MDS1 Flashcards
2 main features that characterize myelodysplastic syndrome (MDS
- ineffective hematopoiesis:
2. increased risk of transformation to acute leukemia:
Ineffective hematopoiesis in MDS
○ 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)
MDS increased risk of transformation to acute leukemia
hematopoietic stem cell clone slowly acquires enough abnormalities → outright AML
2 clinical scenarios of MDS
- Primary (idiopathic) MDS
2. Secondary / therapy-related (t-MDS)
Primary (idiopathic) MDS
- Type of onset?
- Age group:
- Median age of dx:
- Incidence:
○ Insidious onset
○ Usually people >50
○ Median age of dx:70
○ Incidence: 3-5 cases/100,000 persons per year
Secondary / therapy-related (t-MDS)
- Type of onset?
- types of therapy leading to MDS
- 2-8 years latency
- use of alkylating agent
- use of topo II
- Exposure of active marrow to ionizing radiation
List 3 different types of tests that could be performed to make a diagnosis of MDS.
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
Morphologic evidence of dysplasia in marrow for MDS
Dyshematopoiesis: > 10% of cell are dysplastic
- Dyserythropoiesis
- Dysgranulopoiesis
- Dysmegakaryopoiesis
Dyserythropoiesis
RBC precursors with nuclear budding, irregularly-shaped nuclei, lack of coordination between nuclear and cytoplasmic maturation, increased ring sideroblasts
Dysgranulopoiesis
Nuclear hypolobation of mature neutrophils, including neutrophils with bilobed nuclei called pseudo-Pelger-Huet cells, also cytoplasmic hypogranularity of neutrophils
Dysmegakaryopoiesis
Megakaryocytes with hypolobated or non-lobated nuclei, often hyperchromatic nuclei, megakaryocytes often of small size
4 possible causes of secondary myelodysplasia that might mimic MDS.
- Certain drugs, including many chemotherapeutic drugs
- use of alkylating agent
- use of topo II
- ionizing radiation - Vitamin deficiency (B12, folate, ect)
- Viral infection
- Toxin exposure (heavy metals such as arsenic)
LOW GRADE MDS:
- Myeloblasts are not increased in frequency
- Refractory Cytopenia with Unilineage Dysplasia (RCUD): good prognosis
- Refractory Cytopenia with Multilineage Dysplasia (RCMD): worse prognosis
HIGH GRADE MDS
- 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
MDS vs. MPNs:
- source of disease
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
MDS vs. MPNs:
- onset
Both insidious
MDS vs. MPNs:
- hematopoiesis effectiveness
MDS: ineffective
- marrow replaced by malignant clone
MPNs: effective
- marrow fibrosis
MDS vs. MPNs:
- ability to develop into acute leukemia
Both
MDS vs. MPNs:
- age group
MDS: - usually >50 - median age of dx: 70 MPNs: - middle-aged to early adults - rare in children
2 reasons for the frequent occurrence of splenomegaly and hepatomegaly in patients with MPNs
- spleen sequestering RBCs because they make too many
2. Extramedullary hematopoeisis, causes liver and spleen to enlarge
3 possible negative end points for MPNs.
• Without treatment, get:
○ Marrow fibrosis
○ Bone marrow failure
○ Transformation to acute leukemia (less common for MPN than MDS)
4 MPNs
- Chronic Myelogenous Leukemia (CML)
- Polycythemia Vera (PV)
- Primary Myelofibrosis (PMF)
- Essential Thrombocythemia (ET)
Chronic Myelogenous Leukemia (CML)
- What is it?
- blood cell count?
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)
Chronic Myelogenous Leukemia (CML)
Phases
• Marrow findings:
- Initial Chronic phase (stable)
- Accelerated Phase (Intermediate phase -may or may be bypassed to Blast phase)
- Blast phase
Chronic Myelogenous Leukemia (CML)
marrow findings
- 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 - Blast phase:
□ 20% or more blasts in the marrow or blood
Chronic Myelogenous Leukemia (CML)
- cytogenic abnormality
§ BCR-ABL1 fusion gene (must have this for diagnosis)
□ Der(22)t(9:22)→ Philadelphia chromosome
Polycythemia Vera (PV) : - Blood cell counts
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
polycythemic phase vs Spent phase (post PV myelofibrosis)
polycythemic phase: increased blood cell counts
Spent: Fall in blood cell count
Polycythemia Vera (PV) : - marrow findings
§ Trilineage hyperplasia in the marrow
§ Clusters of bizarre megakaryocytes
§ Spent phase/post-PV myelofibrosis:
□ Extensive marrow fibrosis → marrow failure
Polycythemia Vera (PV) : - cytogenic abnormalities
Activating mutation of JAK2, usually a V617F point mutation.
Primary Myelofibrosis (PMF) - Blood cell counts:
Q Prefibrotic stage: □ ↑ Platelets in blood □ ↑ neutrophils in blood Progress to fibrotic stage: □ Falling blood cell count □ Leukoerythroblastosis of blood
Primary Myelofibrosis (PMF) - Marrow finding
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
Primary Myelofibrosis (PMF) - Cytogenic abnormality
§ JAK2 mutations are present in around 50% of PMF cases
§ Cases lacking JAK2 mutations often have mutations of MPL or CALR
Essential Thrombocythemia (ET) what is it? How is it different from PMF
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
Essential Thrombocythemia (ET) - blood cell count
§ Persistent thrombocytosis (↑ platelet count)
§ 50% of ET patients are diagnosed based on CBC results while asymptomatic
Essential Thrombocythemia (ET) - Cytogenic abnormality
§ JAK2 mutations are present in around 50% of ET cases
§ Cases lacking JAK2 mutations often have mutations of MPL or CALR
most common method of death attributable to disease in polycythemia vera (PV) patients
venous or arterial thrombosis, leading to complications such as DVT, MI, and stroke
3 sites where thrombosis should always make one consider the possibility of PV
○ Thrombosis of: 1. mesenteric vein, 2. portal vein 3. splenic vein should always raise the Possibility of PV.
most common treatment for PV.
○ 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
peripheral blood smear of a patient with leukoerythroblastosis
Presence of immature granulocytes and immature (nucleated) red cells
Peripheral blood smear of pt w/ primary marrow fibrosis (PMF)
Leukoerythroblastosis in primary fibrotic stage
Peripheral blood smear of pt w/ primary marrow fibrosis (PMF)
Leukoerythroblastosis in primary fibrotic stage
