Hematology Ii Exam 2

Front 1

Define Leukemia

List the main, general side effects

Back 1

Malignancy of blood cells

Eventually crowd out bone marrow and difficulty fighting infections, controlling bleeding, and transporting oxygen

Front 2

What are the similarities and differences between acute and chronic leukemia?

Back 2

Acute:

Uncontrolled proliferation, arrested maturation, haitus development, decreased to moderately increased WBC, normal to decreased PLT

Chronic:

Uncontrolled proliferation, normal maturation, increased to markedly increased WBC, normal to increased PLT

Front 3

What are the most common types of laboratory testing that may be utilized to diagnose/monitor leukemias?

Back 3

-CBC and morphology of abnormal cells

-Cytochemical stains

-Flow cytometry

-Molecular

-Cytogenetics/Immunohemotyping

Front 4

What is the purpose of performing cytochemical stains?

Back 4

To aid in the diagnosis of acute leukemias (especially in cases where flow cytometry cannot give a definitive diagnosis).

Front 5

What cell type(s) and cell stage(s) is evaluated with the myeloperoxidase (MPO) stain?

Back 5

Blasts of the myelocytic and the monocytic cell lines

Front 6

What substance does the myeloperoxidase (MPO) stain identify and what is the staining pattern?

Back 6

Identifies peroxidase contained in the granules of myelocytic and monocytic cells.

Appears as a black-blue-brown precipitate in the cytoplasm of MPO positive cells.

Front 7

What cell types are pos/neg for myeloperoxidase (MPO) stain?

Back 7

Myelocytic +

Monocytic +

Lymphocytic =

Erythrocytic =

Front 8

What cell type(s) and cell stage(s) is evaluated with the Sudan Black B (SBB) stain?

Back 8

Blasts of the myelocytic and the monocytic cell lines.

Front 9

What substance does the Sudan Black B (SBB) stain identify and what is the staining pattern?

Back 9

Identifies lipids (sterols, neutral fats, phospholipids) that are found primarily in granules of neutrophils and monocytes.

Appears as black staining cytoplasmic granules.

Front 10

What cell types are pos/neg for Sudan Black B (SBB) stain?

Back 10

Myelocytic +

Monocytic +

Lymphocytic =

Erythrocytic =

Front 11

Back 11

MPO

Front 12

Back 12

MPO

Front 13

Back 13

SBB

Front 14

Back 14

SBB

Front 15

What are two helpful aids in interpreting cytochemical stains?

Back 15

Look at Wright's stain peripheral blood smear first to get an idea of roughly how many blasts are present.

Remember to look at cells with a higher N/C ratio (to avoid considering more mature cells in the interpretation)

Front 16

What cell type(s) and cell stage(s) is evaluated with the Specific Esterase stain?

Back 16

Blasts of the myelocytic cell line

Front 17

What substance does the Specific Esterase stain identify and what is the staining pattern?

Back 17

A granulocyte (myelocytic) specific esterase hydrolyzes an ester substrate (in granules) and a napthol compound is released, which then binds with a diazonium salt and precipitates.

Appears as colored precipitate in cytoplasm (color depends on kit but usually bright red)

Front 18

What cell types are pos/neg for Specific Esterase stain?

Back 18

Myelocytic +

Monocytic =

Lymphocytic =

Erythrocytic =

Front 19

What cell type(s) and cell stage(s) is evaluated with the Non-specific Esterase stain?

Back 19

Blasts of the monocytic cell line and weakly positive for the myelocytic cell line

Front 20

What substance does the Non-specific Esterase stain identify and what is the staining pattern?

Back 20

A nonspecific esterase hydrolyzes an ester substrate (in granules) and a napthol compound is released, which then binds with a diazonium salt and precipitates.

Appears as colored precipitate in cytoplasm (color depends on kit but usually bright red)

Front 21

What cell types are pos/neg for the Non-specific Esterase stain?

Back 21

Myelocytic weakly +

Monocytic strongly +

Lymphocytic =

Erythrocytic =

Front 22

What is the combined esterase stain and what is the staining pattern?

Back 22

Both specific and nonspecific esterase on same slide, but will stain myelocytic and monocytic cell lines different colors.

Front 23

What is the second (optional) step of the non-specific esterase stain and what cells are pos/neg?

Back 23

Second step is addition of NaF.

Monocytic cells are inhibited by NaF

Myelocytic cells are unaffected by NaF

Myelocytic w/NaF weakly +

Monocytic w/NaF =

Front 24

Back 24

Specific esterase myeloblasts

Front 25

What is the name of the esterase that the specific esterase stain detects?

Back 25

Napthol AS-D chloroacetate

Front 26

What is the name of the esterase that the non-specific esterase stain detects?

Back 26

Alpha-napthyl acetate or alpha-napthyl butyrate

Front 27

Back 27

Specific esterase myeloblasts

Front 28

Back 28

Non-specific esterase monoblasts

Front 29

Back 29

Non-specific esterase monoblasts

Front 30

Back 30

Non-specific esterase with NaF monoblasts

Front 31

Back 31

Combined esterase

Red myelo

Dark brown mono

Front 32

Back 32

Combined esterase

Blue myelo

Red-brown mono

Front 33

What cell type(s) and cell stage(s) is evaluated with the Periodic Acid Schiff (PAS) stain?

Back 33

Malignant Lymphocytic and Erythrocytic cells **negative for benign cells
Can use for blasts and mature cells meaning can use to diagnose both acute AND chronic leukemias

Front 34

What substance does the Periodic Acid Schiff (PAS) stain identify and what is the staining pattern?

Back 34

1) Periodic acid oxidizes glycogen, mucoproteins, and other high molecular wt. carbohydrates to aldehydes
2) Aldehydes react with Schiff reagent staining bright pink - chunky or block appearance

Front 35

What cell types are pos/neg for the Periodic Acid Schiff (PAS) stain?

Back 35

Myelocytic may be diffuse in neoplastic blasts

Monocytic blasts = (mature cells +)

Lymphocytic +

Erythrocytic +

Megakaryocytic diffuse +

(NOTE: ALL can show varied staining [diffuse] and some lymphoblasts of ALL may be PAS=)

Front 36

Back 36

Periodic Acid Schiff

ALL bone marrow

Front 37

Back 37

Periodic Acid Schiff

Child with ALL

Front 38

Back 38

Periodic Acid Schiff

Erythroid precursors in acute erythroid leukemia

Front 39

Back 39

Periodic Acid Schiff (diffuse +)

Acute megakaryocytic leukemia AML, M7

Front 40

What cell type(s) and cell stage(s) is evaluated with the Leukocyte Alkaline Phosphatase (LAP) stain?

Back 40

Myelocytic cells of the ~myelocyte stage and on (detects enzymatic activity of enzyme found in secondary/specific granules)

Front 41

What substance does the Leukocyte Alkaline Phosphatase (LAP) stain identify and what is the staining pattern?

Back 41

Stains for the substrate found in secondary/specific granules of neutrophils.

LAP enzyme hydrolyzes napthol AS-BI phosphate which then combines with dye and precipitates.

The more enzyme present the more precipitate (color depends on substrate used)

Front 42

How do you interpret the Leukocyte Alkaline Phosphatase (LAP) stain?

Back 42

Score a total of 100 PMNs and bands on a scale of 0-4+ based on amount of precipitate in cell

Then multiply the number of cells receiving each score by the number score they received. Add products of each score for total LAP score

Ex. (0+*20 cells) + (1+*20) + (2+*10) + (3+*30) + (4+*20) = 210

Front 43

What is the scale for grading LAP?

Back 43

Scale: if you pushed all the precipitate to one side, how much of the cell would it fill?

0+ = none?

1+ = 1/4 cell

2+ = 1/2 cell

3+ = 3/4 cell

4+ = whole cell

Front 44

What is the Leukocyte Alkaline Phosphatase (LAP) useful for?

Back 44

Used to investigate a shift to the left and determine the cause.

Malignant granulocytes (CML) = decreased LAP

Leukomoid reaction = increased LAP

Front 45

What are some typical causes of decreased LAP?

Back 45

Malignant granulocytes (CML)

PNH

Sideroblastic anemia

Myeloproliferative disorders

Front 46

What are some typical causes of increased LAP?

Back 46

Leukomoid reaction

CML of child which is Ph22 negative

3rd trimester of pregnancy

Polycythemia vera

Front 47

What are the LAP score interpretations?

Back 47

Condition - Appropriate LAP Score:

Normal - LAP 15-70

Leukomoid Rxn - LAP 150-365

CML - 0-24

**NOTE CML of child Ph22 neg usually high LAP

Front 48

Score these cells

Back 48

Front 49

Back 49

Positive LAP

Front 50

Back 50

Negative LAP

Front 51

What cell type is evaluated with the Tartrate Resistant Acid Phosphatase (TRAP) stain and why?

Back 51

Hairy cells of hairy cell leukemia

Because hairy cells contain acid phosphatase isoenzyme #5 which is resistant to tartric acid so it WILL stain

Front 52

What substance does the Tartrate Resistant Acid Phosphatase (TRAP) stain identify and what is the staining pattern?

Back 52

Hydrolyzed substrate (by acid phosphatase) that couples with a dye to form a red precipitate.

Tartric acid inactivates all normal isoenzymes of acid phosphatase so normal cells won't stain (almost all nonerythroid cells contain acid phos)

Front 53

Back 53

TRAP + hairy cells (red)

(notice neutrophils do not stain)

Front 54

What type of stain is the Terminal deoxyribonucleotidal transferase (TdT) stain, what is it used for and what cell type is it specific for?

Back 54

An immunoflourescent stain (not a cytochemical stain) used in flow cytometry for the detection of lymphocytic precursors.

Front 55

What substance does the Terminal deoxyribonucleotidal Transferase (TdT) stain and what is the interpretation?

Back 55

Stains specific enzyme (cell marker) that catalyzes the polymerization of deoxynucleotides that are found ONLY in lymphocytic precursors (absent in lymphocytes!)

Positive in ALL (L1 and L2)

Must interpret carefully, can be pos. in AML

Front 56

Back 56

TdT in T-cell lymphoblasts of ALL

Front 57

What is the FAB classification for Leukemias based on?

What does FAB stand for?

Back 57

Basedon bone marrow morphology and cytochemicalstains

>30 % Blasts (in both blood and BM)

French-American British

Front 58

What is the WHO classification for Leukemias based on?

What does WHO stand for?

Back 58

Adds cytogenetics andmolecular characteristics >20% Blasts (in both blood and BM)

(Usefulto physicians when diagnosing and planning appropriate treatment)

World Health Organization

Front 59

The analytical method for diagnosing leukemias is flow cytometry. How does it work and why is it useful?

Back 59

Immunohemotype cells by identifying antigen markers on cell surface by reacting with labelled monoclonal antibodies. Cells are also counted.

Useful for determining cell lineage, maturation level, treatment, prognosis, and for monitoring recurrence.

Front 60

What are the common cell markers for:

T-cells

Mature T-cells

B-cell precursors

B-cells

Back 60

T-cells: CD1- CD8

Mature T-cells: CD3

B-cell precursors: CD10

B-cells: CD19 - CD24

Front 61

What are the common cell markers for:

Myeloid cells

Monocytes

All WBCs

Back 61

Myeloid cells: CD11 - CD16

Monocytes: CD14 and CD64

All WBCs: CD45

Front 62

What are the common cell markers for:

Stem cells

MKs/PLTs

Back 62

Stem cells: CD34

MKs/PLTs: CD41, CD42, CD61

Front 63

What is minimal residual disease referring to?

Back 63

It's an early sign that leukemia is coming out of remission. If you catch it early, the better the prognosis for the patient.

Front 64

What is M0?

Back 64

AcuteMyeloblastic Leukemia (AML)

without CytologicMaturation

-Primitiveleukemic blasts that show no distinct myeloid morphological features

-Requires flow cytometry to diagnose

-No auer rods

-5% of adult AMLs

-Poor prognosis compared to other AMLs

Front 65

What is M1?

Back 65

AcuteMyeloblastic Leukemia (AML)

without Significant Maturation

>/= 30 %myeloblasts inblood and/or marrow -Auer rods maybe present

-WBC4000 - 300,000 / mm3

-DecreasedPlt

-Leukemiaof adults but also neonates

-ImmunologicalMarkers

-15%of all AML patients

-Course described as aggressive

Front 66

What cytochemical stains are positive for M1?

Back 66

MPO +

SBB +

Specific Est +

Nonspecific Est +/= (with or w/o NaF)

PAS =

Front 67

What cytochemical stains are positive for M0?

Back 67

None

Lackreactivity with conventional cytochemicalstains so requires flow cytometry or other immunohemotyping

Front 68

What is M2?

Back 68

AcuteMyeloblastic Leukemia (AML)

with Maturation

>/= 30 %myeloblasts inblood and/or marrow -Maturationpromyelocytestage and beyond (still many blasts, but further maturation too)

-Auer rodsmay be present

-25%of adult AMLs

-Maybe “acute phase”or “blast crisis” of CML

-ImmunologicalMarkers

Front 69

What cytochemical stains are positive for M2?

Back 69

MPO +

SBB +

Specific Est +

Nonspecific Est +/= (with or w/o NaF)

PAS =

Front 70

What leukemia can be a "blast crisis" of CML?

Back 70

M2

Front 71

What is M3?

Back 71

AcutePromyelocyticLeukemia (APL)

>/= 30 %myeloblasts and promyelocytes

-FrequentlyhaveAuer rods,some in bundles

-Abnormal promyelocytes haveextremely heavy granulation

-WBC4000 - 300,000 / mm3

-DecreasedPlatelets

-Usuallya leukemia of adults

Front 72

What cytochemical stains are positive for M3?

Back 72

MPO +

SBB +

Specific Est +

Nonspecific Est +/= (with or w/o NaF)

PAS =

Front 73

What is M3m?

Back 73

Acute Promyelocytic Leukemia (APL)

Microgranular variant

-Granulessosmall they cannot be seen by light microscopy

-Abnormalnuclear shape in some promyelocytes

-May bemistaken for an AML or AMoL

-ImmunologicalMarkers

Front 74

What is often a complication of treatment for M3 and M3m and how can patients be further treated for it?

Back 74

Disseminated Intravascular Coagulation (DIC)

-Schistocytes

-This results because when the malignant cells are killed, their heavy granulation is dumped out, which stimulates the coagulation cascade

-Patients need to be heparinized

Front 75

What cytochemical stains are positive for M3m?

Back 75

MPO +

SBB +

Specific Est +

Nonspecific Est +/= (with or w/o NaF)

PAS =

Front 76

What is the typical clue for detecting M3m when viewing a smear with light microscopy?

Back 76

Abnormal nuclear shape

"Overlapping circles"

"H"

"N"

Front 77

Back 77

M3m Abnormal nuclear shape

Front 78

What is M4?

Back 78

AcuteMyelomonocyticLeukemia (AMML)

>/= 30%blast with both myelocytic and monocyticfeatures

-Auer rods may be present

-WBC4000 - 300,000 / mm3

-DecreasedPlt

-20% of adult AMLs

-Immunologicalmakers

Front 79

What cytochemical stains are positive for M4?

Back 79

MPO +

SBB +

Specific Est +

Nonspecific Est +

Nonspecific Est w/NaF =/weakly +

PAS =

Front 80

What leukemia can demonstrate invasion of skin, gums, etc. and why?

Back 80

M4

Because monocyte cells become macrophages that can enter tissues

Front 81

What is M4Eo?

Back 81

Acute Myelomonocytic Leukemia w/Eosinophilia

-Similarto M4 with marrow eosinophilia

(abnormal and immature eosinophils)

-Immunologicalmarkers

Front 82

What is M5a?

Back 82

Acute MonocyticLeukemia (AMoL)

poorly differentiated

>/= 30% monoblasts inblood and/or marrow

-WBC4000 - 300,000 / mm3

-DecreasedPlt

-Usually found in children and young adults

-Infiltrationof the skin, gums, meninges and other body tissues by malignant cells

Front 83

What is M5b?

Back 83

Acute MonocyticLeukemia (AMoL)

differentiated

>/= 30% monoblasts inblood and/or marrow with a preponderance of promonocytes and monocytes in blood and/or marrow

-Usually found in children and young adults

-Infiltrationof the skin, gums, meninges and other body tissues by malignant cells

Front 84

What cytochemical stains are positive for M5a and M5b?

Back 84

MPO +/=

SBB +/=

Specific Est =

Nonspecific Est +

Nonspecific Est w/NaF =

PAS =

Front 85

What is M6a?

Back 85

Acute Erythroid Leukemia

AcuteErythroleukemia - DiGuglielmo

>/= 50% rbcprecursors and > 20% myeloblasts–Otherimmature myeloid cells may be present

-Maysee Auer Rods

Front 86

What is M6b?

Back 86

Acute Erythroid Leukemia

Pure Erythroleukemia

Pure rbcprecursors > 80% of marrow cellularity

Nomyeloid component

Front 87

What are characteristics common for both M6a and M6b?

Back 87

-Megaloblastoidchanges

-Bizarre RBCmorphology

-Many nRBCs(including blasts)

-Immature RBCsextremely abnormal

(giant and multinucleated forms, nuclear budding, nuclearfragmentation, vacuolated cytoplasm, cytoplasmic budding)

-Intenseerythroidhyperplasia

-Abnormalmegakaryocytes andplatelets may be present

Front 88

What cytochemical stains are positive for M6a?

Back 88

(Erythroid)

PAS +

(Myeloid)

MPO +

SBB +

Specific Est +

Nonspecific Est +/= (with or w/o NaF)

Front 89

What cytochemical stains are positive for M6b?

Back 89

PAS +

MPO =

SBB =

Specific Est =

Nonspecific Est =

Front 90

Back 90

Acute Erythroid Leukemia

Front 91

What is M7?

Back 91

AcuteMegakaryocytic Leukemia

-RarestAML, <1% of cases

>30% megakaryoblasts inmarrow

-mayresult in “dry tap” of BM

-ImmunologicalMarker

-Cytoplasmic blebbing in blasts

Front 92

What leukemia has been associated with myelofibrosis (fibrous tissue invading bone marrow)?

Back 92

M7

-Stimulatoryeffect of megakaryoblasts onfibroblasts (fibroblasts are normally in bone marrow but normally not stimulated)

-Somebelieve acute myelofibrosis maybe M7

Front 93

What is AcuteLeukemia of Ambiguous Lineage?

Back 93

Other RareAML like Leukemia

-Both lymphoidand myeloid characteristics

-Bi-lineage -mixed populationof cells

-Biphenotypic -expressed on same cell

Front 94

What is AcuteBasophilic Leukemia?

Back 94

Other RareAML like Leukemia

-Mustdistinguish from CML in blast phase

(CML has a lot of basophils in malignant CML population)

Front 95

What is AcutePanmyelosiswith Myelofibrosis?

Back 95

Other RareAML like Leukemia

-Malignantproliferation in all myeloid celllines (granulocytes, erythroid and megakaryocytes)

-Bonemarrow fibrosis

Front 96

The WHO classification of AML 'AMLwith recurrent genetic abnormalities' includes what FAB leukemias?

Back 96

M4Eo and M3

Front 97

The WHO classification of AML 'AML with multilineagedysplasia' includes what disease states?

Back 97

Thiscategory includes patients who have had a prior myelodysplastic syndrome (MDS) or myeloproliferative disease (MPD) that transforms into AML.

Ex. CML in blast crisis

Front 98

The WHO classification of AML 'AML and MDS, therapy-related' includes what disease states?

Back 98

Thiscategory includes patients who have had prior chemotherapy and/or radiation (for another malignancy) andsubsequently develop AML or MDS.

Front 99

The WHO classification of AML 'Acute Leukemia of Ambiguous Lineage' includes what leukemias?

Back 99

Acute bilineage leukemia

Acute biphenotypic leukemia

Front 100

What is the WHO classification of FAB M3?

Back 100

AMLwith t(15;17)(q22;q12)

Front 101

The WHO classification of AML 'AML not otherwise categorized' includes what leukemias?

Back 101

AML minimally differentiated (FAB M0)

AML without maturation (FAB M1)

AML with maturation (FAB M2)

Acute myelomonocytic leukemia (FAB M4)

Acute monoblastic/cytic leukemia (FAB M5)

Acute erythroid leukemia (FAB M6)

Acute megakaryoblastic leukemia (FAB M7)

Acute basophilic leukemia (FAB M8 ?)

Acute panmyelosis with myelofibrosis

Front 102

What is ALL?

Back 102

AcuteLymphocytic Leukemia

-Diseaseof children(2-10yr) 2ndpeak in midlife

-WBCoften >100,000 /mm3 (but 50% have normal or low WBC)

>/= 30% lymphoblasts inblood and/or marrow

-NOAuer rods

-Plt andgranulocytes decreased

-Immunologicalmarkers

Front 103

What malignancy is CNS infiltration especially common in?

Back 103

ALL

(Very common for patients to get spinal tap to look for malignant cells in CNS. If so, need to alter treatment because drugs won't cross blood/brain barrier)

Front 104

What is L1?

Back 104

Acute Lymphocytic Leukemia (ALL)

-mostcommon

-Smalllymphoblasts (hard to differentiate from mature lymphs)

-Occ. clefting,inconspicuous nucleoli and scanty cytoplasm, uniform population

Front 105

What is L2?

Back 105

Acute Lymphocytic Leukemia (ALL)

-Largelymphoblasts (look like reactive lymph)

-Irregular nucleus, often prominent nucleoli, often moderate/abundant cytoplasm,cellular heterogeneity

Front 106

What is L3?

Back 106

Acute Lymphocytic Leukemia (ALL)

-Leukemicconversionof Burkitt’slymphoma

-Largeblasts with very basophiliccytoplasm

-Punch-outvacuoles

-TdT negative

Front 107

What cytochemical stains are positive for ALL?

Back 107

L1 and L2:

PAS +

TdT +

L3:

PAS +

TdT =

Front 108

Back 108

ALL - L1

Front 109

Back 109

ALL - L2

Front 110

Back 110

ALL - L3

Front 111

What are the WHO classifications or ALL?

Back 111

-Precursor B-cell ALL (Early Pre-B-cell ALL and Pre-B-cell ALL) [L1, L2 morphology]

-B-cell ALL [L3 morphology]

-T-cell ALL [L1, L2 morphology]

Front 112

What are the structural differences between normal and cancer cells?

Back 112

Normal:

Large cytoplasm, Single nucleus, Single nucleolus, Fine chromatin

Cancer:

Small cytoplasm, Multiple nuclei, Multiple and large nucleoli, Coarse chromatin

Front 113

Remember!

Back 113

Patient will have own population of cells when they have a malignant population.

This mixture of malignant and benign cells will continue until the marrow is entirely replaced by the malignant population.

Front 114

What are myelproliferative disorders (MPD)?

Back 114

Clonal disorder of hematopoietic stem cell

Classifications:

*Acute- ANLLs

*Chronic- Myeloproliferative disorder

Front 115

What are the diseases included in the category 'Chronic Myeloproliferative Disorders'?

Back 115

-Chronic Myelogenous Leukemia (CML or CGL)

-Chronic Neutrophilic Leukemia

-Chronic Monocytic Leukemia(?) (used to be?)

-Polycythemia vera (PV)

-Essential (primary) Thrombocytosis (ET)

-ChronicIdiopathic Myelofibrosis

Front 116

What are the common characteristics of MPDs?

Back 116

Varying extents of:

-Panhyperplasia of BM

-Extramedullary hematopoeisis

-BMfibrosis

-Overlapping manifestations between diseases

-Frequently terminate in an acute leukemia

-BM:increased megakaryocytes-often abnormal

-Platelet dysfunction

-Cytogenetic abnormalities

Front 117

What is CML?

Back 117

Chronic Myelogenous Leukemia

-Most common in people over 45 years of age

-Abnormal Philadelphia chromosome (Ph22)

(Ph22negative CML tend to have atypical disease, more acute course, less responsive to chemotherapy)

-Eosinophilic and Basophilic leukemias are rare variants of CML and usually run an extremely acute course.

Front 118

What is Ph22 and what does it do?

Back 118

Philadelphia chromosome

Fusion gene BCR-ABL that results from the translocation of chromosome 22 to chromosome 9 [t(9;22)]

Produces specific tyrosine kinase, which stimulates the uncontrolled production of abnormal blood cells. Apoptotic functions are lost.

Front 119

What are the lab findings of Chronic Myelogenous Leukemia (CML)?

Back 119

~90% ofCML are Ph22 positive

-WBC 50,000-800,000/mm3 (high!)

-Large number mature/immature granulocytes

-Shiftto the Left (fewer than10% blasts)

-LAPdecreased

-Usually remarkablethrombocytosis

-Anemia (maysee a few nrbcs)

-Often have increased basophils (occ. Eos)

-Hypercellular marrow,M:E ratio 10:1 to 50:1

Front 120

What disease could you maybe find pseudo- Pelger-Huet cells and/or pseudo- Gauchercells?

Back 120

CML

(pseudo-Gaucher cells are sea-bluehistiocytes inmarrow)

Front 121

What are the lab findings in CML if the disease is left untreated?

Back 121

-Eventuallydiseaseprogresses to an acute leukemia “blast crisis” or “acute transformation”

-TransformstoAML (M2)or ALL(rarely others)

-Afteracutephase transition, the life expectancy is 2-6 months

Front 122

What disease can look like a leukomoid reaction and what would you do to differentiate?

Back 122

CML because of increased granulocytes and shift to the left

Perform LAP to differentiate

CML- decreased LAP

Leukomoid reaction- increased LAP

Front 123

What is Chronic Neutrophilic Leukemia?

Back 123

-Very rare

-Very high WBC

-Slightlydecreased Plt

-Mildanemia

-Persistenceof neutrophilic leukocytosisw/o evidence of left shift and absence of sepsis

-Bandspresent yet <10% immature neutrophils in blood (mature cells)

-Toxicgran and Dohlebodies may be present

-Extremelyhigh LAP (350 - 400)

Front 124

What disease can look like a Leukomoid reaction AND have a high LAP score? What would you look at to help differentiate?

Back 124

Chronic Neutrophilic Leukemia can look like a leukomoid reaction due to persistence of neutrophilic leukocytosis, possibly toxic granulation/Dohle bodies, and a very high LAP.

Won't have shift to the left, which is the clue that it is not a leukomoid reaction.

Front 125

What is Chronic Monocytic Leukemia?

Back 125

-Very rare

-Nolonger included in WHO classification

-Increasednumberof mature monocytes inblood and/or marrow

-Monocytosis isoften not initially seen

(oftendevelops after splenectomy)

Front 126

What is Polycythemia and what are the types?

Back 126

Polycythemia is an increase in Red Blood cells

Types:

-Polycythemia vera (PV)

-Secondary Polycythemia

-Relative Erythrocytosis

Front 127

What is Polycythemia vera (PV)?

Back 127

-Malignantincreasein RedCell Mass

-JAK2V617Fgene mutation

-Extramedullaryhematopoiesis

-BM: hypercellular- malignant increased erythropoeisis,myelopoesis,and megakaryopoiesis (3 cell lines increased)

-Increased granulocytes and platelets
(increased LAP)
-Normal arterial O2 saturation

Front 128

What are the effects of PV as the disease progresses?

Back 128

-Initiallyrbcsappear normal, but extramedullaryhematopoiesis becomes ineffective and leads to increased aniso and poik

-Iron deficiency develops:

-continualbleeding (plt hypofunction)

-repeatedtherapeutic phlebotomy

-increasedrbcproduction and Fe turnover

-decreasedrbcsurvival

-Long-term PV=tear drop cells (myelofibrosis)

Front 129

A secondary condition usually develops as PV progresses. What is it and why is it actually a desired effect?

Back 129

Iron deficiency develops

Desired effect because it limits the expanding rbc mass. A greatly expanded rbc mass increases chance of thrombosis.

Thick blood-stressful for the heart...

(Portal vein thrombosis is a classic presenting symptom).

Front 130

Why are hemostasis results potentially affected for a patient with PV?

Back 130

Because the patient has increased Hct so blood to anticoagulant ratio will be affected in the sodium citrate tube- will need to correct for it

Front 131

What is the JAK2V617F gene mutation?

Back 131

-Allowsproduction of rbcs independent of erythropoetin (EPO)

-Endogenouserythroid colony formation (EEC)

-Rbcs are extremely sensitive to erythropoeitin (EPO usually decreased, but what is there, body is REALLY sensitive to)

Front 132

What is Secondary Polycythemia?

Back 132

-Dueto hypoxia

-decreasedarterial O2 saturation

-EPOincreased

-Rbcmass increased

-BM: increased erythropoeisis

Normalgranulocytes and platelets (LAPnormal)

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What is Relative Erythrocytosis?

Back 133

-DecreasedPlasma volume

(elevatedHct and normalrbc mass)

-NormalO2 saturation

-NormalEPO

-Normalgranulocytes & plts (LAPnormal)

2groups:

-dehydration: mostcommon

-asymptomaticmiddle-aged white males: hypertensive,obese, long history heavy smoking

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What is Primary Essential Thrombocythemia (ET)?

Back 134

-Primary= True Malignancy

-BM: increased megakaryopoeisis (lots MKs)

(slightlyincreased granulopoeisis)

-Pltcount>600,000 / mm3(often> 1 million!)

-Spontaneousplatelet aggregation& platelet function defects

-Thromoboticand hemorrhagic complications

-30-50%pts have JAK2gene mutation w/EEC

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What will the blood smear look like in Primary ET?

Back 135

-Largemasses of pltaggregates

-Giantand bizarre forms, many small forms also

-Occ. Megakaryocytefragment

-Mild normocytic, normochromicanemia

(unlessiron defic. dueto excessive bleeding)

-ElevatedWBC

-Neutrophilia

-Occ. increased eos and basos

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What is Chronic Myelofibrosis (CIMF)?

Back 136

(Formerly Myeloid Metaplasia w/Myelofibrosis)

-Marrowfibrosis

-JAK2gene mutation (results in higher CD34+ [stem cells] cell count which correlates toprogression to marrow fibrosis)

-Extramedullary Hematopoeisis

-Leukoerythroblastosis (immature WBC+RBC)

-Hallmarkof disease is many tear drop cells and abnormal megakaryocyteproliferation

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What are some side effects of Chronic Idiopathic Myelofibrosis (CIMF) and what happens as the disease progresses?

Back 137

-WBCand Plts: Maybe increased, normal, or decreased. Granulocytesmay have nuclear or cytoplasmicanomalies. Plateletshave impaired aggregation,may be agranular.

-Anemia: Bonemarrow failure. Ineffectiveerythropoeisis and hemolysis. Bleeding.

-Asdisease progresses: more nRBCs,immature granulocytes, megakaryocytic fragments and microplatelets

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What diseases are associated with a JAK2 gene mutation?

Back 138

-Polycythemia vera (PV)

-Primary Essential Thrombocythemia (ET)

-Chronic Idiopathic Myelofibrosis (CIMF)

Front 139

What are Myelodysplastic Syndromes (MDS)?

Back 139

Diverse group of diseases ranging from mild anemia to those that evolve into acute leukemia

Involves Myeloid= everything but lymphs

Previously known as "preleukemias"

(Not quite leukemias by WHO classification meaning not >/= 20% blasts yet but still something going on...)

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What is the general cause of Myelodysplastic Syndromes (MDS)?

Back 140

-ClonalAbnormality of pluripotent stemcell

-Chromosomalabnormalities

mostcommon include:

Deletionof long armof chromosome 5 (5q-)

Monosomy 7(-7)

Trisomy 8(+8)

Deletionof part of chromosomes 11,12, and 20

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What is the Diagnostic Morphology criteria for Myelodysplastic Syndromes (MDS)?

Back 141

Difficultto diagnose by peripheral blood only.Ineffectivehematopoesis – increases apoptosis

All are characterized by the following:

-Progressivecytopenia

-Dyserythropoiesis

-Dysmyelopoiesis

-Dysmegakaryopoiesis

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What are the possilbe signs of Dyserythropoiesis in MDS?

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-aniso and poik

-dimorphicrbcpopulation: Normochromic; Microcytic, Hypochromic; **oval macrocytes

-sideroblasts (possibly ringed), pheimer bodies

-multinuclear, asynchronism

-H.J.bodies and nuclear fragments

-basophilicstippling

-teardrops, schistocytes, acanthocytes

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What are the signs of Dysmyelopoiesis in MDS?

Back 143

-Neutropenia: 60% cases

-Hypogranulation (Occ hypergran w/large gran)

-Usuallyhyposegmented PMNswith abnormal chromatin patterns (pseudo- Pelger-Huet)

-Occ hypersegmentation

-Asynchronousdevelopment (Persistentbasophilic zones- pseudo Dohle bodies)

-Mixedeos and basogranules

-“Hybrid”myelomonocytes (Comb. Est. +)

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What is the difference between Sideroblasts and Ringed Sideroblasts?

Back 144

Sideroblast: Normal nRBC with iron

Ringed Sideroblast: Abnormal sideroblast with perinuclear iron granules. Almost alwyas pathological

Front 145

What are the signs of Dysmegakaryopoiesis in MDS?

Back 145

-Thrombocytopenia: 60% cases

-Micromegakaryocytes

-Abnormalsegmentation (hypo or hyper)

(Sometimesdetached or separate nuclei, not uniform size/shape)

-Hypogranularor agranular

-Giantplatelets

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What is Leukoerythroblastosis?

Back 146

Anemia due to bone marrow invasion

Reduction in normal marrow cells induces early release of immature cells (so you see increased immature WBC and RBC in peripheral blood)

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What is RA and what are the lab findings?

Back 147

Refractory Anemia

-Blood: Anemia, WBC <3,900, No (rare) blastin blood, Neutropenia &/orthrombocytopenia

-Bone Marrow: ٭Erythroiddysplasia only, Ineffective erythropoesis, Mildmacrocyticanemia, Ironstores increased, <15% ringed sideroblasts, (usuallyonly occ), <5% blasts

Basically anemia w/low WBC+weird BM RBC

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What is RARS and what are the lab findings?

Back 148

Refractory Anemia with Ringed Sideroblasts

Similar to RA (basically anemia w/low WBC and wierd BM RBC) plus:

>/= 15%ringed sideroblasts inBM (often much higher)

-ironnot incorporated properly

-normalrbcprecursors alsopresent- erythroiddimorphism

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What classification system do we use for MDS?

Back 149

WHO classification

Front 150

What is RCMD and what are the lab findings?

Back 150

Refractory Cytopenia w/Multilineage Dysplasia

-Blood: Cytopenias (bi-or pan-), No (rare) blasts, NoAuer rods, No monocytosis

-BM: Dysplasiain >10% of cells in 2 or more myeloid celllines, <5% blasts, NoAuer rods, <15% ringed sideroblasts

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What is RCMD-RS and what are the lab findings?

Back 151

Refractory Cytopenia w/Multilineage Dysplasia and Ringed Sideroblasts

-Blood: Cytopenias (bi-or pan-), No (rare) blasts, NoAuer rods, No monocytosis

-BM: Dysplasiain >10% of cells in 2 or more myeloid celllines, <5% blasts, NoAuer rods, >/=15% ringed sideroblasts

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What is RAEB-1 and what are the lab findings?

Back 152

Refractory Anemia with Excess Blasts-1

-Blood: Cytopenias, <5% blasts, NoAuer rods, No monocytosis

-BM: Uni- or multilineagedysplasia, 5-9% blasts, NoAuer rods

Hallmark is increased blasts

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What is RAEB-2 and what are the lab findings?

Back 153

Refractory Anemia with Excess Blasts-2

-Blood: Cytopenias, 5 – 9% blasts, Withor w/o Auer rods, No monocytosis

-BM: Uni- or multilineagedysplasia, 10-19% blasts, Withor w/o Auer rods

Formerlya "smouldering leukemia"

Just under 20% blasts...

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What is MDS-U and what are the lab findings?

Back 154

Myelodysplastic Syndrome, Unclassified

-Blood: Cytopenias, No (rare) blasts, NoAuer rods

-BM: Unilineagedysplasia in granulocytes or megakaryocytes, <5% blasts, NoAuer rods

Dysplasia in one cell line, NOT RBC

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What is Myelodysplastic Syndrome, associated with Isolated Del (5q) and what are the lab findings?

Back 155

Associated with a chromosomal abnormality

-Blood: Anemia, <5% blasts, Plateletsnormal or increased

-BM: Normalto increased megakaryocytes, <5% blasts, NoAuer rods, Isolateddel (5q)

Front 156

What is Chronic Myelomonocytic Leukemia and what are the lab findings?

Back 156

Classified as MDS or MPD (becase has dysplastic characteristics too)

-A leukemia, but yet may have the typical dyspoiesis of MDS

-WBC increased BUT will have monos, promonos, granulocytes, and immature granulocytes + blasts <20%

Front 157

What are some other Myelodyspolastic/Myeloproliferative Diseases?

Back 157

-Atypical Chronic Myeloid Leukemia

-Juvenile Myelomonocytic Leukemia

-Myelodysplastic/Myeloproliferative Diseases, unclassified

Front 158

What are the causes of Secondary or Therapy Related Myelodysplastic Syndromes?

Back 158

-Secondary to treatment of other malignancy

(chemotherapy and radiation)

-Toxins (ex. benzene)

Front 159

What is the difference between leukemia and lympohma?

Back 159

Leukemia: malignancy involving blood and/or marrow

Lymphoma: localized malignancy in lymph tissues

(Lymphoid tissues are sites for antigen recognition + processing and lymphopoiesis)

Front 160

What is CLL and SLL and how are they related?

Back 160

Chronic Lymphocytic Leukemia (CLL)

Small Lymphocytic Lymphoma (SLL)

Considered one entity with different clinical presentations (same disease process just different site that it presents itself in body)

CLL- blood lymphocytosis and BM involvement

SLL- Lymph nodes and other lymphoid organs

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What is the significance of CLL/SLL?

Back 161

-Most common chronic leukemia

-Usually occurs in older adults

-95% of B-cell leukemias

Front 162

What are the lab findings of Chronic Lymphocytic Leukemia (CLL)?

Back 162

-WBC10,000-150,000 /mm3

-predominanceof usually small, mature lymph

-manysmudge cells

-monotonouscell morphology

-suppressionof all Igs asdisease progresses

-marrowinfiltration progresses slowly (years)

-candevelop autoimmune disease

-Chromosomalabnormalities (Mostcommon del 13q 14-23.1)

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What is the classic look of cells in CLL?

Back 163

Very dense chromatin with distinct parachromatin

"cracked mud" look

Front 164

What cytochemical stains are positive for CLL?

Back 164

PAS +

Front 165

What is Hairy cell leukemia and what are the characteristics of the malignant cells?

Back 165

Malignancy of confused cell: B-lymph origin but has features of monocytes

Phagocytic like a monocyte

Morphology of a lymph and can produce Igs

(Usually occurs in middle age patients)

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What are the lab findings of Hairy cell leukemia?

Back 166

-Splenomegally

-Moderateto severe pancytopenia

(WBCoften less that 4,000 / mm3)

-Fewto many “hairy cells” (hairy cytoplasmic projections)

-Often "dry tap"

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What cytochemical stains are positive for Hairy cell leukemia?

Back 167

PAS =

SBB +

Nonspecific Est +

TRAP +

Front 168

What is the most common terminating condition of MDS?

Back 168

Acute leukemia?

Front 169

What must be performed to diagnose lymphomas?

Back 169

Biopsy node

-Look at cell: cleaved?, size, type

-Look at pattern within node: diffuse or nodular?

-May see lymphoma cells in blood

Front 170

What is the Ann Arbor scheme and what does it affect?

Back 170

It is used to stage lymphomas (determine progression) and results will affect treatment and prognosis.

Questions to determine stage:

-How far has it spread?

-How many nodes/organs are involved?

-Which side of the diaphragm?

-Symptomatic or asymptomatic?

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What is Hodgkin's Lymphoma?

Back 171

Malignant clonal proliferation

Majority of cases are B-cell origin

Front 172

What is the classic cell associated with Hodgkin's lymphoma?

Back 172

Reed-Sternberg cell (malignant cell)

-Large bi-lobulated or poly-lobulated nucleus

-Each nucleus surrounded by clear zone

"owl eyes"

-Relatively few in number

NOT diagnostic but can aid in diagnosis

Hodgkin cell- Mononuclear variant

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What is Non-Hodgkin's Lymphoma?

Back 173

-Lymphocytic Malignancy

-Exact mechanism unknown (but highly correlates with chromosomal abnormalities)

-Development of lymphoma is probably due to damage of genetic code that is for regulation of immune cells growth/reproduction

-Inciting agent- exposure to chemicals, radiation, viruses, etc. (mutagenic factors)

Front 174

What are the main differences between Hodgkin's lymphoma and Non-Hodgkin's lymphoma?

Back 174

Hodgkin's Lymphoma:

-Proliferation of malignant clone (usually Bcell)

-Usually progresses in an orderly fashion

Non-Hodgkin's Lymphoma:

-Lymphocytic malignancy of B cells or T cells

-Usually diagnosed in advanced stage

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What is Burkitt's Lymphoma?

Back 175

-B-cellderivation- leukemic conversion L3

-Associatedwith Epstein-Barr virus

-Usuallyseen in kids but can occur in adults with AIDS

-"Punchout" vacuoles (may see only in touch prep)

-"Starrynight" pattern within node

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Back 176

Burkitt's Lymphoma

"Starry night" pattern in node

(Many small neoplastic lymphoid cells with paler histiocytes scattered about)

Front 177

What are the two related disorders of Cutaneous T cell Lymphoma?

Back 177

Mycosis Fungoides

Sezary Syndrome

Front 178

What is Mycosis Fungoides?

Back 178

Cutaneous T cell Lymphoma

-Skinlymphoma

-Characteristiclesions (asit progress, it involves other organs)

Becomes Sezary syndrome when in the blood

Front 179

What is Sezary Syndrome?

Back 179

Cutaneous T cell Lymphoma

-Malignantcells are found in the blood as well as the skin and other organs

-Sezarycells- Classic cell of Sezary Syndrome

Appear as mature lymphs withconvoluted, cerebriformnuclear folds (Just look like lymphs with something weird about them...)

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What are the Plasma Cell Disorders?

Back 180

-SolitaryPlasmacytoma

-MultipleMyeloma(plasma cell myeloma)

-PlasmaCell Leukemia

-Waldenstrom’s Macroglobulinemia

-MonoclonalGammopathy ofUncertain Significance

-HeavyChain Disease

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What is the big difference between Multiple myeloma and Plasma cell Leukemia?

Back 181

-Multiple Myeloma- malignant proliferation of plasma cells pretty much confined to bone marrow

-Plasma cell Leukemia- Malignant plasma cells in the peripheral blood too (usually terminal acute phase of multiple myeloma)

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What is Solitary Plasmacytoma?

Back 182

-Malignantclone of plasma cells localized to one area of bone or soft tissue

-Hightendency to develop multiple myeloma

(Can basically think of this as early stage of multiple myeloma)

Front 183

What is Multiple Myeloma?

Back 183

Malignant proliferation of Plamsa cells in BM

-Fewif any plasma cells in blood

-Immunologicalmarkers

-Immatureplasma cells (proplasmacytes, etc.)

-Abnormalnuclear features

-Maylose halo, cells can be quite large

-Russellbodies, Flamecell (if IgA)

-Replacenormal BM(decreasedRBC, WBC, Plt)

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What is a common clinical finding of Multiple Myeloma?

Back 184

-Osteolytic Lesions: bone breakdown b/c plasma cells produce osteoclast activating factor (OAF)

-So serum Ca2+ and Phosphorous increased because its released when the bone is broken down

Front 185

What SPE pattern will you usually find in Multiple Myeloma?

Back 185

Monoclonal M spike

Most commonly IgG, then IgA (rarely IgD or IgE)

Front 186

What is Bence Jones protein and how is it associated with Multiple Myeloma (MM)?

Back 186

-25%of Multiple Myeloma plasma cells secrete only light chains w/o an associated heavy chain

-BenceJones protein in serum and urine

>50%MM pts. have proteinuria

-Excretionof light chains (precip) candamage nephrons- leads to renal failure

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Why do Multiple Myeloma patients have increased infections, RBC rouleaux, and bleeding problems?

Back 187

Malignantplasma cells secrete a suppressor substance to normal plasma cells so they have decreasednormal Igs (=increased infection and can lead to death)

Igspolymerize which leads to increase plasma viscosity + masking zeta potential and Ig aggregates bind plts andclotting factors

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What is Plasma Cell Leukemia and Primary Plasma Cell Leukemia?

Back 188

Plasma Cell Leukemia:

-Usuallyseen as the terminal acute phase of Multiple Myeloma

-Plasmacells in the blood

Primary Plasma Cell Leukemia (rare):

-Manyimmature plasma cells in blood

Front 189

What is Waldenstrom's Macroglobulinemia?

Back 189

Malignantlymphocyte - plasma cell proliferation disorder

Monoclonalproduction of IgM

Front 190

What are the typical findings in Waldenstrom's Macroglobulinemia?

Back 190

Hyperviscosity

-Neurologicalproblems

-Rouleaux

-Cryoglobulin- protein precip.when exposed to cold (Raynaud’sphenomenon, Thrombosis, Renaldamage)

-Bleedingproblems (Coats plts w/IgM, Coats fibrin monomers- can't polymerize + clot)

-Infection

Front 191

Back 191

Monoclonal M spike- IgG

(Multiple Myeloma)

Front 192

Back 192

IgM spike

(Waldenstrom's Macroglobulinemia)

Front 193

What is MGUS?

Back 193

Monoclonal Gammopathy of Undetermined Significance

-3%of all adults >70 years

-Mild plasmacytosis inmarrow but none of the other abnormalities

-Increased Igs

-Approx.25%progress to multiple myeloma (but the other 75% will just continue with mild plasmacytosis)

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What is Heavy Chain Disease (HCD)?

Back 194

-Excessive production of the heavy chain portion of antibody sub-unit (more HC than LC)

-Very rare