Myelodysplastic Syndrome & Myeloproliferative Neoplasms

Question 1

List the 2 main features that characterize myelodysplastic syndrome (MDS)

Answer 1

a) ineffective hematopoiesis

b) increased risk of transformation to acute myeloid leukemia

Question 2

List the 2 clinical scenarios of MDS

Answer 2

1) Primary / Idiopathic - Usually in persons over 50 years old, insidious onset. Median age of diagnosis is 70. Incidence estimated at 3-5 cases per 100,000 persons per year.
2) Secondary / Therapy-Related (t-MDS) - Occurs as part of the spectrum of t-AML discussed in prior lecture. Usually occurs 2-8 years after use of alkylating agents or exposure of fields of active marrow to ionizing radiation. Usually contains whole or partial deletions of chromosomes 5 and/or 7

Question 3

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

Answer 3

in the presence of persistent (at least several months) peripheral cytopenia in one or more lineages that cannot be otherwise explained, diagnosis is made with

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

Question 4

List 4 possible causes of secondary myelodysplasia that might mimic MDS

Answer 4

• Certain drugs, including many chemotherapeutic drugs
• Deficiencies of vitamin B12, folic acid, or certain essential elements
• Viral infection
• Toxin exposure, especially heavy metals such as arsenic

Question 5

Low grade MDS: diagnostic criteria and prognosis

Answer 5

Diagnostic criteria: Myeloblasts account for less than 5% of marrow cells, and less than 2% of peripheral blood cells.
Prognosis: RC-UD with a relatively good prognosis and RC-MD with a worse prognosis

Question 6

High grade MDS: diagnostic criteria and prognosis

Answer 6

Diagnostic criteria: Myeloblasts account for 5% or more of marrow cells, and/or 2% or more of peripheral blood cells.
Prognosis: Prognosis for high grade MDS is dismal; even if patients don’t progress to AML they frequently die secondary to their bone marrow failure

Question 7

Dyserythropoiesis

Answer 7

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

Question 8

Dysgranulopoiesis

Answer 8

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

Question 9

Dysmegakaryopoiesis

Answer 9

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

Question 10

MDS vs. MPNs: usual number and appearance/functionality of cells in the blood and marrow

Answer 10

• MDS: Morphologic evidence dysplastic changes in at least 10% of the cells in one or more lineages (dyshematopoiesis). (Dyserythropoiesis, dysgranulopoiesis or dysmegakaryopoiesis)
• MPNs: quantitative increase in one or more blood cell types (neutrophils, platelets, and/or RBCs), usually with a correspondingly hypercellular marrow

Question 11

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

Answer 11

MPNs often present with splenomegaly and/or hepatomegaly due to both:

• sequestration of excess blood cells
• extramedullary hematopoiesis

Question 12

List 3 possible negative end points for MPNs

Answer 12

a) transformation to acute leukemia (usually AML, but sometimes ALL) (in the setting of a prior MPN, transformation to acute leukemia is often referred to as blast phase)
b) development of myelodysplasia with ineffective hematopoiesis (transform to MDS)
c) excessive marrow fibrosis with resultant bone marrow failure