Essential Thrombocythaemia (ET)

Epidemiology and Etiology:

• MPN involving primarily the megakaryocytic lineage
• 50-60y average
• Second peak in 30y women
• Infrequently in children (rule out rare cases of hereditary thrombocytosis)

Common sites:

• Bone marrow
• Blood

Gross features:

• Mild splenomegaly (50%) (most of these may actually be PMF if strict criteria applied)
• Hepatomegaly (15-20%)

Histologic features:

• Peripheral Blood:
• Thrombocytosis, marked
• Anisocytosis, from tiny to atypical large, giant platelets
• Bizarre shapes, pseudopods, agranular platelets maybe (uncommon)
• WBC count and leukocyte differential normal usually (borderline elevation may occur)
• absent or minimal basophilia
• RBCs normocytic and normochromic usually
• Microcytic and hypochromic maybe, if iron deficiency caused by bleeding
• Emperipolesis of BM elements frequently (not specific)
• Stainable iron present (40-70%)
• Absent leukoerythroblastosis
• Absent teardrop-shaped RBCs
• Absent granulocytic proliferation (highly unusual, and if present, only mild)
• Presence of even mild combined granulocytic and erythroid proliferation should raise consideration of prodromal stage PV
• Granulocytic proliferation associated with bizarre, highly atypical megakaryocytes should raise consideration of prefibrotic stage of PMF
• Absent myelodysplasia
• Absent blast increase
• Absent significant reticulin fibrosis or collagen fibrosis (excludes ET diagnosis)
• Bone Marrow:
• Megakaryocytes increased, enlarged
• Dispersed patterhn, loose clusters maybe
• Predominance of large to giant forms
• Cytoplasm abundant, mature
• Nuclei deeply lobulated and hyperlobulated (stag-horn like)
• Not as bizarre, highly atypical as in PMF
• Normocellular or moderately hypercellular BM

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

• JAK2 V617F mutation (40-50%) (not specific for ET) (excludes reactive thrombocytosis)
• ABSENT BCR/ABL1 fusion gene (recommended for all patients in whom a diagnosis of ET is considered)
• MPL W515K/L (1%)
• Abnormal karyotype (5-10%)
• +8
• 9q abnormalities
• 20q-
• Rule out MDS if 5q- is found (but isolated 5q- has been reported in ET)

Other features:

• Thrombocytosis sustained, >= 450x10⁹/L (most >= 600x10⁹/L
• Incidental finding on PB mostly
• Thrombosis, hemorrhage episodes
• WHO Criteria for ET diagnosis (all 4 criteria required)
• Plt >= 450x10⁹/L (sustained during the workup process)
• Megakaryocytic proliferation
• Enlarged
• Mature
• No significant increase or left-shift of granulopoiesis or erythropoiesis
• NOT meeting criteria for PV, PMF, BCR-ABL+ CML, MDS (5q-, RARS-T), or other MPN
• (PV) Requires failure of iron replacement therapy to increase haemoglobin level to the PV range in the presence of decreased serum ferritin
• (PMF) Requires the absence of relevant reticulin fibrosis, collagen fibrosis, peripheral blood leukoerythroblastosis, or markedly hypercellular marrow accompanied by megakaryocyte morphology that is typical for primary myelofibrosis including small to large megakaryocytes with an aberrant n:c ratio and hyperchromatic, bulbous, or irregularly folded nuclei and dense clustering
• (CML) Requires absence of BCR/ABL1 gene fusion
• (MDS) Requires absence of dyserythropoiesis and dysgranulpoiesis
• JAK2 V617F+, or other clonal marker positive, OR no evidence for reactive thrombocytosis
• (reactive thrombocytosis causes) Iron deficiency, splenectomy, surgery, infection, inflammation, connective tissue disease, metastatic cancer, lymphoproliferative disorders
• Indolent
• Median survival 10-15y (near normal mostly) (may be underestimate b/c diagnostic criteria have changed)
• Occasional life-threatining thromboembolic or haemorrhagic episodes
• Transformation to AML or MDS (<5%) (likely related to previous cytotoxic therapy)

References:

• Swerdlow et al. (ed) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2008)