Essential Thrombocythemia Flashcards
What is the definition of
essential thrombocythemia ?
- MPN involving primarily the megakaryocytes
- characterized by sustained thrombocytosis (>450) and increased numbers of large, atypical megas with hypersegmented nuclei
- must exclude other causes of thrombosis including reactive conditions
- cannot have BCR-ABL fusion
What is the epidmiology of ET ?
- generally diagnosed ages 50-60
- second peak in mid 30s (also more common in women)
- slight female predilection
- ET can infrequently occur in kids
- must rule out cases of hereditary thrombocytosis
What is the etiology of ET ?
- etiology of ET is not known but
- germline mutations have been identified:
- JAK2
- Gelsolin gene
- seen in families with hereditary thrombocytosis
What is the localization of ET ?
- blood and bone marrow are the primary sites
- spleen is not usually involved by any extramedullary hematopoiesis
- can become a sequestrant for platelets later on
What are the key clinical features of ET ?
- more than 1/2 the cases are asymptomatic
- other 1/2 present with some type of vascular occlusion or hemorrhage
- can have severe occlusion of major arteries and veins
- Budd-Chiari
- splenic or hepatic vein thrombosis
- bleeding usually occurs at mucosal surfaces
- can present with mild spelnomegaly or hepatomegaly in 50% of cases
What clinical features are
usually absent in ET ?
- leukocytosis and erythrocytosis
- increased serum LDH
- leukoerythroblastosis and poikilocytosis are absent
What conditions must be excluded prior to
rendering a diagnosis of ET ?
- must exclude all possible reactive causes of thrombocytosis
- myeloid neoplasms with associated high platelet counts
- MDS associated with del5q
- MDS/MPN with ring sideroblasts and thrombocytosis
- pre-PMF
- a clonal abnormality such as JAK2 etc rules out reactive causes but is not specific to ET
What are the key microscopic findings
of ET in the peripheral blood ?
- platelets with anisocytosis are frequent
- bizarre shapes can also be seen, agranular, large or giant platelets
- mild leukocytosis to normal wbc is typical
- RBC s are N/N unless there has been hemorrhage then may have an iron deficiency anemia
- NO leukoerythroblastosis or tear drops
What are morphologic findings in the
bone marrow in ET ?
- cellularity is normal in most cases to slightly increased
- most striking abnormality is proliferation of megakaryocytes
- large to giant forms
- abundant mature cytoplasm
- deeply lobed/ hypersegmented nuclei
- usually scattered around bone marrow but can be seen in loose clusters
- erythroid proliferation may be seen if there has been hemorrhage
- granulocytic proliferation is highly unusual
- no increase in myeloblasts or left shift should be seen
- no to mildly increased reticulin fibrosis
What morphologic feature if seen
at diagnosis excludes ET ?
- significant reticulin fibrosis or collagen deposition
What morphologic feature is often seen in ET
but is not specific for the diagnosis ?
- emperipolesis
What features would suggest a
prodromal stage of polycythemia vera ?
- low degree of granulocytis and erythroid proliferation
Note: if there is granulocytic proliferation and atypical, bizarre megas …..consider PMF
What does the presence of dypslasia
signify ?
- if there is myeloid or erythroid dyspoiesis it would suggest more of an MDS picture
What is the postulated cell of origin ?
- stem cell
What is the genetic profile for
ET ?
- there are no specific diagnostic molecular alterations specific to ET
- 50-60% of cases have JAK2 V617F
- 30% have CALR
- 3% have MPL
- 12% are triple negative
note: a subset of the triple negative caases have gain of function mutations in MPL S204P and MPL Y591N
