Hematologic Malignancies I Flashcards

1
Q

What is a hematologic malignancy?

A

Abnormal Proliferation of Cells Derived from those normally found in the blood, bone marrow, or lymphatic tissues

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2
Q

T or F: a hematologic malignancy can involve the bone marrow, peripheral blood, lymphatic tissue, another anatomical location or any combination of these sites.

A

True

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3
Q

When a hematologic malignancy referred to as a leukemia?

A

When it only involves bone marrow and/or the bloodstream

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4
Q

Differentiate between an acute and chronic leukemia.

A

Acute Leukemia - cells are dividing rapidly and can be an immediate threat to the patient’s life

Chronic Leukemia - less aggressive proliferations

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5
Q

What abnormal cells are usually present in leukemias?

• why are they called this?

A

Blasts

• Called blasts because they represent neoplastic transformation of rare, morphologically distinct precursor cells in the bone marrow also called BLASTS

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6
Q

What two classifications are typically used in Acute Leukemias?

A

Myeloid/Myeloblastic

Lymphoid/Lymphoblastic

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7
Q

What are hematologic malignancies called when they involve lymph nodes, spleen, or subepithelium of the GI tract?

A
  • Lymphoma

* or Myeloid Sarcoma

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8
Q

How do you determine the difference between a low grade lymphoma and a high grade lymphoma?
• alternative names to low and high grade lymphomas

A

Indolent (low grade) Lymphoma
• Slow proliferation without immediate threat to the patients life

Aggressive (high grade) Lymphoa
• Rapid proliferation that may extend into non-lymphatic tissues

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9
Q

What term refers to abnormal proliferation in peripheral blood and lymphoid tissues simultaneously?

A

Lymphoproliferative Disease = Leukemia/Lymphoma

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10
Q

In the real of next generation sequencing, what does depth of sequencing refer to?
•What does a greater depth of sequencing allow us to do?

A

Depth of Sequencing:
• The number of times a given stretch of DNA is sequenced

• Greater depth allows us to look at how malignancies evolve for individual types of cancer

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11
Q

What types of leukemias are well understood, definitively diagnosed, and treatable but can kill your patient if you miss them?

A
  • CML (chronic myeloid leukemia)
  • Hairy Cell Leukemia
  • Most Pediatric Acute Leukemias
  • Acute Myeloblastic Lekemias with t(15:17)
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12
Q

What are some chronic and manageable leukemias that can blow up in your face?

A
  • CLL (chronic lymphocytic leukemia)
  • Essential Thrombocytopenia
  • some Myelodysplastic Syndromes (MDS)
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13
Q

What are some Leukemias with terrible Px that is slightly better if treated?

A
  • Sezary Syndrome

* Most therapy-related acute myeloid leukemias (t-AML)

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14
Q

What are some large categories full of poorly treatable entities which are not yet understood?

A
  • Diffuse Large B-Cell Lymphoma

* Peripheral T-cell Lymphomas

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15
Q

What type of hematologic malignancy typically results from a combination of mutations that enhance proliferation and inhibit differentiation?
• Cell appearance?
• Cell location(s)?

A

Acute Leukemia

Cell Appearance:
• Features similar to hematopoietic Stem Cells

Cell Location:
• Peripheral Blood, Bone marrow or both

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16
Q

What would you be looking for in a peripheral blood sample of someone with a myeloproliferative disease?
• proliferation and differentiation of these cells.

A
  • Clones proliferate AND DIFFERENTIATE

* Look for increase in a cell type in the peripheral blood smear

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17
Q

Differentiate myelodysplasias from myeloproliferative diseases.

A

Myelodysplasias:
• Clones proliferate and differentiate BUT the combination does not lead to production of a normal looking blood cell.

• Usually is a REDUCTION and ABNORMAL APPEARANCE in one or more or blood cell types

Myeloproliferative Disease:
• Clones proliferate and differentiate to create a larger amount of normal cells

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18
Q

What is required to diagnose subtypes of acute leukemias, myeloproliferative diseases, and myelodysplasias?

A

Must be identified via:
• Morphologic
• Immunophenotypic
• Genetic Methods

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19
Q

What is believe to be the common cause of acute leukemias, myeloproliferative diseases, and myelodysplasias?

A

Acquired mutations in one or more clones of hematopoeitic stem cells

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20
Q

What are 3 presentations of the peripheral blood and bone marrow in patients with acute Leukemias?
• Which is/are most common?
• Note any specific conditions associated with the presentation.

**Note: Acute Leukemias are medical emergencies

A

1) Many Blasts in the blood and Marrow - rapid growth in bloodstream leads to takeover of bone marrow too
• This is most common

2) Few Blasts in the blood and Many in Marrow
• less common

3) Blasts outside the marrow
• Myeloid Sarcoma
• Lymphoblastic Lymphoma

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21
Q

T or F: monoblastic forms of acute leukemias often present outside the bone marrow.

A

True, these are associated with Myeloid Sarcomas where malignant cells are located in Bone or Connective Tissue

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22
Q

What 3 lineages of Hematopoietic Stem cells can cause Acute Myeloid Leukemias (AMLs)?

A
  • Myeloid Lineage
  • Erythroid Lineage
  • Megs
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23
Q

What lineage(s) of Hematopoietic Stem cells can cause Acute Lymphoblastic Leukemia (ALL)?

A

• Lymphocytes

24
Q

Proliferation of what cell type leads to Acute Undifferentiated Leukemia?

A

• Hematopoietic Stem cells that do not appear to have committed to any of the 4 lineages (Myeloid, Erythroid, Megs, or Lymphocytes)

25
Q

What 4 steps are taken to Diagnose Hematologic Malignancies?

A

1) Clinician Recognizes a Possible Malignancy
2) Clinician Requests/Performs Appropriate Initial Tests
3) Clinician Obtains Tissue for Pathologic Confirmation of Dx.
4) Pathologist makes initial assessment and orders confirmatory tests
5) Pathologist Decides on Dx.

26
Q

What are 4 symptoms that might tip you off that a hematologic malignancy is present?

A
  • Leukocytosis
  • Pancytopenia
  • Lymphadenopathy
  • Splenomegaly
27
Q

What tests might you run after you are tipped off that a hematologic malignancy is present?

A
  • CBC
  • Peripheral Blood Smear
  • Imaging Studies
28
Q

What confirmatory tests are used by pathologists to make a Dx on a potential hematologic malignancy?

A
  • Flow Cytometry
  • Immunohistochemistry
  • Cytogenetics
  • Fish
  • DNA sequence Analysis
29
Q

What are some obvious signs that should lead you towards Dx of Acute Leukemia?

A
  • White Cell Count is 120,000 per µL (20x normal)
  • Lab says they are all blasts
  • Patient was well until last week
30
Q

Is it still possible to have an Acute Leukemia with normal White cell count?
• What are some other less obvious symptoms that might tip you off to Acute Leukemia?

A

*Some Pts. with Acute Leukemia will have normal white cell count

What to look for:
• Low Platelet Count
• Peripheral Smear containing even small numbers of Atypical cells
• Bone marrow replaced by blasts

31
Q

What are 2 main reasons to begin suspecting a hematologic malignancy?

A
  • Bone Marrow is not functioning normally and you can’t find a simpler explanation
  • When Lymphatic Tissues have enlarged and Infectious etiology can’t be found
32
Q

What would be some indications of improper bone marrow functioning that might point you to hematologic malignancy?

A
  • Unexplained Low Cell Counts (cytopenias)
  • Unexplained High Cell Counts (-cytosis)
  • Blasts in the blood (or other marrow cells that aren’t typically in peripheral blood)
33
Q

How are blasts defined?
• Characteristics
• Most important?

A

Blasts are simply cells that resemble undifferentiated hematologic Precusor Cells

Characteristics: 
• Large
• High N/C ratio
• Prominent Single or Multiple Nucleoli
• Immature (faint/smudgy) chromatin
• Appearance shared by many cells on the slide**

Shared Appearance = Most important b/c it suggests monoclonal expansion

34
Q

What morphologic feature is ALWAYS indicative of myeloid blasts?
• What physiology underlies this morphologic characteristic?

A

Auer Rods - needle-like eosinophilc (red) crystals formed by proteins normally found in the secondary (red) granules of granulocytes

*Consist mainly of Myeloperoxidase

35
Q

Can blasts be identified solely through flow cytometry?

A

No, morphologic identification is needed but flow cytometry can be used to backup evidence that a cell is a blast

36
Q

How does the workup of any hematological disease begin?

A

*Review of the Peripheral Smear

37
Q

What finding are you typically looking for in a peripheral smear or a patient with a hematologic maligancy?
• How many of these findings suggest pathology?

A
  • Nucleated Red Cell
  • Basophilic Stippling and Howell-Jolly body formation
  • Giant Platelets
  • Myelocytes
  • Blasts

**Seeing any 2 or 3 of the above on a peripheral smear is indicative of pathology

38
Q

T or F: looking at the peripheral smear can tell you the type of bone marrow pathology that is present.

A

False, this requires a bone marrow biopsy

39
Q

What are 3 steps in getting a bone marrow biopsy?

A
  1. Drive needle into bone and draw out 1/2 cc of Hemodilute apsirate
  2. Draw an additional 5-20 cc for SPECIAL STUDIES
  3. Insert larger needle at a different angle to get the CORE BIOPSY
40
Q

What descriptions of the cells should you get from a pathologist in their report?

A

• Description of What Cells look like
• Describes Immunophenotype of any abnormal Cells
• Describes Genotype of any abnormal cells
***They usually make the Dx

41
Q

What is the gold standard for determining if there is abnormal proliferation of blasts or not?
• How many blast should there typically be?

A

Manual count of cell types in BONE MARROW ASPIRATE

• Blasts should make up less than 5% of cells here

42
Q

What should you look for to see if there’s abnormal proliferation in a bone marrow core biopsy?
• what else is the pathologist looking for?

A

In healthy person you should see cellularity that’s approximately 100 - age of pt., the rest should be fat

Pathologist looks for:
• Myeloid: Erythroid Ratio
• Iron Stores Estimate
• Any abnormal cell types

43
Q

Differentiate between the appearance of erythroid and myeloid precursors on a bone marrow core biopsy?

A

Nucleus of Erythroid Precursors will be darker with a higher N/C ratio than Myeloid Precursors

44
Q

What surface antigens are typically present on B cells?

• T cells?

A
B cells: 
CD45
CD79a
CD20
IgG kappa or IgG lambda 
T cells: 
CD45 
TcR (CD3) 
CD7
CD4 or CD8
45
Q

What is the most reliable means to counting particular cells types in bone marrow aspirate?
• Why do you still need a pathologist to count?

A

**Flow cytometry = most reliable means of counting particular cell types in bone marrow aspirate

Still Need pathologist b/c the aspirate is hemodilure and the Red Cell Lysis Procedure lyses most or all of the erythroid precursors.

46
Q

What is measured by forward scatter and side scatter (SSC) in flow cytometry?
**How are other things measured?

A

Forward Scatter:
• roughly proportional to size

Side Scatter (SSC): 
• High for cells that contain lots of internal granules or segmented nuclei 

Everything Else:
• Done by attaching fluorescent antibodies to the target cells are irradiating them with light at different wavelengths

47
Q

What is usually plotted 1st from flow cytometry?

  • Why is this typically used 1st?
  • What cell type is likely to be underreprennted, why?
A

CD45 vs. SSC

• Typically this is used 1st because almost all marrow cells express CD45 and you can get an idea of the types of cells in the marrow

*RBCs are likely to be underrepresented because of the lysis procedure

48
Q

How would you go about finding blasts in flow cytometry?

A

CD34 and CD33

  • CD34 allows you to measure Hematopoietic Blasts
  • CD33 is a marker of granulocytes
49
Q

What is the pitfall of flow cytometry when identifying blasts and other cell types?

A

1) It doesn’t tell you the fraction of bone marrow that the cell represent so you have to rely on the pathologist’s manual count
2) It doesn’t work for unusually large cells
3) Doens’t tell you detailed morphologic details like what cells are hanging out with the cells of interest

50
Q

What is the following report indicative of:
• Abnormal Population of cells
• 60% of Total
• Co-expression of CD34 and CD33

A

These findings are consistent with acute myeloid leukemia

51
Q

T or F: a karyotype is beneficial in diagnosing CML (chronic melogenous leukemia).

A

True, CML is associated with t(9,22) resulting in Philadelphia chromosome that can be seen on karyotype

52
Q

How is FISH performed to find out if a patient has Chronic Myelogenous Leukemia (CML)?
*what indicates that the patient has it?

A

Attach Red Probe to 9q13
Attach Green Probe to 22q11.2

*If you see yellow then these genes are close in proximity and the pt. has CML

53
Q

What is a key advantage to FISH?

• Type of Cell that its performed in.

A

cells don’t have to be growing (this a requirement of most cytogenetic studies)
• Performed in Cells with In Tact nuclei

54
Q

What is the standard of care in cases for which the morphology and immunophenotype leads in the direction of subtypes of a few malignancies?
• Why would you use this over a karyotype or FISH

A

Targeted Sequencing Studies, because they can detect point mutations

  • Karyotypes can only detect translocations etc.
  • FISH can’t detect point mutations very well
55
Q

What are the 2 methods of Immunophenotyping?

A

Immunophenotyping = What are proteins the cells expressing

  1. Flow Cytometry
  2. Immunohistochemistry
56
Q

What 4 methods are used in genotyping a cell that looks malignant?

A
  1. Routine Cytogenetics - Karyotype
  2. FISH
  3. PCR amplification to look at DNA and RNA
  4. Whole Genome/ exome sequencing
57
Q

Will you order Genome Sequencing if you suspect a point mutation?
• why or why not?
• What would you need to give to the geneticists in order to do the tests?

A

No, this method is currently reserved for research purposes

• IF, you did do this you would need to submit malignant cells along with normal cells from the same person so that comparisons can be made