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Heme > Hematologic Malignancies I (Part 1) > Flashcards

Hematologic Malignancies I (Part 1) Flashcards

1
Q

Give examples of malignancies that are well understood, can be definitely diagnosed, are treatable, and will kill your pt if you miss them.

A

CML
Hairy Cell Leukemia
Most pediatric ALLs
AML with t(15, 17)

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2
Q

Give examples of malignancies that are chronic and manageable but can blow up in your face.

A

CLL
Essential thrombocythemia
some MDSs

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3
Q

Give examples of malignancies that have a terrible prognosis but have a slightly better one if treated.

A

Sezary syndrome

t-AMLs

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4
Q

Give examples of malignancies that are poorly treatable and are not well understood.

A

diffuse large B cell lymphoma

peripheral T cell lymphoma NOS

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5
Q

Describe the process of how hematologic malignancies are diagnosed.

A
  1. clinician recognizes possible malignancy: leukocytosis, pancytopenia, lymphadenopathy, splenomegaly
  2. clinician orders CBC, periph smear, imaging
  3. Clinician obtains tissue (BM, periph blood, lymph node) for path/Dx
  4. Pathologist makes initial assessment and orders confirmatory tests (i.e. FISH, flow cyt, immunohistochemistry, cytogenetics, PCR)
  5. Pathologist makes Dx
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6
Q

Workup of any hematological disease begins with a review of ______

A

the peripheral blood smear

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7
Q

What are the 5 characteristics of blasts that Dr. Strom noted in lecture?

A
  1. big cell
  2. inc nuclear:cytoplasmic ratio
  3. immature chromatin
  4. big or multiple nucleoli
  5. a bunch of cells that look a like

*a cell does not have to have all of these characteristics to be considered a blast

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8
Q

What is a “leuko-erythroblastic (myelophthisic) picture”?

A

Stuff normally in BM that is found in periphery

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9
Q

What are examples of cell morphologies that are present in the BM but not (normally) in the periphery?

A 
nucleated red cells
giant platelet
myelocyte
blast 
basophillic stippling
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10
Q

Describe how a BM biopsy is taken.

A
  1. sterile field
  2. Inject local anesthetic
  3. draw 0.5 cc thick bloodly fluid containing bony spicules
  4. draw an addnl 2-20 cc of more hemodilute fluid for addnl studies
  5. insert needle at a very different angle to draw out core biopsy
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11
Q

T or F: the core biopsy is empty of blood-forming elements if it is extracted from the same site that the aspirate was obtained.

A

T

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12
Q

T or F: the local anestheic used to take a BM biopsy will numb the surface and center of the bone.

A

F: will only numb the surface of the bone

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13
Q

Why do you get 3 samples when you take a BM biopsy?

A

The first sample is minimally hemodilute and can be examined/studied more accurately under the microscope.

The 2nd sample is more hemodilute and can be used for studies such as flow cytometry in which the conc of the cells does not affect the results.

And the core biopsy is for histological studies

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14
Q

In general, what does a pathologist do when a clinician sends them a BM biosy to study in which they have requested with every test to be run on the sample.

A

they do all those tests
or
they take an initial look at the aspirate to refine the differential and/or order only the appropriate tests i

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15
Q

What does the pathologist report back with to the clinician after the BM biopsy has been examined?

A
  1. describe what any abnormal cells look like
  2. describe the immunopathy of any abnormal cells
  3. describe the genotype of any abnormal cells
  4. make a Dx (or not)
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16
Q

The aspirated material from the BM will contain ______

A

tiny spicules or bone fragments or clots

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17
Q

Blasts normally make up ___% of cells in the BM

A

less than 5%

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18
Q

What should the ration of myeloid cells : erythroid precursors be?

A

2:1 to 5:1 (lots more myeloid cells = granulocytes and monocytes)

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19
Q

What 5 characteristics are pathologists looking for when examining a BM sample?

A
  1. specimen adequacy
  2. estimate of cellularity
  3. myeloid : erythroid ratio
  4. iron stores esitmate
  5. any abnormal cell type
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20
Q

How is the normal % cellularity of a core BM biopsy determined?

A

100 - age

*ie 50 y/o should have 50% or a bit less of cellularity and the rest is normal fat

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21
Q

What lineages should be present in a good core biopsy?

A

erythroid, myeloid, and megakaryocyte

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22
Q

Describe where iron stores are normally found in the bone marrow.

A

in BM histiocytes (macrophages)

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23
Q

What are the 5 B cell markers?

A

(>10…)

  1. CD45
  2. CD79a
  3. CD20
  4. IgG kappa
  5. IgG lambda
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24
Q

What are the 5 T cell markers?

A

(<10…)

  1. CD45
  2. CD3 (TcR)
  3. CD7
  4. CD4
  5. CD8
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25
Q

What is a hapten?

A

site where Ab binds

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26
Q

How are B and T cell markers detected?

A

with monoclonal Abs specific for each Ag/marker

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27
Q

T or F: One protein can have more than one CD destonation.

A

T: is he implying that a sigle monoclonal Ab can recognize multiple CD markers on cells?

28
Q

What is immunophenotyping?>

A

determining the proteins that a cell expresses

29
Q

What are the 2 methods of immunophenotyping given in lecture?

A
  1. flow cytometry

2. immunohistochemistry

30
Q

What is the most reliable means of counting particular cell types in BM aspirates?

A

flow cytometery

31
Q

What are the limitations of using flow cytometry?

A
  1. red cell lysis step lyses most of the erythroid precursors
  2. the aspirate is usually hemodilute
  3. does not work well for unusually large cells
  4. cannot be immediately correlated to detailed morphologic features (like what cell types are adjacent to it on the slide)
32
Q

Describe how flow cytometry works/is used to study BM aspirate.

A

Add agent to lyse RBCs and add fluorescent Abs specific to the markers/surface you wish to count. The tagged cells are counted and plotted on a graph. Most models/machines can measure 6 diff data points (markers) at a time that cab be plotted

33
Q

What cells express CD45?

A

B and T cells

34
Q

What cells express CD34?

A

hematopoietic stem cells (blasts)

35
Q

What cells express CD33?

A

maturing granulocytes (myeloid blasts)

36
Q

What Dx is consistent with CD34 and CD33 coexpression?

A

AML

37
Q

How is immunostaining different than routine staining?

A

in immunostaining, an enzyme conjugated Ab specific to a suface marker is added and examined

38
Q

What are the 4 methods for genotyping abnormal cells?

A
  1. routine cytogenetics
  2. FISH
  3. DNA/RNA sequencing
  4. complete genome sequencing
39
Q

What does routine cytogenetics identify?

A

provides a karyotype to enumerate the chromosomes present during metaphase

*IDs some translocations, duplications, deletions, trisomies, chromosome fragments

40
Q

Describe the cytogenics of the Philadelphia chromosome. And what disease is this assc with?

A

t(9, 22) w/ CML

*discovered by Janet Rowley

41
Q

What a limitation of cytogenetics? (FISH overcomes this)

A

cells must be dividing/in metaphase

42
Q

Describe how FISH is carried out.

A

Slide with unstained cells + protease digestions to expose DNA + fluorescent oligionucleotide probes for specific chromosomes and genes are added to show location of target genes

43
Q

If FISH and cytogenic studies yield normal results what is the next method used to pick up a malignancy?

A

PCR based DNA/RNA sequencing to pick up internal tandem duplications (ITD) and partial tandem duplications (PTD) in specific genes (I think…)

44
Q

What is currently the “ultimate method” for genetically characterizing malignancies?

A

complete genome sequencing (microarrays are also frequently used but Strom said he doesn’t have time to explain this further)

45
Q

AML pts with normal cytogenic findings had their malignancies sequenced to determine the mutations in them. From the group studied, there was a total of 750 point mutations found. 4 of which were found in at least one other case. What is the implication of this?

A

these 4 are probably relevant to pathogenesis and these are the mutations that need to be characterized to optimally manage pts with AML (Tx and Dx)

*OR epigenetic changes are at work in AML…

46
Q

What are the 3 major categories of hematologic malignancies?

A
  1. Acute leukemia
  2. Myeloproliferative disorders
  3. Myelodysplastic syndrome (MDS)
47
Q

Which of the 3 major categories of hematologic malignancies is described below:

chronically proliferating clones that differentiate to circulating blood cells

A

myeloproliferative diseases

48
Q

Which of the 3 major categories of hematologic malignancies is described below:

poorly functioning cells

A

myelodysplastic syndrome

49
Q

Which of the 3 major categories of hematologic malignancies is described below:

rapidly proliferating clones with blasts seen in marrow and often bloodstream

A

acute leukemia

50
Q

T or F: AML is defined as rapidly proliferating clones of myeloid blasts

A

False: rapidly proliferating clones of myeloid lineages, erythroid lineages, Megs, lymphocytes

51
Q

What is the definition of ALL?

A

rapidly proliferating clones of lymphocytes in the BM and bloodstream

52
Q

What is acute undifferentiated leukemia?

A

rapidly proliferating clones of hematopoietic stem cells in the BM and blood stream

*clones seem to be derived from stem cells that have not committed to a lineage

53
Q

T or F: Leukemia can involve cells that have taken over the BM without raising the WBC in in peripheral blood

A

True

54
Q

How are acute leukemias that do not raise the peripheral WBC Dx?

A

see leuko-erythroblastic findings in peripheral smear

55
Q

What type of leukemia can present outside of both the BM and peripheral smear and in bone or connective tissue as solid tumors?

A

myeloid leukemias with monocyte like features = “myeloid sarcoma”

56
Q

What are the 3 clinical presentations seen with acute leukemias? (where are tumor cells found)

A
  1. many blasts in blood and marrow
  2. few blasts in blood and many in marrow
  3. blasts outside the marrow (myeloid sarcoma and lymphoblastic lymphoma)
57
Q

What are the 4 diagnostic criteria for acute leukemias? (give examples of each)

A
  1. Blast count: marrow blast number > 20%
    • 20% is arbitrary and if cytogenics point to AL without >20% blasts the pt can still be Dx with AL
  2. Immunophenotype
    CD34+ = blasts
    CD34+, CD33+ = myeloid blasts
    CD19+, CD10+ = lymphoid blasts
  3. Blast Morphology (level of differentiation)
  4. specific genotypes: t(15, 17), t(8, 21), t(12, 21)
58
Q

T or F: Flow cytometry can be used to determine the % blasts in the BM.

A

False: the sample used in flow cytometry is too hemodilute, must used the first sample taken from the biopsy

59
Q

T or F: Blasts surface protein expression correlates well to how fast the clone will take over and how well the patient will respond to treatment.

A

False: it does not correlate to either of these

60
Q

What are the advantages to using genotype as a diagnostic criteria for acute leukemias?

A
  1. inc prognostic value
  2. predicts response to therapy
  3. identifies molecular targets for therapy production
61
Q

Describe the 2 classes of mutations/translocations required to Dx acute leukemias.

A

Class I: proliferation/survival advnatge

Class II: Impaired differentiation/apoptosis

62
Q

What are examples of Class I mutations? How are these detected?

A 
Detected by sequencing:
FLT3-ITD
FLT3-TKD
Kit
Ras
PTPN11
Jak2
63
Q

What are examples of Class II mutations? How are these detected?

A 
Detected by routine cytogenetics: 
PML-RARA
Runx1-Runx1T1
CBFB-Myth11
MLL fusions

Detected by sequencing:
CEBPA
NPM1

64
Q

What AML subtypes require only the cytogenetics for Dx (regardless of what the blast count is)?

A

RUNX1-RUNX1T1
CBFB-MYH11
PML-RARA

65
Q

What AML subtypes require cytogenetics AND >20% blasts?

A

MLLT3-MLL
DEK-NUP214
RPN1-EVI1
RBM15-MKL1

Heme (38 decks)

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