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Hematology Review > Leukemia > Flashcards

Leukemia Flashcards

1
Q

Definition

A

Progressive, malignant disease of hematopoietic system
Characterized by unregulated proliferation of one cell type

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2
Q

Pancytopenia

A

decrease in RBC, WBC, and platelet

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3
Q

Proto-Oncogenes

A

Cause cell growth Genetic transformation
Growth factors
Growth factor receptors
Signal Transducers
Transcription factors

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4
Q

Tumor Supressor Genes

A

Function to inhibit cell growth in normal cells
P53 is often source of mutation

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5
Q

Acute Leukemia

A

50% of all leukemias
Aggressive
Sudden Onset
Immature Cells
AML or ALL
Infection/Bleeding

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6
Q

AML

A

Acute Myeloid Leukemia
M0-M7
Adults

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7
Q

ALL

A

Acute Lymphocytic Leukemia
L1-L3
Children

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8
Q

Chronic Leukemia

A

Less Aggressive
Insidious Onset
More mature cells
Adults

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9
Q

Acute Leukemia Clinical Course

A

Fatigue
Pallor
Petechiae/Bruising
Fever
Bone Pain - from abnormal clones placing pressure in bone
Neurologic Abnormalities

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10
Q

Acute Leukemia Laboratory Presentation

A

N/N Anemia (occasionally macrocytic)
Decreased platelet count (some giant)
Variable WBC (begins as high to normal to low)
Differential: Blasts exact same copy from one cell
Bone Marrow is hypercellular
Increased M:E ratio
One cell line predominates
Increased Uric Acid and LD

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11
Q

Classification of Leukemia

A

Based on cell types
Cytochemistry - strains and proteins on WBCs
Immunophenotyping - Flow cytometry to detect CD markers
Genetic features - PCR or karotyping
Importance to classify: Treatment

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12
Q

WHO Classification

A

Based on Cell lineage
Determined by morph, immunophenotype, genetic features, and clinical appearance
Three groups

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13
Q

Three Categories of WHO

A

Hematopoietic
Lymphopoietic
Histiocytic and Dendritic

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14
Q

Hematopoietic

A

Myeloproliferative
Myeloproliferative/Myelodysplastic
Myelodysplastic
Acute Myeloid Leukemia (AML) >20% Blasts

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15
Q

Lymphopoietic

A

Precursor (Acute) lymphoid (T or B cell) ALL
Mature B Cell
Mature T and NK
Hodgkin lymphoma

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16
Q

French-American-British Classification (FAB)

A

Based on morphology and Cytochemistry
Acute Leukemia >30% Blasts in Bone Marrow

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17
Q

AML M0 (Myeloblastic)

A

Adults
>90% Blasts
WBC has blasts and mature (nothing in between)
Positive Stains:
- MPO/SSB
- Specific esterase
- PAS

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18
Q

AML M1 (Myeloblastic)

A

Adults
>90% Blasts
WBC mutation takes place slightly later in development
Auer rods may be seen
Positive Stains:
- MPO/SSB
- Specific esterase
- PAS

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19
Q

AML M2 (Myeloblastic with differentiation)

A

Adults
30-89% Blasts
10% Promyelocytes and Myelocytes
Auer rods may be seen
Positive Stain:
- MPO/SSB
- Specific esterase
- PAS

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20
Q

AML M3 (Promyelocytic)

A

Adults
>30% blasts
Increased promyelocytes
Auer rods
Associated with DIC
Hyper and micro granular variants
15/17 Chromosomal translocation
Positive Stains
- MBO/SBB
- Specific esterase
- PAS

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21
Q

AML M4 (Myelomonocytic)

A

Adults
>30% blasts
Increased monocytes
Positive strains
- MPO/SBB
- Specific esterase
- PAS
- Non-specific esterase

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22
Q

AML M4e Variant

A

Eosinophilic
Same as M4 with increased eos in bone marrow
Inversion of chromosome 16
Specific esterase is positive in these cells - negative in normal eos

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23
Q

AML M5 (Monocytic)

A

Adults
>30% blasts
>80% monocytes (Blasts, promonocytes, monocytes)
Positive Stains:
- MPO/SBB
- Specific esterase
- PAS
- Non-specific esterase

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24
Q

AML M5a

A

Monoblasts predominate

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25
Q

AML M5b

A

Promonocytes predominate

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26
Q

AML M6 (Erythroleukemia)

A

Digugliemo’s Syndrome
>30% Blasts
>50% RBC precursors
Least common acute leukemia
Often evolves from M1 or M2
Positive Stain:
- PAS

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27
Q

AML M7 (Megkaryoblastic)

A

> 30% megakaryoblasts
Increased fibrin and reticulin in marrow: Dry tap
Rare (Down’s syndrome)
Platelet blebbing
Positive Stains:
- PAS
- Acid Phosphatase

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28
Q

Cytochemical Stains

A

Myeloperoxidase (MPO) stains primary granules
Sudan Black B (SBB) stains lipids
Non-specific Esterase stains mononuclear phagocytes
Alpha napthyl esterase stains monocytic proliferation line
Specific esterase stains granulytic WBCs
Chloroacetate esterase stains neutrophil polymorphs
Periodic Acid Schiff (PAS) stains polysaccharides

29
Q

CD Marker for blasts

A

CD34
TdT positive

30
Q

CD markers for T cells

A

CD1, CD2, CD3, CD4, CD5, CD6, CD7, CD8, CD25
Positive Stain: Acid Phosphatase

31
Q

CD markers for B cells

A

CD10, CD19, CD20, CD22, CD34, CD38, CD45
Positive stain: PAS

32
Q

CD marker for megakaryocytes

A

CD41

33
Q

CD markers for myelocytic and monocytic

A

CD13 and CD33

34
Q

ALL FAB Classification

A

L1 - T cell or pre B cell (cells small and uniform)
L2 - T cell or pre B cell (cells large and varied)
L3 - B cell (cells large and varied with vacuoles
- Mature B cell ALL called Burkitt Leukemia

35
Q

WHO ALL Classification

A

Precursor B cell
Precursor T cell neoplasms

36
Q

L1 ALL

A

Children
Small, homogenous blasts
Most common form

37
Q

L2 ALL

A

Adult
Large blasts
Irregular nuclei with clefts

38
Q

L3 ALL

A

Large cells
Very blue and vacuolated cytoplasm
Burkitt’s lymphoma

39
Q

Common Acute Lymphocytic Leukemia Antigen (CALLA)

A

CD10 marker

40
Q

Philadelphia chromosome

A

9:22 translocation
Important in CML

41
Q

M3 chromosome diagnostic

A

15:17 translocation

42
Q

AML chromosome diagnostic

A

8:21 translocation

43
Q

Myeloproliferative Disorders/Neoplasms (MPD/MPN)

A

Increase in RBC, WBC, Platelets
Can be chronic or acute (mostly chronic)
Often terminates in AML
Stem cell defect
Panhypercellularity of bone marrow

44
Q

MPD/MPN Clinical Course

A

Middle age to elderly adult
Insidious onset (slow)
Bleeding, infection, thrombosis, anemia
Fibrosis and extramedullary hematopoiesis

45
Q

Myeloproliferative Neoplasms (MPNs)

A

Eight General Classifications
CMLP (BCR-ABL1) Philadelphia
Chronic Neutrophilic Leukemia (CNL) - no Philadelphia
Essential thrombocythemia (ET) - JAK2 mutation
Polycythemia vera (PV) - JAK2 mutation
Primary myelofibrosis (PMF)
Myeloproliferative neoplasm, unclassifiable (MPN-U)
Myeloid & lymphoid neoplasms associated with eosinophilia
Chronic eosinophilic leukemia, not specified (CEL-NOS)

46
Q

CML (Chronic Myelocytic Leukemia)

A

BCR-ABL1
25-60 yrs
Chloromas - extramedullary tumor of immature WBCs
Gout
Increased uric acid
Increased B12
Increased M:E ratio (10:1 to 50:1)
WBC (200-500K)
Increased eos/basos
Increased platelet

47
Q

CNL (Chronic Neutrophilic Leukemia)

A

Neutrophilia (>25K)
- mature segs and bands predominate
- <10% mature cells
No monocytosis or basophilia
Hypercelluar bone marrow M:E ratio (20:1)
Neutrophils appear toxic, not dysplasia
Mutation in colony stimulating factor 3 receptor (CS F3R)

48
Q

Essential Thrombocythemia ET

A

Middle age adult (50-60 yrs)
Platelets predominate (>1 million)
Unregulated proliferation of megakaryocytes
Bleeding, bruising, thrombosis
WBC count increased
Increased LDH and Uric Acid
Abnormal appearance & function of platelets
JAK2 mutation

49
Q

Reactive Thrombocytosis

A

Platelet count <1 million
Transient Increase in Platelet count
Causes: Post surgery, Post splenectomy, Chronic inflammation, Malignancy, severe exercise

50
Q

Polycythemia 3 types

A

Primary Polycythemia (ruba vera)
- inc. MCV, Hgb, Hct, MCHC
Secondary Polycythemia
Relative Polycythemia - not true elevation, plasma decreased

51
Q

Polycythemia ruba vera

A

40-60 yrs
Insidious onset
Clonal disease
Increase in RBC mass
Symptoms related to viscosity
Bleeding, thrombosis
Ruddy complexion
Bone marrow (Erythrocytic hyperplasia) Decreased M:E ratio
Hgb - 18 g/dl or higher
EPO is normal or low
JAK2 mutationSe

52
Q

Secondary Polycythemia

A

Increase in RBC mass due to another process/disease
Increased Hct - due to decrease in plasma volume
EPO levels higher than primary

53
Q

Primary Myelofibrosis (PMF)

A

> 50 yrs
Insidious onset
Splenomegaly
Bruising, pallor
N/N anemia
- nRBCs
- Teardrops (dacrocytes)
- Anisocytosis
Increased WBC
Decreased platelets
Bone marrow - Dry tap

54
Q

Chronic Eosinophilic Leukemia

A

Middle aged males
Rare Leukemia
Increased WBC
N/N anemia
Decreased platelets
Differential: increased eosinophils and immature eos

55
Q

Basophilic Leukemia

A

Rarest Leukemia
Symptoms relating to increased histamine
Increased WBC
N/N anemia
Decreased platelets
Differential: increased basophils and immature basos

56
Q

Most common abnormal karyotypes

A

5, 7, 8, 20, Y

57
Q

Oncogenes and tumor suppressor genes

A

Most common
- Proto-oncogene mutations JAK2, RAS, RUNX1
- Tumor suppressor gene - TP53

58
Q

MDS Clinical Course

A

> 50 yrs
Anemia
Neutropenia
+/- Thrombocytopenia
RBC - decreased
- Macrocytes
- Dimorphic RBCs (RARS)
- Anisocytosis
- Basophilic stippling
- H-J bodies
WBC abnormalities
Ringed sideroblasts

59
Q

CLL (Chronic Lymphocytic Leukemia)

A

Mature B cell
N/N anemia
Decreased platelets
Neutropenia
Increased WBC
Differential: Lymphocytosis
Smudge cells

60
Q

Prolymphocytic Leukemia

A

B or T cells (mostly B cell)
CD markers different than CLL
Increase in prolymphocytes

61
Q

Hairy Cell Leukemia

A

B cell
Adult disease
Male:female = 7:1
Pancytopenia
Hairy cells
Fibrosis in Bone Marrow
Tartrate resistant acid phosphatase stain (TRAP) positive
BRAFV600E gene

62
Q

Multiple Myeloma - Plasma cell

A

Adult disease
Male predominance
Malignant proliferation of plasma cells
CRAB (Calcium, Renal insufficiency, Anemia, Bone lesions)
Increased plasma cells in bone marrow
Plasma cells have Dutcher bodies (nuclear inclusions of Ig)
Flame cells
Mott cells with Russell bodies (cytoplasm inclusions of Ig)
Rouleaux
Increased ESR

63
Q

Waldenstrom’s Macroglobulinemia

A

Monoclonal gammopathy (IgM)
No bone lesions
Lymphadenopathy
Hepatosplenomegaly

64
Q

Sezary Syndrome

A

T cell lymphoma
Erythrodema
Sezary Cell = T helper with irregular nuclear outline
- CD34 and CD3+

65
Q

Lymphomas

A

Hodgkin’s
Non-hodgkin’s

66
Q

Hodgkin’s

A

Peaks at 20-30 and >50
Localized
Central lymph nodes with contiguous spread
Rare extra-nodal disease
Bizarre cell appearance

67
Q

Non-Hodgkin’s

A

Widespread
Peripheral Lymph Nodes
Non-contiguous spread
Extra-nodal disease common
Normal cell appearance

68
Q

Burkitt’s Lymphoma

A

Often extranodal (facial bones, jaw, intestine, ovaries, kidney)
Typical cell = blue vacuolated (L3) lymphocytes with starry sky appearance

Hematology Review (11 decks)

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