Chronic Myeloid Neoplasms
Myeloproliferative neoplasms (MPN)
Essential thrombocythemia

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 7 March 2017, last major update August 2011

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Essential thrombocythemia [title]

Cite this page: Essential thrombocythemia. PathologyOutlines.com website. http://pathologyoutlines.com/topic/myeloproliferativeET.html. Accessed July 26th, 2017.
Diagrams / tables

Images hosted on other servers:

Diagrams:

Drawing of JAK2 mutation

Drawing of c-Mpl mutation



Tables:

Proposed criteria for ET



Nature Images

WHO 2008 diagnostic algorithm

Clinical features
  • See MDS/MDN - unclassifiable for refractory anemia with ringed sideroblasts plus essential thrombocythemia
  • Prevalence of 2 - 3 per million (Am J Hematol 2008;83:359)
  • Median age of 50 - 60 years at diagnosis but may occur at any age; 2/3 female
  • Rarely occurs in children (must rule out hereditary thrombocytosis)
  • Closely related to polycythemia vera but no increased red blood cell mass
  • More than half of the cases are detected due to routine peripheral blood count
  • Increased proliferation usually confined to megakaryocytes with platelet count > 450 × 109/ L
  • Thrombosis and hemorrhage common, due to qualitative and quantitative abnormalities in platelets
  • Indolent, long asymptomatic periods alternating with thrombotic or hemorrhagic crises; may rarely progress to myelofibrosis
  • Median survival is 10 - 15 years, hence life expectancy is almost normal (Orphanet J Rare Dis 2007;2:3)
  • Bone marrow examination necessary to exclude other myeloproliferative neoplasms (Arch Pathol Lab Med 1991;115:475)

Diagnostic criteria (WHO 2008): must meet all 4 major criteria
  • Criterion #1: sustained platelet count of 450 x 109 / L or more
  • Criterion #2: megakaryocyte proliferation with large and mature morphology, no or little granulocyte or erythroid proliferation
  • Criterion #3: does not meet WHO criteria for CML, PV, PMF, MDS or other myeloid neoplasm
  • Criterion #4: demonstration of JAK2 V617F or other clonal marker OR no evidence of reactive thrombocytosis

Diagnostic criteria (WHO 2001):
  • Not currently used: sustained platelet count > 600K, marrow shows proliferation mainly of megakaryocytes with enlarged mature forms, no other causes of thrombocytosis (thus, is a diagnosis of exclusion), Table
Treatment
  • High risk patients (for thrombosis) get cytoreductive therapy (hydroxyurea) and low dose aspirin
Microscopic (histologic) description
  • Peripheral blood: abnormally large platelets and increased platelets; bizarre shapes, pseudopods and agranular forms
  • Bone marrow: mildly hypercellular, increased number and large forms of megakaryocytes with deeply lobulated or hyperlobulated nuclei (staghorn nuclear appearance), megakaryocytes dispersed throughout the marrow with occasional loose clusters; delicate reticulin fibers (myelofibrosis absent / minimal) but no overt fibrosis
  • Increased angiogenesis (CD34+)
  • Usually no dyserythropoiesis, dysgranulopoiesis, macrocytosis or monocytosis
  • No increased trilineage proliferation; no highly bizarre / dysplastic megakaryocytes, no predominance of small megakaryocytes with monolobulated nuclei

Diagnostic criteria for post ET myelofibrosis:
  • Required criteria: established diagnosis of ET per WHO criteria; and marrow fibrosis grade 2 - 3 (on 0 - 3 scale)
  • Additional criteria (2 required): anemia or decrease in Hb by 2 gm/dL from the baseline level; leukoerythroblastic peripheral blood; splenomegaly; rise in LDH levels; constituitional symptoms including fever, night sweats, > 10% weight loss in 6 months
Microscopic (histologic) images

Images hosted on PathOut server:


Peripheral blood:

Clusters of large platelets (platelet count is 1700K)

Increased megakaryocytes (many megakaryocytes are unusually large) in mildly hypercellular marrow of 66 year old woman with platelet count of 1200K



Images hosted on other servers:

Bone marrow smear:

Increased megakaryocytes

Molecular / cytogenetics description
  • Adults - JAK2 V617F mutation in up to 75% (Blood 2006;108:1865)
  • JAK2 mutant allele burden contributes to clinical phenotype (Haematologica 2008;93:41)
  • Also W515L and W515K mutations in thrombopoietin receptor c-Mpl (J Transl Med 2006;4:41)
  • May have del(20q) and unbalanced translocations between 1q and 7p
  • Must rule out BCR-ABL1 fusion gene status
  • Children - usually have no JAK2 mutation
Differential diagnosis
  • Other myeloproliferative neoplasms
  • An increase in erythroid / granulocytic population should raise suspicion of prodromal stage polycythemia vera (Acta Haematol 2005;113:213)
  • Granulocytic proliferation with bizarre or dysplastic megakaryocytes is suggesive of prefibrotic stage of PMF
  • Reactive thrombocythemia (inflammatory disorders, asplenism, infection, connective tissue disorders, metastatic cancer, lymphoproliferative disorders and iron deficiency: no JAK2 or c-Mpl mutations)