5-17 KRAFTS Malignant Hematopathology Flashcards
What is the difference between leukemia and lymphoma?
Leukemia starts in Bone Marrow
Lymphoma starts in lymph nodes
Are chronic or acute leukemias more aggressive?
Acute
What hematologic malignancies affect myeloid cells?
Acute myeloid leukemia (AML)
Chronic myeloid leukemia (CML)
What hematologic malignancies affect lymphoid cells?
Acute lymphoblastic leukemia (ALL) Chronic lymphocytic leukemia (CLL) Hodgkin lymphoma Non-Hodgkin lymphoma Multiple myeloma (plasma cells)
What happens in a bone marrow biopsy?
Tool is inserted into iliac crest
Middle bevel is removed, leaving hollow drill
Drill is drilled down
Bone is pulled up!
Aspiration of bone marrow is then performed
What happens in bone marrow aspiration?
After BM tissue biopsy is removed, a vacuum is inserted and sucks out BM. Negative pressure causes pain.
What happens to our bone marrow as we age?
It becomes more fatty.
After we have our BM biopsy and aspirate, how do we diagnose the different hematopoietic malignancies (5 ways)?
Clinical setting Cell morphology Immunophenotyping Molecular studies (PCR & western) Cytogenetics
When staining for NSE (non-specific esterase), what cells light up?
Monocytes (b/c they have NSE)
When staining for myeloperoxidase (MPO), what cells light up?
Neutrophils (b/c they have MPO)
What is immunophenotyping?
Look at markers on cells using flow cytometry
Tells us what cell we’re looking at (eg CD8+CD4- is a CTL)
What is cytogenetics?
Look for malignant cells in metaphase and do a karyotype.
How would taking a karyotype of a malignant cell help?
We could see gross chromosomal abnormalities (like Philadelphia chrom)
What are the 4 differences between acute leukemia and chronic leukemia?
Acute Sudden onset Adults OR children Rapidly fatal Involves immature cells (blasts)
Chronic Slow onset Adults only Longer course Involves mature cells
Which leukemia (acute or chronic) can have symptoms of bone marrow failure?
Acute - b/c malignant cells crowd out bone marrow
Define Acute Leukemia
Malignant proliferation of immature myeloid or lymphoid cells in BM
Describe the pathophysiology of Acute Leukemia (cause and effect).
Cause Clonal expansion of cells Maturation failure of cells Effect Crowd out normal BM cells Inhibit normal cell fxn (via cytokines) Invade other organs
What are clinical findings in Acute Leukemia (4)?
Sudden onset
Symptoms of Bone marrow failure
Bone pain (due to expanding marrow)
Organ infiltration
What are symptoms of bone marrow failure (3)?
Fatigue (↓RBCs)
Infections (↓WBCs)
Bleeding (↓platelets)
What lab findings do we see in Acute Leukemia (4)?
Blasts/immature cells in blood
Leukocytosis (↑white count)
Anemia
Thrombocytopenia
What are the 4 things you must know about Acute Myeloid Leukemia?
Definition: malignant proliferation of myeloid blasts in blood, BM
20% cutoff for diagnosis
Many subtypes
Bad prognosis
What do we mean when we say “20% cutoff for diagnosis?”
In order to diagnose acute leukemia, ≥ 20% of cells need to be blast cells
Can be in blood OR bone marrows
What are some morphological clues on a blood smear that could suggest a leukemia is myeloid?
Dysgranulopoiesis (disordered growth/funny looking neutrophils)
Auer rods
Are auer rods over present in lymphoid cells?
NO, NEVER. Auer rod is diagnostic for AML (but not REQUIRED for Dx)
What are the 4 things you must know about AML-M0?
↑↑↑myeloblasts
Bland (hasn’t differentiated; just looks like a blast)
MPO negative
Need cell markers (to diagnose)
What are the 4 things you must know about AML-M1?
↑↑↑myeloblasts
No maturation
Auer rods
MPO POSITIVE
What are the 3 things you must know about AML-M2?
↑myeloblasts
Maturing neutrophils
t(8;21) in some cases
Does the t(8;21) genetic mutation help or hurt AML-M2 prognosis?
Helps prognosis!
What are the 4 things you must know about AML-M3?
↑↑↑promyelocytes Faggot cells (lots of Auer rods make bundles of sticks) DIC (disseminated intravascular coagulation) t(15;17) in all cases
Does t(15;17)) gene mutation help or hurt AML-M4 prognosis?
Helps prognosis! Makes cell responsive to all-trans retinoic acid -> terminal differentiation and apoptosis!!!!!!
What causes the DIC in AML-M3?
Granules in promyelocyte will initiate coagulation
This is problem w/ chemotherapy
What are the 4 things you must know about AML-M4?
↑↑myeloblasts
↑↑monocytic cells
Extramedullary tumor masses
inv(16) in some cases
Does inv(16) gene mutation help or hurt AML-M4 prognosis?
Helps prognosis!
What are the 4 things you must know about AML-M5?
↑↑monocytic cells
NSE positive (makes sense b/c monocytes involved)
M5a and M5b
Extramedullary tumor masses
What do the M5a and M5b designations of AML-M5 indicate?
Two different sub-classifications, M5a is more immature
What are the 3 things you must know about AML-M6?
↑↑erythroblasts
↑↑myeloblasts
Dyserythropoeisis (disordered RBC growth/ funny looking RBCs)
What are the 4 things you must know about AML-M7?
↑↑megakaryoblasts
Bland blasts
MPO negative
Need markers (to diagnose)
What is the “new” classification of AML (5)?
AML w/ genetic abnormalities AML w/ FLT-3 mutaiton AML w/ multilineage dysplasia AML, therapy-related AML, not otherwise classified
What are the different AML’s w/ genetic abnormalities?
t(8;21)
inv(16)
t(15;17)
11q23
Does 11q23 gene mutation help or hurt AML prognosis?
Hurts prognosis!
What is the FLT-3 mutation?
A mutation in a tyrosine kinase -> malignant growth
How prevalent among AML cases is the FLT-3 mutation?
Quite! Present in 1/3 of all AML cases!
What does the FLT-3 mutation indicate about prognosis?
Poor prognosis
Define leukostasis
Tumor cells plugging organs
What’s happening with Therapy-Related AML?
If you get therapy for a tumor and survive, you’re at risk of getting more tumors
Is Therapy Related AML easy or difficult to treat (good vs poor prognosis)?
It has a poor prognosis.
What is the treatment for AML?
Chemo
Bone-marrow transplant
What are the different genetic abnormalities in AML? Where are they seen? What prognosis do they indicate?
t(8;21) – in AML-M2; good prog inv(16) – in AML-M4; good prog t(15;17) – in AML-M3; good prog 11q23 – in many AMLs; bad prog FLT-3 – in 1/3 of AMLs; bad prog
What is myelodysplastic syndrome (MDS)?
A group of disorders we think of as “Pre-leukemia.”
What is the main problem in MDS?
Dysmyelopoiesis (disordered growth of myeloid cells)
In what cells do we see the dysplasia in MDS (3)?
Red cells
Neutrophils
Macrophages
What are some findings in MDS patients (3)?
Older
Macrocytic anemia (remember this one)
BM failure
What is treatment for low grade vs high grade MDS?
Low-grade MDS: support, follow
High-grade: aggression intervention!!!!!
What are the 4 things you must know about ALL?
Malignant proliferation of lymphoid blasts in blood and BM
Classified B vs T (immunophenotype)
More common in kids
Good prognosis
Which has a better prognosis, T-lymphblastic leukemia or B?
B is better prognosis
What are the 4 things you must know about T-Lymhoblastic Leukemia?
= T-lymphoblastic lymphoma (same disease, different start points)
Teenage males w/ mediastinal mass (maybe due to thymus?)
WBC usually ↑↑↑
Bad prognosis
What does a high WBC count in T-lymphoblastic leukemia correspond to?
A bad prognosis
What is the mediastinum?
Space between lungs and rest of chest
Contains heart, thymus, trachea, aorta…
What are the 4 things you must know about B-Lymphoblastic Leukemia?
= B-lymphoblastic lymphoma
Several subtypes
TdT+
Rarely, Ph+
What does Ph+ mean?
It means the Philadelphia chromosome is present!
Is Ph good or bad for prognosis?
Presence of Philadelphia gene indicates poor prognosis
If a kid has leukemia, what do you assume it is?
ALL because it is most common in children
What are 4 prognostic indicators of ALL?
Immunophenotype (T is bad)
Age (1-10 good)
WBC count (<10,000 good)
Cytogenetics (hyperdiploidy is good)
What is Tx of ALL?
Chemo +/- BM transplant
Many children are cured!!!
What do we mean when we say children are “cured” of ALL?
They are free of disease for 5 or 10 years.
What is the Philadelphia chromosome?
Genetic defect that causes CML (chronic myeloid leukemia)
t(9;22) creates BCR-ABL hybrid
