MDS/MPN with RS and thrombocytosis

Question 1

What is the definition of MDS/MPN

with RS and thrombocytosis?

Answer 1

• platelets > 450
• < 1% blasts in the peripheral blood
• >15% ring sideroblasts
• dyserythropoiesis and < 5% blasts in the bone marrow

Question 2

What are the genetic alterations seen in

MDS/MPN with RS and thrombocytosis?

Answer 2

• strong association with SF3B1 mutations
• concurrent JAK2 mutations
  
  • less commonly MPL and CALR

Question 3

Which cases by definition are excluded

from this category ?

Answer 3

• MDS with del 5q or with t(3;3) or inv93)
• BCR-ABL translocations
• prior diagnosis of MPN without ring sideroblasts where the presence or RS may mean progression
• if the case meets criteria for a different MPN
• if the RS are a consequence of therapy

Question 4

What are the diagnostic criteria

for MDS/MPN with RS and thrombocytosis ?

Answer 4

• anemia associated with erythroid lineage dysplasia with or without multilineage dysplasia
  
  • >15% RS, <1% blasts in PB, <5% blasts in BM
• persistent thrombocytosis >450 x 10^9/L
• SF3B1 mutation or if no mutation no recent history of cytotoxic or growth factor therapy
• No other disease defining mutations /fusions (ex: BCR-ABL1)
• No previous history of an MPN, MDS, or MDS/MPN

Question 5

Do you still need >15% RS

if the SF3B1 mutation is present ?

Answer 5

• yes you must have both present

Question 6

What is the epidemiology and the localization

of the overlap syndrome ?

Answer 6

• slightly older median patient age compared to ET
  
  • 74
• slight female predominance
• PB and BM is always involved
• splenomegaly is seen in 40% of cases
• hepatomegaly can also occur

Question 7

What are the clinical features

of MDS/MPN with RS and Thrombocytosis ?

Answer 7

• clinical overlap between MDS-RS and MPN (like ET)
• anemia is always present
• compared to just MDS-RS
  
  • higher Hgb, WBC and platelets counts
  • but lower than ET

Question 8

What are the microscopic findings

in MDS/MPN with RS and thrombocytosis ?

Answer 8

• normochromc, macrocytic anemia
• circulating blasts should be rare
• thrombocytosis is marked
  
  • with atypical and variable morphology

Question 9

What are the morphologic

findings of the bone marrow ?

Answer 9

• increased erythroids due to ineffective erythropoiesis
  
  • dyspoietic
  • >15% RS
• multilineage dysplasia can be seen in some cases
• megakaryocytes are increased in number
  
  • morphology similar to other BCR-ABL negative MPNs
• marrow fibrosis can occasionally be seen

Question 10

What is the genetic profile ?

Answer 10

• many cases harbor the SF3B1 mutation
  
  • often they also have JAK2
  • less common CALR and MPL W515 mutation
• evaluation for these mutations is not required but if evaluated for and present it supports the diagnosis

Question 11

What is the prognosis and predictive

factors for this syndrome ?

Answer 11

• median survival of 78-128 months
• shorter OS compared to ET but longer than MDS-RS and single lineage dysplasia
• presence of SF3B1 and JAK2 are both independently good prognostic factors
• no specific therapy is available for these patients
  
  • generally just get treated with MDS and MPN medications

Question 12

Review/Read MDS/MPN-U

pgs. 95-96

Question 13

In what scenario would MDS/MPN with RS and

thrombocytosis belong in the MDS/MPN-U category ?

Answer 13

• >15% RS
• >1% blasts in PB or >5% blasts in the BM

Question 14

What mutations have been seen in relatively

high frequency of MPN/MDS-U ?

Answer 14

• TET2
• NRAS
• RUNX1
• CBL
• SETBP1
• ASXL1

Question 15

In what other scenario could MDS/MPN U diagnosis

be made?

Answer 15

• if there is an overlap syndrome that comes back with an MPN defining mutation only but no previous history of an MPN in chronic phase
• the current morphology could represent progression of an undiagnosed MPN
• then you can say MPN/MDS-U with a comment