Heme Malignancies 1 - Strom

Question 1

Cancer found in the bone marrow and bloodstream is called a ___________.

Answer 1

Leukemia

Question 2

Cancer of primarily the lymph nodes is called _________.

Answer 2

Lymphoma

Question 3

Myeloma is defined as cancer of the ________.

Answer 3

Bone, or other sites other than the lymph nodes and bloodstream

Question 4

What is a lymphoproliferative disease? (Also called a leukemia/lymphoma)

Answer 4

Abnormally proliferating lymphocytes that simultaneously involve the peripheral blood as well as lymphatic tissue.

Question 5

When the white cell count is 20x normal, what is your automatic diagnosis?

What’s on the differential?

Answer 5

ACUTE LEUKEMIA

Differential: sepsis, but the white cell count is not nearly as high

Question 6

When should you suspect a hematologic malignancy? (2 things)

Answer 6

1. When the bone marrow isn’t functioning normally and you can’t find a simpler explanation.
   - Low cell ct, High cell ct, abnormal cells in peripheral blood.
2. Lymphadenopathy and/or splenomegaly is present and an infectious agent can’t be found.

Question 7

How do malignant lymph nodes present in the physical exam?

What about during an infection?

Answer 7

Malignancy: Diffuse, hard, immovable, painless.

Infection: Red, inflammed, moveable, painful

Question 8

Pancytopenia includes what cell populations?

Answer 8

Anemia (RBCs)

Leukopenia

Thrombocytopenia

ALL MYELOID LINEAGE

Question 9

What histologic feature of a peripheral blood smear is always indicative of myeloid blasts?

Answer 9

Auer rods.

Myeloid precursors produce myeloperoxidase, which precipitates and polymerizes to form Auer Rods. (Eosinophillic crystals of proteins that were supposed to be components of granulocyte granules)

Question 10

When you see Auer rods, what general category of cancer do you think of?

Answer 10

AML (Acute Myeloid/Myelogenous Leukemia) t(8;21)

Acute Premyelocytic Leukemia t(15;17) - piles of Auer Rods.

Question 11

The only way to accurately ID a blast is to use FLOW CYTOMETRY to tell you the IMMUNOPHENOTYPE. What is the immunophenotype of a blast cell?

Answer 11

CD34+ (hematopoietic stem cell marker)

and

CD33+ (granulocyte marker)

Question 12

What does myelophthistic mean?

Answer 12

Myelophthisis is a form of bone marrow failure that results from the destruction of bone marrow precursor cells and their stroma, which nurture these cells to maturation and differentiation. It presents in the peripheral blood as a “LEUKO-ERYTHROBLASTIC” picture.

Question 13

How do you take a bone marrow aspiration?

Answer 13

Aim for the PSIS. (or anywhere along the crest)

Remove 1/2 cc for the aspiration sample.

Draw an additional 5-20 cc for special studies. ( Use of this is limited though, because it is hemodilute…there be blood there.)

Last, take a huge needle and get a “Core” biopsy.

Hand it all to Pathology.

Question 14

What is the “Gold standard” for determining if there is an abnormal proliferation of blasts?

Answer 14

A differential cell count, manually performed by a Pathologist on the bone marrow aspirate.

Question 15

When looking at a bone marrow core biopsy, what are you going to make note of?

Answer 15

1. Cellularity
2. MYELOID/ERYTHROID RATIO
3. Iron stores
4. Presence/absence of abnormal cells.

Question 16

How do you determine what the cellularity of a person’s marrow should be?

Answer 16

100-age = % that should be cells not fat

Question 17

What’s the best way to gauge a person’s iron stores?

Answer 17

Look at it in the bone marrow.

Question 18

You run a sample of bone marrow aspirate through the flow cytometer. What is the one population of cells you won’t get any good info about?

Answer 18

Red cells and erythroid precursors.

The aspirate is hemodilute anyway, and the red cell lysis procedure (part of the prep for flow cytometry) lyses all of the precursors.

Question 19

Forward scatter on the flow cytometer is directly proportional to cell ________. What about side scatter?

Answer 19

Forward scatter = SIZE

Side scatter = granularity/cell contents

Question 20

What test do you run if you want to get a cells’ immunophenotype?

Answer 20

FLOW CYTOMETRY

Question 21

If you see a lot of cells that are CD34+ and CD33+, what cancer do you think of, and what is the cell type?

Answer 21

Blast cell - AML

Acute Myeloid Leukemia

Question 22

Flow cytometry can’t detect a Reid-Sternberg cell. What test can reveal it?

Answer 22

Immunohistochemistry

Immunostain.

PS. Reid Sternberg cells are indicative of Hodgkins Lymphoma.

(all the last names go together… Reid, Sternberg, and Hodgkins)

Question 23

What test/s do you run to detect an abnormal cell genotype? What phase must the cells be in for the test/s?

Answer 23

Cytogenetics. Aka: karyotype - structural
-Need M-phase cells

FISH - fusion genes - can use interphase cells

DNA/RNA sequencing via PCR

Complete genome sequencing of cancer cell and comparison to normal cell.

Question 24

What is the immunopheotype of Reid Sternberg cells?

Answer 24

CD30+
CD15+

2 owl eyes x 15 = 30

Question 25

Philadelphia Chromosome is indicative of what cancer?

Answer 25

Chronic Myelogenous Leukemia

Question 26

What translocation created the Philadelphia Chromosome? What methods would you use to detect it?

Answer 26

9;22 BCL-ABR

FISH or Cytogenetics

Question 27

You’ve already done Cytogenetics and FISH on a person you suspect has AML. The results came back normal. Now what?

Answer 27

Use PCR to detect what mutations are present in the genome.

People without abnormal cytogenetics usually have NPM1, TKD, or IKD mutations.

DNA/RNA sequencing study!!

Question 28

Leukemias with what mutation are considered the most genetically unstable?

Answer 28

p53

Question 29

Why is obtaining the genetic sequence of mutations useful for the treatment of cancer?

Answer 29

1. Predictive ability - mutations can predict prognosis

2. Targeted treatment - specific mutations repond to some treatments better than others.

Question 30

What is a Tier 1 mutation?

Answer 30

Mutation of the coding sequence.

Question 31

What are the 3 clinically relevant translocations on AML? (Subtypes, if you will)

Answer 31

PML-RARA

RUNX1-RUNX1

CBFB-MYH11

Question 32

PML-RARA fusion gene is correlated with what subtype of AML? What is the chromosomal classification of this fusion?

Answer 32

Acute Promyelocytic Leukemia

t(15:17)

Question 33

WTF is RARA anyway?

Answer 33

Retinoic acid receptor alpha. Fused to PML, a TF.

Prevents granulocyte formation.

Question 34

What is a Myeloproliferative disease?

Answer 34

In MYELOPROLIFERATIVE DISEASES, a similar clone (usually evident on the basis of cytogenetics and/or FISH studies) proliferates AND differentiates, yeilding an increase in some type of peripheral blood cell.
ex: Polycythemia Vera (increased RBCs)

Question 35

What is a myelodysplasia?

Answer 35

In MYELODYSPLASIAS, a similar clone (usually evident on the basis of cytogenetics) proliferates and differentiates, but the combination of the two processes does not yield normal blood cell production. Instead it yields (usually) a low count of one or more blood cells types (cytopenia(s)), usually in association with an abnormal appearance of those cell types (dyspoietic features)

CYTOPENIAS

Question 36

What is the definition (according to STROM) of Acute Leukemias?

Answer 36

The ACUTE LEUKEMIAS are conditions in which blasts (which are best enumerated on the basis of morphology, but are best identified by immunophenotype) proliferate in blood, bone marrow, or both.

Can be myeloid or lymphoid.

Question 37

In AML, what cell populations are rapidly proliferating?

Answer 37

Myeloid lineages:
Acute Myeloid Leukemia.

Myeloid precursors (granulocytes)

Erythroid precursors

Megakaryocytes

Question 38

In ALL, what population of cells is rapidly proliferating?

Answer 38

Lymphocytes (naiive)