Polycythemia Vera Flashcards

1
Q

What is the definition of

PV ?

A
  • chronic MPN characterized by increased RBC production independent of the mechanisms that normally regulate it
  • JAK2 V617F mutation virtually in all patients
    • or another functionally similar JAK2 mutation
  • Proliferation:
    • erythroid lineage
    • granulocytes and megkaryocytes
    • aka Panmyelosis
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2
Q

What two phases of PV can be seen ?

A
  • polycythemic phase
    • associated with elevated hemoglobin levels, elevated hematocrit, and increased RBC mass
  • spent phase
    • post-polycythemic myelofibrosis
    • develop cytopenias (anemia)
    • extramedullary hematopoiesis and hypersplenism due to bone marrow fibrosis
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3
Q

What does the natural progression

of PV include ?

A
  • myelofibrosis
  • low incidence of evolution to MDS and or Leukemia
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4
Q

What must be excluded to make

the diagnosis of PV?

A
  • all secondary causes of erythrocytosis
  • heritable polycythemia
  • other MPNs
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5
Q

What is the epidemiology of PV ?

A
  • incidence increases with age
    • lowest rates in Japan and Israel
  • most reports indicate a slight male predominance
  • median patient age: 60 years
    • < 20 years of age, rare reports
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6
Q

What is the etiology of PV ?

A
  • underlying cause is unknown in most cases
  • genetic predisposition in some families is seen
  • Suggested possible causes include:
    • ionizing radiation
    • occupational exposure to toxins
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7
Q

What is the localization of

PV ?

A
  • blood and bone marrow are the major sites of involvement
  • spleen and liver can also be affected
    • these are the major sites of extramedullary hematopoiesis
  • but any organ can be damaged due to vascular consequences of increased RBC mass
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8
Q

What are the criteria required

for the diagnosis of PV ?

A
  • requires that either all 3 major criteria OR the first 2 major criteria plus the minor criteria be true
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9
Q

What are the major criteria for PV ?

A
  • elevated Hgb concentration (> 16.5 g/dL in men, >16 g/dL in women) or elevated hematocrit (>49% in men, >48% in women) or Increased red blood cell mass (>25% above mean normal predicted value)
  • bone marrow biopsy showing age-adjusted hypercellularity with trilineage growth (panmyelosis)
    • includes erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature megakaryocytes (differences in size)
  • Presence of JAK2V617F or JAK2 exon 12 mutation
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10
Q

What is the minor criterion for

PV ?

A
  • subnormal serum erythropoietin level
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11
Q

What are the clinical features

of PV ?

A
  • the major symptoms are associated with hypertension or vascular abnormalities due to the increased RBC mass
    • 20% of cases can have thrombosis (venous or arterial), MI, or other ischemic event be the first presenting symptom
  • IMP
    • mesenteric, splenic, or portal or Budd-Chiari syndrome should lead to a suspicion of PV
  • Other symptoms
    • blurry vision, headache, dizziness, parasthesias
    • pruritis, gout
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12
Q

What are some of the physical

findings in PV ?

A
  • plethora
  • palpable splenomegaly
  • sometimes hepatomegaly
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13
Q

What are the microscopic features

of peripheral blood in PV ?

A
  • mild to overt excess of normochromic RBCs
  • Note:
    • if there is iron deficiency due to bleeding the RBCs may be hypochromic and microcytic
  • Neutrophilia and basophilia may be rarely present
  • occasional immature granulocytes can be seen
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14
Q

What are the microscopic findings of

PV in the bone marrow ?

A
  • cellularity is usually increased
    • hypercellularity is especially noticeable in the subcortical marrow space
    • panmyelosis accounts for the increased cellularity but increased erythroid and megakaryocytes are most prominent
      • erythropoiesis is usually normoblastic (left shifted) with large islands of cells
  • myeloblast proportions are not increased
  • megakaryocytes are increased with frequently hypersegmented nuclei
    • tend to form loose clusters, lie close to bony trabeculae
    • also display significant pleomorphism
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15
Q

At the beginning, which disease

entity can PV mimic ?

A
  • essential thrombocythemia
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16
Q

What is the morphology that can help

point away from ET and towards PV ?

A
  • marrow sinuses are dilated and often filled with erythrocytes
  • plus the panmyelosis
17
Q

What must be done in order

to diagnose PV ?

A
  • bone marrow biopsy with morphologic evaluation is essential in the diagnosis of PV
18
Q

What is the reticulin deposition

in a case of PV ?

A
  • generally see normal reticulin staining in about 80% of cases
  • but other cases have mild to moderate with even collagen fibrosis

Note: cases with a minor increase in reticulin (WHO grade 1) have been associated with more rapid progression to post-PV myelofibrosis

19
Q

What are two other findings in the bone marrow

of PV patients that are typically seen ?

A
  • 20% of cases have reactive lymphoid aggregates
  • >95% of cases have no stainable iron on the aspirate or biopsy
20
Q

What is the most common pattern of disease

progression for PV and how does it present?

A
  • post-PV myelofibrosis
  • during later phases, erythropoiesis progressively decreases, RBC mass normalizes then decreases and the spleen further enlarges
  • persistent leukocytosis occurs around the time of progression
    • associated with more aggressive disease course
  • these changes are usually accompanied with bone marrow changes as well
21
Q

What are the bone marrow findings

in progression of PV (post-PV MF) ?

A
  • myeloid metaplasia
    • leads to leukoerythroblastic peripheral blood smear, poikilocytosis with dacrocytes
  • splenomegaly due to extramedullary hematopoiesis
  • overt reticulin and collagent fibrosis
  • cellularity varies but specimens can be hypocellular
  • clusters of megakaryocytes, some with very hyperchromatic nuclei, are prominent
  • erythropoiesis and megakaryopoiesis are decreased
  • RBCs, granulocytes and megas are sometimes found lying within dilated marrow sinusoids
22
Q

What features are usually not seen

in the post-PV myelofibrosis ?

A
  • >10% blasts in the peripheral blood or
  • presence of substantial myelodysplasia is unusual

If these findings are present they likely represent transformation to an accelerated phase

23
Q

What are cases of PV with >20% blasts called ?

A
  • if there are >20% blasts they are considered the blast-phase of post-PV MF
    • formerly called AML
24
Q

What is the postulated cell of origin ?

A
  • hematopoietic stem cell
25
Q

What is the most common genetic

abnormality in PV ?

A
  • somatic gain of function mutation JAK2 V617F
  • it occurs in >95% of cases but is not specific for this entity
    • Note: <5% of cases of AML, MDS, CML can have this abnormality as well
  • rare cases of JAK2-mutant PV acquire a BCR-ABL1 rearrangement
    • but the significance of this is uncertain
      • however, a phenotypic and morphologic shift to a CML picture can occur
26
Q

What is the other JAK2 mutation

and it’s morphologic findings?

A
  • mutations in exon 12 of JAK2
  • found in 3% of cases
  • predominance of erythroids
27
Q

What are the cytogenetics of PV ?

A
  • at diagnosis, cytogenetic abnormalities are detectable in as as many as 20% of cases
  • most common recurrent cytogenetic aberrations:
    • gain of chromosome 8 or 9
    • del20(q)
    • del13(q)
    • del 9(p)
  • gains of chromosomes 8 and 9 sometimes seen together
  • chromosome abnormalities increase with disease progression
  • if they progress to AML
    • cytogenetics are often similar to those seen in therapy related AML
28
Q

What are the prognostic and

predictive factors associated with PV?

A
  • with current treatment, median survival times. >10 years
  • prognostic factors other than older age remain controversial
    • leukocytosis
    • abnormal karyotype
  • most patients die from thrombotic complications or secondary malignancies
    • 20% succumb to MDS / AML