Myeloproliferative Neoplasms Flashcards
1
Q
CML
A
- MPN
- chronic myeloid leukemia
- granulocytes = abnormal lineage
- all maturation stages
- Philadelphia chromosome (translocation b/w chromosome 9 and 22 - (t(9;22))
> cannot have CML without this abnormality
> translocation creates the BCR-ABL1 fusion gene
2
Q
CML has three major phases
A
- chronic phase = stable for years; most patients
- accelerated phase = progression of the disease
- blast phase = transformation into acute leukemia
3
Q
CML (CBC + PB) findings
A
- leukocytosis (predominantly neuts in diff stages of maturation); no significant dysplasia
- basophilia!! (don’t see this lots; especially in adults/elderly
- blasts rare (<2%)
- PLTs elevated
- anemia often seen but rarely
4
Q
Potential causes of rective neutrophilia
A
- infection (bacterial); occasional virally, fungal, etc.
- tissue damage (trauma, surgery, burns, etc.)
- inflammation
- acute hemorrhage
- acute hypoxia
- medication effect (GCSF, corticosteroids)
- exercise
- smoking
5
Q
CML treatment
A
- tyrosine kinase inhibitors (pill)
- inhibit the activity of BCR-ABL1 pathway
- excellent response with few side effects
- Imatinib (Gleevec) drug most widely known
- Allogenic hematopoeitic stem cell transplantation: curative but high toxicity/ risk of morbidity and mortality
6
Q
Polycythemia vera (PV)
A
- chronic MPN
- primarily increased red cell production but other lineages may be increased too
- EPO independent
- characterized by JAK2 V617F mutation (excessive red cell production)
7
Q
Panmyelosis
A
increased proliferation of all 3 lineages - erythroid, granulocytes, megakaryocytes
8
Q
Other causes of reactive thrombocytosis
A
- infection
- inflammation
- hemorrhage
- surgery/trauma
- iron deficiency
- stress response
- splenectomy/hypisplenism
9
Q
What is dysplasia?
A
A term used to describe the presence of abnormal cells within a tissue or organ. Dysplasia is not cancer, but it may sometimes become cancer. Dysplasia can be mild, moderate, or severe, depending on how abnormal the cells look under a microscope and how much of the tissue or organ is affected
10
Q
MPN vs MDS
A
When a hematological malignancy is characterised by normal differentiation of cells of myeloid cell line, it is referred to as myeloproliferative. On the other hand, when there is abnormal differentiation of cells of myeloid cell line, it is referred to as myelodysplastic.
11
Q
Clinical features of CML
A
- 50% asymptomatic initially
- fatigue, malaise, weight loss, night sweats
- anemia-related symptoms
- splenomegaly +/- early satiety/left upper quadrant pain (~50%)
- hepatomegaly
- bruising/bleeding or gout possibly
12
Q
Chronic phase of CML
A
- insidious onset
- often asymptomatic (incidental discovery)
- blood counts/hepatosplenomegaly stable for years
- progresses to blast in 3-5 years without treatment
13
Q
CML chronic phase findings
A
- hypercellular with granulocytic hyperplasia across all stages of maturation + left shift
- increased eos/basos
- blasts <5%
- may see pseudo-Gaucher cells
- dwarf megakaryocytes
- Reticulin fibrosis
14
Q
pseudo-Gaucher cells
A
Pseudo-Gaucher cells are histiocytes with rounded, blue, lamellar cytoplasm resembling “onion skin” that can be found in up to 40% of the bone marrow of patients with CML
15
Q
this is very important in determining if a cML patient has accelerated CML or not
A
number of basophils
- also worsening counts in general; increased blasts
- splenomegaly worsening
- new cytogenic abrnomalities
16
Q
blast phase of CML
A
- transformation into acute leukemia
- > 20% blasts in Pb or BM
- acute myeloid leukemia usually; 30% into ALL
17
Q
this is BCR-ABL1-like
A
B-lymphoblastic leukemia/lymphoma
- provisional entity
- negative for BCR-ABL1
- complex gene expression testing
18
Q
How to diagnose CML
A
- PB + BM aspirate/biopsy
- cytogenetics: Phil chromosome; other abnormalities (accelerated/blast phase)
- molecular: PCR for BCR-ABL1 (quantitative PCR available once diagnosed); detection + quantitation used to track response to therapy
- ESSENTIAL to prove there is Phil chromosome/BCR-ABL1 fusion gene to establish diagnosis of CML
19
Q
PV etiology
A
- unknown usually
- genetic predisposition
- ionizing radiation + occupational exposure to toxins maybe?
- spontaneous mutations??
20
Q
PV genetics
A
- JAK2 V617F mutation (>95%); can also be seen in other MPNs + other hematologic neoplasms
- JAK2 exon 12 (functionally similar; 3%); test other one first and if negative, test this
21
Q
Clonal Hematopoiesis of Indeterminate Potential (CHIP)
A
- subset of myeloid cells acquire mutation(s) that are often seen in MDS, AML, and MPNs
- patients may be healthy with few/minimal hematologic issues
- associate with decreased overall survival, increase risk of overt hematologic malignancy, increased risk of CV disease
22
Q
Clinical features of Polycythemia Vera
A
- diagnosed incidentally
- increased RBC mass = increased blood viscosity
- headache, dizziness, visual disturbances, paresthesias, pruritus, erythromelalgia, aquagenic pruritus
- palpable splenomegaly
- present initially with venous or arterial clot
- present with hemorrhage (acquired von Willebrand disease esp. if PLTs >1000(
23
Q
Need these to diagnose PV
A
- high Hb,
- BM findings
- JAK2 mutation
24
Q
Secondary polycythemia
A
- more common
- often associated with hypoxia (stimulates EPO - increased RBCs); cyanotic heart disease, chronic lung disease, sleep apnea, high altitudes, abnormal Hb, etc.
- certain cancers may inappropriately increase EPO
- performance-enhancing drugs too
25
PB findings of PV
- persistent excess of RBCs (normochromic, normocytic unless iron deficient)
- thrombocytosis
- maybe neutrophilia
- basophilia is rare
- circulating blasts not generally seen
26
BM findings of PV
- hypercellular marrow
- panmyelosis
- megakaryocytes tend to by hyperlobated, form loose clusters, and pleomorphic (small to large)
- increased reticulin/collagen fibrosis
- sustainable iron?
27
PV treatment
- phleb to keep hematocrit <0.45; may cause iron def
- low-dose aspirin to prevent clotting
- cytoreductive therapy
- JAK inhibitor
28
Essential Thrombocythemia
- chronic MPN
- megakaryocytic lineage
- persistently high PLTs (>450 x 10^9/L)
- megakaryocytic hyperplasia in BM
29
clinical features of ET
- >50% patients asymptomatic; incidental discovery
- thrombosis or hemorrhage most common clinical manifestations
- some patients may develop acquired von Willebrand disease esp. with PLT count > 1000
- minor splenomegaly
30
Genetics for ET
- no specific molecular/cytogenetic abnormality = can be found in other MPNs too
- JAK2 V617F or similar = increased risk of arterial thrombosis; lower risk of transformation to post-ET myelofibrosis
- CALR = low risk of thrombocytosis
- MPL = usually at W515L
- triple-negative (none of the above)
31
Other causes of thrombocytosis
- hematologic malignancies (other MPNs, MDS)
- familial (inherited)
- reactive (common) = infection, inflammation, hemorrhage, surgery/trauma, ID, etc.
32
ET in BM
- usually normal cellularity
| - megakaryocytic hyperplasia (large with abundant cytoplasm and hyperlobulated); may form loose clusters
33
emperipolesis
- intact cell (RBC or neut) passes through another cell's cytoplasm (megakaryocyte) and exits without interfering w function
- can be seen in ET; but not exclusive (reactive conditions for ex)
34
Diagnosis of ET
- can often be mistaken for pre-fibrotic PMF and reactive thrombocytosis
- exclude other MPNs!
- BM morph key
- molecular testing
35
ET treatment
- low-dose aspirin (reduces vascular events and vasomotor symptoms)
- cytoreductive therapy (hydroxyurea); pegylated interferon/anagrelide in refractory patients (reduce risk of thrombocytosis)
36
Primary Myelofibrosis (PMF)
- chronic MPN
- proliferation of predominantly abnormal megakaryocytes and granulocytes
- prominent extramedullary hematopoiesis in later stages
37
PMF Etiology
- sporadic/unknown
- exposure to benzene or ionizing radiation in some cases
- rare cases = familial predispposition
38
PMF clinical features
generally more severe
- splenomegaly (90%) = ab pain/early satiety
- hepatomegaly
- thrombosis
- increased LD
39
This PMF stage can be difficult to distinguish from ET
Pre-fibrotic stage
40
PMF treatment
- symptomatic management (splenectomy, blood transfusions, etc.)
- cytoreductive therapy (hydroxyurea)
- JAK2 inhibitor (ruxolitinib - JAKavi)
- allogenic HSC transplant but most are inelligible
