature granulocytes (usually neutropenia), may see basophilia, eosinophilia. May or may not have pseudo-pelger and/or hypogranular neutrophils. Normocytic, normochromic anemia, NRBCs, elliptocytes may be present. Platelets ALWAYS decreased and may see abnormal forms, may see micromegakaryocytes Bone marrow: hypercellular, sometimes some fibrosis

question

Identify the general morphology of blast cells.

answer

Large cells, high N:C ratio, pale to medium blue cytoplasm, few if any granules, nucleus round or lobulated, 2-5 nucleoli, fine chromatin, may have Auer rods

question

Describe the morphology, significance and composition of Auer rods

answer

FOUND ONLY IN AMLs; fused primary granules, red in color, rod shaped. If they are found, the blasts are myeloid in origin, NOT lymphoid, NOT chronic.

question

Name each of the WHO not otherwise categorized/FAB subtypes of acute myeloid leukemias by number and by cell type(s) for M0-M5

answer

FAB: M0: Acute myeloblastic leukemia: minimally differentiated M1:Acute myeloblastic leukemia with no maturation M2: Acute myeloblastic leukemia with maturation M3: Acute promyelocytic leukemia (not in WHO) M4/eo: Acute promonocytic leukemia/with eosinophilia M5a/b: Acute monoblastic leukemia with or without maturation

question

List the cell lineages that are included in acute myeloid leukemias

answer

The myeloid cell line-granulocytes: neutrophils, basophils, eosinophils, monocytes

question

Peroxidase

answer

The myeloperoxidase stain distinguishes between the immature cells in acute myeloblastic leukemia (cells stain positive) and those in acute lymphoblastic leukemia (cells stain negative)

question

Sudan Black B

answer

Granulocytic precursors demonstrate groups of coarse blue-black deposits. Other hematopoietic cells are typically negative.

question

Chloroacetate esterase (specific)

answer

This stain identifies granulocytes, which show red granules

question

"alpha-naphthol butyrate" or Nonspecific esterase

answer

- Monocytes and their precursors (promonoblasts and monoblasts) stain a pretty red color with this stain. Neutrophils and their precursors (including myeloblasts), and most of the other types of cells in the bone marrow (except cells of the megakaryocytic lineage, which are sometimes positive), are negative.

question

acid phosphatase

answer

The TRAP stain is primarily used to identify hairy cell leukemia cells. These cells stain with purple to dark red granules.

question

terminal deoxynucleotidyl transferase (TdT)

answer

TdT stain differentiates between acute lymphoblastic leukemia (cells stain positive) and acute myelogenous leukemia (cells stain negative).

question

State the morphologic criteria of the WHO not otherwise classified subtypes of the acute myeloid leukemias (cell types involved, immunophenotype, special stains, cytogenetics

answer

M0-AML minimally differentiated-Blasts; NO AUER RODS-CD13, 33, 34, CD14 M1-AML without maturation->90% myeloblasts, rarely auer rods-CD13, 33, 34 M2-AML with maturation-all stages of neutrophil maturation; 30-89% blasts; maybe auer rods; pseudo-pelger, agranular neuts-CD13, 33, 34, can be CD19+ M4-Acute myelomonocytic leukemia (AMML)-neutrophil and monocyte precursors present; >20% myeloblasts, monocytes >20% but 80% of nonerythroid cells are monocytic M0-stains negative M1-M2-peroxidase, sudan black B and s. esterase + M4-peroxidase + s. esterase + ns esterase +/-

question

Identify the significance of the CD markers: CD34, CD13, CD33, CD14, and CD19.

answer

CD13, 33, 65-to differentiate AML from ALL-usually positive and ID AML CD13, 33-to differentiate subtypes of AML-present in most myeloid cell types. CD 14 MONOCYTOID CD34 is a stem cell marker and may be positive in early, extremely immature AML or ALL blasts

question

Identify the significance of the following cytogenetic and/or molecular abnormalities in AML: t(15:17), t(8:21), inv(16), t(16:16)(p13:q22)/WHO-AML with genetic abnormalities and trisomy 8

answer

t(15: 17)-acute promyelocytic leukemia; predominant cell is the promyelocyte t (18:21)-AML1/ETO fusion (M2) inv(16) or t(16:16)(p13:q22)-monocyte and granulocyte immature cells seen; presence of abnormal eosinophils in the BM; AMML Eo (M4) Trisomy 8: (M1)-Acute myelocytic leukemia without maturation; >90% myeloblasts

question

Define lymphoma and differentiate from leukemia

answer

Lymphoma is a disease that begins in the lymph nodes or other lymph tissue-most often B cells but rarely T cells Leukemia is a disease that primarily affects the bone marrow and peripheral blood

question

Recognize synonyms for acute lymphocytic leukemia

answer

Lymphoblastic leukemia Lymphoid leukemia

question

Describe the typical peripheral blood picture (counts and smear morphology) in acute lymphocytic leukemia.

answer

WBC count varies, neutropenia, LYMPHOBLASTS; normocytic, normochromic anemia. Might see elliptocytes, thrombocytopenia. BM: hypercellular, >20% blasts; NO AUER RODS

question

Describe the reactions of the following special stains in acute lymphocytic leukemia: Peroxidase sudan black b specific esterase nonspecific esterase acid phosphatase

answer

a. Peroxidase-negative b. Sudan Black B-negative c. Chloroacetate esterase (specific esterase)-negative d. Nonspecific esterase-negative or weak positive in B and Null cell ALL bit positive in T cell types e. Acid phosphatase-positive

question

Identify the significance of the results of terminal deoxynucleotidyl transferase (TdT), CD10, CD19, the presence of cytoplasmic mu chains, surface immunoglobulin, CD2, CD5, CD7 in identifying the immunophenotypes of the acute lymphocytic leukemias

answer

TdT-differentiate lymphoblasts from mature lymphocytes CD10-Intermediate Pre-B CD19-B cell marker CD2, 5, 7-T cell markers sIg-CLL, PLL, HCL Cmu-Pre B cell

question

Identify the cellular morphologic features that distinguish L1, L2, and L3 types of blasts (FAB)

answer

L1: small blast, nucleus regular shape, occasional clefts; chromatin homogeneous; cytoplasm scant L2: typical blast, nucleoli more obvious; nucleus irregular in shape, indentations; chromatin pattern heterogeneous; cytoplasm abundant L3: # of vacuoles in cytoplasm, very deep basophilia

question

Differentiate 4 immunologic types of acute lymphocytic leukemias based on the immunophenotype.

answer

Pro-B cell ALL TdT, CD34, 19 Intermediate Pre-B cell ALL TdT, CD19, 10 Pre-B cell ALL CD19, 20, cIg mu T-ALL TdT, CD2, 5, 7

question

Identify the significance of karyotype analysis in the acute lymphocytic leukemias.

answer

60-75% of ALL patients have some type of chromosome abnormality in the abnormal lymphoblasts

question

State the approximate over all incidence of leukemia in the general population and the most common subtypes in adults and in children

answer

Overall incidence: 8-10 new cases per 100,000 per year ALL most common in children ages 2-5 AML most common in adults over 50

question

Identify the factors associated with the etiology of leukemias

answer

Oncogenes, tumor suppressor genes

question

Describe the symptoms, consequences, and complications associated with acute leukemias

answer

Symptoms: fever, fatigue, weakness, weight loss, night sweats, persistent bone or joint pain, blurred vision, nausea, vomiting; enlarged lymph nodes, liver, spleen, neurologic symptoms Consequences: increase in infections and bleeding

question

Identify the types of treatment used for leukemias. Explain laboratory involvement in treatment

answer

Chemotherapeutic agents; bone marrow, stem cell, cord blood, transplants; radiation; growth factors Lab monitor the treatment's effects on lab values

question

Identify factors that affect prognosis of patients with acute leukemias

answer

Long complete remission with treatment, age 2-9 best, ALL better than AML

question

Name three conditions included as chronic lymphoid disorders

answer

Chronic lymphocytic leukemia Hairy cell leukemia Prolymphocytic leukemia

question

Describe or explain the relationship of these cells in these conditions in the normal B cell maturation scheme

answer

Chronic lymphocytic leukemia-intermediate B cells Prolymphocytic leukemia- intermediate B cell Hairy cell leukemia-mature B cell

question

chronic lymphocytic leukemia

answer

A progressive clonal accumulation of lymphocytes that morphologically appear mature, but they are functionally incompetent.

question

chronic lymphocytic leukemia age range

answer

adults >50

question

chronic lymphocytic leukemia possible immunologic cell types and the approximate percentage of each

answer

95% are B cell in origin

question

Chronic Lymphocytic Leukemia: Describe the peripheral blood picture, the bone marrow picture and the typical immunophenotype

answer

PB: leukocytosis; lymphocytes >5 x 10^9/L; cracked appearance of the nuclear chromatin, many "smudge cells", appearance is monotonous; may have anemia and thrombocytopenia BM: monotonous cell picture >30% of cells; at least 30% lymphocytes Immunophenotype: MHCII +, CD19 +, CD10 -, weak sIg, CD5 postiive, may be CD23 + (T cell markers)

question

Chronic Lymphocytic Leukemia: Identify complications of the disease

answer

Some develop autoimmune hemolytic anemia

question

CLL: Describe the clinical course of the disease

answer

May live 2-20 years; can become more aggressive disease->prolymphocytic leukemia or Richter transformation

question

List some diseases that may be confused with chronic lymphocytic leukemia and explain how they can be separated

answer

Reactive lymphocytosis: difference-monotonous cell picture, cracked chromatin appearance of nucleus

question

For hairy cell leukemia: Identify the cell type involved and where it fits in the scheme of lymphocyte development

answer

Most often B cells more mature than the lymphs in CLL and PLL; no normal counterpart

question

HCL: State the most common age and sex of the patient

answer

More common in males, usually older

question

Describe some frequent symptoms of HCL

answer

Splenomegaly, fatigue, weight loss, abdominal discomfort, bleeding, infections

question

Describe the peripheral blood picture of HCL

answer

Pancytopenia, Hairy cells, normocytic normochromic anemia

question

describe the immunophenotype of HCL

answer

Similar to CLL (MHCII +, CD19 +, CD10 -) except CD5-, strong sIg, CD25+

question

Identify morphologic features of a "hairy cell" seen with Wright's stain

answer

Hairy cells-large lymphocytes; cytoplasm pale-light blue with "hairy" projections

question

Describe the bone marrow morphology on hairy cell leukemia

answer

"dry tap", widely spaced cells with "halo" or "fried egg" appearance

question

Name and identify the principle of the special stain's most useful for the diagnosis of hairy cell leukemia

answer

TRAP-tartrate resistant acid phosphatase: Iso enzyme 5 tartrate resistant found in HCL

question

For prolymphocytic leukemia: Describe the morphology of the peripheral blood on Wrights' stain

answer

Extreme lymphocytosis >300 x 10^9/L

question

Prolymphocytic leukemia: Identify the immunophenotype

answer

B cell-Strong sIg, CD22+, CD11c-, CD5- T-cell-CD2, 3, 5+

question

Describe the morphology of a normal plasma cell. Explain the cellular constituent responsible for the color of the cytoplasm.

answer

Oval, eccentric nucleus, spoked chromatin; the rough ER where antibody production occurs.

question

Define and name two synonyms for multiple myeloma.

answer

Malignant disease in which abnormal plasma cells proliferate; plasma cell myeloma, plasma cell dyscrasia.

question

Name the conditions that are defined as plasma cell disorders

answer

Plasma cell myeloma/multiple myeloma, plasmacytoma, primary amyloidosis, heavy chain disease, monoclonal gammopathy of undetermined significance (MGUS)

question

Plasma cell disorder

answer

Plasma cell disorder-clonal diseases in which abnormal plasma cells proliferate and produce excess immunoglobulins

question

Myeloma

answer

bone marrow tumor

question

Multiple myeloma

answer

a malignant disease in which abnormal plasma cells proliferate

question

Para-protein

answer

an immunoglobulin or immunoglobulin light-chain that is produced in excess by the clonal proliferation of plasma cells.

question

Describe the pathophysiology of multiple myeloma

answer

One plasma cell undergoes malignant transformation; malignant plasma cells have ability to divide by mitotic division. In bone marrow they proliferate as a clone. Cells migrate and produce multiple tumors. MONOCLONAL ANTIBODY

question

Describe prominent clinical symptoms and finding sin multiple myelomas.

answer

Expanding plasma cell mass. Replaces normal marrow-pancytopenia; pain. Increased monoclonal immunoglobulin, IgG or IgA; hyperviscosity. decreased normal Igs, kidney damage, bleeding, lytic bone lesions, pathologic fractures.

question

Describe the morphology of the peripheral blood and bone marrow of a patient with multiple myeloma.

answer

PB: rouleax, usually no plasma cells; normocytic, normochromic anemia; decreased leukocyte and platelet count; increased sed rate. BM: increased plasma cell-at least 10%; abnormal morphology

question

List laboratory tests that are useful in the diagnosis of multiple myeloma and correlate the results of the tests with the disease process.

answer

Serum and urine protein electrophoresis-monoclonal spike Quantitative immunoglobulins, increased BUN, increased calcium, increased uric acid, decreased albumin, C-reactive protein, bence jones proteins

question

Identify the nature and significance of Bence Jones protein

answer

Bence-Jones proteins are excess immunoglobulin light chains

question

Dysplastic

answer

change of phenotype (size,shape and organization of tissue)

question

Dispoiesis

answer

a disorder of formation; abnormal maturation division and production in the bone marrow

question

Myelodysplastic syndrome

answer

involve ineffective production (or dysplasia) of the myeloid class of blood cells

question

Name the disorders classified by the FAB group as myelodysplastic syndromes.

answer

Refractory anemia (RA)-anemia did not respond to treatment, 15% ringed sideroblast Refractory anemia with excess blasts (RAEB) 5-19% blasts Refractory anemia with excess blasts in transformation (RAEBt) >20% blasts Chronic myelomonocytic leukemia (CMML) increased monocytes

question

State the criteria used by the FAB group in classifying the myelodysplastic syndrome

answer

Percent of blasts in the blood Percent of blasts in the bone marrow Presence of ringed sideroblasts Presence of Auer rods Presence of monocyte forms

question

State the age range of patient with myelodysplastic syndrome.

answer

Primary disorder: >50 yrs Secondary: <50 yrs

question

Identify the primary differences between the FAB and WHO classification systems for the myelodysplastic syndromes

answer

Removed RAEBt-now an AL Made new categories such as refractory cytopenia with multilineage dysplasia (RCMD) and 5q syndrome. Removed CMML and made new category: myelodysplastic/myeloproliferative disorders.

question

Identify some factors associated with the pathophysiology of the myelodysplastic syndromes

answer

Many genetic alterations occurring probably beginning in a myeloid stem cell; proposed mechanisms involve elevated tumor necrosis factor-alpha which leads to premature intramedullary cell death/apoptosis of the hematopoietic precursor cells. Unbalanced genetic abnormalities are thought to be responsible for ineffective hematopoiesis and cytopenias. Additional mutations as the disease progresses resulting in alteration of additional genes.

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