Leukemia Flashcards
Definition
Progressive, malignant disease of hematopoietic system
Characterized by unregulated proliferation of one cell type
Pancytopenia
decrease in RBC, WBC, and platelet
Proto-Oncogenes
Cause cell growth Genetic transformation
Growth factors
Growth factor receptors
Signal Transducers
Transcription factors
Tumor Supressor Genes
Function to inhibit cell growth in normal cells
P53 is often source of mutation
Acute Leukemia
50% of all leukemias
Aggressive
Sudden Onset
Immature Cells
AML or ALL
Infection/Bleeding
AML
Acute Myeloid Leukemia
M0-M7
Adults
ALL
Acute Lymphocytic Leukemia
L1-L3
Children
Chronic Leukemia
Less Aggressive
Insidious Onset
More mature cells
Adults
Acute Leukemia Clinical Course
Fatigue
Pallor
Petechiae/Bruising
Fever
Bone Pain - from abnormal clones placing pressure in bone
Neurologic Abnormalities
Acute Leukemia Laboratory Presentation
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
Classification of Leukemia
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
WHO Classification
Based on Cell lineage
Determined by morph, immunophenotype, genetic features, and clinical appearance
Three groups
Three Categories of WHO
Hematopoietic
Lymphopoietic
Histiocytic and Dendritic
Hematopoietic
Myeloproliferative
Myeloproliferative/Myelodysplastic
Myelodysplastic
Acute Myeloid Leukemia (AML) >20% Blasts
Lymphopoietic
Precursor (Acute) lymphoid (T or B cell) ALL
Mature B Cell
Mature T and NK
Hodgkin lymphoma
French-American-British Classification (FAB)
Based on morphology and Cytochemistry
Acute Leukemia >30% Blasts in Bone Marrow
AML M0 (Myeloblastic)
Adults
>90% Blasts
WBC has blasts and mature (nothing in between)
Positive Stains:
- MPO/SSB
- Specific esterase
- PAS
AML M1 (Myeloblastic)
Adults
>90% Blasts
WBC mutation takes place slightly later in development
Auer rods may be seen
Positive Stains:
- MPO/SSB
- Specific esterase
- PAS
AML M2 (Myeloblastic with differentiation)
Adults
30-89% Blasts
10% Promyelocytes and Myelocytes
Auer rods may be seen
Positive Stain:
- MPO/SSB
- Specific esterase
- PAS
AML M3 (Promyelocytic)
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
AML M4 (Myelomonocytic)
Adults
>30% blasts
Increased monocytes
Positive strains
- MPO/SBB
- Specific esterase
- PAS
- Non-specific esterase
AML M4e Variant
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
AML M5 (Monocytic)
Adults
>30% blasts
>80% monocytes (Blasts, promonocytes, monocytes)
Positive Stains:
- MPO/SBB
- Specific esterase
- PAS
- Non-specific esterase
AML M5a
Monoblasts predominate
AML M5b
Promonocytes predominate
AML M6 (Erythroleukemia)
Digugliemo’s Syndrome
>30% Blasts
>50% RBC precursors
Least common acute leukemia
Often evolves from M1 or M2
Positive Stain:
- PAS
AML M7 (Megkaryoblastic)
> 30% megakaryoblasts
Increased fibrin and reticulin in marrow: Dry tap
Rare (Down’s syndrome)
Platelet blebbing
Positive Stains:
- PAS
- Acid Phosphatase
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
CD Marker for blasts
CD34
TdT positive
CD markers for T cells
CD1, CD2, CD3, CD4, CD5, CD6, CD7, CD8, CD25
Positive Stain: Acid Phosphatase
CD markers for B cells
CD10, CD19, CD20, CD22, CD34, CD38, CD45
Positive stain: PAS
CD marker for megakaryocytes
CD41
CD markers for myelocytic and monocytic
CD13 and CD33
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
WHO ALL Classification
Precursor B cell
Precursor T cell neoplasms
L1 ALL
Children
Small, homogenous blasts
Most common form
L2 ALL
Adult
Large blasts
Irregular nuclei with clefts
L3 ALL
Large cells
Very blue and vacuolated cytoplasm
Burkitt’s lymphoma
Common Acute Lymphocytic Leukemia Antigen (CALLA)
CD10 marker
Philadelphia chromosome
9:22 translocation
Important in CML
M3 chromosome diagnostic
15:17 translocation
AML chromosome diagnostic
8:21 translocation
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
MPD/MPN Clinical Course
Middle age to elderly adult
Insidious onset (slow)
Bleeding, infection, thrombosis, anemia
Fibrosis and extramedullary hematopoiesis
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)
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
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)
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
Reactive Thrombocytosis
Platelet count <1 million
Transient Increase in Platelet count
Causes: Post surgery, Post splenectomy, Chronic inflammation, Malignancy, severe exercise
Polycythemia 3 types
Primary Polycythemia (ruba vera)
- inc. MCV, Hgb, Hct, MCHC
Secondary Polycythemia
Relative Polycythemia - not true elevation, plasma decreased
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
Secondary Polycythemia
Increase in RBC mass due to another process/disease
Increased Hct - due to decrease in plasma volume
EPO levels higher than primary
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
Chronic Eosinophilic Leukemia
Middle aged males
Rare Leukemia
Increased WBC
N/N anemia
Decreased platelets
Differential: increased eosinophils and immature eos
Basophilic Leukemia
Rarest Leukemia
Symptoms relating to increased histamine
Increased WBC
N/N anemia
Decreased platelets
Differential: increased basophils and immature basos
Most common abnormal karyotypes
5, 7, 8, 20, Y
Oncogenes and tumor suppressor genes
Most common
- Proto-oncogene mutations JAK2, RAS, RUNX1
- Tumor suppressor gene - TP53
MDS Clinical Course
> 50 yrs
Anemia
Neutropenia
+/- Thrombocytopenia
RBC - decreased
- Macrocytes
- Dimorphic RBCs (RARS)
- Anisocytosis
- Basophilic stippling
- H-J bodies
WBC abnormalities
Ringed sideroblasts
CLL (Chronic Lymphocytic Leukemia)
Mature B cell
N/N anemia
Decreased platelets
Neutropenia
Increased WBC
Differential: Lymphocytosis
Smudge cells
Prolymphocytic Leukemia
B or T cells (mostly B cell)
CD markers different than CLL
Increase in prolymphocytes
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
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
Waldenstrom’s Macroglobulinemia
Monoclonal gammopathy (IgM)
No bone lesions
Lymphadenopathy
Hepatosplenomegaly
Sezary Syndrome
T cell lymphoma
Erythrodema
Sezary Cell = T helper with irregular nuclear outline
- CD34 and CD3+
Lymphomas
Hodgkin’s
Non-hodgkin’s
Hodgkin’s
Peaks at 20-30 and >50
Localized
Central lymph nodes with contiguous spread
Rare extra-nodal disease
Bizarre cell appearance
Non-Hodgkin’s
Widespread
Peripheral Lymph Nodes
Non-contiguous spread
Extra-nodal disease common
Normal cell appearance
Burkitt’s Lymphoma
Often extranodal (facial bones, jaw, intestine, ovaries, kidney)
Typical cell = blue vacuolated (L3) lymphocytes with starry sky appearance
