MDS1

Question 1

2 main features that characterize myelodysplastic syndrome (MDS

Answer 1

1. ineffective hematopoiesis:

2. increased risk of transformation to acute leukemia:

Question 2

Ineffective hematopoiesis in MDS

Answer 2

○ The clone (hematopoietic stem cells) is not able to make normal functioning blood cells.
○ Cells often die before leaving the marrow, and usually look abnormal (dysplastic)

Question 3

MDS increased risk of transformation to acute leukemia

Answer 3

hematopoietic stem cell clone slowly acquires enough abnormalities → outright AML

Question 4

2 clinical scenarios of MDS

Answer 4

1. Primary (idiopathic) MDS

2. Secondary / therapy-related (t-MDS)

Question 5

Primary (idiopathic) MDS

• Type of onset?
• Age group:
• Median age of dx:
• Incidence:

Answer 5

○ Insidious onset
○ Usually people >50
○ Median age of dx:70
○ Incidence: 3-5 cases/100,000 persons per year

Question 6

Secondary / therapy-related (t-MDS)

• Type of onset?
• types of therapy leading to MDS

Answer 6

• 2-8 years latency
• use of alkylating agent
• use of topo II
• Exposure of active marrow to ionizing radiation

Question 7

List 3 different types of tests that could be performed to make a diagnosis of MDS.

Answer 7

1) Morphologic evidence of dysplasia in marrow
2) Increased myeloblasts, but less than 20% of blood and marrow cells
3) Presence of a clonal cytogenetic abnormality

Question 8

Morphologic evidence of dysplasia in marrow for MDS

Answer 8

Dyshematopoiesis: > 10% of cell are dysplastic

• Dyserythropoiesis
• Dysgranulopoiesis
• Dysmegakaryopoiesis

Question 9

Dyserythropoiesis

Answer 9

RBC precursors with nuclear budding, irregularly-shaped nuclei, lack of coordination between nuclear and cytoplasmic maturation, increased ring sideroblasts

Question 10

Dysgranulopoiesis

Answer 10

Nuclear hypolobation of mature neutrophils, including neutrophils with bilobed nuclei called pseudo-Pelger-Huet cells, also cytoplasmic hypogranularity of neutrophils

Question 11

Dysmegakaryopoiesis

Answer 11

Megakaryocytes with hypolobated or non-lobated nuclei, often hyperchromatic nuclei, megakaryocytes often of small size

Question 12

4 possible causes of secondary myelodysplasia that might mimic MDS.

Answer 12

1. Certain drugs, including many chemotherapeutic drugs
   - use of alkylating agent
   - use of topo II
   - ionizing radiation
2. Vitamin deficiency (B12, folate, ect)
3. Viral infection
4. Toxin exposure (heavy metals such as arsenic)

Question 13

LOW GRADE MDS:

Answer 13

• Myeloblasts are not increased in frequency
• Refractory Cytopenia with Unilineage Dysplasia (RCUD): good prognosis
• Refractory Cytopenia with Multilineage Dysplasia (RCMD): worse prognosis

Question 14

HIGH GRADE MDS

Answer 14

• Myeloblasts are increased in frequency, (less than 20%)
• Refractory Anemia with Excess Blasts-1 (RAEB-1) : dismal prognosis
• Refractory Anemia with Excess Blasts-2 (RAEB-2): VERY dismal prognosis

Question 15

MDS vs. MPNs:

- source of disease

Answer 15

MDS: marrow is REPLACED by a malignant clone, derived from a transformed stem cell or progenitor cell
MPS: Clonal hematopoietic NEOPLASM arising from a transformed hematopoietic stem cell

Question 16

MDS vs. MPNs:

- onset

Answer 16

Both insidious

Question 17

MDS vs. MPNs:

- hematopoiesis effectiveness

Answer 17

MDS: ineffective
- marrow replaced by malignant clone
MPNs: effective
- marrow fibrosis

Question 18

MDS vs. MPNs:

- ability to develop into acute leukemia

Answer 18

Both

Question 19

MDS vs. MPNs:

- age group

Answer 19

MDS: 
- usually >50 
- median age of dx: 70
MPNs: 
- middle-aged to early adults 
- rare in children

Question 20

2 reasons for the frequent occurrence of splenomegaly and hepatomegaly in patients with MPNs

Answer 20

1. spleen sequestering RBCs because they make too many

2. Extramedullary hematopoeisis, causes liver and spleen to enlarge

Question 21

3 possible negative end points for MPNs.

Answer 21

• Without treatment, get:
○ Marrow fibrosis
○ Bone marrow failure
○ Transformation to acute leukemia (less common for MPN than MDS)

Question 22

4 MPNs

Answer 22

1. Chronic Myelogenous Leukemia (CML)
2. Polycythemia Vera (PV)
3. Primary Myelofibrosis (PMF)
4. Essential Thrombocythemia (ET)

Question 23

Chronic Myelogenous Leukemia (CML)

• What is it?
• blood cell count?

Answer 23

CML is an MPN that manifests primarily as a persistent neutrophilic leukocytosis
○ Blood cell counts:
§ Often incidental diagnosis due to abnormal CBC results
§ WBC ranges from 12,000 – 1,000,000 (averages 100,000)

Question 24

Chronic Myelogenous Leukemia (CML)

Phases

Answer 24

• Marrow findings:

1. Initial Chronic phase (stable)
2. Accelerated Phase (Intermediate phase -may or may be bypassed to Blast phase)
3. Blast phase

Question 25

Chronic Myelogenous Leukemia (CML) | marrow findings

Answer 25

1. Initial Chronic phase (stable) □ Prominent leukocytosis due to a prominent neutrophilia □ Increased basophils in blood □ Increased platelets in blood □ Markedly hypercellular bone marrow with prominent granulocytic hyperplasia 3. Blast phase: □ 20% or more blasts in the marrow or blood

Question 26

Chronic Myelogenous Leukemia (CML) | - cytogenic abnormality

Answer 26

§ BCR-ABL1 fusion gene (must have this for diagnosis) | □ Der(22)t(9:22)→ Philadelphia chromosome

Question 27

``` Polycythemia Vera (PV) : - Blood cell counts ```

Answer 27

Lots of RBCs due to RBCs "really" - PV usually is diagnosed in a polycythemic phase with: □ increased blood cell counts □ Increased neutrophils and platelets in the blood

Question 28

polycythemic phase vs Spent phase (post PV myelofibrosis)

Answer 28

polycythemic phase: increased blood cell counts | Spent: Fall in blood cell count

Question 29

``` Polycythemia Vera (PV) : - marrow findings ```

Answer 29

§ Trilineage hyperplasia in the marrow § Clusters of bizarre megakaryocytes § Spent phase/post-PV myelofibrosis: □ Extensive marrow fibrosis → marrow failure

Question 30

``` Polycythemia Vera (PV) : - cytogenic abnormalities ```

Answer 30

Activating mutation of JAK2, usually a V617F point mutation.

Question 31

``` Primary Myelofibrosis (PMF) - Blood cell counts: ```

Answer 31

``` Q Prefibrotic stage: □ ↑ Platelets in blood □ ↑ neutrophils in blood Progress to fibrotic stage: □ Falling blood cell count □ Leukoerythroblastosis of blood ```

Question 32

``` Primary Myelofibrosis (PMF) - Marrow finding ```

Answer 32

Prefibrotic stage: □ Granulocytic and megakaryocytic hyperplasia, but no erythrocytosis □ Bizarre megakaryocytes in marrow Progress to fibrotic stage: □ Significant reticulin (collagen) fibrosis of the marrow □ Bone marrow failure

Question 33

``` Primary Myelofibrosis (PMF) - Cytogenic abnormality ```

Answer 33

§ JAK2 mutations are present in around 50% of PMF cases | § Cases lacking JAK2 mutations often have mutations of MPL or CALR

Question 34

``` Essential Thrombocythemia (ET) what is it? How is it different from PMF ```

Answer 34

ET is an MPN characterized by a persistent thrombocytosis. - Lacks the marrow granulocytic hyperplasia often seen in PMF, - atypical megakaryocytes in ET are even larger than those in PMF

Question 35

``` Essential Thrombocythemia (ET) - blood cell count ```

Answer 35

§ Persistent thrombocytosis (↑ platelet count) | § 50% of ET patients are diagnosed based on CBC results while asymptomatic

Question 36

``` Essential Thrombocythemia (ET) - Cytogenic abnormality ```

Answer 36

§ JAK2 mutations are present in around 50% of ET cases | § Cases lacking JAK2 mutations often have mutations of MPL or CALR

Question 37

most common method of death attributable to disease in polycythemia vera (PV) patients

Answer 37

venous or arterial thrombosis, leading to complications such as DVT, MI, and stroke

Question 38

3 sites where thrombosis should always make one consider the possibility of PV

Answer 38

``` ○ Thrombosis of: 1. mesenteric vein, 2. portal vein 3. splenic vein should always raise the Possibility of PV. ```

Question 39

most common treatment for PV.

Answer 39

○ Serial phlebotomy ○ Aspirin therapy (to help prevent clots) ○ If symptoms are problematic, mild chemotherapy can be used, but this increases risk of transformation to acute leukemia

Question 40

peripheral blood smear of a patient with leukoerythroblastosis

Answer 40

Presence of immature granulocytes and immature (nucleated) red cells

Question 41

Peripheral blood smear of pt w/ primary marrow fibrosis (PMF)

Answer 41

Leukoerythroblastosis in primary fibrotic stage

Question 42

Peripheral blood smear of pt w/ primary marrow fibrosis (PMF)

Answer 42

Leukoerythroblastosis in primary fibrotic stage