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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
AML M5b
Promonocytes predominate
26
AML M6 (Erythroleukemia)
Digugliemo's Syndrome >30% Blasts >50% RBC precursors Least common acute leukemia Often evolves from M1 or M2 Positive Stain: - PAS
27
AML M7 (Megkaryoblastic)
>30% megakaryoblasts Increased fibrin and reticulin in marrow: Dry tap Rare (Down's syndrome) Platelet blebbing Positive Stains: - PAS - Acid Phosphatase
28
Cytochemical Stains
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
CD Marker for blasts
CD34 TdT positive
30
CD markers for T cells
CD1, CD2, CD3, CD4, CD5, CD6, CD7, CD8, CD25 Positive Stain: Acid Phosphatase
31
CD markers for B cells
CD10, CD19, CD20, CD22, CD34, CD38, CD45 Positive stain: PAS
32
CD marker for megakaryocytes
CD41
33
CD markers for myelocytic and monocytic
CD13 and CD33
34
ALL FAB Classification
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
WHO ALL Classification
Precursor B cell Precursor T cell neoplasms
36
L1 ALL
Children Small, homogenous blasts Most common form
37
L2 ALL
Adult Large blasts Irregular nuclei with clefts
38
L3 ALL
Large cells Very blue and vacuolated cytoplasm Burkitt's lymphoma
39
Common Acute Lymphocytic Leukemia Antigen (CALLA)
CD10 marker
40
Philadelphia chromosome
9:22 translocation Important in CML
41
M3 chromosome diagnostic
15:17 translocation
42
AML chromosome diagnostic
8:21 translocation
43
Myeloproliferative Disorders/Neoplasms (MPD/MPN)
Increase in RBC, WBC, Platelets Can be chronic or acute (mostly chronic) Often terminates in AML Stem cell defect Panhypercellularity of bone marrow
44
MPD/MPN Clinical Course
Middle age to elderly adult Insidious onset (slow) Bleeding, infection, thrombosis, anemia Fibrosis and extramedullary hematopoiesis
45
Myeloproliferative Neoplasms (MPNs)
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
CML (Chronic Myelocytic Leukemia)
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
CNL (Chronic Neutrophilic Leukemia)
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
Essential Thrombocythemia ET
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
Reactive Thrombocytosis
Platelet count <1 million Transient Increase in Platelet count Causes: Post surgery, Post splenectomy, Chronic inflammation, Malignancy, severe exercise
50
Polycythemia 3 types
Primary Polycythemia (ruba vera) - inc. MCV, Hgb, Hct, MCHC Secondary Polycythemia Relative Polycythemia - not true elevation, plasma decreased
51
Polycythemia ruba vera
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
Secondary Polycythemia
Increase in RBC mass due to another process/disease Increased Hct - due to decrease in plasma volume EPO levels higher than primary
53
Primary Myelofibrosis (PMF)
>50 yrs Insidious onset Splenomegaly Bruising, pallor N/N anemia - nRBCs - Teardrops (dacrocytes) - Anisocytosis Increased WBC Decreased platelets Bone marrow - Dry tap
54
Chronic Eosinophilic Leukemia
Middle aged males Rare Leukemia Increased WBC N/N anemia Decreased platelets Differential: increased eosinophils and immature eos
55
Basophilic Leukemia
Rarest Leukemia Symptoms relating to increased histamine Increased WBC N/N anemia Decreased platelets Differential: increased basophils and immature basos
56
Most common abnormal karyotypes
5, 7, 8, 20, Y
57
Oncogenes and tumor suppressor genes
Most common - Proto-oncogene mutations JAK2, RAS, RUNX1 - Tumor suppressor gene - TP53
58
MDS Clinical Course
>50 yrs Anemia Neutropenia +/- Thrombocytopenia RBC - decreased - Macrocytes - Dimorphic RBCs (RARS) - Anisocytosis - Basophilic stippling - H-J bodies WBC abnormalities Ringed sideroblasts
59
CLL (Chronic Lymphocytic Leukemia)
Mature B cell N/N anemia Decreased platelets Neutropenia Increased WBC Differential: Lymphocytosis Smudge cells
60
Prolymphocytic Leukemia
B or T cells (mostly B cell) CD markers different than CLL Increase in prolymphocytes
61
Hairy Cell Leukemia
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
Multiple Myeloma - Plasma cell
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
Waldenstrom's Macroglobulinemia
Monoclonal gammopathy (IgM) No bone lesions Lymphadenopathy Hepatosplenomegaly
64
Sezary Syndrome
T cell lymphoma Erythrodema Sezary Cell = T helper with irregular nuclear outline - CD34 and CD3+
65
Lymphomas
Hodgkin's Non-hodgkin's
66
Hodgkin's
Peaks at 20-30 and >50 Localized Central lymph nodes with contiguous spread Rare extra-nodal disease Bizarre cell appearance
67
Non-Hodgkin's
Widespread Peripheral Lymph Nodes Non-contiguous spread Extra-nodal disease common Normal cell appearance
68
Burkitt's Lymphoma
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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