Pathoma - Myeloproliferative Disorders - Fundamentals Of Pathology

Front 1

What do we call an accumulation of mature myeloid cells?

Back 1

Myeloproliferative disorder

Front 2

If RBCs are overproduced, what do we call that?

Back 2

Polycythemia vera

Front 3

If granulocytes are overproduced what do we call that?

Back 3

CML

Front 4

Of megakaryocytes or platelets are overproduced, what do we call that?

Back 4

Essenetial thrombocytemia

Front 5

True or false: In myeloproliferative disorders, you get a proliferation of one cell lineage at a time.

Back 5

False. Actually, it involves every single lineage. However, we name it based on the predominant cell type.

Front 6

What age group do we see myeloproliferative disorders in?

Back 6

it is a disease of late adulthood

Front 7

What do we see in marrow and on count in myeloproliferative disorders?

Back 7

Results in high WBC count (granulocytes) and hypercellular marrow

Front 8

Complications that are common in myeloproliferative disorders include?

Back 8

(1) Increased risk for hyperuricemia and gout (lets say you overproduce RBCs, the marrow spits out all the nuclei and those nuclei has to be degraded)
(2) Progression to marrow fibrosis

Front 9

Progression to marrow fibrosis is called the?

Back 9

Spent phase

Front 10

Many myeloproliferative disorders can progress to what?

Back 10

Acute leukemia (accumulating mutations)

Front 11

CML is proliferation of what?

Back 11

Neoplastic proliferation of mature myeloid cells, especially granulocytes

Front 12

What cell type is characteristically increased in CML?

Back 12

Basophilia

CML is also the only leukemia with thrombocytosis.

Front 13

This might be?

Back 13

Chronic myeloid leukemia, look at all the neutrophils, a myeloid precursor cell in the bottom and basophil.

Front 14

CML is driven by what?

Back 14

t(9;22), a BCR-ABL fusion gene

Front 15

First line treatment of CML is what?

Back 15

Imatinib, which blocks tyrosine kinase activity.

Front 16

In CML, _____________ is common. What phase does this correspond to?

Back 16

Splenomegaly.

Chronic phase.

Front 17

You can divide CML into three phases, what are they?

Back 17

(1) Chronic phase
(2) Accelerated phase
(3) Transformation phase (acute leukemia)

Front 18

A man with CML has had stable splenomegaly for some time. All of a sudden it enlarges. What phase does this correspond to?

Back 18

Accelerated phase

Front 19

When does transformation in CML occur?

Back 19

Usually shortly after accelerated phase

Front 20

Transformation, when it occurs in CML can result in either ________ or _________.

Back 20

AML (2/3) or ALL (1/3)

Front 21

What cell proliferates in CML?

Back 21

Because CML can transform into either ALL or AML, it must be at the level of the HSC.

Front 22

What is a leukemoid reaction?

Back 22

Physiologic response to stress or infection

Front 23

On a smear, you observe a bunch of granulocytes and early percursors. What is your differential diagnosis?

Back 23

(1) Acute infection
(2) CML

Front 24

How can you make the distinction between a leukemoid reaction and CML?

Back 24

(1) CML granulocytes are LAP negative (secondary granules)
- Cells of CML have no intention of fighting an infection, they are basically having a party. That's why LAP is negative.

(2) CML is associated with increased basophils.

(3) CML granulocytes exhibit t(9;22)

Front 25

What is polycythemia vera?

Back 25

Myeloproliferative disorder with neoplastic proliferation of mature myeloid cells, especially RBCs.

Front 26

What cells are increased in polycythemia vera?

Back 26

RBCs especially, but also granulocytes and platelets.

Front 27

Polycythemia vera is associated with a ________ mutation.

Back 27

JAK2 kinase mutation

Front 28

Clinically, patients with PV are going to get symptoms of what?

Back 28

Symptoms of hyperviscosity.

(1) Blurry vision, headache
(2) Increased risk of venous thrombosis (hepatic v.; budd chiari)
(3) Flushed face due to congestion
(4) Itching after bathing (they also have extra mast cells)

Front 29

Treatment of PV?

Back 29

Phlebotomy.

Second-line is hydroxyurea.

Front 30

In PV, without treatment, death will usually occur within __________.

Back 30

one year

Front 31

PV must be distinguished from what?

Back 31

Reactive polycythemia

Front 32

List the oxygen saturation and EPO findings in PV, lung disease and ectopic EPO production.

Back 32

PV: SaO2 normal, EPO is decreased (negative feedback)
Lung disease: SaO2 decreased, EPO increased
Ectopic EPO: SaO2 is normal, EPO is high

Front 33

A tumor that typically produces EPO?

Back 33

Renal cell carcinoma

Front 34

What cells are increased in essential thrombocythemia?

Back 34

Especially PLTs. RBCs and granulocytes are also increased.

Front 35

Essential thrombocythemia is associated with what mutation?

Back 35

JAK2 kinase mutation

Front 36

What should you think about when you see tons of platelets in a blood smear?

Back 36

Essential thrombocythemia
Iron deficiency anemia (reactive phenomenon)

Front 37

What are the symptoms of essential thrombocythemia?

Back 37

Increased risk of bleeding (underfunctioning PLTs) and/or thrombosis (overfunctioning)

Front 38

Most myeloproliferative disorders have the ability to ___________, however ET rarely progresses to ___________ or _________.

Back 38

burn out; marrow fibrosis; acute leukemia

Front 39

In what myeloproliferative disorder is there NOT an increased risk for hyperuricemia and gout?

Back 39

ET. No nucleus in PLTs.

Front 40

What is myelofibrosis? What mutation is it associated with?

Back 40

A myeloproliferative disorder. Neoplastic proliferation of mature myeloid cells, especially megakaryocytes.

Associated with a JAK2 kinase mutation.

Front 41

Why is it called myeloFIBROSIS?

Back 41

Because megakaryocytes produce excess PDGF and this results in marrow fibrosis.

We see way too much fibrosis on the picture. Should be fat and bone marrow elements.

Front 42

Clinical features of myelofibrosis include? Explain each feature.

Back 42

(1) Splenomegaly due to extramedullary hematopoiesis (fibrosis --> no hematopoiesis in marrow --> hematopoiesis in spleen)

(2) Leukoerythroblastic smear (WBC and RBC immature cells in blood because spleen does not have a reticulin gate preventing their departure from the marrow)

(3) Increased risk for infection, thrombosis, bleeding (marrow is gone; spleen is tiny compared to bone marrow, it cannot produce sufficient amounts.

Front 43

What prohibits cell from exciting the marrow when they are too immature?

Back 43

reticulin "gates"

Front 44

In what myeloproliferative disease do we see these cells?

Back 44

Myelofibrosis.

Think of it like this: Some hematopoiesis still occurs in marrow, but it is highly fibrosed and cells get stretched as they try to leave the bone marrow.