Essential Thrombocythemia



Essential Thrombocythemia


Kaaren K. Reichard, MD





Key Facts


Terminology



  • Clonal hematopoietic myeloproliferative neoplasm


  • Proliferation largely restricted to megakaryocytic lineage


Clinical Issues



  • Vascular disturbances in 50% of individuals


Microscopic Pathology



  • Peripheral blood



    • Variable thrombocytosis but ≥ 450 × 109/L


    • No leukoerythroblastosis


    • No significant left shift in the granulocytic series


    • Circulating blasts unusual


    • Red and white blood cell morphology unremarkable


  • Bone marrow



    • Normal cellularity to mildly hypercellular


    • Blasts < 5%


    • Striking megakaryocytic proliferation


    • Absent/minimal reticulin fibrosis


Ancillary Tests



  • Cytogenetics typically normal


  • ∽ 50% of cases with JAK2 V617F mutation


Top Differential Diagnoses



  • Reactive thrombocytosis



    • Numerous causes


    • Cause is usually clinically apparent


    • BM examination not required


  • BCR-ABL1-negative MPNs


  • CML with thrombocytosis



    • BCR-ABL1 fusion present






This PB smear shows the typical appearance of ET: Thrombocytosis with unremarkable neutrophil and red blood cell morphology. Reactive thrombocytoses often exhibit a similar appearance.






This BM shows the typical appearance of ET: Increased, markedly enlarged, hyperlobulated megakaryocytes in loose clusters. There is no significant proliferation of granulocytic and erythroid series.


TERMINOLOGY


Abbreviations



  • Essential thrombocythemia (ET)


Synonyms



  • Essential thrombocytosis


  • Primary thrombocytosis


  • Primary thrombocythemia


Definitions



  • Clonal hematopoietic myeloproliferative neoplasm (MPN)


  • Proliferation largely restricted to megakaryocytic lineage


  • Sustained thrombocytosis ≥ 450 × 109/L


ETIOLOGY/PATHOGENESIS


Molecular Pathogenesis



  • Approximately 50% of cases harbor the JAK2 V617F activating mutation


  • Approximately 4% of cases harbor an MPL mutation


  • Exclusion of BCR-ABL1(+) disease


Familial ET



  • Rare


  • Incidence of JAK2 mutation lower than in sporadic ET


  • Incidence of thrombosis lower than in sporadic ET


  • Activating MPL mutation thought to be main cause


  • Spontaneous megakaryocyte formation


  • Reported 100% 10-year survival


CLINICAL ISSUES


Epidemiology



  • Incidence



    • 0.6-2.5/100,000 people per year


  • Age



    • Typically adults


    • 6th and 7th decades of life


    • May present in children; exclude familial


  • Gender



    • No gender predilection


Site



  • Peripheral blood (PB), bone marrow (BM)


Presentation



  • Abnormal complete blood cell count (CBC)


  • Thrombocytosis


  • Vascular disturbances in 50% of individuals



    • Thrombosis


    • Hemorrhage


    • Increased risk of miscarriage


Laboratory Tests



  • CBC with differential


  • PB and BM examination


  • Conventional cytogenetics


  • Molecular studies as needed



    • JAK2 V617F seen in ˜ 50% of cases


    • MPL mutations in < 5%


Treatment



  • Low-dose aspirin, unless contraindicated


  • Cytoreductive therapy



    • Aim is to reduce thrombotic complications


    • Hydroxyurea


    • Anagrelide


Prognosis



  • Generally indolent


  • Predictors of thrombosis



    • Age > 60 years


    • Prior history of thrombosis


  • Acute leukemia transformation



    • Poor prognosis


    • Rare event



MICROSCOPIC PATHOLOGY


Peripheral Blood



  • Variable thrombocytosis but ≥ 450 × 109/L


  • Striking platelet anisocytosis



    • Small and large platelets


    • Hypogranular forms may be seen


  • Circulating megakaryocytic nuclei


  • No leukoerythroblastosis


  • Neutrophilia may occasionally be observed


  • No significant left shift in the granulocytic series


  • No significant basophilia


  • Circulating blasts unusual


  • Red blood cell morphology unremarkable


  • White blood cell morphology unremarkable


Bone Marrow



  • Normal cellularity to mildly hypercellular


  • Generally no significant granulocytic or erythroid proliferation



    • Occasionally may encounter mild granulocytic hyperplasia



      • Consider early phase of primary myelofibrosis in such cases


  • Blasts < 5%


  • Striking megakaryocytic proliferation



    • Increased numbers


    • Loosely clustered


    • Markedly enlarged



      • ET megakaryocytes are largest of all BM disorders


    • Hyperlobulated


    • Mature


    • May see intrasinusoidal/perisinusoidal distribution


  • Absent/minimal reticulin fibrosis


  • Rare lymphoid nodules


  • Normal iron stores



    • Unless concurrent iron deficiency



      • Exclude iron-deficient polycythemia vera


  • Normal bone


ANCILLARY TESTS


Histochemistry



  • Reticulin



    • Absent to minimal fibrosis


    • Progressive fibrosis in rare cases


Immunohistochemistry

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Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Essential Thrombocythemia

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