5-17 KRAFTS Malignant Hematopathology Flashcards

1
Q

What is the difference between leukemia and lymphoma?

A

Leukemia starts in Bone Marrow

Lymphoma starts in lymph nodes

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2
Q

Are chronic or acute leukemias more aggressive?

A

Acute

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3
Q

What hematologic malignancies affect myeloid cells?

A

Acute myeloid leukemia (AML)

Chronic myeloid leukemia (CML)

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4
Q

What hematologic malignancies affect lymphoid cells?

A
Acute lymphoblastic leukemia (ALL)
	Chronic lymphocytic leukemia (CLL)
	Hodgkin lymphoma
	Non-Hodgkin lymphoma
	Multiple myeloma (plasma cells)
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5
Q

What happens in a bone marrow biopsy?

A

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

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6
Q

What happens in bone marrow aspiration?

A

After BM tissue biopsy is removed, a vacuum is inserted and sucks out BM. Negative pressure causes pain.

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7
Q

What happens to our bone marrow as we age?

A

It becomes more fatty.

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8
Q

After we have our BM biopsy and aspirate, how do we diagnose the different hematopoietic malignancies (5 ways)?

A
Clinical setting
	Cell morphology
	Immunophenotyping
	Molecular studies (PCR & western)
	Cytogenetics
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9
Q

When staining for NSE (non-specific esterase), what cells light up?

A

Monocytes (b/c they have NSE)

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10
Q

When staining for myeloperoxidase (MPO), what cells light up?

A

Neutrophils (b/c they have MPO)

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11
Q

What is immunophenotyping?

A

Look at markers on cells using flow cytometry

Tells us what cell we’re looking at (eg CD8+CD4- is a CTL)

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12
Q

What is cytogenetics?

A

Look for malignant cells in metaphase and do a karyotype.

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13
Q

How would taking a karyotype of a malignant cell help?

A

We could see gross chromosomal abnormalities (like Philadelphia chrom)

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14
Q

What are the 4 differences between acute leukemia and chronic leukemia?

A
Acute
		Sudden onset
		Adults OR children
		Rapidly fatal
		Involves immature cells (blasts)
	Chronic
		Slow onset
		Adults only
		Longer course
		Involves mature cells
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15
Q

Which leukemia (acute or chronic) can have symptoms of bone marrow failure?

A

Acute - b/c malignant cells crowd out bone marrow

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16
Q

Define Acute Leukemia

A

Malignant proliferation of immature myeloid or lymphoid cells in BM

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17
Q

Describe the pathophysiology of Acute Leukemia (cause and effect).

A
Cause
		Clonal expansion of cells
		Maturation failure of cells
	Effect
		Crowd out normal BM cells
		Inhibit normal cell fxn (via cytokines)
		Invade other organs
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18
Q

What are clinical findings in Acute Leukemia (4)?

A

Sudden onset
Symptoms of Bone marrow failure
Bone pain (due to expanding marrow)
Organ infiltration

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19
Q

What are symptoms of bone marrow failure (3)?

A

Fatigue (↓RBCs)
Infections (↓WBCs)
Bleeding (↓platelets)

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20
Q

What lab findings do we see in Acute Leukemia (4)?

A

Blasts/immature cells in blood
Leukocytosis (↑white count)
Anemia
Thrombocytopenia

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21
Q

What are the 4 things you must know about Acute Myeloid Leukemia?

A

Definition: malignant proliferation of myeloid blasts in blood, BM
20% cutoff for diagnosis
Many subtypes
Bad prognosis

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22
Q

What do we mean when we say “20% cutoff for diagnosis?”

A

In order to diagnose acute leukemia, ≥ 20% of cells need to be blast cells
Can be in blood OR bone marrows

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23
Q

What are some morphological clues on a blood smear that could suggest a leukemia is myeloid?

A

Dysgranulopoiesis (disordered growth/funny looking neutrophils)
Auer rods

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24
Q

Are auer rods over present in lymphoid cells?

A

NO, NEVER. Auer rod is diagnostic for AML (but not REQUIRED for Dx)

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25
Q

What are the 4 things you must know about AML-M0?

A

↑↑↑myeloblasts
Bland (hasn’t differentiated; just looks like a blast)
MPO negative
Need cell markers (to diagnose)

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26
Q

What are the 4 things you must know about AML-M1?

A

↑↑↑myeloblasts
No maturation
Auer rods
MPO POSITIVE

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27
Q

What are the 3 things you must know about AML-M2?

A

↑myeloblasts
Maturing neutrophils
t(8;21) in some cases

28
Q

Does the t(8;21) genetic mutation help or hurt AML-M2 prognosis?

A

Helps prognosis!

29
Q

What are the 4 things you must know about AML-M3?

A
↑↑↑promyelocytes
	Faggot cells (lots of Auer rods make bundles of sticks)
	DIC (disseminated intravascular coagulation)
	t(15;17) in all cases
30
Q

Does t(15;17)) gene mutation help or hurt AML-M4 prognosis?

A

Helps prognosis! Makes cell responsive to all-trans retinoic acid -> terminal differentiation and apoptosis!!!!!!

31
Q

What causes the DIC in AML-M3?

A

Granules in promyelocyte will initiate coagulation

This is problem w/ chemotherapy

32
Q

What are the 4 things you must know about AML-M4?

A

↑↑myeloblasts
↑↑monocytic cells
Extramedullary tumor masses
inv(16) in some cases

33
Q

Does inv(16) gene mutation help or hurt AML-M4 prognosis?

A

Helps prognosis!

34
Q

What are the 4 things you must know about AML-M5?

A

↑↑monocytic cells
NSE positive (makes sense b/c monocytes involved)
M5a and M5b
Extramedullary tumor masses

35
Q

What do the M5a and M5b designations of AML-M5 indicate?

A

Two different sub-classifications, M5a is more immature

36
Q

What are the 3 things you must know about AML-M6?

A

↑↑erythroblasts
↑↑myeloblasts
Dyserythropoeisis (disordered RBC growth/ funny looking RBCs)

37
Q

What are the 4 things you must know about AML-M7?

A

↑↑megakaryoblasts
Bland blasts
MPO negative
Need markers (to diagnose)

38
Q

What is the “new” classification of AML (5)?

A
AML w/ genetic abnormalities
	AML w/ FLT-3 mutaiton
	AML w/ multilineage dysplasia
	AML, therapy-related
	AML, not otherwise classified
39
Q

What are the different AML’s w/ genetic abnormalities?

A

t(8;21)
inv(16)
t(15;17)
11q23

40
Q

Does 11q23 gene mutation help or hurt AML prognosis?

A

Hurts prognosis!

41
Q

What is the FLT-3 mutation?

A

A mutation in a tyrosine kinase -> malignant growth

42
Q

How prevalent among AML cases is the FLT-3 mutation?

A

Quite! Present in 1/3 of all AML cases!

43
Q

What does the FLT-3 mutation indicate about prognosis?

A

Poor prognosis

44
Q

Define leukostasis

A

Tumor cells plugging organs

45
Q

What’s happening with Therapy-Related AML?

A

If you get therapy for a tumor and survive, you’re at risk of getting more tumors

46
Q

Is Therapy Related AML easy or difficult to treat (good vs poor prognosis)?

A

It has a poor prognosis.

47
Q

What is the treatment for AML?

A

Chemo

Bone-marrow transplant

48
Q

What are the different genetic abnormalities in AML? Where are they seen? What prognosis do they indicate?

A
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
49
Q

What is myelodysplastic syndrome (MDS)?

A

A group of disorders we think of as “Pre-leukemia.”

50
Q

What is the main problem in MDS?

A

Dysmyelopoiesis (disordered growth of myeloid cells)

51
Q

In what cells do we see the dysplasia in MDS (3)?

A

Red cells
Neutrophils
Macrophages

52
Q

What are some findings in MDS patients (3)?

A

Older
Macrocytic anemia (remember this one)
BM failure

53
Q

What is treatment for low grade vs high grade MDS?

A

Low-grade MDS: support, follow

High-grade: aggression intervention!!!!!

54
Q

What are the 4 things you must know about ALL?

A

Malignant proliferation of lymphoid blasts in blood and BM
Classified B vs T (immunophenotype)
More common in kids
Good prognosis

55
Q

Which has a better prognosis, T-lymphblastic leukemia or B?

A

B is better prognosis

56
Q

What are the 4 things you must know about T-Lymhoblastic Leukemia?

A

= T-lymphoblastic lymphoma (same disease, different start points)
Teenage males w/ mediastinal mass (maybe due to thymus?)
WBC usually ↑↑↑
Bad prognosis

57
Q

What does a high WBC count in T-lymphoblastic leukemia correspond to?

A

A bad prognosis

58
Q

What is the mediastinum?

A

Space between lungs and rest of chest

Contains heart, thymus, trachea, aorta…

59
Q

What are the 4 things you must know about B-Lymphoblastic Leukemia?

A

= B-lymphoblastic lymphoma
Several subtypes
TdT+
Rarely, Ph+

60
Q

What does Ph+ mean?

A

It means the Philadelphia chromosome is present!

61
Q

Is Ph good or bad for prognosis?

A

Presence of Philadelphia gene indicates poor prognosis

62
Q

If a kid has leukemia, what do you assume it is?

A

ALL because it is most common in children

63
Q

What are 4 prognostic indicators of ALL?

A

Immunophenotype (T is bad)
Age (1-10 good)
WBC count (<10,000 good)
Cytogenetics (hyperdiploidy is good)

64
Q

What is Tx of ALL?

A

Chemo +/- BM transplant

Many children are cured!!!

65
Q

What do we mean when we say children are “cured” of ALL?

A

They are free of disease for 5 or 10 years.

66
Q

What is the Philadelphia chromosome?

A

Genetic defect that causes CML (chronic myeloid leukemia)

t(9;22) creates BCR-ABL hybrid