Hematologic Malignancies: Path & Dx Methods Flashcards Preview

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1

What is a hematologic malignancy?

A hematologic malignancy is an abnormal proliferation of cells derived from those normally found in the blood, bone marrow, or lymphatic tissues

2

What is a leukemia?

A hematologic malignancy that only involves the bone marrow and/or bloodstream.

3

What is acute leukemia?

When cells found in bone marrow, blood, or lymphatic tissues are found to be proliferating rapidly, they can be an immediate threat to the pt's life. This is acute leukemia.

4

What are blasts, in the context of leukemia? (definition of 'blast' varies based on context)

The abnormal cells in cases of hematologic malignancy are usually called blasts because they are thought to represent a neoplastic transformation of rare, morphologically distinct precursor cells in the bone marrow that carry the same name.

5

What is chronic leukemia?

When the abnormal cells are proliferating slowly and are not an immediate threat to the patient’s life, the condition is called a chronic leukemia.

6

What is lymphoma/myeloid sarcoma?

When it only involves lymphatic tissue (lymph nodes, spleen, the subepithelium of the GI tract) or other sites, it is called a lymphoma or a myeloid sarcoma.

7

What is lymphoproliferative disease?

Abnormally proliferating lymphocytes can simultaneously involve the peripheral blood as well as lymphatic tissue. General terms in use for these conditions are lymphoproliferative disease or leukemia/lymphoma.

8

Describe how hematologic malignancies are Dx'd.

How hematologic malignancies are diagnosed:

Clinician recognizes a possible malignancy:
- Examples: Leukocytosis. Pancytopenia. Lymphadenopathy. Splenomegaly.

Clinician requests/performs appropriate initial tests
- Examples: CBC, peripheral smear review, imaging studies

3) Clinician obtains tissue for pathologic confirmation of diagnosis
- Examples: Peripheral blood. Bone marrow biopsy/aspirate. Lymph node biopsy.

Pathologist makes an initial assessment, orders confirmatory tests
- Examples: Flow cytometry. Immunohistochemistry. Cytogenetics. FISH. DNA sequence analysis.

5) Pathologist makes the diagnosis. Or not.

9

When should you suspect a hematologic malignancy?

1) When the bone marrow is not functioning normally, and you can’t find a simpler explanation.
Examples:
- Unexplained low cell counts (cytopenias; leukocytopenia; pancytopenia)
- Unexplained high cell counts (leukocytosis, erythrocytosis, thrombocytosis)
- Cells normally found in the bone marrow are present in the peripheral blood (leukoerythroblastic or myelophthisic features). This can include the presence of blasts.

2) When the lymphatic tissues have enlarged (lymphadenopathy, splenomegaly) and an infectious etiology can’t be found.

10

What is a blast? (based on morphology)

The most commonly accepted, gold standard definition is based on morphology:
It’s a cell with an appearance similar to that of undifferentiated hematologic precursor cells.

Features:
Large cells
High nuclear/cytoplasmic ratio
Prominent, single or multiple nucleoli
Immature (faint/smudgy) chromatin
Their appearance is shared by many cells on a slide

11

Is there an easy morphologic tip-off that the cell you’re looking at is a MYELOID blast?

Auer rods are needle like, eosinophilic (red) crystals formed by proteins normally found in the secondary (red) granules of granulocytes (chiefly myeloperoxidase).

Auer rods are always diagnostic of myeloid blasts.

12

The workup of any hematologic disease begins with a review of:

the peripheral smear

13

Blasts normally make up __% of the cells present in a bone marrow aspirate.

< 5%

14

In the bone marrow, myeloid cells (monocytes, and granulocytes) should outnumber erythroid precursors by __:__ or __:__, representing the majority in the bone marrow.

2:1 to 5:1

15

_____________ of the cell types in the bone marrow aspirate is currently the “gold standard” for determining whether there is an abnormal proliferation of blasts or not.

** Manual count **

16

When observing a core biopsy of bone marrow, describe what the normal cellularity looks like, based on age of the pt.

cellularity is 100-age
i.e. if the pt is 30, there should be 70% cellularity, the rest being fat and bone spicules.

17

When looking at a bone marrow core biopsy under the scope, you will observe myeloid precursors as (choose: light/dark) staining and erythroid precursors as (choose: light/dark) staining cells.

Myeloid: lighter staining
Erythroid: darker staining

18

What is the best way to gauge a pt's Fe stores, just using a microscope? (according to Dr. Strom, this is the best method, period)

Prussian Blue stain of bone marrow core biopsy

19

In immunophenotyping, you can tell what type of cell you are looking at by:

using Abs specific for cell surface proteins that are only present on certain cell types.

ex: CD3, CD4, or CD8 on T cells
CD20 on B cells

20

The most reliable means of counting particular cell types in bone marrow aspirates is:
Why does this complicate the red cell precursor count?

Flow cytometry
Because the aspirate contains many red cells from the circulation (hemodilute: not representing actual contents of the bone marrow), there is a red cell lysis step that will also lyse the red cell precursors that were present in the bone marrow aspirate.

21

In flow cytometry:
“Forward scatter” represents laser light scattered just slightly off-beam, and its intensity is roughly proportional to:

cell size

22

In flow cytometry:
“Side scatter” (SSC), measured at about 90 degrees off-beam, is high for:

cells with a lot of internal granules or segmented nuclei
"complex cells"

23

In flow cytometry, remaining measurements besides forward scatter and side scatter indicate:

laser-induced fluorescence - which we control by adding specific antibodies tagged with fluorescent ligands that emit light, when hit with a laser, at characteristic wavelengths.
This is how particular cell types are tagged (via Abs) and accounted for

24

Can flow cytometry currently be used to measure what fraction of bone marrow cells a sample represents?

No. But it is great for characterizing blasts!

25

In flow cytometry, when characterizing blasts, CD34 represents what kind of blasts?

hematopoietic stem cells (myeloid blasts)

26

In flow cytometry, when characterizing blasts, CD33 represents what kind of blasts?

granulocytes (myeloid blasts)

27

Describe routine cytogenetics as a method of genotyping abnormal cells.

Routine cytogenetic studies identify and enumerate the chromosomes present in dividing (metaphase) cells.

28

Describe fluorescent in situ hybridization (FISH) as a method of genotyping abnormal cells.

It’s not always easy to visualize chromosomes in metaphase cells. A method to do so in cells with intact nuclei (“interphase” cells) would be useful. FISH is that method. Key advantage to FISH is that the cells don't have to be growing (as they do in conventional cytologic methods)

29

What diagnostic technique is essential in the Dx of acute myeloid leukemias (AML)?

sequencing of targeted genes

30

The ultimate method (from our current perspective) for genetically characterizing malignancies is:

to sequence them entirely – either the entire genome (in the range of 3 billion nucleotides) or the exome. This requires comparison, of course, to the presumably unmutated DNA in each patient’s unaffected genome – usually obtained via a skin biopsy sample.